Exosome Therapy for Hair Loss

What are your thoughts on exosome therapy?

I’ve selected this question below for this week’s question of the week. It allows us to review some concepts in new therapies, including exosomes.

Question

I have been suggested by my dermatologist exosome therapy, one injection per month for three months for MPB. I understand this is a novel therapy with limited studies.

I wanted to know your opinion, if you have had experience or know of results and/or side effects.

Thank you so much,

Answer

Thanks for the great question. I’m not sure what country you live in but here in North America (Canada and the United States), exosome therapy is not permitted - except under very special circumstances whereby a doctor has applied for and received a special IND application from the FDA (or equivalent in Canada).

I have yet to use it in my practice. In North America, if I wanted to use exosomes, I’d only be permitted to use it in the the context of a research study and I’d need to do all the paperwork to have my study approved. I’ll get back to that in a moment but you can already see how new and experimental exosome therapy truly is (as of the date of your question).

Exosome therapy is a potentially interesting therapy. To date, there have been very few published studies that actually show exosomes are all that helpful for treating hair loss. There was one study, however, by Chang-Hun et al back in 2019 in the Journal of the American Academy of Dermatology. That study had just 20 patients and followed the for just 12 weeks. However, the authors of that study found a 16 % increase in hair density and an 11% increase in thickness with use of exosome therapy. Not a lot - but some improvement. There were no serious side effects. That’s a nice change in hair density - but certainly not dramatic. With only 12 weeks of follow up, it’s unclear really what this means.

There have been a variety of in-vitro studies showing that exosomes can increase proliferation of dermal papillae (DP) cells, hair matrix cells, and outer root sheath cells as well as promote hair follicle stem cell proliferation and differentiation. I follow the world of exosomes closely!

Let’s dive deeper now.

What are exosomes?

Exosomes were only recently discovered - about 40 years ago. They are now being studied in various parts of medicine. Exosomes are extracellular vesicles that are produced by some type of cell. They are essentially tiny communication vesicles about 20-50 nm in size. It was first thought that exosomes were just cellular waste that got booted out of cells. Fortunately, it eventually came to be recognized that exosomes were important carriers of signaling molecules and were used for communication between cells. They contain many things including protein, nucleic acids, growth factors, lipids. It’s the growth factors in particular that are believed to be helpful in hair loss.

There are a wide range of cells that may be used to produce exosomes. However, donated human amniotic mesenchymal stem cells are one common source. Exosomes from adipose-derived stem cells are another source. There’s more yet - including exosomes from bone marrow derived mesenchymal stem cells.

Creation of exosomes. FROM: Graça Raposo and Willem Stoorvogel. Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol . 2013 Feb 18;200(4):373-83. USED WITH CREATIVE COMMONS LICENSE. All credit to original source

The FDA Regulates Exosomes in the USA; Health Canada does the Same in Canada

The US Food and Drug Administration (FDA) has authority to regulate regenerative medicine products, including stem cell products and exosome products. The FDA has not given the green light to exosome therapy. It can only be used in a research setting by clinics that have a defined research study in place. The same is true in Canada. In Canada, exosomes fall under the jurisdiction of the Food and Drugs Act.

A US or Canadian physician who uses exosome therapy without having all the documents in place to show that they are conducting a research study could be subject to fines, and a variety of other penalties. It’s a serious issue and so exosome therapy is more common in other countries outside North America. In North America, a clinic needs to have applied for and received approval for an ‘investigational new drug” (IND) application before doing anything with exosomes.

I don’t do exosome therapy in my office. I’ve certainly had lots of conversations and phone calls with various regulatory bodies about these therapies. The message is always the same: A doctor can’t use these therapies unless they have been approved to do a clinical trial. Obviously in these kind of trials, the patient would sign a lot of forms indicating they know they are part of a clinical trial and the patient would be provided with proof that the clinic is part of such a trial. In other words, it would be pretty clear if a clinic in North America has an IND to study exosomes.

At the present time, there are no FDA or Health Canada approved exosome products for treating hair loss of any kind. Clinics can’t offer them (unless the patient receiving them is a research study patient).

The US FDA and Health Canada are very very worried about these types of therapies getting to the public without first doing the proper study. That’s why they want to study them ! In 2019, the FDA published a document for the public to warn of their concerns.

FDA’s Public Safety Message on Exosome Therapy

FDA’s Safety Alert for Exosome Therapy

CDC Warning About Exosomes

Health Canada Warnings on Autologous Therapies

Investigational New Drug Applications (IND Applications)

An “IND” is a submission to the FDA to request permission to study a drug. The goal of the entire IND process to help collect information that a given drug is indeed safe to use in humans. An ‘investigator IND’ is a special type of IND submission whereby the IND is submitted by a doctor who then initiates and conducts the clinical study. In order for a doctor in North America to conduct any kind of study with exosomes, they need an investigator IND.

Exosomes are considered “drugs” by many regulatory organizations including the FDA and Health Canada because they are used to treat some sort of medical issue. Here, in our discussion today, that medical issue we are speaking about here is hair loss. That’s the first point that makes an IND needed for anyone wanting to use or study exosomes for hair loss. The second issue is that the drug is used in human beings. Studies on human beings using drugs that have not been approved in the past need an IND. There are no exceptions for exosomes: all users need an IND application. Exosomes are not an approved ‘drug’.

A clinic or researcher with an approved IND application has permission to ship across the country and then to use exosomes in a formal study. It does not give physicians permission to use exosomes in any way they wish - only in a pre-approved research study.

Summary

In summary, exosomes are a potential new therapy. The data to date on effectiveness is promising (although not super exciting). The concept sure is exciting. We don’t really know much about exosome therapy but more information is going to emerge in the next few years. Stay tuned. It seems safe in small studies but these studies are extremely small. We have no idea how often treatments will be needed and no idea if 5 treatments is safe but 55 treatments is unsafe. We have no idea if 1 year of treatment poses different risk than 10 years of continuous treatment. Exosomes are completely new.

Exosome therapy is not FDA approved and not Health Canada approved. Here in North America, clinics can’t offer them without first formally registering and being approved to conduct a clinical trial with the US of Canadian government. A patient in North America can’t receive these therapies yet without being part of a clinical trial. In other words, exosome therapy not just another therapy option like PRP. It’s completely different. It’s not possible to walk into a clinic and choose exosome therapy like one would choose PRP or a hair transplant. Exosomes can only be offered to North American patients in the context of a clinical trial. That’s important for North American readers of this article to be aware of.

Thanks again for the great question.

REFERENCE

Chang-Hun et al. Exosome for hair regeneration: From bench to bedside. J Am Acad Dermatol. VOLUME 81, ISSUE 4, SUPPLEMENT 1, OCTOBER 01, 2019

Graça Raposo and Willem Stoorvogel. Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol . 2013 Feb 18;200(4):373-83.

Does inflammation in the scalp help minoxidil work better or worse?

How does inflammation affect how minoxidil helps over time?

I’ve selected this question below for this week’s question of the week. It allows us to review some concepts in treatment of androgenetic alopecia with minoxidil and the relationship to inflammation.

Question

I have androgenetic alopecia and my scalp is red at time as I have seborrheic dermatitis or some say psoriasis. I have heard that inflammation in the scalp may mean minoxidil works less well and other say it will work better.

What is the correct answer?

Answer

This is such a great question. The full answer as to whether inflammation causes minoxidil to work better or worse really comes down to what is causing the inflammation. There are 100 causes of inflammation in the scalp!!!! Some causes might make it work better and some might cause it to work less well.

As we tackle this subject, it’s important to keep in mind that few studies have actually been done.

Inflammation and fibrosis are known to affect responses to minoxidil. In 1993, Dr Whiting showed that patients with significant perifollicular inflammation and fibrosis have poorer responses to topical minoxidil. We don’t routinely evaluate inflammation in the scalp with males and females with androgenetic alopecia in deciding whether minoxidil will work or not. However, this 1993 study reminds us that it’s relevant.

There are other situations whereby inflammation probably makes the minoxidil work better. We sometimes add retinoic acid to minoxidil for example to make it more irritating and therefore get into the scalp better. Here is an example where we think inflammation helps minoxidil work better rather than worse. It’s not entirely clear if inflammatory states like seborrheic dermatitis, psoriasis, lupus, contact dermatitis are associated with better responses to minoxidil or not. The companies that make minoxidil warn users not to use if they have these sorts of inflammatory conditions. That is due to concern it might get into the scalp better.

All in all, there may be some inflammatory states where minoxidil works better and gets into the scalp more efficiently. This may also be associated with a greater chance of side effects like hair on the face or body, palpitations, headaches, etc. Be sure to discuss your specific situation with your dermatologist or hair specialist. If may not be a strict contraindication to use minoxidil if there is inflammation on the scalp but you will likely need a bit closer monitoring to ensure you are not developing worsening inflammation and not getting side effects from the treatment.

I have FPHL and have used everything imaginable. What else is there?

What are the other options for female pattern hair loss?

I’ve selected this question below for this week’s question of the week. It allows us to review some concepts in treatment of female androgenetic alopecia.

Question

I am 41 and have been diagnosed with FPHL and have used Rogaine, laser, PRP and spironolactone. Nothing works! What else is there? Have I exhausted all the options?

Answer

Thanks for the question. Let me being by saying that you’ll want to make sure that you have the right diagnosis. That’s always the first key step. My question when I see patients with a story like this is:

1) Is androgenetic alopecia the correct diagnosis ?

2) Are there other diagnoses here in addition to androgenetic alopecia ?

If there is any uncertainty, a biopsy may be needed. If you and your doctors are indeed confident it’s AGA then there are alternatives but what to use really depends on a person’s age, medical history, plans for pregnancy, emotional and psychiatric health, cardiovascular health and liver and kidney health. I’ll also assume that you have given each of these 6 months because that’s how long it takes to figure out if it’s working or not. I see patients every day who use Rogaine or spironolactone for 1-2 months and conclude it’s not working and stop. It takes a long time to evaluate effectiveness.

There are options for oral minoxidil, oral finasteride, oral dutasteride, topical finasteride, bicalutamide and hair transplantation. Be sure to give each and every treatment you try 9 months before you evaluate if it worked or not. I’ve included a list of first line, second line and third line treatments for premenopausal women. These may be a starting point for further discussions with your doctors. Some of these may not be options in young women on childbearing potential so you’ll want to discuss these in great detail. Often in a situation like you’ve described oral minoxidil or topical antiandrogens would be a next step with consideration given to a scalp biopsy to rule out any mimicking conditions.

Switching from Oral to Topical Minoxidil

How easy is it to switch from Oral Minoxidil to Topical Minoxidil?

I’ve selected this question below for this week’s question of the week. It allows us to review some concepts in switching from oral to topical minoxidil.

Question

I am using 2.5 mg of oral minoxidil with success. Unfortunately, there is a shortage of oral minoxidil in my area so I’m going to need to switch to topical minoxidil until we get the supply back. Will I experience shedding when I start topical minoxidil? I hear that many people do!

Thank you.

Answer

Thanks for the question. You are likely to experience shedding but for a different reason than you ask about and perhaps a different reason than you think.

You are not likely to get shedding simply because you are “starting” topical minoxidil. No. However, you are likely to experience shedding because you are not able to supply your scalp with the equivalent amount of minoxidil by using the topical compared to the oral minoxidil. 5 % foam is NOT equivalent to 2.5 mg so you hair and scalp will likely say “where is my minoxidil?” “why am I suddenly being deprived?”

If you have been using oral minoxidil for a very short time, it may not be a big issue. But if you have been using oral minoxidil at 2.5 mg for some time it could be an issue. Be sure to discuss fully with your dermatologist.
The key point here is that 2.5 mg of oral minoxidil is not equivalent to topical minoxidil so you are now likely underdosing. There are options to have a compounding pharmacy in your area make up minoxidil pills for you. Not all pharmacies have this experience but many do. That is a far better option for most than switching to topical. But be sure to discuss with your health care providers.

Thank you again for the question!

How long do I need treatment for my FFA?

How long do I need treatment for my FFA?

I’ve selected this question below for this week’s question of the week. It allows us to review some concepts in treating FFA.

Question

I was diagnosed with frontal fibrosing alopecia last month. I’ve started on hydroxychloroquine and steroid injections. How long am I going to need to do this treatment?

Answer

Thanks for your question. Some patients with FFA need treatment for 1-2 years and some patients with FFA need treatment for 10-20 years. Some never can stop treatment without losing hair. It’s difficult to say for any given person how long they will need treatment but over time you’ll come to know the answer for yourself and your specific case.

The first step in treatment is to stop the disease so that it does not keep getting worse and worse. Once your doctor stops the disease, he or she will want to continue medications a bit longer and see if it stays quiet for many years or starting acting up again and causing more hair loss. If the conditions stays quiet, it may be possible to starting slowly ‘tapering” medications or reducing the dose bit by bit. If the disease stays quiet and you don’t start losing hair again when the dose is tapered then it means that things are truly quiet.

Step 1 therefore is to stop the disease

Step 2 is to keep the disease stopped

Step 3 is to slowly taper some medications (if possible)

There is a view out there in the internet that scarring alopecia simply burn out after a year or two. This is not correct. Some patients of course do have a form that goes inactive rather quickly. But not all do. Some patients need to try many different medications before they find a combination that finally stops the disease. some get the treatment right on the first try.

What treatments for Androgenetic Alopecia Regrow Hair and Which just Stop it from Getting Worse?

Treatments for Androgenetic Hair Loss in Women

I’ve selected this question below for this week’s question of the week. It allows us to review treatments for androgenetic alopecia.

Question

I know there are many treatments for female androgenetic hair loss. I would like to know which treatments come with the chance that it will regrow hair and which just stop it from getting worse? How are these divided

Thank you

Answer

Thanks for the great question.

Every single recognized treatment for androgenetic hair loss comes with the potential to 'regrow hair.' That does not mean that it actually will regrow hair for any given person, but all come with some chance.

Again, it might not do that for every single user, but every treatment has this chance. If it does not, it doesn't work at all! There is no treatment in the world that "just maintains" hair. We do not categorize treatments in terms of “this group is a group that grows hair” and “this group is a group that just maintains it.”

Every single treatment has a certain percent of patients that will regrow some hair, a certain percent that will regrow a lot of hair, a certain percentage that will not regrow all that much but will maintain, and a certain percentage that the product won't help at all and hair loss will occur.

Example with topical minoxidil

For example, consider topical minoxidil:

30%-40% of women using topical minoxidil will regrow some hair with a 15-20% of women will regrow a lot of hair

30% of women using topical minoxidil will not regrow all that much but will still benefit from using the product because it will help maintain density.

30-40 % of women using topical minoxidil won't get much help at all from using the product.

Thanks and I hope this helps.

Spironolactone and Low Blood Pressure: How much will it drop?

Spironolactone and the Risk of Hypotension

I’ve selected this question below for this week’s question of the week. It allows us to the review some key data regarding blood pressure changes with spironolactone.

Question

I have been given a prescription for spironolactone for female pattern hair loss. I am concerned it might lower my blood pressure as my blood pressure often runs on the lower side of normal. Do you have any data on the chances of patients getting low blood pressure among users of this drug. How much does blood pressure usually drop?

Answer

Thanks for the great question. We’ve talked about the side effects of spironolactone in prior posts.

As far as changes in blood pressure among healthy women, the data has not been all that clear - until recently.

Garg and colleagues recently published a retrospective case series of 403 adult women treated for acne with spironolactone between 2008 and 2019. If we look into that data a bit closer, we can gain some valuable information on how it might affect blood pressure in those with androgenetic hair loss.

Does spironolactone affect blood pressure in health individuals? A new study suggests yes, but not by very much.

The median age of women in this study was 26. For 85 % of patients, the initial dose was 100 mg. Thereafter the dose increased for 50 % of women, stayed the same for 37.5 % and decreased in the remaining women.

Data was available regarding before and after blood pressure readings in 267 patients. The mean decrease in systolic blood pressure was 3.5 mm Hg (95% CI, 2.0 to 4.9) and the mean decrease in diastolic blood pressure was 0.9 mm Hg (95% CI, -0.2 to 2.1). The data was “statistically significant” meaning that spironolactone truly does affect blood pressure - it’s just the changes are quire small. No patient in the study needed to stop spironolactone because of blood pressure problems.

Summary and Comment

This was a nice study because good data and numbers on exactly how spironolactone affects blood pressure in healthy women have been hard to come by. We know that spironolactone can lower blood pressure in those with “ high blood pressure” by as much as 16 mm Hg systolic and 6 mm Hg diastolic. This data comes from a recently meta-analysis by Liu et al. This would lead many to believe that there must be a pretty big risk of low blood pressure in all our patients who use the drug for androgenetic hair loss. However, the real data says otherwise: healthy women who use spironolactone don’t get all that big of a change in their blood pressure and if they do - it does not typically affect them all that much

This study gives us some really good numbers to go on. For most healthy individuals spironolactone doesn’t affect blood pressure enough to really make a difference. If one is concerned, then baseline blood pressure testing and periodic follow up blood pressure testing is appropriate along with a slow increases in the dose. I have prescribed spironolactone to many patients who report low blood pressure and most patients tolerate 50-100 mg doses without any issues. So, is there ever an issue? Of course there is. Fortunately, it’s not common and patients who report lower blood pressure don’t necessarily need to lose out on a potentially effective treatment for them. We need to be cautious about going up too fast or to too high of a dose. Far too many people with androgenetic hair loss have completely shut off any sort of discussion about using spironolactone out of fears about low blood pressure. This study suggests we need to be cautious but not fearful. Low blood pressure is usually not a significant problem.

Reference

Garg et al. Long-term use of spironolactone for acne in women: A case series of 403 patients. J Am Acad Dermatol. . 2021 May;84(5):1348-1355.

Lui et al. Addition of spironolactone in patients with resistant hypertension: A meta-analysis of randomized controlled trials. Clin Exp Hypertens. 2017;39(3):257-263.

How does my treatment plan for LPP sound to you?

Treatment of LPP

I’ve selected this question below for this week’s question of the week. It allows us to the review some key concepts in the treatment of lichen planopilaris and the importance of photos in the long term evaluation of LPP disease activity.

Question

I have been diagnosed by biopsy 18 months ago with lichen planopilaris. I am a 74 year old woman and I noticed about three years before that I was thinning at the front of my head. My dermatologist has tried to help me with an antibiotic which I took for 6 months, to help the inflammation, or lower it. It wasn't effective and I don't think one should remain on this antibiotic for a longer time. The hair loss is also behind my ears and a little on my crown.

Since the beginning of April, I have been taking Hydroxychloroquine 200 mg every day in an attempt to stem the hair loss. I have not had any of the possible side effects thankfully. In fact, in the two months since I started this medication, I notice that I really don't have an itchy scalp any longer and much less frequently, an itchy back, My scalp isn't tender and not red close to the hairline as it was before this medication. Thankfully, I do not have any health problems and the only medication I take is for an under active thyroid.

Can you please advise if this would be a plan of action that you would advise?

Answer

Thanks for the great question. I’m so glad things seem moving in the right direction for you.

I can’t tell you if you are using the perfect plan because not enough time has elapsed. What I can say is there are good things in your story above that indicate you are indeed on track.

However, if you take a photo of your scalp in 2 years from now and it looks 100 % the same (or better) than the that photo that I’m going to enoucrage you to please take tonight ….. I can tell you that you are indeed on the right track!

Let’s look at some important points.

When we successfully treat scarring alopecia, we want several things to happen:

a) We want the rate of hair shedding to return back to ”normal”

b) We want scalp symptoms to disappear such that there is no itching, burning or tenderness

c) We want any scalp redness to disappear

d) We want hair loss to stop such that it’s not getting worse and worse over time.

e) Finally, if we catch LPP “early enough” in its disease evolution, we even want a bit of improvement in hair density to occur.

So are you successfully treating your scarring alopecia ?

It certainly sounds like you are treating your LPP quite well so far in your treatment journey. However, I can’t know for sure if the disease activity has “stopped”. Sometimes there will be clues when your dermatologist examines your scalp up close with trichoscopy that the disease activity has been reduced. For example, if you once had perifollicular scale (scale around the hairs) or had perifolliicular redness (redness around the hairs) when the scalp was examined by trichsocpy and now you do not have these findings, it means that your LPP disease activity has been reduced. If it was once possible to easy pull a great number of hairs from the scalp (i.e. a positive pull test) and now it is not so easy to extract hairs, then it may mean your disease activity has reduced.

The mistake that many patients and physicians make is assuming that zero redness, zero shedding and zero scaling means zero scarring alopecia disease activity. That’s not quite accurate. However, it sure sounds good. But it’s certainly a really important “first step.”

You see, it could be that for some patients that the redness goes away, and shedding reduces and flaking goes away and still the hair loss continues a little bit. That’s why photos are so important! I would encourage everyone with scarring alopecia to take photos or have someone take them for you.

I often get referrals from doctors who ask me to help the figure out if their patient’s disease activity is zero or not. If I don’t see much activity on the scalp when I perform a scalp examination, I reply to the patient and referring doctor by saying “things seem quiet today but I’ll give you my final answer in two years.”

I’ll take a photo now and then again 6 months, 12 months, 18 monks and 2 years. Sometimes we will take even more photos. If the photos look the same over a 2 year period of careful observation and there has been no further loss at all … then the scarring alopecia disease is deemed inactive.

I will point out at this juncture that the word inactive is not the same as burnt out. Inactive means the disease is quiet but it could be that the use of medications brought it to that state. Burnt out means the disease is completely over. One can take away all medications from true burnt out scarring alopecia and the disease still stays quiet.

Is your disease active?

You are only a few months into hydroxychloroquine treatment. It could be that the medication has slowed your LPP disease activity down or it could be that the medication has completely stopped the disease. We won’t know for sure a while. For some patients, it takes just a matter of months to see that the hair loss has in fact still continued. For others, it will take a full 1 or even 2 years to really get an appreciate that the hair loss is still continuing. It just depends one the speed of the hair loss.

If one’s LPP is progressing along fast, I can tell in 1- 2 months if the disease is still active

If one’s LPP is progressing along moderately fast, I can tell in 4-6 months if the disease is still active

If one’s LPP is progressing along moderately slowly, I can tell in 9-15 months if the disease is still active

If one’s LPP is progressing along really slowly, I may need 18-24 months to tell if the disease is still active

So I would encourage you to take lots and lots of photos every 3-6 months. When it comes to treating scarring alopecia, photos are so so important.

Of course, you’ll want to check in sooner with your doctors than 2 years in order to figure out how well you are doing on your treatment. In fact, you’ll probably want to be checking in with your doctors every 4-6 months. I’m glad you have no side effects with hydroxychloroquine but do keep in mind that some side effects with hydroxychloroquine happen after 1-2 months (ie changes in blood counts or liver enzymes) and some side effects don’t really become all that common until 5-10 years have gone by (ie retinopathy) So, if you do stay on this medication, be sure to have periodic follow up to monitor side effects.

If you find that hair loss seems to be continuing when when see your doctors at the 4-6 months follow up or the 1 year follow up, then that means you may want to bring on board other treatments to help the hydroxychloroquine. There are many treatments for LPP.

Sometimes, a patient keeps losing hair despite the fact that the every doctor thinks the scarring alopecia is quiet. In some cases, the scarring alopecia is not quiet and the impression of the doctors is wrong. In other cases, the scarring alopecia is, in fact, really quiet but other types of hair loss are present in the patient too that nobody has picked up on.

For example, if a patient’s scarring alopecia has been brought under good control but they have a telogen effluvium present from some other medication they recently started then guess what? Hair shedding is going to continue and hair density is not going to get better. Every hair loss condition needs to be addressed!

If a patient has both a scarring alopecia and a telogen effluvium, then both the scarring alopecia and the telogen effluvium need to be properly treated. If a patient has scarring alopecia and androgenetic alopecia, then both the scarring alopecia and the androgenetic alopecia need to be properly treated in order to maximize regrowth. If a patient has scarring alopecia and a telogen effluvium and androgenetic alopecia (all three), then a treatment plan needs to be created that addresses all three of these conditions.

Conclusion

Thanks again for the great question. I am glad things have improved. I would encourage you to take photos as this issue going to be the best way to get a really good sense of how well you are doing in the long run. I am always encouraged when patients report they are improving but what matters most to me is really how well a person is doing over a very extended period of time.

Doctors and patients can sometimes debate about whether they are better or not after a few months. However, there is absolutely no debate after 1 or 2 years. A photo captures the essence of the disease activity completely.

Can I reduce the dose of minoxidil for treating my AGA and if so, how?

Minoxidil (Rogaine) for the treatment of Androgenetic Hair loss: How soon after starting can I go down on the dose?

I’ve selected this question below for this week’s question of the week. It allows us to the review some key concepts in the treatment of androgenetic alopecia - particularly the need for ongoing lifelong treatment.

Question

I have female pattern hair loss and I’ve been on minoxidil 1/2 cap daily for about 1 year now. It seems to be helping. I was advised this week by my provider that it’s okay to go down to 3 or 4 times weekly. What protocol do you recommend for reducing the dose and how do you taper safely so as to not lose hair?

Answer

Thanks for the question. The answer is simple: If you have androgenetic alopecia and Rogaine is helping you, then this medication probably can’t be tapered to any significant degree without you losing some hair.

If Rogaine has not been helping you all these months and you’ve actually been wasting your time in the last 12 months applying it - you can stop it without any immediate negative effects. The hair won’t mind at all that Rogaine was stopped because it wasn’t helping in the first place.

However, if Rogaine was helping (which I imagine for you it probably must be), it can NOT be tapered without losing hair. I don’t know how this concept has started permeating in this world - I’ve heard it myself. But Rogaine can’t be stopped if it was helping. You can’t go from 7 days a week to 5 without some negative effect on the hair. You can’t go 7 days to 4. You can’t go twice daily to once daily. Sure you might be able to go 7 to 6 but there’s a fine line for what its acceptable.

If all a person is able to do is apply Rogaine 5 or 6 days per week, then I say try to apply it five or 6 days per week. That’s fine. It still has a chance of helping even if it’s not perfectly daily. . But to start at a higher dose and then reduce the dose at a future time just doesn’t work well for most people.

Reducing the dose of Rogaine usually leads to hair loss (if it was helping). Consider the female patient who starts using Rogaine 5% twice daily because she really wants to try to stop her hair loss, or the patient who even uses a full cap instead of the recommended 1/2 cap. Then, imagine that the patient winds up in the clinic of a specialist 12 months later and the specialist says confidently to her“Oh, Rogaine for women only needs to be used once daily at 1/2 cap - so you can reduce your dose”

Guess what happens when the patient goes from a full cap twice daily to 1/2 cap daily?

She loses hair! !!!!!!

Hair is not pleased with a four-fold reduction in the dose.

Summary and Conclusion

All the treatments for androgenetic alopecia are lifelong. If a patient is going to use Rogain to treat their AGA, then they should plan to start it with the intention to use it lifelong. If a patient is going to use anti androgens to treat their AGA, then they should plan to start it with the intention to use it lifelong. If a patient is going to use low level laser therapy to treat their AGA, then they should plan to start it with the intention to use it lifelong. If a patient is going to use PRP therapy to treat their AGA, then they should plan to start it with the intention to use it lifelong.

We would to think that it’s possible to reduce the dose of Rogaine after some time. It sure sounds like a nice plan …. and a convenient one too! It’s just that it doesn’t really work like this and reducing the dose carries a high risk of hair loss.

Now for all the people who are using Rogaine for other types of hair loss besides androgenetic alopecia - the rules are a bit different. If one uses Rogaine for alopecia areata, one can stop Rogaine once the hair grows back. Sometimes (but not always) that’s true for other types of hair loss as well. But for androgenetic alopecia the rules are pretty straight forward. If a certain dose or amount of Rogaine has helped, then that dose or amount needs to bee continued exactly the same way to maintain results. A reduction in dose will likely lead to hair loss.

The following chart is helpful to differentiate the use of Rogaine in these conditions

Should I stop my immunosuppressants when I get my COVID vaccine?

Do patients with immune mediated hair loss who use immunosuppressants need to stop their medications when they get a COVID 19 vaccine?

I’ve selected this question below for this week’s question of the week. It allows us to the review the decisions that go into stopping (or not stopping) medications after getting a COVID vaccine.

QUESTION

My daughter is 16 years old and was prescribed methotrexate for her alopecia areata. The treatment is working extremely well and she has had full hair for 9 months. She is planning to have her COVID vaccine in a few weeks and we are trying to get a sense as to whether she is supposed to stop her methotrexate or not before she gets her shot. Our various doctors have mixed views on what to do!

What are your recommendations for your patients?

ANSWER

Thanks for the great question. It’s an important one!

Short answer - it’s probably okay to continue !

Let me begin by saying that at present, there are still no clear-cut, definite and universally agreed upon guidelines on what to do for patients with alopecia areata (or other immune based hair loss conditions). We only have guidelines from other medical organizations that then need to be interpreted for hair loss patents.

There is one recommendation, however, that is pretty clear - keep the appointment for the vaccination! That’s a far more important decision for your daughter than the decision to stop the methotrexate or not!

Let’s get into the key part of the question - should your daughter stop methotrexate or not?

I’d like to point out that there are many different types of immune-mediated hair loss conditions for which immunosuppressive medications are prescribed. These include alopecia areata and patients with various scarring alopecias like lichen planopilaris, frontal fibrosing alopecia, discoid lupus, etc.

Methotrexate, cyclosporine, mycophenolate, TNF inhibitors, hydroxychloroquine, JAK inhibitors, oral steroids are all immunosuppressive medications that may be used by patients with immune-mediated hair loss. I prescribe them every day.

So does being on an immunosuppressive make it any more difficult for a patient to mount a full and normal immune response after getting a vaccination?

For some immunosuppressive medication that answer is a “yes.”

The Famous Park et al Study from South Korea

We know from data in the past that rheumatoid arthritis patients using the drug methotrexate had antibody responses to the influenza vaccine that were “slightly worse” when patients were told to continue their methotrexate compared to when they were told to stop taking the methotrexate for 2 weeks. This well known study has prompted many physicians to consider withholding methotrexate (if possible) before giving the influenza vaccine.

Let’s look at the study in more detail.

The South Korean study by Park and colleagues involved 156 patients with rheumatoid arthritis who continued their methotrexate before getting their influenza vaccine and 160 patents who stopped their methotrexate for 2 weeks AFTER getting their influenza vaccine. 75.5 % of patients who paused their methotrexate had satisfactory vaccine responses compared to 54.5 % of patients who kept taking the methotrexate. In addition, it’s important to take note that there was no change in disease activity between the groups and patients who took paused methotrexate for two weeks did not experience a disease “flare.”

The question then arises as to whether our hair loss patients who use immunosuppressive medications should withhold their treatment before or after getting COVID vaccine. The challenge with answering this question is we don’t have any good data on antibody responses in patients with specific autoimmune “hair loss” conditions. We have some guidelines for how patients on various drugs for rheumatologic disease should proceed with vaccination. In addition, we have some recommendation on how patients with skin diseases like psoriasis should proceed. However, we don’t have any studies or advice to specifically guide hair loss patients.

Being a hair loss doctor, these sorts of answers are important to me!

Should a 16 year old on methotrexate for alopecia areata stop her methotrexate for a period of time after getting a COVID vaccination?

Should a 16 year old on methotrexate and 10 mg prednisone for alopecia areata stop her methotrexate for a period of time after getting a COVID vaccination?

Should a 16 year old on methotrexate and 40 mg prednisone for alopecia areata stop her methotrexate for a period of time after getting a COVID vaccination?

Should a 16 year old on methotrexate for alopecia areata stop her methotrexate for a period of time after getting a COVID vaccination if her hair is thick and full and has been full for a long time?

Should a 16 year old on methotrexate for alopecia areata stop her methotrexate after getting a COVID vaccination for a period of time if her hair only started growing back last month?

Should a 21 year old on tofacitinib for alopecia areata stop her tofacitinib for a period of time after getting a COVID vaccination?

Should a 41 year old female using methotrexate for lichen planopilaris stop her methotrexate for a period of time after getting the COVID vaccine?

Let’s review some key stuff.

Recommendations from the Rheumatology Field

Rheumatologists frequently use immunosuppressive medications for treating autoimmune diseases so we frequently turn to the rheumatology field for guidance on how we might treat autoimmune hair loss. Various rheumatology organizations have put forth broad recommendations to help patients and their doctors. These organizations often recommend stopping some mediations for one week and rarely two weeks. We’ll take a look at some key studies and then we’ll take a look at their formal recommendations. Then, we’ll jump over to recommendations from other fields of medicine (other than rheumatology).

The Giesen and Colleagues Study

A study by Giesen and colleagues examined if patients with chronic inflammatory disease who use immunosuppressive medications mount good antibody responses after COVID vaccination and whether these vaccines flare underling disease. The researchers studied 42 healthy controls and 26 patients with inflammatory disease (including psoriasis, psoriatic arthritis, lupus, rheumatoid arthritis, spondyloarthropathy). Antibody responses at week 1 were good in patients with chronic inflammatory disease who were using immunosuppressives although antibody titers were about 20 % less than controls. The main conclusion of the Giesen study was that patients with various immune mediated diseases still mount pretty good antibody responses and the authors proposed these antibody responses should still be fairly protective. That wasn’t studied in the research study so it’s a bit of a best guess.

The Deepak and Colleagues Study

Preliminary data from the Washington University in St. Louis and the University of California, San Francisco suggests that immunosuppressive medications blunt the antibody responses in patients who get the COVID mRNA vaccine. The authors found that oral steroids and B cell depleting agents (i.e. rituximab) are most likely to impair antibody responses but that drugs like tofacitinib and methotrexate can also impair antibody responses - but to a lesser degree. The use of TNF inhibitors had only minimal effects.

To provide more detail, the authors found that compared to immunocompetent controls, there was a three-fold reduction in anti-S IgG antibody titers (P=0.009) and SARS-CoV-2 neutralization (p<0.0001) were observed in immunosuppressed patients. Patients using B cell depleting therapies and corticosteroids had a 36- and 10-fold reduction in humoral (antibody) responses, respectively (p<0.0001). Janus kinase inhibitors and antimetabolites, including methotrexate, also blunted antibody titers (P<0.0001, P=0.0023, respectively). For methotrexate , there was an average a two- to-three-fold reduction in antibodies and neutralization. For JAK inhibitors, it was approximately 4.5 fold reduction. Other targeted therapies, such as TNF inhibitors, IL-12/23 inhibitors, and integrin inhibitors, had only modest impacts on antibody formation and neutralization.

The American College of Rheumatology recommends STOPPING some (but not all) immunosuppressive medications for 1 week after vaccination in order to help improve the effectiveness of the vaccine. This is mainly for those with well-controlled disease who have low chances of flaring when the drug is stopped.

a) Mycophenolate - skip for 1 week after each vaccine dose

b) JAK inhibitors - skip for 1 week after each vaccine dose

c) Methotrexate - skip for 1 week after Pfizer or Moderna (skip 2 weeks after J&J)

d) Hydroxychloroquine (Plaquenil) - no need to stop the drug

The ACR also recommends that patients have the exact same vaccine the second time if they are having an mRNA vaccine. In other words, if a patient gets the Pfizer vaccine for his or her first dose, they should get the Pfizer vaccine for his or her second dose. The ACR does not recommend switching up vaccines depending on availability.

The Canadian Rheumatology Association has published helpful guidance. Their recommendations are different than the American College of Rheumatology. The Canadian group recommends that only two drugs should really change how vaccines are given. Those are high dose prednisone (more than 20 mg per day) and rituximab (which is not used in treating hair loss). Other drugs can be continued including

a) TNF inhibitors - no need to stop after getting the vaccine

b) Azathioprine - no need to stop after getting the vaccine

c) Cyclosporine - no need to stop after getting the vaccine

d) Hydroxychloroquine - no need to stop after getting the vaccine

e) Methotrexate - no need to stop after getting the vaccine

f) Prednisone (20 mg or less) - no need to stop after getting the vaccine

The European Alliance of Associations for Rheumatology (EULAR) advises that most drugs can be continued in those undergoing vaccination. The only exception is the drug rituximab (which is different than Ruxolitinib so readers should not confuse the two!)

The Korean College of Rheumatology has recommended withholding MTX for 1-2 weeks and to consider withholding tofacitinib and JAK inhibitors one week (but recognize that data for JAK inhibitors is less clear than for methotrexate).

The British Society of Rheumatology has recommended that everyone get vaccinated “regardless of treatment regimen or underlying diagnosis”

Other researchers have put for recommendations to stop methotrexate up to 2 weeks after vaccination.

Recommendations from the Psoriasis Field

The National Psoriasis Foundation (NPF) does NOT recommend that patents with psoriasis stop most medications before getting the vaccine. The only exception is the Ad26.COV2.S (Johnson & Johnson or “J&J” vaccine in which case the NPF recommends possibly stopping the J&J vaccine for 2 weeks if the patient is older than 60, has at least one risk factor for poor COVID outcomes, and his or her psoriasis is stable and his or her doctor agree with this plan.

This seems to be the only exception in the psoriasis field. It’s important to point out that we don’t actually know if stopping makes any difference to improve vaccine responses. But this has been the take on the NPF’s recommendations.

Summary of Study Results to Date in the World Regarding Vaccines, COVID Vaccines and Immunosuppressive Medications

The following is a helpful summary of the main key findings of data so far:

1. Current vaccines reduce the chance of developing COVID 19.

2. Current vaccines reduce the chances of developing severe disease even if one does get COVID 19.

3. Some protection against COVID 19 in better than no protection.

4. We still have no clear cut idea about what antibody level after vaccination signals that a person is protected. Fortunately, most people do have pretty good protection after vaccination (but not all).

5. If at all possible, vaccinate patients when their immune disease is quiet.

6. Younger patients have better vaccine responses than older patients.

7. Some immunosuppressive drugs reduce the amount of antibodies that are formed to the Sars-COV-2 virus. Rituximab (which we don’t typically use in any hair loss condition) impairs antibody responses the most - and second highest are the oral steroids. In one study, JAK inhibitors like tofacitinib impair antibody responses 4.5 times and Methotrexate reduces responses by 2-3 fold. There is no good studies yet to suggest these antibody reductions mean the patient is more likely to get COVID19 disease.

8. Organ transplant patients on various immunosuppressant medications don’t mount very good antibody responses to the COVID vaccine. A study from John Hopkins found that only 15 % of patients had good antibody responses after 1 dose and just over one half had good responses after two doses.

9. Doses of prednisone of less than 10 mg daily seem to be associated with good antibody responses. Ideally, patients should not be vaccinated if possible until the doses of prednisone fall below 20 mg.

10. Sulfasalazine, hydroxychloroquine, azathioprine and leflunomide may reduce vaccine antibody titers but have not been shown to inhibit a seroprotective response to the pneumococcal or influenza vaccines. Most of the main world medical organizations suggest these drugs NOT be stopped when patients go for their vaccine.

11. TNF inhibitors probably don’t affect the vaccine response all that much. Most of the main world organizations suggest these drugs not be stopped when patients go for their vaccine.

12. In organ transplant patients, mycophenolate was shown to reduce antibody titers after vaccination but not below the threshold for protection. In one study of mycophenolate users, only 27 % of 11 patients using mycophenolate had good antibody responses. Some organizations like the American College of Rheumatology (ACR) suggest stopping 1 week. Other organizations do not.

13. JAK inhibitors impair vaccine response slightly after various types of immunizations. It’s not clear if this really reduces antibody responses below a protective level after COVID 19 vaccinations or not. Holding it one week could make sense in a stable well controlled patient. This is the view of the American College of Rheumatology and the view of the Korean College of Rheumatology
    

Final Summary: Should patients with alopecia areata pause any of their drugs?

Now that we have reviewed some of the key guidelines in other fields of medicine we can come back to the question raised in the beginning. Should the 16 year old patient in this question stop her methotrexate?

There’s probably no need to stop. However, I would need a bit more information in order to really feel confident that tis the right answer for your daughter. . That’s why it’s so important that you and your daughter have a thorough discussion with her doctor. For some 16 year olds the answer will be “yes - stop it” and for some it might be “no- don’t stop it.” For most of my patients right now the answer would be not to stop. However, there is more to the answer than a simple yes or no. Also, there is still no consensus agreement across the world so I can understand that there will be mixed views from all your doctors.

Let me offer the following important pieces of information:

1. Until new formal guidelines come out, I would generally NOT recommend stopping methotrexate for “most” of my 16 year old patients who take methotrexate and have alopecia areata. There are however, still some patients in my practice that I probably would stop for 1-2 weeks, but these are exceptions right now rather than rules. This could change as more and more studies come in and guidelines get updated. This will happen.

2. I would probably be inclined to consider stopping for 1 week for children and adolescents with alopecia areata who also have obesity, diabetes, asthma or chronic lung disease, sickle cell disease, as these groups of children may be at increased risk for severe illness from COVID-19. This too is not a yes or no answer but this needs a bit of discussion with the doctor. I’d probably be on the side of favoring stopping for a week.

3. I would be inclined to consider stopping methotrexate for 1 -2 weeks for children and adolescents who also are using any amount of oral steroids. ideally, however, I would wait until the oral steroid are finished before vaccinating - if the use of oral steroids will be a short term thing.

4. I would be more inclined to consider pausing methotrexate for 1 -2 weeks if a patient’s alopecia areata has been completely stable with full hair regrowth being present for more than 5 months. In fact, I would also consider meeting with the patient to discuss even reducing the dose of methotrexate in a few monthsbecause it could be that the patient does not need this high dose any more. For methotrexate, less medication is better (if it’s at all possible and does not trigger hair loss again).

5. I would be more inclined to consider pausing methotrexate for 1-2 weeks if a patient lives with someone at very high risk. Should we stop methotrexate for 1 week if the 16 year old patient lives I the same house with a terminally or chronically ill parent or grandparent at high risk for severe COVID disease? There are no guidelines, but I’d likely say yes. Once we get better data, this answer could change.

6. For other immune based hair conditions, similar thoughts apply. Patients with extremely stable (i.e. 100% inactive) immune mediated hair loss such as alopecia areata or scarring alopecia who have been completely inactive for more than 6 months probably can skip 1 -2 week of immunosuppressants (especially methotrexate and possibly tofacitinib) without issue. Again, if a patent is super stable, stopping these drugs for 1-2 weeks should not have a big effect for most. If patients have inactive hair loss issues but are obese, or have other chronic diseases, such a stable patient probably should strongly consider skipping the dose. However, the guidelines in other fields would suggest that patients with autoimmune and immune mediated hair diseases who are less stable can probably keep taking their medications and simply go in and get the vaccine whenever their chance comes up. In other words, if there is any worry that hair loss will flare if medications are stopped, it’s probably a reasons to keep taking them and no stop.

7. For patients who are immunosuppressed, checking antibody titers after vaccination (anti S antibody titers) is something that should be strongly considered. More guidance will be needed from regulatory bodies about how best to do this. We don't yet know exactly what antibody titer means a person is protected so routine antibody testing is not something that has become mainstream

8. Further studies will be needed in the future to determine if patients on certain types of immunosuppressants need more frequent booster vaccinations that those who do not used immunosuppressive drugs.

I hope this helps. Thanks for the excellent question.

Reference

Adler et al. Protective effect of A/H1N1 vaccination in immune-mediated disease–a prospectively controlled vaccination study. Rheumatology 2012;51:695–700.

Deepak P et al. Glucocorticoids and B Cell Depleting Agents Substantially Impair Immunogenicity of mRNA Vaccines to SARS-CoV-2. medRxIv 2021 (preprint)

Fischer et al. Pneumococcal polysaccharide vaccination in adults undergoing immunosuppressive treatment for inflammatory diseases - a longitudinal study. Arthritis Res Ther 2015;17:151.

Fomin et al. Vaccination against influenza in rheumatoid arthritis: the effect of disease modifying drugs, including TNFα blockers. Ann Rheum Dis 2006;65:191–4.

Franca et al. Ribeiro ACM, Aikawa NE et al. TNF blockers show distinct patterns of immune response to the pandemic influenza A H1N1 vaccine in inflammatory arthritis patients. Rheumatology 2012;51:2091–8.

Gabay C et al. ; H1N1 Study Group. Impact of synthetic and biologic disease-modifying antirheumatic drugs on antibody responses to the AS03-adjuvanted pandemic influenza vaccine: a prospective, open-label, parallel-cohort, single-center study. Arthritis Rheum 2011;63:1486–96.

Geisen et al. Immunogenicity and safety of anti-SARS-CoV-2 mRNA vaccines in patients with chronic inflammatory conditions and immunosuppressive therapy in a monocentric cohort. Annals of Rheumatic Disease. 2021;0:1–6. doi:10.1136/annrheumdis-2021-220272

Keshtkar-Jahromi M et al,. Argani H, Rahnavardi M et al. Antibody response to influenza immunization in kidney transplant recipients receiving either azathioprine or mycophenolate: a controlled trial. Am J Nephrol 2008;28:654–60.

Park et al. Impact of temporary methotrexate discontinuation for 2 weeks on immunogenicity of seasonal influenza vaccination in patients with rheumatoid arthritis: a randomised clinical trial. Ann Rheum Dis. 2018 Jun;77(6):898-904.

Increased Shedding: Should I start treatment for Male Pattern Balding?

Does increased shedding indicate that a male should start finasteride?

I’ve selected this question below for this week’s question of the week. It allows us to the review the diagnosis and work up of increased hair shedding in males.

QUESTION

I am a male, 30 years old who has been monitoring his hair for quite some time as I don't want to lose my hair to androgenetic alopecia (AGA). I have been counting the hairs that I shed in the shower since around 2016. Since I have usually midlength to long curly hair I stretch out the days I wash my hair, otherwise it gets dry. I have always shed around 210/220 hairs when showering every third day. This has increased to 280 since a few weeks now.

Since I said every third day this means the average on a day was: 210/3=70 . Now it has become 280/3=93 a day, for the last month or so. I know that 100 hairs a day is normal, but considering that the number I was shedding was consistently around 70 for years I am a little worried. The majority of the shed hairs look healthy and thick and long. My hairline, crown and density are still the same. Could this be temporary and could the shedding go down within the next few months?

When should I start finasteride? As soon as I see recession / lessening in density / thinning?

In short, is a little increase in shedding a reason to go on treatment?

ANSWER

Thanks for submitting this question.

I’d like to discuss several important things in the question you ask and the information you have submitted.

Before we do go further, I’d like to point out that the ideal way to diagnose hair loss is using what I termed the ”Diagnostic S.E.T.” I refer to these as the diagnostic “set” because theses 3 aspects all go together. These 3 items include:

1) the patient’s story

2) the findings uncovered during the process of the scalp examination including trichoscopy

3) the results of relevant blood tests. 

The first letter of each of the three words 1) story, 2) examination and 3) tests spell out the word “S.E.T.” - again a helpful reminder of how the information obtained from reviewing each of these 3 aspects helps solidify a proper diagnosis. I don’t have a full story in your case and I don’t have photos (or a chance to examine the scalp) and I don’t have the opportunity to review any tests …. so I am limited to some degree in my helpfulness. Nevertheless, I do think the discussion here will be helpful.

The main phenomenon you are describing is increase shedding. You have gone from 70 hairs per day of shedding to 93 hairs per day . Although both are considered within the realm of normal, I would agree that in your case this likely represents a true increase in shedding. This does not necessarily mean that this will be long term shedding or that it will actually translate into a loss of hair density or thickness. There are some unknowns here.

There are 3 potential considerations for why you are shedding more hair in the last month:

a) a telogen effluvium has occurred

b) the initiation of androgenetic hair loss has taken place

c) an autoimmune mimicker of telogen effluvium is present rather than telogen effluvium

d) combination of the above

Let’s take a look at these in more detail.

a) Is this a true telogen effluvium and if so what is the cause?

It’s quite possible that you are having a minor telogen effluvium. Hair shedding does not need to be over 100 hairs per day to have a telogen effluvium - it just needs to be more than one’s original shedding rates. If a person shed 38 hairs per day before and now sheds 68 - it’s abnormal. In your case, your shedding from 70 to 93 is abnormal. Of course, there is a big difference between something being abnormal and something being serious. Your hair shedding may not be serious and might only be temporary. We’ll get to that in moment. But this shedding suggests a potential diagnosis of telogen effluvium. As we’ve reviewed in the list above, a diagnosis of telogen effluvium is not the only cause of shedding. So it would be a mistake to assume otherwise.

A variety of ‘triggers’ are responsible for telogen effluvium. These triggers include stress, low ferritin levels, thyroid problems, medications, weight loss, seborrheic dermatitis, scalp psoriasis, immunizations, infections and internal illness inside the body.

You and your doctors really need to go through each of these potential triggers step by step very carefully to see if anything fits with your story. If your shedding started at the beginning of April, then you’ll want to go back to January or February (2-3 months prior) and ask yourself if something changed in your life. If this is a telogen effluvium, that’s probably when the body felt some sort of a trigger.

So, you and your doctors will want to evaluate that answers to the following

1) Did you experience higher stress levels in January or February?

Stress in January can trigger shedding 8-12 weeks later.

2) Did levels of any of your key blood test parameters change in January or February?

Clearly, blood tests are going to be needed if you really want to get to the bottom of why you are shedding more. There are over 75 blood test abnormalities that can trigger shedding. Fortunately, most of those 75 are rare and we don’t go about even ordering them. The ones we mainly check are iron (ferritin levels) and thyroid (TSH test) along with basic hemoglobin level and 25 hydroxy vitamin D level. However, your doctor will need to review your story from start to finish and examine your scalp and ideally perform aa physical examination too. If there’s anything that crops up as a concern, more blood tests besides just ferritin and TSH might be needed. For example, patient who has lost 25 pounds in 2 months and has no idea why they are losing so much weight is likely going to need an extensive work up.

3) Did you start any new medication or vitamin or supplement in January or February?

Starting medications can sometimes be a trigger - and the same is true for some supplements, herbal medications, teas, and vitamins. This all needed to be reviewed.

4) Did you stop any sort of medication or vitamin in January or February?

Stopping medications can sometimes be a trigger - and the same is true for some supplements, herbs, teas, vitamins. This all needed to be reviewed. In addition to stopping medications. sometimes even changing brands can be an issue. For some people, a change in drug A from brand name to generic is enough to trigger a shed. You can see that we’re going to need aa pretty detailed understanding of what’s been happening in your life to determine why you area shedding.

5) Did you receive any sort of immunization in January or February?

Immunizations are not common causes of shedding but that does not mean they are not on the list. Immunizations of all kinds have a slight chance to trigger some temporary shedding. COVID vaccination rarely does too. I don’t know if you received a vaccine or not, but your doctors will need to review this carefully. If you were vaccinated in January or February, it most certainly could give a shed now. Fortunately, it’s pretty rare - but we’ve seen it.

6) Did you get any kind of infection in January or February?

Infections of any kind can trigger shedding. Granted, severe infections associated with someone being quite ill are more likely overall to trigger shedding than less severe infections. But even minor infections can trigger shedding. Tooth infections, flus, COVID 19, all can trigger shedding. Many patients who have been infected with COVID 19 do not even know they had COVID 19 but some still get shedding. In fact, about 10 % of patents with hair shedding due to COVID 19 didn’t really have any COVID 19 symptoms. You and your doctors are going to want to evaluate that carefully and whether there is any possibility of an asymptomatic COVID 19 infection happened in January or February. Antibody tests can help address this question in some patients.

Other infections may also be relevant to ask about. Again, over 300 infections can cause shedding but most of the time, none are all that relevant for the patent in front of the doctor. But a variety of bacterial, viral, protozoal infections can cause shedding. In some of my patients from outside of North America, Dengue fever (spread by dense virus) is a common cause of shedding. There are estimated to be 390 million Dengue viral infections every year in the world. Sometimes we test for infections like HIV and syphilis in patients with risk factor who have chronic shedding. So depending on your story, more broad testing could be needed. For most people, we don’t need much in the way to these sorts of tests.

7) Did you develop any kind of illness inside my body in January or February?

Any illnesses inside the body can trigger shedding. Most often these are illnesses that a significant impact on the body. For example, an illness that causes diarrhea or a bad cough or an intensively sore joint that affects the motion in the joint all have the potential to cause shedding.

8) Did you have any kind of surgery or procedure in January or February?

Any proper evaluation for shedding examines whether or not the patient had any type of surgery or hospitalization in the months leading up to the shedding. Medications used in surgery, blood loss during surgery are well known triggers of telogen effluvium.

In summary, you can see that if you want to get to the bottom of what is happening with your hair, you are going to need a proper history and examination and you are going to need blood tests. Whether you get blood tests now or simply wait a month or two if things don’t improve is a clinical decision that is left to you and your doctors. But the only way right now to be sure that an abnormality in some blood test is not the reason why your shedding went from 70 to 93 is to order these blood tests.

Three Important Patterns of Telogen Effluvium

Before we leave the concept of telogen effluvium, it’s important to mention a few more points regarding the patterns of shedding that you might see. There are a few scenarios that might happen. If the diagnosis of your hair shedding is telogen effluvium and there is some well defined trigger that happened to you in January or February and then went away you will have some shedding in April through July but then the months of August September and October will be associated with less shedding and things should return to normal by November or December (assuming you don’t have genetic hair loss). If you do have genetic hair loss, that’s a bit of a different story as patients who are en route to slowly developing genetic hair loss may not find there shedding goes back completely to normal once the trigger of the telogen effluvium is fixed. We say in this case that the TE precipitated or unmasked an androgenetic hair loss.

Let’s take a look at scenario 2 now. If the diagnosis of your hair shedding is telogen effluvium and there is some well defined trigger that happened to you in January or February but is not going to end up being fixed until July then you will have a bit more prolonged shedding. This could be a scenario whereby an individual went on a diet from January to July or had intense stress from January to July or developed a thyroid problem in January and could not get into the doctor until July to get it fixed. If scenario 2 applies in your case, you will not slow your shedding quite as quickly. You will have some shedding in April through July but then the months of August September and October will be associated with less shedding and things should return to normal by November or December (assuming you don’t have genetic hair loss). If you do have genetic hair loss, that’s a bit of a different story as patients who are en route to slowly developing genetic hair loss may not find there shedding goes back completely to normal once the trigger of the telogen effluvium is fixed.

Let’s take a look at scenario 3 now. If the diagnosis of your hair shedding is telogen effluvium and there is some well defined trigger that happened to you in January or February but it simply goes unfixed then you will have a prolonged shedding and it’s not going to stop. This could be a scenario whereby an individual developed a chronic illness like inflammatory bowel disease in January and does not get connected with the right treatment because either the diagnosis has not yet been even uncovered or the medications are not working. Another example would be a patient who experience high stress starting January because they are caring for a terminal ill member of the family and the stress just continued to run high. Another example is patient who develops an unknown chronic illness in January but just can’t get the right diagnosis and shedding just goes on and on because the issue is not addressed.

If scenario 3 applies in your case, you will not slow your shedding at all until the problem is fixed. You will have some increased shedding starting in April but then it will persist. Only when the trigger actually gets fixed will you shedding resolve.

b) Is this the start of androgenetic hair loss?

You are very wise to consider the possibility that your increased shedding is actually a reflection of androgenetic alopecia arriving on the scene. Very wise. More hair specialists and patients need to get into the frame of mind that hair shedding means potentially so much more than simply a diagnosis of telogen effluvium. What’s the most likely cause of chronically increased shedding in a healthy 30 year old male with normal blood tests? Androgenetic alopecia is the answer.

Now, are you a 30 year old male with chronically increased hair shedding and normal blood tests? No, you are not. You are a 30 year old male with acutely increased shedding (just a few weeks so far) and I have no idea what your blood tests show.

So you could have the early stages of endogenetic alopecia and this diagnosis becomes more and more likely if your shedding does not reduce as time goes on and more and more likely if all your blood tests come back normal.

Is now the right time to start finasteride?

You have asked a great question - is now the right time to start finasteride? In my opinion, a male should only every consider finasteride if five conditions are met. Interested readers can read more about these in a previous article that I wrote last year.

Criteria 1: The individual has a proven (confirmed) diagnosis androgenetic alopecia

Criteria 2: The individual does not have any contraindications to finasteride

Criteria 3: The individual accepts the potential side effect profile of this drug

Criteria 4: The individual has considered the other treatment options but feels they are not better than finasteride as a starting point (topical minoxidil, oral minoxidil, laser, PRP)

Criteria 5: The individual plans to use the medication lifelong.

A little bit of shedding that is due to AGA is certainly a reason to consider starting treatment but it does not necessarily mean it has to be with oral finasteride. It could be topical minoxidil, topical finasteride, laser or PRP . There’s nothing wrong with being conservative in the early stages and seeing if the AGA can be halted with minimal coaxing.

Before leaving the topic, let me reiterate how important criteria one actually is. If you had some major stress in January or February and telogen effluvium is actually the cause of your shedding rather than a diagnosis of androgenetic alopecia, starting finasteride would not be the right step, If you are shedding 93 hairs because your diet is poor and you have a micronutrient deficiency, starting finasteride is not the right step, However, fixing the diet or starting a vitamin in the meantime would be .

c) Is this a mimicker of telogen effluvium ?

There are many conditions that look like telogen effluvium, sound like telogen effluvium but aren’t telogen effluvium. Unfortunately, they can be tough to spot for even clinicians. Fortunately, they are not common. Alopecia areata incognito is not common but presents with shedding. Trichoscopy is needed for the diagnosis (or a biopsy). It’s usually not so perfectly symmetrical as seen with AGA but it can be of course. It responds to topical steroids and Rogaine. Lichen planopilaris and folliculitis decalvans are scarring alopecias that can mimic AGA in some cases. They generally have associated itching, burning or scalp tenderness. Some patients have all three symptoms and some have only two and some have no symptoms at all .

The other common mimicker of classic TE is seborrheic dermatitis and scalp psoriasis. These are common in the population so every hair specialist needs to know everything there is to know about scalp seborrheic dermatitis and scalp psoriasis because these are common concerns. . About 5-10 % of people have seborrheic dermatitis and 2-3 % of all people have psoriasis. In mild cases, seborrheic dermatitis and psoriasis don’t give much in the way of shedding. In moderate to severe cases, they most certainly do. These can mimic a telogen effluvium.

Conclusion

Thanks again for your great question. I hope this helped.

In summary, it’s likely your shedding is abnormal but it could be temporary. A full exam together with review of your story and completion of some key blood tests would be part of an ideal plan. Taking photos every 3 months is probably the most helpful thing you can do for yourself. If your shedding settles but density seems to be dropping off it’s likely there is some AGA present and starting one of the treatments is a good idea if your goal is to halt hair loss. If your shedding stabilizes in the next few months and density stays high, watchful waiting is probably the way to go. This later situation probably means you had some form of telogen effluvium.

Combination Treatments for Frontal Fibrosing Alopecia

Can acitretin and finasteride be combined for the treatment of FFA ?

I’ve selected this question below for this week’s question of the week. It allows us to the concept of combination treatments for frontal fibrosing alopecia and specifically address whether finasteride and acitretin can be combined.

QUESTION

I am 49 years old (female) and the clinical diagnosis was initially FFA, but the biopsy was ‘inconclusive’. It is thought that I probably have a combination of telogen effluvium and FFA.  I am still losing hair and the front hairline has receded more than half an inch. So far I've only taken a mild topical steroid for 4 months and then Dermovate for 4 months. I am on HRT and on Lipitor {statin} for high cholesterol, and on cod liver oil.

My doctor suggests either Acitretin or finasteride. It is up to me to decide which I will take.

My question: could I combine both medications?

You have always suggested combination treatments, but I don’t actually recall having read about the combination of Acetrin and Finasteride. 

Also, my doctor suggests 1mg Finasteride – however, some medical articles mention a dose of 2.5mg.

Would you suggest I start with a higher dose and if necessary, decrease it in case of side effects? 

QUESTION

Thanks for the question.

Yes, finasteride and acitretin can be used together by a great number of post-menopausal patients with FFA - but I am not usually a big fan of starting a large number of treatments together on day 1. I generally like starting one treatment and then adding another in the near or distant if at all possible. In other words, if I can “stagger” the start dates, I prefer that for my patients. I’ll go more into that in just a minute. Sometimes we do need to be more aggressive with treatment than other times and need to combine drugs from the start. That’s a clinical judgment. Even when we do start drugs together, I still like to stagger by 2-4 weeks in the event one causes any sort of rare side effect (i.e. rash, nausea, etc) when starting.

But the short answer to your question is that provided you don’t have any contraindication to using finasteride and provided you don’t have any sort of contraindication to using acitretin, you can use them together.   These two treatments are amongst the most effective treatments for FFA and I’m glad you have been considering them. I refer to these as the gold medal or first line treatments for FFA.

You and your doctor can review all the contraindications to these drugs and confirm whether or not you have any contraindications. Women with past or present depression, or past or current breast cancer may not be good candidates for finasteride and similarly women with high cholesterol or any sort of issue related to dryness  (dry lips, dry eyes, vaginal dryness) may not tolerate high doses or acitretin. You have high cholesterol treated with statins. It does not mean you can’t start acitretin but it does mean you are susceptible to cholesterol numbers bumping up. You’ll simply need to follow the numbers with repeat lab tests if you do start. Most are fine.

It always needs to be emphasized for readers that both of these drugs cannot be used in pregnancy and strict attention to contraception is needed in women who still have menstrual cycles.

You are correct that I combine treatments very often when treating scarring alopecia. But I’m not usually one to just pile on the drugs and send someone out the door with 37 prescriptions. If my patient needs only one drug to control the disease, then why use two drugs? If one can get some good control of the disease with one oral medication along with a course of steroid injections or topical calcineurin inhibitors there is no need to use 2 oral medications.  As mentioned above, it’s not always so simple and sometimes clinical judgment tells us that we need to hit the emergency button and pull out all the stops.   Sometimes we don’t even need pills at all and use of topical finasteride, steroid injections and topical minoxidil might be a good plan. Again it comes down to clinical judgment and of course - shared decision making with the patient.

In FFA, we can get a good sense of how well any newly initiated treatment is working in about 3-6 months. So periodic re-evaluation is key and often more important than the first appointment. (A second appointment is often more involved than the first and decisions can become trickier). Remember though that we might be looking for at the follow up appointment might simply be stopping hair loss as our main goal or we might be looking for some hair regrowth as our main goal. It just depends on the specific patient and the exact details of their FFA so far. Not everyone with FFA regrows any hair back - but some of course do. However, stopping the disease from getting worse is the main goal for everyone. 

In cases where I am a bit more worried or situations where past experience tells me one drug is not going to be enough, I might add 2 drugs. So unfortunately there are no definitive rules to treatment of scarring alopecias. I might start finasteride 2.5 mg at a frequency of 3-7 times per week with isotretinoin or acitretin 10 mg daily or isotretinoin or acitretin every other day. In other situations, I will prefer to start one drug and review how the skin and hair is doing in 3-6 months and adjust accordingly.

At the follow up appointment in 3-6 months, we might go up on finasteride if we started 3 times weekly or stay the course with the dosing we used. Similarly, once I review the mandatory blood tests I like to see for anyone with FFA on acitretin , we may similarly go up or down on the dose of this drug. If we just started finasteride at a past appointment, we might add isotretinoin or acitretin at the follow up if we did not start the drug at the first appointment. But if things are going well on finasteride and the other treatments we started (topicals, injections) .. I might not add acitretin at all. 

Finasteride should be at 2.5 mg rather than 1 mg and use of the drug is 3-7 times per week.  Now, before we leave the topic of finasteride it’s probably worth noting that the related drug dutasteride may be slightly more effective than finasteride in treating FFA. More good studies are needed to definitely prove how different each drug is bit that is important to keep in mind. Sometimes I start a patient on 2.5 mg finasteride daily and depending on how things go I might alternate finasteride 2.5 mg daily with dutasteride 0.5 mg daily in the future or switch completely from finasteride to dutasteride. Dutasteride has a very long half-life so if I have any worry about side effects or potential side effects I might start finasteride rather than dutasteride. However the reality is that for most women with FFA these two drugs are very well tolerated.  

As another example, some women find dutasteride and finasteride worsen hot flashes and so if I am worried about this as a side effect in someone already dealing with hot flashes, I might start finasteride 2.5 mg 3 times weekly not dutasteride daily. Of course, depending on the clinical situation, I might not even start it at all - or might prescribe topical finasteride instead.

Sometimes we need to go higher on acitretin or isotretinoin dosing than 10 mg daily. Whether we do depends on how the patient is tolerating the drug and whether they have side effects. A patient with the side effect of unbearable dry lips or dry eyes is not a patient that we are going to want to increase the dose of acitretin or isotretinoin. In fact, we may even go down on the dose or stop and bring on board a silver medal (second line treatment) like hydroxychloroquine.   Similarly, if cholesterols is jumping up (ie LDL cholesterol or triglycerides), we may want to go down one the dose and bring on board another treatment that won’t impact cholesterol.

 

The Treatment of FFA: Combination Examples

The treatment or scarring alopecia requires a lot of decisions based on what the patient sitting in front of me feels about these treatments and the past health of the patient and the activity of the disease currently. If you dig through the charts of patients with FFA in my practice you’ll see a lot of different treatment plans:

a) some use no pills only creams (steroid or calcineurin inhibitors) and/or steroid injections 

b) some use dutasteride or finasteride and creams +/- steroid injections 

c) some use dutasteride or finasteride with doxycycline and/or hydroxychloroquine plus creams +/- steroid injections 

d) some use oral doxycycline +/- oral hydroxychloroquine alone and creams +/- steroid injections 

e) some use dutasteride or finasteride with creams and isotretinoin or acitretin +/-steroid injections 

f) some use dutasteride or finasteride with acitretin or isotretinoin with creams  +/- steroid injections   +/- hydroxychloroquine 

g) some use acitretin or isotretinoin with creams  +/- steroid injections   

h) some use acitretin or isotretinoin with creams  +/- steroid injections   +/- oral hydroxychloroquine 

i) some use topical finasteride in place or oral finasteride or dutasteride in the above

j) some also have oral minoxidil, topical minoxidil, laser therapy, mycophenolate mofetil, methotrexate, cyclosporine, apremilast, tofacitinib added into various patterns of the above examples

Variations on the Same Theme.

It is important to note that within each example there can be hundreds of variations.  Consider two patients who say, “I take dutasteride, hydroxychloroquine and isotretinoin.” 

One  patient might be on dutasteride 4 times each week PLUS at 10 mg isotretinoin 2 times per week PLUS hydroxychloroquine 200 mg daily.

The other patient might be on dutasteride 7 times per week PLUS at 10 mg isotretinoin 3 times per week PLUS hydroxychloroquine 200 mg 4 times per week.

Combinations that Are Not Permitted.

 I have reviewed a lot of the common combinations above in how we manage FFA. Some treatments cannot be used together due to side effects. Common examples are doxycycline with isotretinoin or hydroxychloroquine with cyclosporine. 

I hope this helps. Thanks for submitting the question.

REFERENCE

[1] Acitretin Handout for Patients with Scarring Alopecia

[2] Finasteride Handout for Women

Drug Induced Alopecia Areata: Can Drugs Cause Alopecia Areata?

Can medications cause alopecia areata ?

I’ve selected this question below for this week’s question of the week. It allows us to discuss the concept of drug induced alopecia areata.

Drug induced Alopecia Areata: 14 drugs to date have been implicated in the development of alopecia areata. The association is still considered very rare even in those who take one of these medications.

QUESTION

Hi Dr Donovan,

I am a 29 year old female and developed alopecia areata in late January 2021. I first developed a patch at the top of the scalp on Jan 23rd and then a second at the back of the scalp on Feb 8. They have fortunately both now grown back with steroid injections using Kenalog.

I am trying to understand this condition and what might have caused it. There is nobody in my family with this condition so I am perplexed. I am quite healthy, eat well and exercise 5 days per week. I have mild asthma and take puffers only very rarely. I developed a urinary tract infection in December and was treated with the antibiotic trimethoprim/sulfamethoxazole (Septra). I’ve been wondering if this could be the cause.

I have been researching if medications can cause alopecia areata but I’m not sure that medications are really all that commonly implicated.

Can you tell me if some medications are strongly connected with developing alopecia areata?

ANSWER

Thanks for submitting your question.

The short answer is no. Mediations are not really all that strongly connected with developing alopecia areata. That’s not to say that some medications have not been linked - it’s just the chances are very low and the vast majority of medications are not strongly associated with development of alopecia areata.

To date, there have only been about 25 patients reported in the medical journals with suspected drug induced alopecia areata. Could it be that there are more? Absolutely. But one thing is likely that drugs are probably not all that commonly connected with alopecia areata.

A nice research paper published in the journal called Clinical and Experimental Dermatology looked at these 25 patients so far who were felt to have ‘drug induced alopecia areata.’ The average age of patients with this condition was 42. Alopecia areata developed about 3-4 months after the drug was started.

Features of Drug Induced Alopecia Areata

Here are some of the key features of “drug induced alopecia areata”:

 1) There can sometimes be an itchy widespread skin rash on the body plus an itchy scalp eruption that precedes the alopecia by 2-3 weeks. Unlike many drug rashes, the patient here has no fever or joint pains. This itchy rash might not always be present.

2) The hair grows back very rapidly when the drug is stopped and further recurrences of patches of alopecia areata are unlikely to occur provided the drug is avoided.

3) Patches of alopecia areata occur again within weeks when the drug is restarted.

4) Blood tests for autoimmune tests, organ function, etc are normal.

What drugs have been implicated in drug induced alopecia areata so far? 

So far, most cases of drug induced alopecia areata that have been published in the medical journals have been with new so called monoclonal antibodies. In fact,  ¾ of cases involve a monoclonal antibody. The list of implicated drugs include 14 medications.

The monoclonal antibodies include:  Adalimumab, Denosumab, Sulfasalazine, anti PDL 1  inhibitors, Alemtuzumab, Nivolumab, Dupilumab and Secukinumab. The others include Lansoprazole, Rifampicin, Phenobarbital, Acitretin, Abacavir, and Carbocysteine.

Summary

Thanks again for your question. About 2 % of the world will develop alopecia areata during their lifetime and it seems that for 99.999% of patients with alopecia areata a drug is not the cause. But for some it could be. The list of drugs will certainly grow beyond the 14 listed above as we continue to understand this concept of drug induced alopecia areata. Perhaps it’s even a bit more common now than we even realize.

But this diagnosis is so much more complex than simply “I took a drug and then got alopecia areata.”

It’s actually closer to “I took a drug and got an itchy skin rash and then got alopecia areata and then stopped and I did not have a patch of alopecia areata at all until I chose to take the drug again.

But for most people, the chances of developing alopecia areata was present the day they were born into the world. There’s a number of genes that increase the risk of developing alopecia areata. So these are really the key factors. But there certainly are environmental factors (exposures) that cause the alopecia areata to develop in someone with the right genes. We don’t understand all these environmental factors but the factors that are being studied are include infections, viruses, stress and others. it’s possible drugs are on that list for now.

What’s striking about drug induced alopecia areata is how fast hair grows back when the drug is stopped. Now, we very rarely decide to give the drug again so it’s hard to know in many cases about criteria number 3 (hair loss occurs when drug is restarted). But if hair loss does occur rapidly when the drug is restarted, it really increases the odds that the drug is implicated.

Taken together, trimethoprim/sulfamethoxasole is not on the list of drugs currently implicated in drug induced alopecia areata. That does not mean it can’t be but there is no really convincing evidence. If a person had a rash when using this drug and developed a patch again with the use of this drug it could support a connection. But if there are patches of alopecia areata that develop when a person is completely off the drug, it really makes it less likely that a drug induced alopecia areata is the correct diagnosis.

REFERENCE

Murad A et al. Drug-induced alopecia areata? Clin Exp Dermatol. 2021 Mar;46(2):363-366.

What is the reason for my hair loss?

Why am I shedding ?

I’ve selected this question below for this week’s question of the week. It allows us to discuss shedding issues in women with hair loss.

QUESTION

Hi!

I am a 42 year old women and have been shedding about 200 hairs a day since March, 2020. I have seen 4 dermatologists and my General Practitioner and they have different diagnoses from TE to FPHL or a combination of both. Prior to March, 2020 I was under extreme stress which started in November 2019. In March 2020 my hair loss was sudden and I have had diffuse shedding since then for the past 10 months. I have always had full, thick and healthy hair and no issues with my hair until the past 10 months. There is no family history of hair loss and my bloodwork came out normal.

Increased hair shedding.

I have been taking vitamins, biotin and Lysine (since June 2020) daily. I am washing my hair every other day, air dry my hair and do not use styling or heating products and eat healthy. I am also taking spirolactone since December 2020 (one month as of today). My dermatologist suggested I take spirolactone (50 mg twice a day) because I have irregular periods. My hair loss slowed down in September 2020 to about 100 hairs a day and went back up to 200 plus in November 2020. I am experiencing itchiness, pins and needles sensation on my scalp and my hair texture changed from straight to wavy for the past 10 months. My hair is also now flat, dull and I have some dandruff that comes and goes. My middle part is widening (compared to pre-March 2020 before the shedding) and with the ongoing shed the part has somewhat looked the same since March.

I lost about 30% of my hair and cannot style it the way I used to because of the thinning in the front. The last two dermatologists I saw performed a pull test and scalp examination and one of them said it is CTE and that there is nothing I can do but wait it out. The other doctor said it's FPHL and that she can tell just by looking at the front of my hair because of the way its thinning. I do see hair growth and my hair is full of static with short hairs coming out but I am also losing a lot of hair in all different lengths including short ones every day. I am frustrated because it has been 10 months and my shedding is not stopping. I do not know which diagnosis is right and what treatment I should start. Also It would be great for the itching and "pins and needle" feeling on my scalp to go away...

Thank you for reading and I'm so happy to find this website.

ANSWER

Thanks for the question.

I’d like to discuss several important things in the question you ask and the information you have submitted.

Before we do go further, I’d like to point out that the ideal way to diagnose hair loss is using what I termed the ”Diagnostic S.E.T.” I refer to these as the diagnostic “set” because theses 3 aspects all go together. These 3 items include:

1) the patient’s story

2) the findings uncovered during the process of the scalp examination including trichoscopy

3) the results of relevant blood tests. 

The first letter of each of the three words 1) story, 2) examination and 3) tests spell out the word “S.E.T.” - again a helpful reminder of how the information obtained from reviewing each of these 3 aspects helps solidify a proper diagnosis.

There is lots more to your story that I need. I would want to know exactly what your lab tests showed and which ones were tested. In about 20 % of patients who tell me they had blood tests and all came out normal, the labs are either insufficient (more are needed based on their story and examination) or the labs are not in fact really normal. I always like to see the labs. I would want to know about other symptoms like joint pains, headaches, fatigue, weight loss, eyebrow changes, eyelashes changes, body hair changes, nail changes, and rashes.

I strongly suspect that androgenetic alopecia with seborrheic dermatitis are part of the diagnoses. The 2 key questions here in your case are:

1. Do you have really have telogen effluvium as well ?

2. What really is the reason for the ‘pins and needles’ sensation ?

Let’s look at a few key points.

POINT 1. Androgenetic alopecia (female pattern hair loss) appears to be at least one of the diagnoses.

I do think that at least one of the diagnoses here is androgenetic alopecia (also called female pattern hair loss, FPHL). The widening of the part does not itself mean the diagnosis is AGA. however, the pattern of the part widening is not the same front to back. There is a slight increase in thinning noted in the mid scalp and crown compared to the frontal one third of the scalp. This leads me to believe there is a patterned nature of the hair loss. I’m open to the possibility that some of the hair loss is diffuse in nature (ie all over) but some is likely not. In other words, I don’t think this is entirely a diffuse type of hair loss.

Also, when I look up close at the images, it’s clear that some follicles are thinner than others. This is a phenomenon called anisotrichosis and is a feature of AGA. Some hair follicles are miniaturization (getting thinner).

Women with AGA often experience shedding of hair in the early stages and shedding can fluctuate in intensity. Other hair loss conditions can cause shedding as well so we’ll address that in just a moment. Women with AGA often notice that the texture of hair changes. There are many such patterns of texture change and a change from straighter to curlier is quite common as you too have described.

The fact that you note increasing numbers of short hairs is not confirmatory for a diagnosis of AGA but certainly is supportive of this diagnosis.

POINT 2: Seborrheic dermatitis/dandruff is likely another diagnosis.

I agree with you that dandruff (or its close cousin called seborrheic dermatitis) is likely present. Flakes are noted in some of the photos. I’d need to perform trichoscopy to confirm this diagnosis but it appears to be a component of the issues present. Mild dandruff is not usually a cause of hair loss but it certainly can cause all sorts of scalp symptoms. To eliminate the possibility that dandruff or seborrheic dermatitis is contributing to symptoms, I often encourage my own patients to aggressively treat their seborrheic dermatitis so we can remove this as a factor. Shampoos with zinc pyrithione, ketoconazole, selenium sulphide or ciclopirox can be used 2 times per week and left on 90 to 120 seconds before being rinsed off. The duration that these shampoos are left on the scalp can certainly be increased but I don’t recommend that to start with as many antidandruff shampoos can be drying and then the dryness starts causing itching and symptoms. I often recommend to my own patients that 5-10 drops of betamethasone valerate lotion 0.1 % can be applied in the scalp after their hair is shampooed and dried. This is a weak steroid and can be safely used for 2 week periods to help settle itching. If the use of shampoos settles the itching, tingling and pins and needles, then it’s not needed.

POINT 3: Telogen effluvium could be present.

Telogen effluvium is one of those conditions that can come and go. Sometimes it’s easy to prove a TE is present and sometimes it’s a bit more challenging. It could be that a TE was present when your AGA first started. You were under extreme stress in November 2019 and yes this could most definitively give shedding in March 2020. Telogen effluvium usually follows 2-3 month after some kind of trigger and can last 3-6 months or more. Other causes of telogen effluvium are low ferritin levels, thyroid issues, medications, diets, weight loss and internal illness. I don’t really have enough information to evaluate these other issues so I’ll go with your assessment that your blood tests were normal. Hopefully you had a reasonable set of tests including TSH, ferritin, CBC. With your irregular periods you describe it would make sense to have FSH, DHEAS, testosterone. One needs to consider whether you are entering a perimenopausal transition and how this could contribute to hair shedding and AGA. With any pins and needles sensation, it’s nice to know that liver enzymes (AST, ALT) are normal and that kidney function is normal (creatinine).

Telogen effluvium can sometimes precipitate or accelerate an underlying AGA. This is a well accepted phenomenon. it does not happen to all women with AGA. However, women with shedding who have AGA that is about to begin (ie very early onset AGA) often find that the AGA component of the hair loss gets sent into a more rapid speed of development if a TE is present. This could be a feature here.

With your normal blood tests, it’s unlikely that a TE is still driving hair loss all this time. Not impossible of course, but unlikely. What is more likely is that AGA is not fully being treated. Spironolactone helps but does not fully suppress AGA in all women at 50 mg twice daily. Sometimes higher doses are needed OR other treatments for AGA are needed (other anti androgens, laser, minoxidil, etc)

POINT 4: If you want to assess the degree to which AGA and TE are present, you could have a biopsy or 5 day modified hair wash test (or a proper trichoscopic examination). I don’t think these are really needed.

For your physicians/specialists who think that AGA is not a diagnosis here for you, a biopsy or 5 day modified hair wash test could help prove them wrong (… or prove them right!). This is a wonderful test but adds to the stress of collecting hairs so I’m not always in favour of it. Biopsies leave scars but if interpretted by a knowledgable dermatapathologist, they can be very helpful.

But, let’s be clear. A biopsy showing a terminal to vellus hair ratio of less than 4:1 taken from your mid scalp area puts to rest any argument about whether AGA its present of not. End of discussion. A 5 day modified hair wash test (done properly !) showing less than 100 hairs and more than 10% hairs being tiny 3 cm hairs also points to an underlying AGA.

Of course, simply examining the scalp with trichoscopy can also confirm this diagnosis but not all specialists are skilled with trichoscopy. If a specialist knows how to use a handheld dermatoscope, we don’t even need biopsies or hair collections to diagnose AGA. If they don’t then yes, we need to go to the extra effort to prove it.

POINT 5: The ‘pins and needles’ is a bit trickier given how many conditions can cause this.

There are a very large number of conditions that can cause pins and needles in the scalp. Stress can cause it. AGA can cause it. TE can cause it. Alopecia areata can cause it. Dandruff can cause it. Scarring alopecias cn cause it. The list is long and includes issues even outside the scalp like cervical spine disease.

I would need to know more about your story and carefully examine the scalp and eyebrows and eyelashes and nails to get a sense of what is causing this.

For pins and needles sensations, I usually advise treating any dandruff or seborrheic dermatitis and using a few drop of betamethasone lotion as outlined above. If it’s still there and the patient has AGA, I usually recommend treating the AGA more aggressively. This often help stop pins and needles. Low level laser, minoxidil and other antiandrogens can be considered.

Conclusion/Summary

Thanks for the question. I hope this helps you in your search for answers and helps with further discussion with your doctors. I think it’s really important for you and your doctors to feel confident with the diagnosis and not proceed with any sort of “maybe.” It would appear that AGA is a component of the issues here but if there is any doubt, a trichoscopic examination, biopsy or 5 day modified hair wash test can help confirm this.

Photos are really important moving forward to document changes - hopefully for the better.

if spironolactone is not fully helping then you and your dermatologists might discuss together whether or not to increase the dose or whether other treatments need to be considered. These include topical minoxidil, oral minoxidil other topical or oral antiandrogens and low level laser. PRP can be considered too. The important thing to note about minoxidil, laser and PRP is that if there is any amount of chronic shedding issue present these treatments can help promote more normal shedding patterns. This is assuming all your blood tests are normal. If any of your blood tests are abnormal and if, in fact, you have not had a proper work up then those issues need to be addressed first. it sounds like you’ve had a good set of blood tests through all the doctors you have seen.

Thank you.

Acitretin, Isotretinoin and Minoxidil for Patient with FFA & AGA: What if they cause shedding?

Retinoids for Patient with FFA & AGA: Do they cause hair shedding that worsens hair loss?

I’ve selected this question below for this week’s question of the week. It allows us to discuss the use of retinoids and minoxidil in FFA .

QUESTION

I am a female age 67. My diagnosis is frontal fibrosing alopecia (FFA) - with a new diagnosis of underlying androgenetic hair loss (AGA). My dermatologist originally planned to put me on Acetrin for FFA but she now says that the shedding usually caused by retinoids will in cases with underlying AGA not be temporary, but will precipitate permanent hair loss, and therefore she does not want to prescribe it.

For review, I have itching all over scalp at different times [behind ears; frontal hairline, crown, temples]. Rosacea [onset only after topical clobetasol ]; thinning all over scalp with exception of crown; hair already thinning at age 50; eyebrow thinning at age 35/40. medicated since April 2020 by first Betnovate, then Dermovate [Clobetasol], then topical Pimecrolimus with Lymecyline. Other medications: HRT [estrogen only], statins [Rosuvastatin], ARB [Candesartan, as the only BP medication that is not linked to alopecia]; in the past decades [but now discontinued because of links to alopecia]: sun blockers and retinol creams.

I do not understand why underlying AGA should make a difference in prescribing this medication. However, I am concerned about hair follicles affected by FFA. I worry that the hair near my hairline, once shed, will not grow back because in FFA, the follicles that still produce hair may not generate new hair after the shedding, as more and more follicles become affected by FFA. I don't know if hair follicles, once affected by FFA, (but not yet dead) continue their cycle from catagen to anagen until such time when they are truly dead.

I have the same concern with Minoxidil, in particular as it was confirmed by another hair clinic that they do not advise the use of Minoxidil in patients with FFA, as Minoxidil stimulates initial shedding and FFA affected follicles would not produce new hair after that. - I would be very grateful if you could give me your opinion on the use of Minoxidil and Acetrin in a case of FFA with AGA.

Many thanks for your help and kind regards

ANSWER

Thanks for the great question. There is a lot to discuss, so let’s get to it.

First, let me say how relevant this question is. A very large proportion of women over 50 years of age with a diagnosis of FFA have a diagnosis of AGA in my opinion. I’d put the number around 55 % to even as high as 70%. So the most common scenario is treating both. Do I worry that any of my treatments are going to worsen the AGA? Not all that much. Is it possible? Sure. Do I see it? Yes, but I’d say less than 1 in 150 women. This is my experience in treating large numbers of patients with FFA.

POINT 1. The Question is Important Because Retinoids are among the Most Effective Treatments for FFA

Retinoids like isotretinoin and acitretin are among the most effective treatments for FFA. They are what I called “gold medal” treatments or first line treatments. Retinoids together with 5 alpha reductase inhibitor drugs are the most effective treatments for FFA. There is still a bit of debate about which drugs are actually better in treatment FFA. A 2017 study by Rakowska and colleagues suggested retinoids are the clear winner. Other studies by Vañó-Galván and colleagues suggested that finasteride and dutasteride (especially dutasteride) are the top treatments.

Here are the treatments that I consider top treatments:

POINT 2. Acitretin and Isotretinoin Can not be Used with Lymecycline

I’m not sure from your story if you are still on Lymecycline or not. It’s important to be aware that these two drugs can’t be used together - ever. So that’s not an option. But if you are off lymecycline, acitretin could be an option provided your cholesterol is under good control with the statin. If you are still on lymecycline and feel that it’s helping, you might decide to continue it and look to other options like dutasteride, finasteride or hydroxychloroquine. Acitretin won’t be possible. These are all discussions that you would want to have with your dermatologist. For some patients with FFA, they are good options - but not everyone.

POINT 3. Shedding can occur with Acitretin but is Not Common on Small Doses used in FFA.

Let’s come back to acitretin. Acitretin can cause shedding in 3 -5 % of users at the typical doses used in treating various diseases. The issue is that in FFA, I normally use much smaller doses - like 10 mg daily or even every other day to start. The risk of shedding is a lot less than 3-5 %. Do we have a number to quote you? Not really but I’d estimate it’s around 1 % and probably less.

How do I know? Well I have a large number of patients with FFA and AGA with on retinoids and I am not answering emails and phone calls very often about shedding issues. It still happens.

Provided you are not on Lymecycline, you certainly could consider going slowly on the dose if that issue something you want to discuss with your dermatologist again.

There are other options too - especially dutasteride (and finasteride). If your dermatologist is worried about shedding and won’t use, then dutasteride is an option. Do these drugs cause shedding? Sure, sometimes. Anything can. Fortunately, it is just not common either. shedding is less likely with dutasteride than acitretin but fortunately both are fairly uncommon. Sometimes, I prescribe acitretin and dutasteride together.

So, to summarize. It’s not impossible to have shedding from acitretin. It’s just not so common at the doses we use in FFA.

POINT 4: If shedding does occur, shed hair is not necessary gone forever.

There is an assumption that is wrong here - and that is that any shed hair is guaranteed to be gone forever. That’s just simply not accurate. You are shedding hairs all the time - and some are going to pop back up through the scalp. The more active the FFA is the less likely the hair is to come back up - but a lot still does even in active FFA. If the FFA is only mildly active - then probably a good deal of the hairs are going to return.

Granted, you are correct that we don’t want shedding if we don’t have do.

But if shedding is going to occur it will be mild most likely and happen around 6-8 weeks after treatment . You’ll have a few week window to stop. So I said that shedding is not common with 10 mg acitretin and I’ll point out that even if shedding does occur, it’s usually not common to massive shedding. So we have two “not commons’ in a row.

The risk of massive chaos with the hair is low.

Is it zero? Well no. But it is low.

Do be sure to review with your dermatologist the role of dutasteride too. Now, you might have contraindications to the drug so that is something you’d need to review with your doctors. I don’t have enough information. But often in situations like this I might consider starting dutasteride 0.5 mg 3 times weekly with acitretin or isotretinoin 10 mg three times weekly (along with steroid injections and topical pimecrolimus) and see where things are at in 4 months. We can go up on dutasteride dosing or up on acitretin dosing. That’s often my plan in situations like this but it may or may not apply to your situation.

POINT 5. Minoxidil is a common treatment for FFA.

Minoxidil can cause shedding. Sure. Is there a big risk that if you get shedding, the hair is not coming back? No. Is there a small chance it’s not coming back? Sure, but it’s small.

Minoxidil can be an important part of managing FFA sometimes. It can also play a key role in helping androgenetic alopecia.

Many of my dermatology colleagues who treat FFA like I do also use minoxidil. It’s not off the table as a treatment. I consider it a silver medal treatment - meaning that I might not start it right away in everyone but I often add it down the road. Some hair specialists use minoxidil immediately in treating FFA. I don’t but some do. I use it as an “add on” in many patients.

Conclusion and Summary

Thanks again for the question. I hope this helps. Minoxidil is commonly used in treating FFA and even in those who have AGA. Is it a first treatment to reach for? Not in my opinion but it’s a good option for many once things are coming a bit more stable. Minoxidil is worked into many patient’s treatment plans for FFA - even if they have AGA.

The acitretin is a good option for many (provided you are not still on Lymecycline or any sort of tetracycline antibiotic). In my opinion there are three treatments that a really need to be discussed for anyone with FFA - the retinoids (acitretin, isotretinoin), the 5 alpha reductase inhibitors (dutasteride or finasteride) and steroid injections. Those discussions are worth having with the dermatologist.

I’m not sure exactly why the other clinic you went to did not want you to use minoxidil. You can read my previous article on “The Six Reasons Why My Practitioner Won’t Start the Treatment You Were Hoping” - the answer certainly lies in one or more of these 6 reasons.

Thank you again

Hydroxychloroquine (Plaquenil) for Frontal Fibrosing Alopecia

Hydroxychloroquine (Plaquenil) for FFA

I’ve selected this question below for this week’s question of the week. It allows us to discuss the use of hydroxychloroquine (Plaquenil) in FFA as well as the rare cardiac effects of hydroxychloroquine.

QUESTION

I am a female in my late 70s with frontal fibrosing alopecia, confirmed by a scalp biopsy. It is being treated with clobetasol .05%, one application per day. I have read that this is not a very effective treatment when used alone. What would you suggest might be used with it?

My dermatologist suggested hydroxychloroquine (plaquenil), but I read that this might have an adverse effect on people with heart disease. Do you agree? The first symptom about six months ago was drastically thinning eyebrows. I am in the third month of treatment and hair loss around the hairline is not yet apparent. I have cardiomyopathy and atrial fibrillation, for which I am taking a blood thinner (Eliquis) plus daily irbesartan, bisoprolol and spironolactone. Do you think any of these drugs might be the cause of my FFA?

ANSWER

Thanks for the great question. I’d like to discuss several important points in the question you ask and the information you have submitted.

Before we go further, I’m going to assume here in your question that the diagnosis is correct. Can I be 100 % sure you have FFA? Well no - not at all. I haven’t seen your scalp and eyebrows and I don’t know all the details of your story. You might reply to me that you have already told me you had a biopsy. Well, biopsies are not 100% either. Nevertheless, it sure sounds like many aspects of your story do, in fact, support a diagnosis of FFA. So I’ll proceed with this assumption. If you do have FFA, this answer then helps. If the diagnosis is not correct, then the answer has helpful points nevertheless for others with the condition.

Let’s look at some aspects of your question:

a) How good is hydroxychloroquine in FFA?

Hydroxychloroquine is helpful in some patients with FFA. I tell my patients it’s a silver medalist. In other words, it can be helpful, it’s just that other treatments are probably better. We will get into that a bit later. That does not mean hydroxychloroquine is useless as a treatment. Not at all. For some patients with FFA, hydroxychloroquine does help. It does not help everyone that is for sure.

Let’s look at some helpful studies from the past evaluating the effectiveness of hydroxychloroquine in FFA treatment.

in 2013, Ladzinski and colleagues proposed that hydroxychloroquine had some benefits in about 50 % of patients,

In a much larger study conducted in 2014, Vano Galvan et al showed that a 15 % of patients with FFA using hydroxychloroquine had some improvement in their disease. 59 % had their disease stabilized. For about one quarter of patients, the drug did nothing helpful at all.

in 2018, Strazzulla and colleagues found that about 70 % of patients had some benefit with hydroxychloroquine - with results being more or less the same ass doxycycline.

A 2010 study by Samroa and colleagues found that hydroxychloroquine reduced redness and inflammation in FFA patients.

Treatment Options for FFA

Before we leave the subject of hydroxychloroquine for treatment of FFA, let’s look at the options for treatment. Every single type of hair loss has treatment options. The thing that is often forgotten is that not all treatments are the same. Some are good. Some are not so good. Some are good but crazy expensive. Some are good and not so expensive. Some are good and fairly safe and some are good and incredibly risky. I divide every disease into gold, silver and bronze medal treatments. 

I personally like this analogy of categorizing treatments because it reminds us of a couple of key things. First, not all treatments are equal. We select treatments by balancing benefit and risk and take into account the safety, affordability, feasibility and effectiveness of treatment (what I have previously termed the "S.A.F.E." Principle. )

The second reason I like the analogy of gold and silver and bronze medal treatments is because it reminds us that this is not always going to be the order. The athlete that received the gold medal in the recent Olympics may not be the athlete that gets the gold medal in the next Olympics. Of course, if the athlete is really good - he or she will probably be up there one the podium in the top spot again in 4 years. The same is true with hair loss treatments. 

As new treatments come out and as they are studied more and more, a certain treatment might just rise into the gold medal spot and push out other treatments that are there now down into silver or bronze positions. Sometimes, a treatment gets removed from the market entirely just as some Olympians get disqualified from the Olympics. They disappear entirely.

In the diagram below, I outline what I consider the gold, silver and bronze treatments for FFA. In FFA, Plaquenil is a silver medallist. It’s not useless. It has reasonable safety (although I will discuss the heart issues next). It’s relatively inexpensive (Plaquenil is about $1300 USD per year whereas Apremilast is $ 18,000 USD per year). It’s easy to use. It’s somewhat helpful. In terms of the SAFE principle, it’s an okay option to keep in mind for many.

b) Does hydroxychloroquine have effects on the heart?

Hydroxychloroquine can have effects on the heart. Fortunately, they are not common but risks do increase with advancing age. In fact, physicians need to be much more on alert for eye, muscle, heart side effects in patients over 65 compared to those under 65. Of course, side effects of this nature can happen at any age - but they are more common with advancing age. Hydroxychloroquine cardiotoxicity is non common - but it is a serious side effect.

Plaquenil “cardiotoxicity” (potential toxicity on the heart) has best been studied inn patients with the autoimmune disease lupus who take the drug and also to seem degree in patients with rheumatoid arthritis. Could it be that a these groups are more likely to experienced heart muscle side effects with Plaquenil? Could be, but more studies are needed. For now, it’s a potential side effect that needs to be considered in everyone. There’s nearly 100 reports in the medical journals now of hydroxychloroquine induced heart toxicity. When it does occur, the patient usually develops a restrictive or dilated cardiomyopathy or has conduction system abnormalities including atrioventricular block and bundle branch block. Studies by Costedoat-Chalumeau showed that when cardiomyopathy is present other signs of toxicity are often present as well - eye toxicity, nerve toxicity, and muscle toxicity.

So who is more likely to get hydroxychloroquine induced cardiomyopathy ? Risk factors are currently proposed to include older age, female sex, longer duration of therapy (>10 years), higher doses of the drug, pre-existing cardiac disease, and renal insufficiency (kidney disease). It’s important to remember that most patients who develop hydroxychloroquine cardiotoxicity have been on the drug a long time - ie 10 years or more. Of course, there are reports in the medical journals of those who have been on it just a few months before developing side effects.

The Lane and Colleagues 2020 Study

Finally, I’d like to tell you about an important study by Lane and colleagues. This was recently published. This was a study of almost 1 million ( 956,374) hydroxychloroquine users so it’s a massive study. Massive studies of this size are important because they allow us to get a better sense of the risk associated with certain drugs. Lane’s study focused non patents with rheumatoid arthritis (not FFA) so we need to always keep that in mind. The researcher showed that long-term hydroxychloroquine use increased cardiovascular mortality 1.65 times compared with control treatments There are some limitations of the study (as there are with any study). nevertheless, it points to the fact that there may be a slight increase risk of heart related effects with long term use of hydroxychloroquine - at least in patients with rheumatoid arthritis. Fortunately, side effects of this nature are still quite uncommon.

In conclusion, there are some small risks with hydroxychloroquine use in your case. This is something you’d certainly want to review with your heart doctors too. Depending on the degree of heart issues (class of heart failure, etc), it may be something they agree with at a low dose, or something they advise against.

c) What would you suggest might be used with clobetasol?

This is actually a very involved question. If you find that use of clobetasol in the manner described and recommended by your doctors stops further hair loss completely - then you don’t need to use anything else. The key to treating FFA is not to pile on more and more drugs but rather to use the safest and simplest approach possible that stops the disease. if clobetasol stops your FFA 100% - then you need not look for anything else.

Is it likely that clobetasol stops your disease 100%? Well, no. But again - it’s not impossible that it does. It’s a silver medallist.

There are some 20 other options available. Again we follow a logical approach to deciding on which other treatments to use. We select treatments that have good evidence from good studies as well as treatments that have good safety.

You may want to review with your doctors other options like topical calcineurin inhibitors (like Pimecrolimus) as well as low doses of steroid injections (2 mg per mL) every few months. Topical clobetasol is going to give atrophy after a few months of daily use so you and your doctors are going to need to decide when to start reducing that dose.

You can also review options like topical anti androgens (topical finasteride) or even oral dutasteride. Starting two times weekly could be something that you are your doctors discuss. You’ll want to carefully review if you have any contraindications to its use (depression, cancer risks, osteoporosis). Adding acitretin once weekly or twice weekly may also be something you discuss.

d) I am taking a blood thinner (Eliquis) plus daily irbesartan, bisoprolol and spironolactone. Do you think any of these drugs might be the cause of my FFA?

Some drugs do contribute to the development of FFA. For example, the antiestrogen tamoxifen is one of them. The drugs on your list have not been implicated to date in the development of FFA. However, some can cause hair loss - just not FFA.

I’ll make a few additional comments at this point. First, your patterns of hair shedding are going to be important in giving you the fullest answer possible. Your story is interesting in that it seems that you have eyebrow loss without scalp frontal loss yet. Yes, that sure sounds like FFA but again I can’t say much more because I don’t know much about your story and haven’t seen your scalp. If your hair shedding is markedly increased the question must be posed to your health care team as to whether there is any component of telogen effluvium as well. All the drugs on your list can cause telogen effluvium - fortunately that’s still really unlikely overall. Most people have no issues of the sort.

Now on to the tricky part. it’s not possible to 100% say that the drugs you are taking had nothing to do with the development of FFA. Beta blockers (like bisoprolol), angiotensin II receptor blockers (like irbesartan) and spironolactone have rarely been involved in skin rashes known as “lichenoid” drug eruptions. There is some similarity between lichenoid drug eruptions and the lichenoid eruption that is part of the pathology of frontal fibrosing alopecia. Have any of the drugs you are taking been convincingly implicated in the development of FFA? No. It is possible there is some link in those with some sort of predisposition to this disease ? Yes.

Conclusion and Summary

Thanks for submitting your question. I do hope this will be helpful in the discussions you have with your doctors. I’ve included references below in the event they too are helpful. I wish you the best of health.

Reference

August C, Holzhausen HJ, Schmoldt A, et al. Histological and ultrastructural findings in chloroquine-induced cardio- myopathy. J Mol Med (Berl) 1995; 73: 73–77.

Baguet JP, Tremel F and Fabre M. Chloroquine cardiomypathy with conduction disorders. Heart 1999; 81: 221–223.

Clark C, Douglas WS. Lichenoid drug eruption induced by spironolactone. Clin Exp Dermatol. 1998 Jan;23(1):43-4

Costedoat-Chalumeau N, Hulot JS, Amoura Z, et al. Cardiomyopathy related to antimalarial therapy with illustra- tive case report. Cardiology 2007; 107: 73–80.

Fesssa et al. Lichen planus-like drug eruptions due to β-blockers: a case report and literature review. Am J Clin Dermatol 2012 Dec 1;13(6):417-21.

Ladzinski et al. Frontal fibrosing alopecia: a retrospective review of 19 patients seen at Duke University. J Am Acad Dermatol. 2013 May;68(5):749-55.

Lane, J. C. E. et al. Risk of hydroxychloroquine alone and in combination with azithromycin in the treatment of rheumatoid arthritis: a multinational, retrospective study. Lancet Rheumatol. (2020).

Massa MC, Jason SM, Gradini R, Welykyj Lichenoid drug eruption secondary to propranolol. Cutis. 1991 Jul;48(1):41-3.PMID: 1831116

Nord JE, Shah PK, Rinaldi RZ, et al. Hydroxychloroquine cardiotoxicity in systemic lupus erythematosus: a report of 2 cases and review of the literature. Semin Ann Rheum Dis 2004; 33: 336–351.

Pfab et al. Lichenoid drug eruption due to an antihypertonic drug containing irbesartan and hydrochlorothiazide. Allergy 2006; 61(6):786-7

Samrao A et al. Frontal fibrosing alopecia: a clinical review of 36 patients. , Chew AL, Price V.Br J Dermatol. 2010 Dec;163(6):1296-300.

Schön MP, Tebbe B, Trautmann C, Orfanos CE. Lichenoid drug eruption induced by spironolactone.Acta Derm Venereol. 1994 Nov;74(6):476.

Strazzulla LC et al . Prognosis, treatment, and disease outcomes in frontal fibrosing alopecia: A retrospective review of 92 cases.. J Am Acad Dermatol. 2018 Jan;78(1):203-205. doi: 10.1016/j.jaad.2017.07.035.

Vano-Galvan S. Frontal fibrosing alopecia: a multicenter review of 355 patients. J Am Acad Dermatol . 2014 Apr;70(4):670-678.

Yogasundaram H, Putko BN, Tien J, Paterson DI, Cujec B, Ringrose J, Oudit GY. Hydroxychloroquine‐induced cardiomyopathy: case report, pathophysiology, diagnosis, and treatment. Can J Cardiol 2014; 30: 1706–1715.

Cyclosporine and Hydroxychloroquine Drug Interactions

Why is their a concern about using cyclosporine with hydroxchlorquine?

I’ve selected this question below for this week’s question of the week. It allows us to discuss an important drug interaction between cyclosporine and hydroxychlroquine (Plaquenil).

QUESTION

Dear Dr. Donovan.

I'm a 25 yr old woman with diagnosed lichen planopilaris (LPP). It's proven difficult to treat. My doc just prescribed plaquenil and cyclosporine, but I noticed on your handout that it says these drugs interact. Why do you not prescribe them together?

Thank you for your time!

ANSWER

Thanks for your excellent question. The reason is this: hydroxychloroquine (Plaquenil) can potentially Increase cyclosporine levels in the blood leading to higher cyclosporine in the blood and increase the risk of cyclosporine side effects.

Cyclosporine and hydroxychloroquine are two drugs that may have benefit the treatment of lichen planopilaris. The use of the two medications together (at the same time) carries the risk of increased side effects and elevated serum creatinine. Use of the two medications together is generally discouraged but if they are used together it should be done only under supervision of doctors who understand the proper monitoring that is necessary. Frequent blood pressure monitoring and frequent measurement of serum creatinine and frequent evaluation of side effects will be required.

Let’s take a look at what is known in the past.

The first indication of a potential interaction between cyclosporine was with “chloroquine” - a close cousin of hydroxychloroquine. In 1993, Finielz and colleagues published a study in the journal Nephron of a 28 year old kidney transplant patient who was stable on cyclosporine, prednisone and azathioprine. His creatinine level was 200 umol/L. His blood cyclosporine level was 105 ng/mL and his blood pressure was normal 130/80.

He then decided to go on vacation and started treatment with chloroquine for prevention of malaria. His blood pressure just 6 days later increased to 160/100, his creatinine level rose to 234 and his blood cyclosporine level rose more than four times to 470 ng/mL. His levels reduce again when chloroquine was stopped and levels rose yet again when the drug was given back.

An increase in cyclosporine levels has also been noted in patients using hydroxychloroquine (Plaquenil). Some rheumatologists in years gone by have studied this combination. But that’s not to say it’s not without potential risk - there are.

A 1996 study examined the benefits of combining cyclosporine to patents with rheumatoid arthritis who were not improving with hydroxychloroquine or methotrexate. We’ll focus here on the results of combining cyclosporine and hydroxychloroquine because this is what your question pertains to.

The study included 12 patients using both hydroxychloroquine and cyclosporine. During the study, the mean daily dose of CsA ranged from 2.5 to 4.2 mg/kg and at 6 months it was 3.3 mg/kg. The mean serum creatinine levels increased by 0.1 +/- 0.2 mg/dl in the patients treated with the two drugs. In 5 of 12 patients (41.6 %) there was a concerning increase in creatinine of more than 130 %. Other side effects seen in the combination were gastrointestinal side effects (41.6%), hypertrichosis (25%), gingival hyperplasia (25%), liver test abnormalities (8.3 %), and neurological problems (16.6%). This is not by any means a complete lists of side effects of cyclosporine - those will need to be reviewed with your doctor.

Conclusion

Thanks again for the great question. Yes, there most certainly is a potential drug interaction between cyclosporine and hydroxychloroquine that is very important for patients and treating physicians to be aware. Cyclosporine is notorious for drug interactions so I recommend that anyone who uses cyclosporine get in a routine of shouting out loudly “I am on cyclosporine - does this drug interact?”

Any patient started on combined hydroxychloroquine and cyclosporine treatment will need to first check that this was not an error by the prescriber. Sometimes this is what the prescriber intended - as seen above in the 1996 study I mentioned. This is not, however, all that common anymore. If it was not an error, the patient will need very, very close monitoring. Blood pressure will need to be measured daily during the starting period. Serum creatinine levels and serum cyclosporine levels will need to be measured very frequently and side effects will need to be closely monitored.

References

1] Uptodate.com

2] https://www.drugs.com/interactions-check.php?drug_list=763-0,1298-0

3] Salaffi et al. Combination therapy of cyclosporine A with methotrexate or hydroxychloroquine in refractory rheumatoid arthritis. Scand J Rheumatol. 1996;25(1):16-23.

Excessive Shedding in the 30's: Why is my hair still shedding?

Excessive hair shedding in the early 30s: What are the reasons?

I’ve selected this question below for this week’s question of the week. It allows us to discuss diagnosis of hair loss in women 30-40 years of age with chronic shedding. Here is the question….

QUESTION

Can oral vitamin + iron supplementation increase shedding the way minoxidil does?

I am a 35 years old female. I have always been under a lot of stress, especially in 2016-2017. In spring 2018 I noticed my hair got thinner (I always had rather fine hair); my scalp could be seen under direct light. I used castor oil and took spiruline tablets hoping it would improve; got the impression it did so I stopped. I was vegetarian then, too. I got preoccupied with the fear of getting bald, did a lot of research on the Internet that frightenend me even more and finally I got the courage to get an appointment with a dermatologist this summer (2020). She didn't notice hair loss (pull test); said my density was normal and scalp looked ok. She said it didn't look like AGA at all. She prescribed my iron supplementation (low ferritin (24)) and advised me to change my diet. I lack vitamin B12 too. From the end of July onwards I've been taking iron, spiruline, biotin and B12 supplementation. Since I didn't agree with the diagnosis ("no visible hair loss") I began counting the hair I'm shedding each day. The amount is horrible: it's more than 200 hair/day! The supplementation I'm taking and the changes I made to my diet don't seem to decrease the shedding at all. I've booked a appointment with anonther dermatologist for a second opinion (I'm truly terrified: my scalp feels strange; a bit of itching and burning + "crawling" sensations; my hair keeps falling out and for my dermatologist there's no problem...!) I'm surprised I still have hair left on my scalp when I see the amount that's falling every day... 
I have read that those who use Minoxidil experience shedding in the first months which is a sign that new hair is on the way (I do see regrowth but it doesn't make my hair volume look any better). So I am wondering: can oral supplementation cause a similar shedding, which proves that the treatment is working? If not, what should I do? I got no "real" dagnosis; from what I read on the internet it seems to look like TE but how can I be sure?

I would like to add that from time to time I have small pimples on my scalp that come and go. Not a lot of them though, but they can be itchy. My skin (on face) is oily, I have the same sort of sores on my face from time to time too. I don't know if this information is important.

Thank you for reading and I hope you'll be able to answer my question since my own dermatologist doesn't seem to take my problem seriously...I think the thinning is all over, but mostly noticable on the top of my scalp and at the temples. My hair become very flat, no volume at all. I wash it daily because it greases very fast (eversince I was in my early teens).

ANSWER

Thanks for the question. There’s really two very good ways to determine the cause of your hair loss - and that is to share your story with a hair specialist and have him or her

1) Evaluate your scalp up close with “trichsocopy” (magnified imaging)

or

2) Perform a 4 mm scalp biopsy

So there is a way for you to get your answer.

I’d like to discuss several important things in the question you ask and the information you have submitted. Let’s get to it.

Before we do go further, I’d like to point out that the ideal way to diagnose hair loss is using what I termed the ”Diagnostic S.E.T.” I refer to these as the diagnostic “set” because theses 3 aspects all go together. These 3 items include:

1) the patient’s story

2) the findings uncovered during the process of the scalp examination including trichoscopy

3) the results of relevant blood tests. 

The first letter of each of the three words 1) story, 2) examination and 3) tests spell out the word “S.E.T.” - again a helpful reminder of how the information obtained from reviewing each of these 3 aspects helps solidify a proper diagnosis.

AGA must be the Default Diagnosis in Women 30-40 with Increased Hair Shedding

I would need to examine your scalp to determine if you have androgenetic alopecia or telogen effluvium or both …. or some other diagnosis.

However, I strongly believe that the first diagnosis that must be ruled in or ruled out in any female patient with hair loss in the 30s is androgenetic alopecia. One must not move on until this issue has been fully settled. Once that it settled one can determine if the patient has or does not have telogen effluvium (with AGA or by itself ) and whether or not the patient has some other hair loss condition.

How does AGA present or ‘announce itself in women’? With shedding ! .. and with thinning in the top or often also diffusely!

How does telogen effluvium TE present itself or announce itself? With shedding ! …and with thinning diffusely !

It’s important to be aware that TE and AGA can look identical - at least at first glance.

What’s the most likely cause of hair loss in a 30-35 year old female with hair loss for 3 years and shedding and thinning? Androgenetic alopecia by far.

Of course, I can’t say what you have as I have not examined your scalp. But these are the principles that guide the entire discussion.

Therefore, the key question that must be asked in your story is “Does this patient have androgenetic alopecia (AGA)?” That’s the key question. That’s the number one question. The key question should not be what supplement can this patient take? ….. or what shampoo should this patient use? The key question is “does this patient have androgenetic alopecia?”

What is needed now is proof that you do have AGA or proof that you don’t have AGA. One should not rest until this question has been solved. Once we solve that question, we can move on to figuring out if any other diagnosis is present.

For now, we need to determine if AGA is present. That is what is needed now. Your doctors might be able to solve this with trichoscopy or they might need to solve it with a biopsy.

We can not always solve it with simply looking at the scalp from afar.

Only you know what your hair looked like before and your doctors do not. If you hair looks thinner to you but just fine to another person - then guess what? You still have hair loss.

The Three Stages of Hair Loss

There are 3 stages of hair loss that I describe for patient’s with androgenetic alopecia. What is so important in your case is to determine once and for all as to whether you are in stage 2 AGA or whether you don’t even have AGA at all. Here are the stages.

Stage 1 of Androgenetic Alopecia

In stage 1, hair density is slowly reducing but the patient is unaware. There may be a slight increase in hair being shed in the shower or coming out daily in the brush. However, this generally goes by unnoticed by the patient. A biopsy can sometimes (but not always) capture a T:V ratio below 4:1 and some degree of miniaturization (and anisotrichosis) may be present. Much of the time it's challenging to confidently diagnose AGA in this stage. Some stay in stage 1 for a very long time; others just a matter of months.

Stage 2 of Androgenetic Alopecia

In stage 2, the patient first becomes aware that something is not quite right. They may see a bit more scalp showing when they look in the mirror. They may feel the hair does not feels as thick when they run their fingers through the hair. Under bright lights they may feel a bit more aware of these changes. When the hair is wet, the thinning is evident.

Nevertheless, in this second stage everyone else tells the patient they look fine. Some patients are told they are "crazy". Even some physicians will tell the patient they "look fine" and need not worry. Patients often feel isolated in this stage because nobody believes them when they say they are losing hair! A biopsy definitely shows a T:V ratio less than 4:1 and miniaturization is clearly seen in more than 20 % of hairs. Many never progress to stage 3 especially those with onset of AGA later in life.

Stage 3 of Androgenetic Alopecia

In stage 3, the hair loss has progressed to a stage where hair loss may become evident not only to the patient but also to others. Of course with use of various hairstyles, products, camouflaging agents it may still be possible to hide one's hair loss from others. As stage 3 progresses it becomes more and more difficult to hide hair loss.

Understanding the Patterns of Hair Loss

Both AGA and TE can cause hair to look thinner. With AGA is typically affects the middle of the scalp whereas with TE is affects all of the scalp fairly equally. We call this a ‘diffuse’ pattern. AGA can sometimes have a diffuse pattern too but very often than not it affects the middle more than other areas. In addition, AGA often affects some areas of the middle a bit more than others.

Your photos show the hair parted in the middle. These types of photos are great for evaluating the scalp. If your part width at the back of the scalp seems smaller than the front of the scalp, the chances start to increase that you might have AGA. By part width, we simply mean the amount of scalp showing when you part your hair in the middle.

In your photos, it’s difficult to get a sense of the exact patterns because I only have photos of the middle. But when I look at these photos I do wonder whether the density towards the crown is a bit less than the density up front. In other words, it seems that even in the mid scalp the density is not reduced equally.

Summary: Putting it All Together

Thanks again for the question. Let’s review everything again.

1. You first asked if oral vitamins can increase shedding like minoxidil does. That answer is not usually. The mechanism is different.

2. You have high shedding rates so something is probably different with your hair cycles than it was 20 years ago.. One can shed 200 hairs daily in AGA and 200 hairs daily in TE so this information is not helpful to actually get to the diagnosis. You could have one, You could have both. You might have neither. Statistically speaking, a 30-35 year old female with shedding has either AGA or TE and with your history AGA is far more likely to be a diagnosis. Of course, we are not statistics and each person requires a proper examination.

3. You mention increased oiliness of the face so one needs to also consider whether you have a component of “seborrheic dermatitis”. This can increase these scalp sensations like you describe - and so can telogen effluvium. Your doctors can determine if you have SD by carefully examining your scalp.

4. Overall, it may be that you’ve had TE at some point in time - and perhaps you also have it now too. It may be that stress was a trigger before for a TE and perhaps maybe now you have different triggers that are causing a TE (such as lower iron). I suspect there was some component of TE back in 2016-2017 when your hair shedding stopped. Your doctors can evaluate these ‘triggers’ for shedding in greater detail. You may or may not need more blood tests but your doctors can review that in detail.

A full work up is needed at this point. You may need more blood tests. However, what you do need next is a thorough scalp examination with trichoscopy. If there is significant “anisotichosis” on trichoscopy then you may have AGA. I can’t tell these with your photos - it needs an up close examination. If it’s still difficult for your doctors to determine with trichsosopy, then a scalp biopsy (with use of horizontal sections) is going to be helpful. The pathologist can determine the number of large terminal hairs and tiny vellus hairs and the number of telogen hairs. A terminal to vellus hair ratio of less than 4:1 usually signals a diagnosis of AGA in women. You can review more about scalp biopsies here Scalp Biopsy Interpretation

I hope this helps and thank you again for the question.

Why am I shedding with zinc supplements?

Localized Shedding with zinc supplements

I’ve selected this question below for this week’s question of the week. It allows us to discuss some of the finer aspects of zinc on the human body and how to approach atypical or unexpected reactions in the human body.

Here is the question….

QUESTION

I shed hair when taking zinc supplements. I cannot find any information on this at all. Most suggest zinc helps the hair cycle not cut it short and shed. The shedding appears to occur in locations that already had issues. It is not global (all over the body).  Is zinc connected to the hair growth/shed cycle or is it inflammation? Thank you.

ANSWER

This is a terrific question. Not one that I encounter often - but a fascinating one. There’s a lot to review with this question, so let’s get to it!

Before we go further, I’d like to point out that the ideal way to diagnose hair loss is using what I termed the ”Diagnostic S.E.T.” I refer to these as the diagnostic “set” because theses 3 aspects all go together. These 3 items include:

1) the patient’s Story

2) the findings uncovered during the process of the scalp Examination and

3) the results of relevant blood tests. 

The first letter of each of the three words 1) story, 2) examination and 3) tests spell out the word “S.E.T.” - again a helpful reminder of how the information obtained from reviewing each of these 3 aspects helps solidify a proper diagnosis.

I’d like to know a lot more about this story ideally but of course the magic of the “question of the week” is that I tackle questions with limited information. It could be relevant if the patient takes zinc for one weekend because they heard it was good to boost their immune system or took zinc for one year to finish the bottle that they purchased one day on sale. It could matter if the patient is obese or thin, malnourished or well nourished and elderly or young. It could matter if the patients knows their actual zinc levels through blood tests or not. Finally, it could matter and probably does matter if the patient has early staged adnrogenetic alopecia, mid staged androgenetic alopecia or advanced androgenetic alopecia. All these things matter in fully answering these questions.

With that behind us, let's return to our question of the week again.

WHAT’S THE MOST LIKELY EXPLANATION FOR SHEDDING WITH ZINC?

Well, the most likely explanation (given that I don’t know anything else about you), is that:

1) you have some male pattern balding and you are not using finasteride or dutasteride to treat your male balding and that zinc has trigger a mild effluvium of hairs that are in the early balding phase. We call this phenomenon immediate telogen release and it’s common with every treatment that acts on male balding including minoxidil, laser therapy, PRP therapy, finasteride therapy …. and sometimes zinc.

2) The second explanation is that you actually do have diffuse loss of hair on the scalp and you are just noticing it more in the areas that are already thin. In this scenario, the male balding has nothing to do with the discussion, it just so happens you notice hair loss more in areas that are already thinner.

3) The third explanation is that you have something else going on that is not related at all.

It zinc related to my hair loss? A Closer Look at the Naranjo Scale

Before we go further, I’d like to introduce you and readers to a wonderful system of determining how likely it is that a person’s rare observation is linked to the drug or supplement they are taking. It’s called the Naranjo Scale. I always refer to the Naranjo scoring system when some observation a patient is experiencing is uncommon because it helps to get a better sense of just how plausible things really are. If someone tells me their new supplement is causing hair loss, I might pull up the Naranjo Scale. If someone tells me their new cat is causing them hair loss, I might pull up the Naranjo Scale. We’ll take a look at this scale in a moment.

Now, it seems pretty obvious that if you say that when you take zinc you get more shedding that I believe you that zinc is causing your hair shedding. First off, I believe you. I have seen this phenomenon before so I’m not introducing the Naranjo scale as a way to prove whether you are correct in your observation or not. Rather, the Naranjo Scale helps us look at causation with a little greater precision - something a bit more scientific.

The Naranjo scale involves use of 10 simple question. You might want to try it yourself. The questions are below and I’ve worded each questions specifically to pertain to zinc although the Naranjo scarring system itself pertains to any drug not just zinc. You answer “yes", "no" or "don't know" and different points are assigned to each answer (-1, 0, +1, +2). 

Typical Questions in the Naranjo Scale

1. Are there previous conclusive reports of zinc causing hair loss from areas that already have an issue?

Yes (+1) No (0) Do not know or not done (0)

2. Did the shedding appear after zinc was given?

Yes (+2) No (-1) Do not know or not done (0)

3. Did the shedding improve when the zinc was discontinued ?

Yes (+1) No (0) Do not know or not done (0)

4. Did the shedding appear when the zinc was readministered?

Yes (+2) No (-1) Do not know or not done (0)

5. Are there alternative causes that could have caused the shedding?

Yes (-1) No (+2) Do not know or not done (0)

6. Did the shedding reappear when a placebo was given?

Yes (-1) No (+1) Do not know or not done (0)

7. Was the zinc detected in the blood at higher levels?

Yes (+1) No (0) Do not know or not done (0)

8. Was the shedding more severe when the zinc dose was increased, or less severe when the zinc dose was decreased?

Yes (+1) No (0) Do not know or not done (0)

9. Did the patient have a similar shedding to the same or similar zinc pills in any previous exposure?

Yes (+1) No (0) Do not know or not done (0)

10. Was the adverse event confirmed by any objective evidence?

Yes (+1) No (0) Do not know or not done (0)

Determining the Naranjo Score

Scores for the Naranjo Scale can range from -4 to + 13. A score of 0 or less means the likelihood of the drug causing the side effect is doubtful, a score 1 to 4 indicates it is 'possible', a score 5 to 8 means it is 'probable' and a score 9 to 13 means it is 'definite'. The website http://www.pmidcalc.org/index.php provides a free online calculator for clinicians to calculate the Naranjo Score. It is easy to use and has been embedded below as an example. Individuals wanting to know if a specific drug caused hair loss should be sure to speak to their dermatologist. For you, I’m guessing you are somewhere between 5 and 8 and probably and 6 or 7. This just simply reinforces that what you are experiencing is probable.

What are the effects of zinc on the body and on hair ?

Zinc is well known to affect the human body in about 50 different ways. Actually, it’s best to say that there are at least these are the 50 different ways that have been studied. There are probably 250 ways that zinc affects the human body - we just haven’t studied them all. Here are some of the more common effects of zinc under different conditions. You can see that zinc has a profound effect on many hormones, inflammatory markers and immune system components.

Zinc and Hormones.

Zinc has a complex relationship with hormones. Zinc supplementation seems act as an anti androgen in most scenarios. In women with PCOS, it’s clear that zinc supplementation helps PCOS and reduces hirsutism and improves hair loss. However actually hormone levels (DHEAS) don't seem affected. In prostate cancer cells grown in the lab, it’s clear that zinc acts as an androgen receptor blocker. Zinc blocks male hormones.

Zinc containing shampoos have a positive effect on male balding. In a 2003 study, Berger et al showed a benefit for 1 % zinc pyrithione (found in Head and Shoulders and other shampoos). The researchers performed a 6 month randomized study in healthy men 18-49 with Hamilton Norwood type III vertex or type IV baldness to assess the benefits of daily use of 1 % ZP shampoo. The researchers compared growth with zinc pyrithione shampoo compared with three other groups: 1) those using minoxidil 5 % twice daily, 2) those using a placebo shampoo, and 3) those using a combination of minoxidil and the 1 % ZPC shampoo. The results of the study showed hair growth with zinc pyrithione shampoo alone was almost as good as with minoxidil. Whether these effects are due to the anti-inflammatory effects of zinc on yeast and Malassezia (the causes of dandruff and seborrheic dermatitis) or specific zinc effects on the scalp are not clear.

Depsite all the studies showing zinc has antiandrogenic effects, there are studies showing that zinc supplementation may have the effect to increase testosterone. Zinc supplementation to subfertile men increased testosterone and DHT levels and improved the chances that the female partners of these men became pregnant.

SUMMARY AND FINAL CONCLUSION

There is a lot we have learned about zinc so far and here is a lot we still need to learn when it comes to zinc.

For most people, taking zinc doesn’t have any effect on the hair in any way. However, there will be some people who experience a reduction in daily shedding - especially if they had low zinc to begin with. For a very small proportion a bit of shedding might occur for 1-4 weeks but this is not something that is seen commonly. We do see it in patients with early androgenetic balding - but again even then it’s not common. Most individuals with androgenetic hair loss who use zinc either have no effects or experience a slight improvement.

Your question suggests you have a degree of underlying androgenetic alopecia (male balding) and what you are experiencing is a telogen effluvium of the hairs in that area. Of course a dermatologist can help confirm this.

Hairs that are found in the balding areas of the scalp are notiously more loose than hairs that are found in other areas. They wiggle out of the scalp very easily. We refer to this medically by saying that the hairs are in the telogen phase. Taking zinc supplements certainly gives the hairs some 50 to 250 reasons to wiggle out (or shed) but why this happens for some people and not other is not clear.

There are many different so called genetic polymorphisms that people are born with hat affect how they process zinc and what zinc does to the body. These too have been researched over the years. Polymorphisms in IL6 (IL 6 -174) and ZIP2 Lue- (Arg43Arg) are all examples of genetic changes inside of a person’s DNA that affect how they respond to zinc and why one person might respond differently than another person.

If you have used treatments for male balding before (like laser, minoxidil, finasteride, PRP) and developed some shedding when you started these treatments, you are likely to be experiencing the same sort of phenomenon with your zinc. Although it is unusual to shed hair with zinc supplementation, I must add that it is extremely unusual for males who are currently on finasteride to shed hair with zinc supplements given that the androgens pathways inside hairs are so effectively suppressed. Not impossible but unusual in my experience.

If you shed more with higher doses of zinc and less with lower doses of zinc, and stop shedding completely when you stop the zinc pills, the Naranjo score tells us you are onto something. The fact that you shed when you start zinc does not necessarily mean you will continue to shed forever. Just like with finasteride, laser, PRP, minoxidil, most shedding when related to male balding actually settles down in 6-8 weeks. So most men who continue zinc will find their shedding eventually slows down.

I’m not a fan of my patients taking zinc forever. Zinc level should be kept above 85 µg/dL (13 mmol/L) and below 118 µg/dL (18 mmol/L). Excessive zinc causes copper deficiency which is also a rare cause of hair loss. Long term copper deficiency leads to a great number of problems in the body. Zinc should always be taken with the goal to measure zinc levels over time. If you notice shedding every time you take zinc for a few days, that’s one thing, but if you notice shedding everytime you take zinc for months at a time, that’s a different thing. If zinc is causing a pure telogen effluvium due to low copper for example, it is never going to settle down.

As mentioned in the opening it is going to matter if the zinc is taken for the weekend or for one year. The longer the zinc is used (beyond 4 months), the less likely the shedding is due to helpful actions on the balding process and more likely this zinc is detrimental (or something else entirely is going on). It could matter if the patient is obese or thin, malnourished or well nourished and elderly or young. The more obese the patient is (above a BMI of 30) the more likely the zinc supplementation is going to significantly change hormones, insulin sensitivity and lipid metabolism. Mind you, these changes are probably for the good, but there is a chance they are going to set off some shedding in these patients. It could matter if the patients knows their actual zinc levels through blood tests or not. If one is taking zinc, and the levels skyrocket above 150 ug/dl (23 mmol/L) we often see zinc issues with the hair.

Finally, I hope I’ve made the point that all of this probably does matter if the patient has early staged androgenetic alopecia, mid staged androgenetic alopecia or advanced androgenetic alopecia. The earlier the AGA the more likely that zinc is going to cause a bit of temporary shedding. It’s still an uncommon phenomenon overall - but it’s the patients with early AGA that are the most likely to report shedding with zinc supplements in our clinic.

I hope this helps. It’s an interesting question and you and your doctor may want to consider how zinc is potentially affecting the androgenetic hair loss issues on the scalp and how the levels of zinc are changing over time when you supplement. The actual levels of testosterone and DHT may or may not have any relevance because some people could have slight elevations without it actually causing hair loss (or actually inhibiting hair loss as time goes by.

Thank again for the question.

Reference

Barnett et al. Effect of Zinc Supplementation on Serum Zinc Concentration and T Cell Proliferation in Nursing Home Elderly: A Randomized, Double-Blind, Placebo-Controlled Trial. Am J Clin Nutr 2016 Mar;103(3):942-51.

Ebrahimi et al. The Effects of Magnesium and Zinc Co-Supplementation on Biomarkers of Inflammation and Oxidative Stress, and Gene Expression Related to Inflammation in Polycystic Ovary Syndrome: A Randomized Controlled Clinical Trial. Biol Trace Elem Res 2018 Aug;184(2):300-307.

Foroozanfard et al. Effects of Zinc Supplementation on Markers of Insulin Resistance and Lipid Profiles in Women With Polycystic Ovary Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial. Clin Endocrinol Diabetes. 2015 Apr;123(4):215-20.

Giacconi et al. Effect of ZIP2 Gln/Arg/Leu (rs2234632) Polymorphism on Zinc Homeostasis and Inflammatory Response Following Zinc Supplementation. Biofactors.. Nov-Dec 2015;41(6):414-23.

Hosui et al. Long-Term Zinc Supplementation Improves Liver Function and Decreases the Risk of Developing Hepatocellular Carcinoma. Nutrients. 2018 Dec 10;10(12):1955

Jamillan et al. Effects of Zinc Supplementation on Endocrine Outcomes in Women With Polycystic Ovary Syndrome: A Randomized, Double-Blind, Placebo-Controlled TrialTrace Elem Res. 2016 Apr;170(2):271-8.

Kahmann et al. Zinc Supplementation in the Elderly Reduces Spontaneous Inflammatory Cytokine Release and Restores T Cell Functions. Rejuvenation Res. . 2008 Feb;11(1):227-37.

Kim et al. Effect of Zinc Supplementation on Inflammatory Markers and Adipokines in Young Obese Women.Biological Trace Element Research 2014 Feb;157(2):101-6.

Lomagno et al. Increasing Iron and Zinc in Pre-Menopausal Women and Its Effects on Mood and Cognition: A Systematic Review. Nutrients. 2014 Nov 14;6(11):5117-41.

Mariani et al. Effect of Zinc Supplementation on Plasma IL-6 and MCP-1 Production and NK Cell Function in Healthy Elderly: Interactive Influence of +647 MT1a and -174 IL-6 Polymorphic Alleles. Exp Geront.  2008 May;43(5):462-71.

Mocchegiani et al. Zinc: Dietary Intake and Impact of Supplementation on Immune Function in Elderly. Age.  2013 Jun;35(3):839-60.

Ranasinghe et al . Zinc Supplementation in Prediabetes: A Randomized Double-Blind Placebo-Controlled Clinical Trial. J Diabetes. 2018 May;10(5):386-397.

Diphencyprone (DPCP) For Patients with Breast Cancer

I’ve selected this question below for this week’s question of the week. It allows us to discuss some of the finer aspects of using a treatment for alopecia areata that some are unfamiliar with - diphencyprone .

Here is the question….

Question

I am a late 60s year old woman and I have had Alopecia Areata verging on Totalis, for 20 years. I have tried cortisone injections, minoxidil, simvastatin, etc., with varying results. Finally I used DPCP starting summer 2018 and had a good response by early Spring 2019. I even had 2 haircuts! But by mid summer 2019, some new bald patches appeared. I was diagnosed with breast cancer in the Fall of 2019, at which point DPCP was stopped. Hair shedding continued for the next 2-3 months. I had 2 surgeries to remove the cancer in the last few months of 2019, then radiation for 4 weeks in early 2020. I noticed diffuse patchy hair regrowth in January and now have approximately 70% regrowth coming in.

Question 1:
With the removal of the tumor, and associated immune stimulation, could this affect the beginning of hair regrowth?

Question 2:
I there a known link between DCPC use and my breast cancer?

Question 3:
Should I continue using DCPC in the future?

Answer

Thanks for the great question. First, I hope you are doing well after your surgery and treatments. As far as alopecia areata and breast cancer goes, we don’t have a lot of good evidence to link the removal of the breast cancer and the ability of the hair to grow back. It is certainly possible. Of course, the “how likely” this is probably depends a bit on the patient’s cancer exact histological type, size, etc. A small tumor is going to stimulate the immune system differently than a large tumor. A localized tumor is going to stimulate the immune system differently than a cancer that has spread.

We don’t have any evidence that diphenycprone enters the blood to any significant degree and we we don’t have evidence that there is no known link to DPCP and breast cancer.

See previous article : Does DPCP Get absorbed ?

DPCP is not an immunosupressing medication and has its advantages for patients with alopecia areata with a previous diagnosis of cancer. It also has advantages for patients with alopecia areata with a previous diagnosis of cancer who are going through a pandemic due to COVID 19. You’ll clearly want to speak to your dermatologist about all the facts as I don’t have all the facts in front of me with the information given in this question. But it’s quite likely that returning to DPCP is an excellent option.

Thank you again for the great question.

References

[1] Can one apply DPCP at home?

[2] DPCP for treating Alopecia areata

[3] Information for Patients on DPCP