Shingles (Herpes zoster) Infections in Patients Who Use Hydroxychloroquine (Plaquenil)

Do Users of Hydroxychloroquine Have a Higher Change of Shingles?

I’ve selected this question below for this week’s question of the week. It allows us to review some concepts related to zoster infections in patients using hydroxychloroquine

Question

I am a 63 year old female and I use hydroxychloroquine (Plaquenil) for lichen planopilaris. I also have topical mometasone furoate steroid lotion and receive steroid injections at my doctor’s office every 2 months or so. I have developed shingles and I am specifically wondering if the patients who use hydoxychloroquine are at increased risk to develop shingles?

Hydroxychloroquine (Plaquenil) Increases the Risk of Shingles.

Hydroxychloroquine (Plaquenil) is an oral medication that is commonly used in the treatment of many types of autoimmune hair loss conditions. The list of hair loss conditions that we use hydroxychloroquine for includes lichen planopilairs, frontal fibrosing alopecia, discoid lupus and pseudopelade.

Some immunosuppressants are known to increase the risk of patients developing infections. Today, we’ll take a look at the risk of a specific infections known as shingles in patients who use hydroxychloroquine. Shingles is caused by the herpes zoster virus.

Hu SC et al, 2016

In 2016, Hu and colleagues set out to examine the risk of zoster infections in patients who use hydroxychloroquine. The researchers evaluated the risk of zoster (shingles) in patients with lupus (SLE) treated with different immunosuppressants. The authors found that hydroxychloroquine use did increase the risk of shingles. In fact, the risk was dependent on dose with patients using higher doses having slightly higher risk of shingles. Other medications associated with greater herpes zoster (shingles) risk in patients with SLE included oral corticosteroids, intravenous methylprednisolone, oral cyclophosphamide, intravenous cyclophosphamide, azathioprine, methotrexate, and mycophenolate mofetil.

Liao TL et al, 2017

In 2017, Liao and colleagues set out to determine the risk factors and outcomes of herpes zoster (shingles) among patients with RA. The researchers found that exposure to Plaquenil was associated with a two fold increased risk of developing shingles (aOR=1.95, 95% CI 1.39 to 2.73, p<0.001)). Other immunosuppressants were also associated with an increased risk including corticosteroids (≥10 mg/day adjusted OR (aOR)=2.30, 95% CI 1.25 to 4.22, p=0.01), anti-tumour necrosis factor biologicals (aOR=2.07, 95% CI 1.34 to 3.19, p=0.001) and conventional synthetic disease-modifying anti-rheumatic drugs (methotrexate (aOR=1.98, 95% CI 1.43 to 2.76, p<0.001). To read the paper yourself, simply click on the link below.

Zamora et al. 2020

In contrast to other studies, a 2020 study by Zamora and colleagues showed that certain patient groups may be less likely to develop zoster while on hydroxychloroquine. The purpose of this 2020 study was to identify clinical risk factors associated with developing herpes zoster (HZ) infections in patients with systemic lupus erythematosus (SLE). The authors performed a case control study of zoster infections in SLE patients. Cases were matched 1:2 to SLE controls without HZ infection for age, sex, and disease duration.

The study involved 65 SLE patients who developed zoster compared to 130 SEL patients who did not develop zoster. Prednisone, cyclophosphamide, and mycophenolate mofetil use increased the risk of developing zoster. Surprisingly, hydroxychlorqouine use reduce the risk of zoster by 87% (adjusted odds ratio 0.13, P = .003). The authors of this study felt that hydroxychloroquine use confers a protective role against developing zoster.

Qian J et al. 2021

A 2021 study by Qian and colleagues showed that patients who used hydroxychlroqouine had an increased risk of developing shingles. The risk of shingles was higher for hydroxychloroquine users than methotrexate users.

The authors’ study set out to evaluate the association between use of certain types of antiinflammatory medications (namely DMARD type drugs) and subsequent risk of herpes zoster. To do so, the authors used a heterogeneous and prospective population-based cohort study.

There were slightly over 250,000 participants in the study. There were 6295 new DMARD users and 17 024 incident herpes zoster events. Compared with non-users, the risk of zoster was higher in those who used biologic (b)DMARDs, either alone or in combination with conventional synthetic (cs)DMARDs than in those who only used csDMARDs (adjusted hazard ratio [aHR] 2.53 [95% CI: 2.03, 3.16]) for bDMARDs vs 1.48 [95% CI: 1.33, 1.66] for csDMARDs, P-heterogeneity < 0.001; reference: non-users). Among users of csDMARDs, compared with non-users, zoster risks were highest in those using exclusively cyclophosphamide (aHR 2.69 [95% CI: 1.89, 3.83]), more moderate in those using azathioprine (aHR 1.57 [95% CI: 1.07, 2.30]) and hydroxychloroquine (aHR 1.43 [95%CI: 1.11, 1.83]) and not elevated in users of methotrexate (aHR 1.24 [95% CI: 0.98, 1.57]), sulfasalazine (aHR 1.00 [95% CI: 0.71, 1.42]) and leflunomide (aHR 0.41 [95% CI: 0.06, 2.88]).

Conclusions: The risk of zoster was high among bDMARD and cyclophosphamide users. Also, the risk was increased in those using hydroxychloroquine alone and in combination with methotrexate but not methotrexate alone. Preventative strategies such as zoster vaccination or antiviral therapies should be considered in these populat

Mok CC et al 2023

A 2023 study published in the journal Clinical Rheumatology also showed that hydroxychloroquine is associated with an independent risk of zoster - at least in Rheumatology patients. In this study, 1,479 patients were studied (88.3% women, age 45.0 ± 15.8 years). Th commonest rheumatic diseases in this study were systemic lupus erythematosus (SLE) (38.7%) and rheumatoid arthritis (28.3%). The cumulative risk of having HZ reactivation after 2 years was 4.9 % and after 4 years it was 7.6%. Cox regression analysis revealed that a diagnosis of SLE, increasing age, higher NLR, use of cyclophosphamide, and increasing doses of prednisolone, azathioprine, hydroxychloroquine and leflunomide were independently associated with HZ infection.

Conclusion

Hydroxychloroquine (Plaquenil) appears to increase the risk of shingles in patients with Rheumatoid arthritis and patients with lupus. Whether it increases the risk in patients with scarring alopecia has not been studied but there is no reason to believe it should not. By virtue of affecting the risk of shingles, it would seem quite reasonable to classify hydroxychloroquine as a true immunosuppressant.

REFERENCE

Zamora  LD et al. Risk factors for herpes zoster infection among Filipinos with systemic lupus erythematosus. Int J Rheum Dis. 2020 Feb;23(2):197-202

Liao TL, et al. Risk and severity of herpes zoster in patients with rheumatoid arthritis receiving different immunosuppressive medications: a case-control study in Asia. BMJ Open. 2017.

Hu SC, et al. Immunosuppressive medication use and risk of herpes zoster (HZ) in patients with systemic lupus erythematosus (SLE): A nationwide case-control study. J Am Acad Dermatol. 2016.

Mok CC et al. Prevalence and risk factors of herpes zoster infection in patients with rheumatic diseases not receiving biologic or targeted therapies. Clin Rheumatol. 2023 Apr;42(4):1019-1026.

Qian J et al. Use of disease-modifying antirheumatic drugs and the subsequent risk of herpes zoster in older adults. Rheumatology (Oxford). 2021 Nov 3;60(11):5042-5051.

Scalp Sweating in Frontal Fibrosing Alopecia (FFA): is there a link?

Is excessive facial & scalp sweating part of frontal fibrosing alopecia ?

I’ve selected this question below for this week’s question of the week. It allows us to review some concepts related to excessive sweating of the scalp and face among patients with FFA.

QUESTION

I am 59 years and was diagnosed with FFA five years ago. Since I was a teenager I have had problems with excessive sweating around my scalp and face. Is there a relationship between the two? And is there any way to stop the sweating? Thank you!

ANSWER

Thanks for the question. Yes, there appears to be a link but we don’t yet know how commonly it occurs. I always recommend a really good history and examination patients with FFA who report excessive sweating. It seems to be true that there is some kind of a link - but we don’t want to miss other medical conditions that give excessive sweating. So before jumping to discussing treatments for the sweating, I always advise to pause and make sure other conditions are not missed. This is especially true if the sweating is generalized (meaning all over the body) as opposed to just the scalp. There are probably 30 medical conditions that can cause excess sweating! A variety of conditions including thyroid issues, infections, cancers, diabetes, endocrine issues, and medications can all carry the potential to cause generalized or ‘diffuse’ sweating.

Scalp Sweating in FFA

It’s my personal belief that this link between scalp sweating and FFA has not been given the attention it deserves - or even the recognition. I’m not even sure that all hair experts are up to acknowledging the link between scalp sweating and FFA. Now, granted excess sweating does not occur in all patients with FFA - but it’s certainly something that not uncommon.

Interestingly, this is something we reviewed many years ago. You might find this link helpful.

Dr Harries and Colleagues Study of 2016

A 2016 study reported 11 women with FFA reported increased sweating in the areas of hair loss. Many treatments seemed to be helpful including topical steroids, steroid injections, and antibiotics. Interestingly, botulinum toxin treatments (Botox) was also found to be helpful.

I have seen many patients with refractory sweating improve with steroid injections and doxycycline and many who improve with BOTOX injections. I do think that it’s important to keep BOTOX injections in the plan if other treatments don’t help. Botox is commonly used to treat sweating issues of many parts of the body including the underarm area and palms (for excess hand sweating).

We still don’t have all the answers as to why some women with FFA develop this sweating. Sweating is controlled in part by the nervous system and this raises the possibility that a specific type of inflammation known as ‘neurogenic’ inflammation may be relevant in FFA.

More research is needed in this area.

Reference

Harries et al. Frontal fibrosing alopecia and increased scalp sweating: Is neuorgenetic inflammation the common link. Skin Appendage Disord May 2016; 1(4):179-84

Are patients with alopecia areata at increased risk of hearing loss?

Are patients with alopecia areata more likely to have hearing loss?

I’ve selected this question below for this week’s question of the week. It allows us to review some concepts related to hearing loss in patients with alopecia areata.

Question

I am a 52 year old female with alopecia totalis. After many years of wondering, I have been formally diagnosed with hearing loss. It is troubling to me an I may need a hearing aid. I now have trouble hearing colleagues at work and in social settings. Is there any relationship between having alopecia areata and having hearing loss? Will I get this hearing back if I treat my alopecia totalis?

Answer

Thanks for the question. There does seem to be a relationship between alopecia areata and hearing loss. A brand new study found a three fold increased risk of what’s known as sensorineural hearing loss in patients with alopecia areata compared to controls.

Now, I don’t know enough about your story to connect it with alopecia areata. Certainly, hearing loss increases with age and so it’s not uncommon as we age. You and your doctors can review all your risk factors including current and past medications, past infections, past injuries.

It does not seem that getting hearing back is all that common in patients with alopecia areata who treat their alopecia areata. The two phenomenon do not have the same mechanism and the same course.

REFERENCE

Kuang-Hsu Lien, TzoTzong-Yun Ger, Ching-Chi Chi. Association of alopecia areata with sensorineural hearing loss: a systematic review and meta-analysis. Dermatology. 2023 Apr 24.

Frontal Fibrosing Alopecia (FFA): Is there a case for preventing further loss?

Frontal Fibrosing Alopecia: Can Further Hair Loss be Prevented?

I’ve selected this question below for this week’s question of the week. It allows us to review some concepts related to treating frontal fibrosing alopecia (FFA).

Question

I have been dealing with a slow onset of hair loss for the past two years. The loss frames the front of my face, otherwise, I have very thick hair in the back and quite a bit still on the sides. It’s mostly from the top of one ear around to the other. I am a 67 year old female. I am hypothyroid. My mother also had frontal hair loss. She was never diagnosed with anything. I attempted to have a transplant and the professionals at that office told me just from appearances of hair loss, and eyebrow complete loss, that I was suffering from frontal fibrosing alopecia. I have read so many stories of different treatments from different patients and have come to the conclusion that with FFA there is really nothing that’s going to bring my hair back but is there a case for preventing further loss? I am currently using oral and topical minoxidil. I also take 5000 mcg biotin per day. I used spironolactone for about nine months but really saw no measurable change so I have stopped taking that. I am simply now trying to save my hair and prevent further loss. I don’t have any redness or itching.

Answer

Thanks for the question.

In 2023, we not only are able to stop FFA in a good proportion of patients - but we improve the hair density in some patients with FFA as well. Now, we might not get the right combination of treatments on the first try and sometimes not even on the second try. But in 60-70% of patients. we’ve either halted the disease or improved it within 18 months of diagnosis. Usually much sooner. Unfortunately, not every single patient will have their disease stopped - but a very large proportion do.

Let me start our discussion by sharing a photo from a 2015 paper titled Finasteride-mediated hair regrowth and reversal of atrophy in a patient with frontal fibrosing alopecia. You can see in the image a patient with FFA that not only had her disease stopped but had improvement. Granted, this does not happen to every single patient but it happens way more often than people realize. And so does halting of the disease.

Of course, this happens more often if the right treatments are administered. We’ll get to that in a minute.

Hair regrowth and reversal of atrophy in a patient with frontal fibrosing alopecia. A and C, Before introduction of finasteride. B and D, 12 months posttreatment with finasteride, 2.5 mg. Note hair regrowth and reduction in atrophy. from Donovan J. Finasteride-mediated hair regrowth and reversal of atrophy in a patient with frontal fibrosing alopecia. JAAD Case Reports 2015

The “GOLD SLIVER AND BRONZE” FFA Treatments.

As many people know, I often refer to treatments that one can choose for any disease in three categories. These are the “gold”, “sliver” and “bronze” categories. Now, physicians sometimes call these categories first line, second line and third line treatment categories but I like to call them gold, silver and bronze.

Gold treatments come with the highest chances of halting the disease (or improving it) or are just really reasonable options given their safety and affordability and effectiveness. If gold treatments don’t work well (or one can’t use them for whatever reasons), then one should look at whether there are any other gold treatments that can be used before finally thinking about starting a “silver” treatment. One should consider one or more silver treatments as the next step. And if silver treatments don’t work (or can’t be used for whatever reason), one might consider bronze treatments.

There is of course a fourth category - and that is a category of treatments that I don’t think do that much.

So here’s the list!

Now, not everyone is a candidate for every medication. So it’s not simply that one takes this list to their doctor and says “give me this medication.” It does not quite work that way. A patient with severe dry eyes may not tolerate isotretinoin. A young patient who wishes to become pregnant should never be prescribed finasteride or isotretinoin. A person with severe depression may not be a great candidate for finasteride (as it rarely affects mood).

So there are reasons why one might and might not consider certain medications - and this all needs to be reviewed with the doctor overseeing care.

But here you have it - you have the Gold, Silver and Bronze list for treating FFA!

What’s so valuable about the list?

This list gives us a framework. Patients come in the office all the time and say to me “I have FFA , Dr Donovan and nothing works! I tried rosemary oil and zinc pills and every supplement you can imagine. Nothing works! This is hopeless”

So then I look at my trusty gold, silver and bronze chart and see that nowhere is rosemary oil and zinc pills and supplements seen on that list.

So effectively, the patient has tried nothing.

and so I tell the patient - effectively you have tried nothing so far.

A Typical Patient with FFA

Not every patient with FFA starts the same treatment. I don’t really believe in cookbook recipes and templates to treat any type of hair loss. I need to understand everything about the patient and her or his past health and current medications and current treatment goals. But it would not be uncommon in a post-menopausal patient with FFA to start (after getting baseline blood tests and assuming no contraindications to these treatments) oral dutasteride 0.5 mg five times weekly with isotretinoin 10 mg three times weekly with pimecrolimus cream 3-5 times weekly on the hairline and consider steroid injections in the hairline with 2.5 mg per mL. I’ll then repeat the steroid injections in 3-4 months and follow how the patient’s hair loss is doing. I’ll take a zillion photos before starting and another zillion as we go along. If it’s clear we are winning we might stay the course with this plan. Otherwise I might increase isotretinoin and dutasteride dosing to daily and possibly bring on board treatments like oral hydroxychloroquine (Plaquenil) and/or oral cetirizine. We’ll repeat the steroid injections and I’ll see the patient back in 3-5 months.

Again, you can see that I methodically follow the gold, silver and bronze ladder of treatments. I don’t follow what’s popular or what’s new or what’s trending. I follow what’s proven to work. Now this list above changes year to year as new research confirms what works better than others and once research confirms what new treatments are useful.

The Gold, Silver and Bronze Treatments.

The Gold, Silver and Bronze List shown here is my list. Another doctor who treats lots and lots of patient with FFA will have a similar list - but it could be slightly different. It won’t be dramatically different if that doctor treats lots and lots and lots of patients with FFA. Why? Because these are the treatments that help!

If a doctor does not treat lots and lots of FFA, then yes, their list will differ quite a bit.

I often hear patients say to me “Dr So and So likes to start all patients with FFA with platelet rich plasma or PRP.”

That’s fine. That doctor is saying that his or her first line treatment is PRP. In my opinion, that’s not a first line treatment for FFA. That’s a third line treatment. There’s nothing wrong with PRP - but in my opinion it does not come with the same chance of halting the disease as what you see in the first line category.

Do I ever user PRP treatments for patients with FFA?

For the sake of discussion, let’s continue this PRP topic and ask the question “Do I ever user PRP treatments for patients with FFA?” Sure, I use every single treatment you see listed above. If you see a treatment on the list above, I use it or will refer the patient to someone who does it. Now, I don’t use them all in the same patient at the same time. But I might add PRP treatments for a patient who is doing fairly well on oral dutasteride and oral isotretinoin and hydroxychloroquine and topical pimecrolimus and needs a bit more help to get this disease shut off. We’ll add PRP to the plan!

Do I start PRP as the first treatment? Not usually, no. But of course, if a patient says to me “I’ve listened to all your gold and silver treatments and I don’t want them right now. I want to start PRP first and then we’ll take it from there.”

What might I do?

Well, I’ll tell the patient that I support their decision and I’ll also remind the patient that other options probably will give a better chance of helping but provided the patient is informed - I’m okay with that plan!

Conclusion

Thanks for your question. In short, there is a case for preventing hair loss! But there is so much more. Some patients with FFA actually get improvements too - so that’s not an impossibility.

I’ve included a link to a video below as well which outlines many many aspects of FFA. You might find it helpful.

Good luck!

Late stage traction alopecia: Is use of a serum worth it?

Options for late stage traction alopecia

I’ve selected this question below for this week’s question of the week. It allows us to review some concepts related to treating late stage traction alopecia.

Question

I am a 28 year old black woman and I have been told that I have “late stage traction alopecia.” I want to buy a specific serum from the internet to grow my hair back. Is this a good idea or am I wasting my money?

Answer

Well, if you are using the term late stage traction properly, then no - a serum is not likely to help all that much in the case of late stage traction alopecia. Unfortunately, a person with true late stage traction is not likely to experience much regrowth - at least not easily and not likely regrowable to any significant extent. A serum is not likely to achieve the regrowth goals that most people are looking for.

I would ideally like to see the scalp up close myself to determine if the term late stage traction is appropriate to describe the entire scalp and the real chance of regrowth. Sometimes the term late stage is given in a biopsy report but the reality is that the patient does have some reasonable chance of regrowth. Too often, clinicians just take the diagnosis from the biopsy report and give that diagnosis to the patient.

That’s not quite how it works.

By strict clinical definition, the term late stage traction means that the follicles are poorly responsive and there may even be some fibrosis. Late stage traction alopecia is poorly responsive to most treatment.  But if it's really not late stage traction alopecia and rather it's early or mid stage traction alopecia ....then topical minoxidil can help and so can other treatments too (see chart below). For early and moderate traction alopecia stages, I prefer to go all out with periodic use of steroid injections every 2-3 months, use of topical minoxidil along with oral minoxidil (assuming there are no contraindications). Forces on the hair that contributed to the traction must be stopped such as braids, weaves, pony tails, cornrows, clips from hair pieces, and glue from hair pieces.

Rarely, I will also recommend adding PRP but never before using the prior options. Sometimes I include doxycycline too if an aggressive plan is needed to halt inflammation. If there is any evidence of CCCA in the mid scalp zones, I may even be more likely to recommend doxycycline and an aggressive treatment plan. For now, we’ll assume that traction alopecia alone (and not traction + CCCA) is present.

Hair transplantation is reserved for patients with traction alopecia that fail to respond well to treatment. It can work wonderfully well provide that traction alopecia is not in an actively progressive form and provided there are no other hair conditions present (like central centrifugal cicatricial alopecia).

I wish I could say that alot of options exist for “late stage” traction. More options exist for “earlier stages” of traction alopecia. Traction alopecia often requires more aggressive treatment than many realize.  The only exception is traction alopecia of very short duration - such as when someone wore a certain hair style to a party or wedding or celebration one weekend and now the hair is falling out due to that hairstyle. Otherwise, there is inflammation and often fibrosis that needs to be aggressively addressed. 

Good outcomes with traction  often come with aggressive treatment and diligent follow up and multimodal treatments. 

Here are some helpful treatment approaches to early/moderate and late stage traction alopecia.

REFERENCES

Donovan J. Helping Patients Reduce the Chances of Traction Alopecia.

Donovan J. Traction Alopecia: How long is too long?

Low ALP Levels and Hair Loss

Are there underlying conditions associated with low ALP that could be worsening my hair loss?

I’ve selected this question below for this week’s question of the week. It allows us to review some concepts related to low serum alkaline phosphatase (ALP).

QUESTION

I am 40 yrs old and have been diagnosed with androgenetic alopecia. I am currently on spironolactone (200 mg), oral min (2.5 mg), topical minox and finasteride solution, and keto shampoo, I think I am at least maintaining on this protocol. I just had blood work completed and noticed the only thing out of range (with the exception of my total cholesterol) is my alkaline phosphatase, which is low and has been low or below 4 out of 6 years that I have been tested. Could this show a deficiency in b12/zinc/etc that could be worsening my condition?

ANSWER

Thanks for the question. There are many reasons to have a low ALP. Whether or not the ALP is potentially worsening your condition will depend on the cause of the low ALP. Good questioning and a good examination done by your doctor can help uncover the cause. Some of these causes will have nothing to do with hair loss and some will. First, you’d need to figure out the cause of the low ALP.

What is ALP?

Alkaline phosphatase is an enzyme. It was first discovered about 100 years ago. It’s made in many parts of the body including the liver (main source) as well as the bones, intestines, kidneys and pancreas.

ALP LEVELS: What is a normal range?

ALP levels are normally in the range 30-115 IU/L. When levels are well below this cut off, once starts to think about a variety of causes. The exact range of ALP will differ between various laboratories - and some even have a lower cut off of 20 IU/L.

In one study, issues associated with low ALP included cardiac surgery and cardiopulmonary bypass (26.5%), malnutrition (12.0%), magnesium deficiency (4.8%), hypothyroidism (2.4%), and severe anaemia (1.2%), zinc deficiency, hypophosphatasia, pernicious anemia, vitamin C deficiency, estrogen therapy, chronic renal osteodystrophy, excess intake of vitamin D, celiac disease, hypoparathryoidism. Genetic conditions like hypophosphatasia need to be considered too - as it’s underdiagnosed and easily missed.

Evaluating Low ALP Starts with A Good History and Good Examination

What is needed for anyone with abnormal blood tests is a really good history and really good examination done by the practitioner. Information about prior surgeries, dental issues and gum issues, dietary intake, fatigue, weight loss or gain, tremors, neurological issues, diarrhea, constipation, bone pain, broken bones, muscle and joint pains, abdominal pain, blood pressure issues, mental health issues, fatigue need to be obtained by the practitioner.

Additional Blood Tests for Patients with Low ALP

Additional blood tests may be helpful for patients wth low ALP but the exact tests to order really depends on what information was uncovered during the questioning by the practitioner (i.e. the “medical history”). These may include one or more of the following: serum albumin, zinc, creatinine, urinalysis, serum ascorbic acid, TSH, complete blood count, ferritin, serum phosphate, B12, B6, 25 hydroxy vitamin D, calcium, AST, ALT, bilirubin, PTH and anti-tissue transglutaminase. Other tests may also be helpful depending on the exact medical history of the patient. For example serum copper and ceruloplasmin are to be ordered if Wilson’s disease is a consideration.

For many patients, a bone x ray and/or bone mineral density test will also be ordered - but that needs to be reviewed on a case by case basis with each patient. There are mild genetic and metabolic conditions that can cause bone issues and sometimes teeth issues that cause low ALP. Again, a full history and full examination can help uncover causes.

Conclusion and Summary

There are many causes of low ALP ranging from nutritional issues to medical conditions to drug related causes to rare genetic conditions. A full history and examination is needed. Some of the causes of low ALP have no impact on hair loss whereas others do. Hypothyroidism, zinc deficiency, nutritional issues, celiac disease, anemias are among the causes of low ALP most likely to impact hair.

I would suggest that you see your primary care to have a baseline history and examination and labs drawn. He or she can decide what other blood tests or urine tests or bone scans are relevant. Speaking with an endocrinologist could make sense if most tests turn up normal in order to rule out mild cases of adult hypophosphatasia. Otherwise, treating the abnormality that turns up with the additional blood tests may be the way to go (ie the zinc deficiency or the celiac disease or the anemia or the nutritional issues).

One important tip as to whether there could be a contributor to hair loss is shedding. If a patient has normal daily shedding rates and constant improvement with therapy for the androgenetic alopecia (like oral minoxidil and spironolactone, etc) - it becomes less and less likely that the low ALP is reflective of an underlying cause that affects the hair. if shedding rates are elevated above normal or there has been a poor or suboptimal response to treatment, it becomes more and more likely that the low ALP is related to some cause that gives hair loss.

Thanks again for the question.

REFERENCE

Lum G et al. Significance of low serum alkaline phosphatase activity in a predominantly adult male population. Clin Chem. 1995 Apr;41(4):515-8.

CGRP Monoclonal Antibodies and Inhibitors: Can they trigger alopecia areata?

What is the Risk of Alopecia Areata Flare with CGRP Blocking Drugs? Do we know?

I’ve selected this question below for this week’s question of the week. It allows us to review some concepts related to the relationship between alopecia areata, CGRP signalling and drugs that block this pathway.

QUESTION

I have been diagnosed with diffuse alopecia areata. I am currently treated with 2 mg bacicitinib (Olumiant), 1.25 mg oral minoxidil and a topical steroid. My shedding is under control and I’ve regrown much of my hair. I also suffer from migraines and my neurologist prescribed Atogepant (Qulipta). I haven’t started it yet because I’m worried about hair loss associated with these drugs. Is someone with alopecia areata more likely to have hair loss while taking a CGRP medication?

Thank you.

ANSWER

Thanks for the great great question.

Theoretically speaking, one would think that patients with alopecia areata would be more likely than patients in the general population to have hair loss from these drugs. The reality, however, is we really haven’t seen that signal or evidence of this thus far. I haven’t really seen it commonly in my patients either. In other words, in the 5 years since the CGRP monoclonal antibodies came to market and in the 2-3 years since the CGRP receptor antagonists came to market, we really haven’t seen good evidence that there is an increase in cases of alopecia areata.

For most of my patients with alopecia with migraines, I advise follow the advice of their general physicians, internists or neurologists regarding management of the headaches and not let alopecia areata factor too much into the decision. We really are not seeing good evidence that these drugs worsen alopecia areata. It’s true that more studies are needed and it’s true that these drugs haven’t been out all that long. However, it’s also true that if there was a very strong connection between these drugs and alopecia areata - we probably would have seen something by now. Is there a weak connection? That’s not known but it does not seem so.

Let’s back up and talk about a) CGRP blocking medications and the risk of hair loss then b) then talk about alopecia areata and CGRP signalling and then talk about c) the relationship between alopecia areata and migraines and then d) make some sort of a summary about what we know in 2023 about using these drugs in patients with alopecia areata.

1) Hair Loss from CGRP Monoclonal antibodies and CGRP Receptor Antogonists

Calcitonin gene-related peptide-targeted drugs have proven safe and effective for migraine prevention in large randomized-controlled, double-blind trials with an average duration of six months.

There are two types of CGRP inhibitors – monoclonal antibodies and CGRP receptor antagonists (gepants).

The monoclonal antibodies include: Aimovig (erenumab), Ajovy (fremanezumab), Emgality (galcanezumab), Vyepti (eptinezumab). The “gepants” (like you refer to) include: Ubrelvy (ubrogepant), Nurtec ODT (rimegepant sulfate), Qulipta (atogepant) and Zavegepant (Zavzpret).

Hair loss can certainly occur with these drugs. The hair loss seems to be in the form of a telogen effluvium. The study by Evers and Wald estimated the risk of hair loss at around 2 %. It’s not clear if the various monoclonal antibodies have similar risk or not. Most reports have been with erenumab (1158), followed by galcanezumab (554), fremanezumab (175), eptinezumab (23), rimegepant (26), ubrogepant (4), and atogepant (3). A key message here is that the gepants have fewer eports of hair loss to date. They are also the newest drugs so there has not been the same amount of time to accumulate information.

In 2022, a study by Dr Woods suggested these CRGP monoclonal antibody drugs come with a 12 times higher risk of hair loss compared to the triptans. Woods suggested that the order of risk may be: fremanezumab (PRR 5.42; 95% CI 4.66-6.29), erenumab (PRR 4.29; 95% CI 4.05-4.54), galcanezumab (PRR 4.11; 95% CI 3.78-4.48), and eptinezumab (PRR 2.06; 95% CI 1.25-3.40) so it could be that some drugs in the class have a higher risk of hair loss than others. For example, this data suggests that fremanezumab would be more likely to cause hair loss than eptinezumab.

Overall, mores studies are needed to understand the precise risk of hair loss.

Most hair loss from patients using these drugs is felt to be a telogen effluvium. Other forms of hair loss are much less common. Alopecia areata has been reported with use of these drugs… but it’s not clear if this is a true risk or just a coincidence. After all, alopecia areata can occur in the population anyways so a certain proportion of patients are likely to develop alopecia areata in any study. For example, in the phase 3 studies of galcanezumab, alopecia areata occurred in 0.01 % to 0.1% of study patients. This is really not too different from the expected rate of alopecia areata in any population so it’s not enough yet to say these drugs are implicated in the development of alopecia areata.

b) Alopecia areata and CGRP signaling

From a molecular and genetic point of view, it’s not completely unreasonable to postulate that blocking CRGP signaling with drugs like CGRP monoclonal antibodies and CGRP receptor antagonists can favour the development of alopecia areata. In 1997, Rossi et al showed that in biopsies of patients with alopecia areata there was a reduction of skin levels of CGRP (and substance P). In 2003, Meyronet D et al showed similar findings namely that CGRP levels are lower in alopecia areata. In 2012, work by Dr Paus and colleagues (Kindori et al 2012) suggested that having high CGRP may help protect the “immune privilege” of hair follicles and prevent collapse of immune privilege in response to interferon-γ-(IFN-γ).

Despite the limited studies that suggest a reduction in CGRP signals in hair follicle might be a ‘bad’ thing - the reality is that in the world of clinical medicine —- we aren’t really seeing this phenomenon.

c) The Relationship between Alopecia Areata and Migraines

A 2021 study really changed how I think about the relationship between alopecia areata and migraines. I discussed the study in the past but will cover it again here. The study was a population based cohort study from Taiwan and showed that patients with alopecia areata were more likely to develop migraine headaches. Surprisingly, the data from the study also suggest that patients who experience migraine headaches are more likely to develop alopecia areata. This data suggested a ‘bidirectional’ relationship between migraine and alopecia areata. Patients with alopecia areata are at increased risk to develop migraines and patients with migraines are at increased risk to develop alopecia areata. A link to the 2021 article is found below.

There is certainly more and more evidence accumulating that suggests that there is some sort of immune dysfunction taking place in the pathways leading to migraine headaches.

This data opens the door to the possibility that properly and fully treating migraine headaches in patients with alopecia could be a good thing. Now, we don’t yet have good data to support this. But there is at least a possibility that the pathways that favour the development of migraine headaches are not so good for alopecia areata.

d) Summary about what we know in 2023 about using CGRP Blocking Drugs in patients with Alopecia Areata.

We need to be very clear about what we know and what we don’t know in 2023. It seems that these CGRP blocking drugs slightly increase the risk of hair loss. But this hair loss is mainly in the form of a temporary telogen effluvium. 2-3 % of patients might get this side effect - but 97-98% of patients will not get any sort of hair loss with use of these drugs. It’s not clear if CGRP monoclonal antibodies come with a greater risk of hair loss than the gepants - but it sure seems this way so far. We need to keep in mind we have way more data with the monoclonal antibodies than the gepants. More studies are needed as we get more experience with using gepants in the real world.

Let’s face the facts - we don’t have any good data that suggests either the monoclonal antibodies or the gepants increase the risk of developing alopecia areata. We certainly have zero data to suggest that using these drugs in someone with alopecia areata worsen outcomes in patients with alopecia areata. We have zero data to suggest that using a gepants would potentially worsen outcomes of patients with AA who are already doing quite well on baricitinib and oral minoxidil.

All this data is relatively new and I’ll be following its evolution. 5 years ago, I would have thought there was enough information to make me worried about these migraine drugs for my patients with alopecia areata. The reality is that as more and more data pours in over the past few years, I have no reason to continue to feel worried. There is really nothing that rises up as any kind of signal to suggest that gepants would increase the risk of a flare in a patient with alopecia areata who is regrowing on baricinitib.

We don’t have all the data yet and clearly this field is in its infancy. I would encourage you to review all these studies with your doctors. I’ll place the studies in the references. Together with your doctors, you can decide if you feel comfortable with the data we have so far in 2023. I have followed several patients of my own with alopecia areata on these drugs without evidence of disease worsening. We need more data over time but it’s looking encouraging so far.

REFERENCE

Kinori M, Bertolini M, Funk W, et al. Calcitonin gene-related peptide (CGRP) may award relative protection from interferon-γ-induced collapse of human hair follicle immune privilege. Exp Dermatol 2012; 21: 223–226
Evers S and Wald S. Effluvium and alopecia associated with monoclonal calcitonin gene-related peptide antibody use. Headache. 2023 Jan;63(1):165-167.

Meyronet D et al. Decreased CGRP staining in alopecia areata. Br J Dermatol. 2003 Aug;149(2):422-4.

Rossi R, Del Bianco E, Isolani D, et al. Possible involvement of neuropeptidergic sensory nerves in alopecia areata. Neuroreport 1997; 8: 1135–1138.

Ruiz M et al. Alopecia as an emerging adverse event to CGRP monoclonal antibodies: Cases Series, evaluation of FAERS, and literature review. Cephalalgia. 2023 Feb;43(2):3331024221143538.

Woods RH. Alopecia signals associated with calcitonin gene-related peptide inhibitors in the treatment or prophylaxis of migraine: A pharmacovigilance study. Pharmacotherapy. 2022 Oct;42(10):758-767.

Oral Minoxidil - Can it cause rapid fluid retention?

Fluid Retention with Oral minoxidil

I’ve selected this question below for this week’s question of the week. It allows us to review some concepts related to the early onset of fluid retention with oral minoxidil treatment.

Question

Hi Dr Donovan,

I have started oral minoxidil for treating hair loss just 5 days ago and I now feel my face is puffier. I know that fluid retention can be a side effect but I have read that most people develop swelling around month 3. Do you think I could just be imagining it? Is swelling like this at day 5 even possible?

Answer

Thanks for the great question. There’s a few key things to be aware of here. First, the three month time point is the latest point at which most people will have experienced swelling it it is going to occur. In other words, if swelling and fluid retention has not occurred by month 3, there is a very high likelihood it will not occur. That’s why we advise patients to wait three months before making dose adjustments.

But the key fact not to miss is that humans differ in their responses to medications just like they differ in how their disease presents. For example, a very very low proportion of patients will start getting fluid retention around month 4, 5 or 6. It’s a low proportion - but nevertheless it’s real.

Similarly, a very low proportion of patients will develop fluid retention by month 1 and and even lower proportion will already have fluid retention by week 2-4.

The key point here is that the timing of fluid retention differs for everyone! For the vast majority - fluid retention if it is going to occur is starting to become an issue around month 2-3. But some are sooner than this and some are later.

Conclusion

It’s not impossible for a very small proportion of patients to have early onset fluid retention. It’s quite rare to have it by day 5 - but not absolutely impossible.

How best to proceed is handled on a case by case basis. So you and your doctor will want to sit down and review all this.

Some patients decide to stop for 2 weeks and then proceed with a plan that uses oral minoxidil at a lower dose. Some proceed with the same oral minoxidil dose and add a diuretic (torsaemide etc). In my professional opinion, there is a big difference between a patient scenario where a patient comes to see me and we ALREADY KNOW that minoxidil caused swelling and fluid retention and the scenario here where it is not yet clear.

My own advice is not to be on doses of oral minoxidil that cause fluid retention if possible. But we’ll go into that in a moment.

I would advise my own patients with similar stories to consider the following steps. (Whether this is a good idea for you should simply be confirmed with your own doctors).

1) the patient should weigh himself or herself today

2) the patient should take photos of his or her face today

3) the patient should stop minoxidil today

4) the patient should weigh himself or herself daily for the next 10 days and take photos daily for the next 10 days

5) the patient make consider restarting oral minoxidil in 10 days at a much lower dose than prior (assuming everything ultimately returned back to normal)

6) the patient should weigh himself or herself every day and take photos of the face every day for 2 weeks and then every 3 days for 2 weeks and then every 5 days for 2 months.

7) The dose can be increased at the three month mark if weight is stable and there is no observed puffiness, or fluid retention in the face or feet or weight gain

8) On the new dose, and every dose increase, the patient should again weigh himself or herself every day and take photos of the face every day for 2 weeks and then every 3 days for 2 weeks and then every 5 days for 2 months.

Together, these recordings on body weight and these photos will be helpful to assess if swelling truly is occurring. It’s takes only a few seconds to weigh oneself and only a few seconds to snap a photo. These two peices of information will be helpful for you and your doctors to determine if truly you are sensitive to the fluid retaining effects of minoxidil.

The timing of how often to take photos and the timing of how often to obtain a body weight depends on the possible speed of real or perceived fluid retention.

The following example would be in keeping with a minoxidil fluid retaining effect

Changes in body weight and facial puffiness in a patient who is having a side effect of fluid retention from low dose oral minoxidil

Considerations for the Patient Already Using Oral minoxidil for many Months and now has Fluid Retention

The scenario above (i.e. the question of the week) pertained to a situation where the patient has JUST STARTED ORAL MINOXIDIL is not sure if minoxidil caused swelling. As reviewed above, my advice there is generally to get some good body weights by stepping on the scale, take some really good photos and then stop the dose for a while and then restart - again with lots of photos and lots of body weight measurements.

Now let’s look at a different scenario. What do we do when a patient has already been on oral minoxidil for some time? Consider the case of a 43 year old female patient who is referred to me regarding management of oral minoxidil side effects. She is ecstatic at her improvement on oral minoxidil. She was started 2.5 mg LDOM by a practitioner and now has considerable ankle swelling.

The options to consider here depend on the degree of fluid retention and the severity. If there is any amount of shortness of breath or marked body swelling or chest pain or dizziness, we have no choice by to stop the minoxidil and seek expert consultation. This may be from the emergency department or from a cardiologist. When patient’s present with swelling we need to ask ourselves “Where exactly could the swelling be?” If you are not willing to consider the possibility of fluid in the lungs, or accumulating around the heart or accumulating in the body, you are going to miss cases of pericardial effusions, pleural effusions and widespead anasarca. If you don’t know the basics of pericardial effusions, pleural effusions and anasarca, some might even say you probably should not be even prescribing oral minoxidil. Fortunately, these are extremely rare side effects - but yes, they do occur.

Below is a summary of a nice report from Dr Dlova and colleagues that reminds us all of the need to be humble when using LDOM

Now, let’s consider the more common scenario where the patient has swelling in the feet but there is no worries about cardiovascular or hemodynamic instability. The patient does not seem to have problems with breathing, chest pain, shortness of breath. There is no reason to suspect a pericardial effusion and no reason to suspect a pleural effusion.

The options here include such options as

1) reduce the dose of oral minoxidil to 1.25 mg or 1.875 mg and see what happens with fluid over time. There likely will be some hair loss with a dose reduction of LDOM.

2) reduce the dose of oral minoxidil to 1.25 mg or 1.875 mg and add spironolactone 50-100 mg once daily if there are no contraindications and the patient accepts the potential side effects. One would then see what happens with fluid over time. There may or may not be hair loss depending on how much the spironolactone can compensate.

3) reduce the dose of oral minoxidil to 1.25 mg or 1.875 mg and add spironolactone 50-100 mg and topical minoxidil if there are no contraindications and the patient accepts the potential side effects. One would then see what happens with fluid over time. There may or may not be hair loss depending on how much the spironolactone and topical minoxidil can compensate. This is an aggressive plan but reduces the likelihood of hair loss

4) reduce the dose of oral minoxidil to 1.25 mg or 1.875 mg and start topical 5% minoxidil if he patient accepts the potential side effects and see what happens with fluid over time. There may or may not be hair loss depending on how much the extra topical minoxidil can compensate

5) continue the 2.5 mg oral minoxidil and start a diuretic if there are no contraindications and the patient accepts the potential side effects.. This might include torsamide in countries where it is available or hydrochlorothiazide or furosemide. This is not without risk of side effects from the diuretic itself and diuretic side effects needs to be thoroughly reviewed with patients.

6) continue 2.5 mg oral minoxidil and severely salt restrict. The fluid retention with oral minoxidil does seem to be dependent on sodium intake (at least a bit). Many people who are high salt users notice marked improvements once they reduce their salt intake.

I have hair loss in the donor area. How is that even possible???

Hair Loss in the Donor Area

I’ve selected this question below for this week’s question of the week. It allows us to review some concepts related to hair loss in the occipital scalp.

Question

Hi Dr Donovan,

I have heard har loss does not affect the donor area. Is that correct? My donor area seems much much thinner! How can that be? I am so confused.

Answer

First, hair loss is possible in the donor area. Absolutely!

Anywhere there is hair - there are usually several human hair loss conditions that have the potential to take away those hairs.

Lichen planopilaris, frontal fibrosing alopecia, alopecia areata, diffuse unpatterned alopecia (DUPA), dissecting cellulitis, psoriasis, seborrheic dermatitis, trichotillomania all commonly affect the back of the scalp - or what you are terming the “donor area”.

Even in males who do not have DUPA, there can be some “retrograde” thinning - starting from the neck upwards. there can also be some slight thinning that happens over time as well. Many males in their 40s, 50, 60s and 70s do not retain the same density they had at age 18. This is not talked about all that much - but there is some slight thinning that goes on in the donor area too. Fortunately, it’s relatively minor for most males.

Alopecia areata is an autoimmune condition which can cause hair loss at the back of the scalp. The form of alopecia areata that causes hair loss at the back of the scalp is called the ophiasis form of alopecia areata.

Dissecting cellulitis affecting the back of the scalp; the occipital area is a common site for this condition.

Hair loss sure can affect the donor area!

The way you really should be stating this is “Males with a diagnosis of androgenetic alopecia rarely experience hair loss in the occipital scalp (donor area). However, some males with androgenetic alopecia can have hair loss in the donor area if they have a diagnosis of “diffuse unpatterned alopecia (DUPA)”, a diagnosis of significant “retrograde” alopecia and males with other diagnoses besides androgenetic alopecia can often experience hair loss in the donor area.” Even some slight reduction in donor density is expected in males with advanced androgenetic alopecia as well.

So there are lots of reasons for donor area density to be less than it once was!

Be sure to review with your practitioners what your reason might be.

I hope this helps.

Thanks again for the interesting question.

Excessive Facial Hair Growth within One Month of Starting Oral Minoxidil

Facial Hair Growth with Oral Minoxidil in a Female

I’ve selected this question below for this week’s question of the week. It allows us to review some concepts related to the development of hypertrichosis in female minoxidil users.

Question

Hi, I am a female prescribed 2.5 mg minoxidil. I have been taking about one month. So far, I am seeing results. My thin spot on my head is filling in nicely however, hair is growing all over my face! My eyebrows look like caterpillars. For the first time ever I had to get them waxed and had to have my whole face. Is it possible that I can reduce to half or fourth of a tablet to get good results on just my head?

Thanks in advance for answering my question.

Answer

Thanks for the question.

The benefits of oral minoxidil - and many of the side effects - seem dose dependent. In other words, higher doses may give better results for many patients - but the use of higher doses comes with the risk of more side effects.

It could be that use of 1/4 of a 2.5 mg pill or even 1/2 of a 2.5 mg pill gives you satisfactory results and reduces the risk of excessive hair growth on the face of body. The only way to know is to try it. It could also be that you are extremely sensitive to the effects of minoxidil - and even these very low doses could cause excessive hair on the face or body.

I would urge you to speak to your doctors as soon as possible. Clearly, the dose will need to be reduced. One might even consider a trial of “topical” minoxidil rather than oral minoxidil in a situation like this. You are sensitive to the effects of minoxidil. On one hand this is great, because it means that low doses and even topical minoxidil could work well. On the other hand, it means you are going to need to watch very closely for unwanted side effects if you use too much.

FOR MANY WOMEN, TOPICAL MINOXIDIL MAY BE JUST AS GOOD AS VERY LOW DOSES OF ORAL MINOXIDIL

It’s really critical to know about an important study done back in 2020. A 2020 study by Ramos and colleagues showed that for women with androgenetic alopecia, 5 % topical minoxidil was fairly similar in effectiveness compared to 1 mg of oral minoxidil. So it’s not necessarily true that oral minoxidil is always better than topical minoxidil - (at least for treating androgenetic alopecia.) We love to feel that way in our world today. We love to feel that oral minoxidil is the cure to all problems and topical minoxidil is just archaric and a treatment for the dinosaurs. It’s just not always true - especially when one is speaking about the lower doses of oral minoxidil. There is still very much a valuable role for topical minoxidil in the treatment of many types of hair loss in the year 2023.

Not a single day goes by that I don’t recommend topical minoxidil and not a day goes by that I don’t recommend oral minoxidil. Both are in the modern treatment toolbox.

Given that you’ll need to reduce the dose, you and your doctors will need to discuss if 5 % topical minoxidil might be must as effective as some of the lower oral minoxidil doses you’ll also be considering. Those lower doses will be less likely to cause hair on the face and body.

We don’t know if your case if topical minoxidil will be as effective for you as 1.25 mg or 0.625 mg. We can’t predict all that well. You’ll need to try different doses to really get a sense of how well various treatments work, But the key point is that there remains a possibility for any of the following scenarios to be true:

a) that 5 % topical minoxidil gives you good results

b) that 5 % topical minoxidil does not give you good results

c) that 0.625 mg oral minoxidil gives you good results

d) that 0.625 mg oral minoxidil does not give you good results

e) that 1.25 mg oral minoxidil gives you good results

f) that 1.25 mg oral minoxidil does not give you good results

g) that topical minoxidil 5 % with 0.25 mg oral minoxidil gives you good results

h) that topical minoxidil 5 % with 0.25 mg oral minoxidil does not give you good results

It might sound like alot but one thing is important to keep in mind. We already know you respond well to oral minoxidil. We already know a whole lot of great information about how your hair responds. So it’s quite likely that most of the options above will be helpful to your hair. You and your doctors just need to review and carefully monitor HOW WELL it works and HOW MANY side effects you end up getting with a given plan.

SIDE EFFECTS OF ORAL MINOXIDIL

Let’s talk a bit about oral minoxidil.

First let’s talk about side effects. You may find the link below helpful.

There are several side effects including hair on the face, swelling in the feet, dizziness, palpitations, swelling around the eyes. What’s important for you to know is that these side effects may come out at different times after starting. Headaches and dizziness and palpitations usually occur first (within the first days to weeks). Issues like hair growth on the face and fluid retention may not come out fully until 3 months after starting. The fact that you have hair growth on the face at month 1 is an indication that you are very sensitive to this medication. You also may not be at your maximal amount of hair growth on the face or body yet. You may get even more growth over the next few months. Reducing the dose now will lessen that chance.

In addition, some of the possible side effects could still occur for you in month 2, 3, 4 5 if you continue the same dose. Maybe they won’t occur, of course, but we never fully understand side effects of oral minoxidil until a patient has used the drug a full 5 months. We don’t know if these will happen to you or not but these side effects include swelling in the feet and swelling around the eyes and general fluid retention. That takes about 3 months to fully develop those 2 side effects for most users.

HAIR GROWTH ON THE FACE IN FEMALE USERS OF ORAL MINOXIDIL

Hair growth on the face is common among female users of oral minoxidil. Fortunately, for many patients who use 0.625 and 1.25 mg doses it’s more toward the minimal side and more manageable side. But as the dose increases up towards 2.5 mg, it becomes much more common to get hair growth on the face. In fact, some estimates suggest that about 50 % of women using 2.5 mg will experience more significant amounts of hair on the face and body.

2.5 MG ORAL MINOXIDIL IS NOT AN IDEAL STARTING DOSE FOR WOMEN

In my 2021 article, I reviewed 5 Common Errors that Practitioners Make in Prescribing Oral Minoxidil. The first error on the list is starting doses that are too high. Yes, 2.5 mg is too high of a starting dose in my opinion for females. Sure sure, there are many patients that start this dose and are fine. But there are many patients who are not. When patients say to me “I know many people who started 2.5 mg and were okay” I say to them “you have not spoken to enough people.”

When doctors say to me, “I have started many patients on 2.5 mg and they were fine” I say to them “ you have not treated enough patients with oral minoxidil yet.”

You see, oral minoxidil side effects are fairly common with 2.5 mg doses in women. I see many many patients using 2.5 mg with swollen ankles due to fluid retention. I see many patients using 2.5 mg with swelling around the face due to fluid retention. I see many patients using 2.5 mg with puffy eyes due to fluid retention. I see many patients with excessive hair on the face and body on 2.5 mg.

In my opinion, the starting dose in women is ideally 0.625 mg for 1-3 months and then an increase at that time to 1.25 mg. If all is going well, patients can increase to 1.875 mg or even 2.5 mg in the future. But future increases beyond 1.25 mg need to go really slowly with dose adjustments every 3-5 months.

Why the slow adjustment? Well, it takes 3 months AT LEAST to really get a sense if a certain dose is going to be a problem. It takes THREE months to see if a certain dose is going to be a problem with causing too much hair on the face. It’s going to take THREE months to see if a certain dose is going to be a problem with causing excessive fluid retention.

Final Summary

Thanks again for the great question. I would encourage you to speak to your doctors as soon as possible. Yes, reducing the dose is an option and so is switching to topical minoxidil (ie Rogaine and other topicals). You and your doctors will need to discuss what sort of risk you are willing to take as far as excessive hair goes and what sort of timeline you are on to get rapid improvement in your hair.

There are some patients in my practice who accept alot of hair growth on the face and body because of the good benefits they see happening on the scalp. Many choose to remove hair on the face and body with laser, electrolysis threading, waxing. Other patients find the increased hair extremely unacceptable.

It would appear that you are predisposed to experienced excessive growth and that really the only good option is to reduce the dose. You are your doctors can review what risk you are willing to take and to what degree you are willing to remove facial and body hair.

It could be that lower doses are not as effective for you. It could be that they work pretty well too. Time will tell if lower doses are still quite satisfactory to you or not. But certainly 2.5 mg gives better results for many people than 1.25 mg - but that comes at the risk of possible side effects.

As reviewed above, I don’t ever start 2.5 mg in my patients.

Some patients do amazingly well with 0.25 mg oral minoxidil or even 0.625 mg oral minoxidil. Yes, yes, some patients need 1.25 mg or 1.875 mg or 2.5 mg. But we get up to that dose slowly.

As mentioned above, some patients do amazingly well on topical minoxidil (Rogaine etc). Some patients to well on topical minoxidil combined with use of 0.25 mg to 0.625 mg oral minoxidil added a few times per week.

There is lots for you and your doctors to talk about.

Thanks again

REFERENCE

Ramos PM et al. Minoxidil 1 mg oral versus minoxidil 5% topical solution for the treatment of female-pattern hair loss: A randomized clinical trial. .J Am Acad Dermatol. 2020 Jan;82(1):252-253.

Do I need testosterone levels in order to have a complete set of blood tests for androgenetic alopecia?

Should I have my doctor order testosterone levels to better evaluate my hair loss?

I’ve selected this question below for this week’s question of the week. It allows us to review some concepts related to measuring testosterone levels in women.

Question

I am a 32 year old female. I have recently been diagnosed with androgenetic alopecia (female pattern hair loss). My ferritin is 38 and my TSH is 2.31. I see that my doctor did not order testosterone levels! How important is that? My understanding is that these are very important to complement all the tests that are needed.

Answer

For women with androgenetic alopecia, tests such as CBC, ferritin, TSH, fasting cholesterol levels (LDL, HDL, triglycerides), 25 hydroxyvitamin D and hemoglobin A1c/glucose are routinely important. The other tests to order will depend on the information obtained at the appointment and the clinical examination findings.

No, testosterone levels are not always needed!

For androgenetic alopecia, 85 % of women with AGA have normal levels so one can have AGA with normal levels. Put another way… you have have AGA if your levels are low, if your levels are normal and if your levels are high. Your testosterone levels do no influence whether you will be given a diagnosis of AGA or not. It’s the pattern of hair loss and the finding of miniaturization in certain areas of the scalp that determine if you have AGA - not the testosterone levels!

I would need to know more about your story to really know if testosterone levels are needed in your case … or not.

Generally speaking, I often order testosterone levels for my own pre-menopausal female patients with androgenetic alopecia to try to better evaluate if the patient has one of the known underlying causes of elevated testosterone. You may wish to see the prior article for the top 10 causes of elevated testosterone levels in women with hair loss.

I generally order serum testosterone for my own pre-menopausal female patients with androgenetic alopecia if ONE or MORE of the following situations are true :

1. The patient also has acne

2. The patient also has hair growth on the face, or body (i.e. hirsutism)

3. the patient has also experienced a deepening of the voice

4. the patients also has irregular menstrual cycles

5. The patient has been diagnosed with polycystic ovarian syndrome (PCOS)

6. The patient has clinical signs of high androgens (enlargement of clitoris, markedly increased muscle mass)

7. The patient has possible, suspected or known congential andrenal hyperplasia (CAH)

8. The patient has possible, suspected or known or possible Cushing syndrome

9. The patient has known ovarian cancer

10. The patient uses androgen replacement (DHEA, testosterone, anabolic steroids)

11. The patient has experienced infertility

12. The patient has obesity

13. The patient has type 2 diabetes

14. The patient had elevated testosterone levels before

15. The patient has thyroid disease

16. The patient has known pituitary disease (prolactinomas, and other pituitary diseases)

In general, I prefer that patients have these tests done in the morning between 6 am and 10 am. I prefer that testosterone levels be ordered on day 3-8 of the menstrual cycle but timing of testosterone is really less important for evaluating hair loss that other tests. Getting the test is the morning is far more important if there are concerns about high testosterone. I often order sex hormone binding globulin (SHBG) so that I can calculate the free androgen index and often order DHEAS too. In some cases, I order free testosterone, but total testosterone is far more important for evaluating hair related issues. Other androgen hormones includes androstenedione and other hormones such as estradiol, progesterone day (21), 17 hydroxyprogesterone (day 3-5) may be ordered depending on the exact story.

One needs to to keep in mind that oral contraceptives reduce testosterone levels and so patients who use OCPs will not have accurate testosterone readings.

Conclusion

Thanks again for the question. Testosterone is not really all that helpful to order for most premenopausal women with androgenetic alopecia and regular periods who do not have acne and who do not have hirsutism. Generally speaking, one can determine if order testosterone levels is worth doing with a series of simple questions and a good examination. There are many question to ask but the 4 most helpful are:

a) Are your periods regular when not on birth control?

b) Do you experience acne?

c) Do you experience hair growth on the face, chest, body, abdomen?

d) Do you have any medical issues or would you say you feel quite healthy?

Many thanks again.

Scalp Dysesthesia: What Topical Treatments Can I use?

What are helpful treatments for scalp pain?

I’ve selected this question below for this week’s question of the week. It allows us to review some concepts related to scalp pain and topical treatments that can address pain.

Question

I have periodic scalp pain. I have been told it is all due to a scalp nerve problem (scalp dysesthesia). I have had several scalp biopsies to rule out all the worrisome stuff and they always come back normal. I am told I don’t have lupus. I don’t have scarring alopecia. Despite so many negative tests, I still have a lot of scalp discomfort and pain - but it comes and goes and is not present constantly. My scalp looks pretty normal - but there are times where it really is uncomfortable. I have fibromyalgia but can’t tolerate many of the medications I have tried like amitriptyline.

What topical treatments can I use for scalp pain from a scalp dysesethesia? I do not want to use pills that were recommended to me by my dermatologist such as oral gabapentin and oral pregabalin.

Answer

This is a really great question. There are many things to try. It’s a bit of a trial and error process unfortunately so it can take time to get to the right answer. You’re right that oral gabapentin, oral pregabalin are options and so are oral amitriptyline, low dose naltrexone.

But let’s shift our attention to topical treatments as per your queston.

You and your dermatologist can discuss a variety of topical treatments if oral treatments are something you do not want to consider

1) Apple cider vinegar rinses (4 parts water: 1 part ACV)

ACV rinses are easy to do. One fills up a spray bottle with 4 parts water to 1 part ACV and then sprays the scalp generously in the shower and leaves the ACV mixture on the scalp for 5-10 minutes. It can then be rinsed off.

2) Topical ketamine/amitriptyline/lidocaine (TKAL)

I really like topical TKAL for challenging cases of dysesthesia whereby patients don’t want to use oral medications. TKAL is short for topical ketamine, amitriptyline and lidocaine. We have reviewed topical TKAL in prior posts. This must be made by a compounding pharmacy. It’s not FDA approved but rather used as an option off label.

3) Topical 6% gabapentin

This can block pain. We’ve reviewed this option before (see link). Oral gabapentin is helping in dysesthesias but some patients prefer to try to go with topical agents. Topical gabapentin has helped many patients. Again, this must be made by a compounding pharmacy. It’s not FDA approved but rather used as an option off label.

4) Periodic Use of Topical Steroids

Most patients with dysesthesia do not find that topical steroids helps. In fact, that’s part of the definition. However, there can sometimes be some components of a dysesthesia that are helped by topical steroids. It could be that some patients have a completely different second condition and by reducing the activity of that condition, we can help the main dyesthesia. I will often recommend small amounts of betamethasone lotion if it helps or periodic use of Clobex shampoo once every 2-3 weeks. This can help some patients.

5) Periodic Use of Antidandruff shampoos

Similar to steroids, most patients with dysesthesia do not find that dandruff shampoos help. In fact, that’s part of the definition. However, there can sometimes be some components of a dysesthesia that are helped by limiting Malassezia yeast on the scalp. It could be that some patients have a mild seborrheic dermatitis in addition to their dysesethesia and by reducing the activity of the seborrheic dermatitis, we can help the main dyesthesia. I will often recommend use of a dandruff shampoo every 7-10 days.

6) Topical 1 % cetirizine

Topical cetirizine has best been studied for androgenetic alopecia and chemotherapy related hair loss. But sometimes I will prescribe for patients with a dysesthesia. The hope is that by affecting histamine pathways, we can help the patient’s pain. This must be made by a compounding pharmacy. It’s not FDA approved but rather used as an option off label.

7) Topical 5% Amitriptyline

I tend to prescribe topical TKAL over topical amitriptyline. However, topical amitriptyline is also an option to reduce pain.

Amitriptyline is a tricyclic antidepressant that is widely used to treat chronic neuropathic pain (pain due to nerve damage). It is recommended as a first line treatment in many guidelines.

This must be made by a compounding pharmacy. It’s not FDA approved but rather used as an option off label.

8 ) Low Level Laser Therapy

Low level laser devices sometimes help our patients with dysesthesias. Some patients find the slight warmth actually makes them feel worse. So, it’s not a guarantee. But for the most part it’s a pretty safe option and some patients find it helps. Use of a laser device a few times per week can bring relief to some.

9) Camphor-Menthol 0.5 %-0.5 % Lotion

Camphor and menthol are often mixed together to bring soothing and cooling relief. Menthol has analgesic effects on acute and inflammatory pain primarily by activating cold-sensitive TRPM8 receptors in the skin. Camphor also can block pain.

Applied topically, menthol and camphor initially induce their TRP receptors to release inflammatory mediators that include calcitonin gene-related peptide (CGRP) and substance P, which is a neuropeptide that modulates the transmission of pain signals to the CNS.

10) Capsaicin (0.075 %)

Capsaicin can help in nerve pain.

Capsaicin is a neurotoxin that acts to deplete sensory nerves of their substance P content and thereby interfere with certain sensory functions

11) Hypoallergenic Bland shampoos.

Some of our patients find a switch to hypoallergenic shampoos really helps. This can be a helpful step even when there is no clear evidence of irritant or allergic contact dermatitis. Several hypoallergenic shampoos are on the market that are devoid of fragrance, preservatives. We have reviewed these in the past

12. Witch Hazel

Several herbal ingredients are proposed to have an anti-irritant tendency and can be helpful in scalp pain syndromes. These include chamomile (Marticaria chamomilla), heart seed (Cardiospermum halicacabum), peony (Paeonia lactiflora), and the virginian witch hazel (Hamamelis virginiana). Witch hazel in particular has received great attention. We generally recommend application of pure witch hazel with a cotton ball for periods of 5-10 minutes before rinsing off. Many patients find relief from these agents.

13) Meditation/ Relaxation Exercises/Mindfulness

There is little doubt that meditation and mindfulness exercises as well as breathing exercises and tai chi and QiGong help many of our patients with more challenging nerve issues. Training in these disciplines are widely available online as well as in some communities.

14) Neck Massage and Scalp Exercises

A variety of scalp exercises are helpful for some patients.

15) Doing Less

Finally, an important principle for patients is to often do less. Less brushing of hair. Less heat. Less styling, Less tight tying of hair back. Less use chemicals. Doing less often helps a great deal for patients with dysesthesias.

Conclusion

Thanks for the great question. There are many topical options and non systemic (non-pill) options. It’s a bit of a trial and error and step by step process to determine what helps, but many many patients find one or more of these 15 things are helpful. Sometimes they are life changing! I really hope this helps you !

Persistent Red Scalp After Use of Topical Minoxidil

Why is my scalp red after minoxidil?

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

Question

I used topical Rogaine and now have a red scalp! I used to use a tar based shampoo in the past and really liked using it… but now I can’t because my scalp is so sore.
What should I do?

Answer

Be sure to see a dermatologist to help figure this out. Either you have an 1) irritant contact dermatitis to Rogaine or 2) true allergic contact dermatitis to Rogaine or 3) the minoxidil has flared underlying seborrheic dermatitis or 4) the red scalp is due to something completely different and the Rogaine is just a coincidence.

If you want to read more about the possible causes of a red scalp, be sure to check out the link below.” You and your doctors can slowly sleuth this all out.  Sometimes a biopsy is needed to figure out what causes a red scalp. Sometimes patch testing is needed. But in every single case - a really good history and really good examination is needed.

Regardless of the exact cause, you’ll likely need some topical steroids for a few days (or weeks) to reset things and get back on track. Topical steroids are very safe when used for short periods of time and under supervision from someone who understands how to prescribe them.

I’m not worried about the tar shampoo discomfort right now. Any shampoo will often hurt when applied to a scalp that is really inflamed. A tar shampoo will likely be fine again once you sort things out as to what’s causing the current issue. You may need a new formulation of minoxidil if you are irritated by it or a good dandruff shampoo if the reason for the redness is a flare of seborrheic dermatitis. If you are truly allergic to minoxidil, you’ll possibly need some patch testing to prove it and you’ll need to stop using it all together if you are truly allergic to the minoxidil compound. Rogaine is not the only option for treating hair loss so get some good advice and see where it takes you.

If the cause of the red scalp is felt to be a scarring alopecia, such as lichen planopilaris or folliculitis decalvans you may need a biopsy. Be sure to see a dermatologist for a detailed evaluation of all the possible causes.

What treatment is possible for a red scalp?

The treatment all depends on the cause. We can’t talk about treatments until we determine exactly the cause. If the cause is related to a scalp disease that has now flared, treatment of the particular scalp condition may be needed and you may be able to continue Rogaine. If the cause of the scalp redness is a true allergic contact dermatitis, you’ll need to stop Rogaine. However, many patients with topical minoxidil allergies can still tolerate oral minoxidil. Other treatments for androgenetic alopecia can also be considered such as topical antiandrogens, oral antiandrogens, laser, PRP.

Good luck.

Does my body reject my hair transplant grafts over time?

Why am I losing hair after my hair transplant?

I’ve selected this question below for this week’s question of the week. It allows us to review some concepts related to hair loss post hair transplant?

Question

I am a 48 year old male. I had a transplant in 2018 (2,534 grafts). My results looked okay at first (not great … but also not bad). Now I would say I look almost worse than before I had the transplant. My scalp now is red and at times it’s quite itchy and sore. Is my body rejecting the grafts? Will another transplant work well? What can be done?

Answer

Thanks for the really good question. This is a challenging scenario and I would want to know more information about your general health and, of course, examine the scalp up close. It’s quite likely that you’ll need a scalp biopsy - or two.

In a scenario like this, I’d be pretty concerned about a diagnosis of a scarring alopecia. It’s a little too long to think about a chronic infection but of course there are surprises and a broad list of possibilities needs to be considered.

Let’s take a look at a few scenarios. 

MECHANISM 1

For some patients with a story like this, a situation arises whereby the transplanted hairs survive and existing original hairs in the area thin out and are lost over time. That leads to ongoing loss a feeling from the patient that hair loss is occurring after a transplant. Usually this kind of a scenario takes 6-20 years to develop. Your story is a bit too short in duration for this to be a mechanism. After 5 years, we would not expect a patient to feel that things are worse than before the transplant.

There are patients that have balding and don’t want to start any treatment … except go for a hair transplant. If a patient rejects the idea of going on medical treatment, that’s just fine - but they need to expect some improvement in density after transplant followed by steady hair loss again in the years after the transplant. The loss is usually very slow but can be moderately fast in some - but not this fast.  

I don’t think mechanism 1 describes your story.

MECHANISM 2

Sometimes a transplant results wanes over time because the patient has diffuse AGA (a condition called DUPA) and was never really a good candidate to begin with. In this case, the surgery can improve hair for a while .. but ongoing thinning just keeps happening because donor hairs are not permanent in patients with DUPA. This scenario is more common in women undergoing hair transplants than men but does happen in males with the DUPA form of AGA.  In this case, the scalp would not be red or sore and I wouldn’t expect the hair loss to be so fast.

I don’t think mechanism 2 describes your story.

MECHANISM 3

Sometimes, an inflammatory hair loss condition was actually present on the day of the transplant but was not properly recognized and therefore not diagnosed. This hair loss disease continues to destroy original and transplanted hairs after surgery. Lichen planopilaris, frontal fibrosing alopecia, central centrifugal cicatricial alopecia and folliculits decalvans are examples. It’s possible even with these conditions for a person to get a bit of improvement after the transplant and then experience hair loss and further disease activation as time goes on.

A patient with mechanism 3 may have suboptimal growth after a transplant and then at some point - proceed to lose hair more rapidly.

Mechanism 3 is a possibility in this scenario you present today.

MECHANISM 4

Finally, if another hair loss condition arrives on scene after a transplant one can expect further loss after transplant. Lichen planopilaris is sometimes a missed diagnosis before a transplant as outlined in Mechanism 3 (above) but sometimes a hair transplant also triggers this condition to develop de novo. Any human can develop an array of conditions such as alopecia areata telogen, effluvium and scarring alopecia - and if these conditions happen post transplant the result is a deterioration in results. Sometimes the transplant triggers some conditions and sometimes some conditions just happen by coincidence.

Mechanism 4 is a possibility in this scenario you present today.

Conclusion

The redness and soreness in the scalp suggest there is some inflammation going on. The poor outcome suggests that inflammation is likely contributing in some way.

In general, mechanism 3 and 4 are the most likely mechanisms in a scenario like this but I would need to know more about the story and see the scalp up close to confirm exactly what is going on. It’s possible the diagnosis can come from a thorough examination of the scalp and use of trichoscopy. But even with this, I’d probably be inclined to do a biopsy. The biopsy should come from the maximal area of soreness or redness or where there are concerning features seen on trichoscopic examination.

A biopsy outside the transplanted area is helpful too in the event that pathologist can see what is happening in a non-surgical area. There will be fibrosis that develops simply from a transplant surgery - and to differentiate these on biopsy by taking an extra sample from a non surgical area is helpful. Of course one or more biopsies should come from the transplanted zones.

Thanks again for the great question and good luck.

What can I use for my eyebrow alopecia areata?

Can I use clobetasol on my eyebrows? I don’t want steroid injections!

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

Question

Hi Dr. Donovan. I’m a 28 year old male. I have alopecia areata and have had patches on my scalp for a few years. I’ve been able to get it back with steroid injections and clobetasol. I’m losing eyebrows now and really freaking out. I am scared to get injections as I always faint and pass out. I know it’s silly but I’m having trouble getting myself to this stage. Can I use clobetasol on the eyebrows? It’s been helpful for the scalp but the dermatologist says no. I think we’re now running out of treatment options.

Answer

Eyebrow alopecia areata is treated differently than scalp alopecia areata. First, the eyebrow area has thinner skin than the scalp skin, so potential local and systemic side effects from treatment are different. Second, the area is close to the eye so effects on the eye need to be considered. Clobetasol is too strong for the eyebrow skin!

There are a large number of potential treatments as outlined in the image above. First line treatments for eyebrow alopecia areata include topical minoxidil, topical steroids, steroid injections and topical bimatoprost (Latisse). Steroid injections are most effective but injections do not help everyone and can be quite painful for some patients. (It would not be a consideration in a small child but we have performed steroid injection in patients as young as 15 years).

I understand your worries about the eyebrow injections. There are things that help alot including lying the patient down flat on a pillow when the injections are done and having it done by someone with a lot of experience who can puncture the skin quickly and with less pain. iI’s all over in 40 seconds. That said, I still understand that this is not the right treatment for everyone.

Typically, treatment for alopecia of the eyebrow starts with topical minoxidil in the morning and mid potency topical steroids (like fluocinonide gel) in the evening for four weeks. As mentioned, a strong steroid like clobetasol is not generally appropriate for use on the eyebrow (there are exceptions where very short courses may be). After the four weeks is up, minoxidil continues nightly and fluocinonide is reduced to three times weekly for two more weeks.

If there is good growth, and it appears things are on track, I may continue minoxidil daily and slowly reduce fluocinonide gel to twice weekly for two weeks and then once weekly for two weeks and then stop. Minoxidil may be continued in most cases until eyebrow density has been stable for a long time. Side effects need to be monitored by a physician knowledgeable about these treatments.

Once eyebrows have grown in, the minoxidil too will be stopped.

Eyebrow alopecia areata often is associated with a tougher to treat and more resistant alopecia areata, so it’s quite likely for further hair loss to occur at some point. The same protocol can be started up again if patches occur.

What is eyebrows don’t grow with minoxidil and fluocinonide gel?

If eyebrows are not responding well to minoxidil and fluocinonide gel after the first four weeks, then I will revisit the possibility of doing steroid injections with my patients. The answer still may be no, and that’s okay. But if yes, injections can be done every 6-8 weeks with 2.5 mg per mL triamcinolone acetonide with 6-7 little injections per brow (assuming complete loss). Smaller patches require fewer injections.  If not responding well, I may increase to using 5 mg per mL of the triamicinolone medication. Side effects like atrophy need to be discussed with the patient as a dimple in the eyebrow skin, while temporary, can be disfiguring and extremely concerning for patients.

If injections are not desired, or the physicians is not comfortable performing them, then one may move on to topical minoxidil in the morning and Bimatoprost in the evening. Bimatoprost is sold under the trade name Latisse.  This routine can be continue daily for 8 weeks before re-evaluating response.

If there is good growth, then minoxidil can be continued daily and Bimatoprost can be reduced to three times weekly for 8 more weeks before deciding on whether to reduce further two 2 times per week. I likely would continue twice weekly long term (6-8 months or more) but this is evaluated on a case by case basis.

If minoxidil, fluocinonide and Bimatoprost are not helpful and steroid injections are not possible OR if they are only partially helpful I will consider adding oral minoxidil or a topical JAK inhibitor.

Oral minoxidil would be a first step and together with topical minoxidil and topical bimatoprost and/or topical tofacitinib (which we’ll review below) …. these treatments can be really helpful. Doses of oral minoxidil are 0.625 mg to 1.25 mg daily for adult female patients and 1.25 mg to 2.5 mg in adult male patients. Higher doses are possible on a case by case basis and some males increase to 5 mg daily. The requirement for oral minoxidil signals a more resistant and tougher to treat form and the expectation should be that this treatment will be needed 9 month to several years. Side effects, as for all treatments discussed above, need to be carefully reviewed and consent obtained. These include hair growth on the face or body, fluid retention, heart palpitations, fatigue, chest pain. Medications are contraindicated in pregnancy for female patients.

Topical JAK inhibitors are a good second line option as well. A compounding pharmacy can make 2 % to 2.5 % topical tofacitinib creams, foams and lotions and topical ruxolitinib ointment is commercially available in the United States (although it is only available as a greasy ointment). The  topical JAK inhibitor drug can be applied once to twice daily. The decision on whether to use once or twice daily will depend on the response to the treatments in the steps above. Complete failure to regrowth eyebrow hair with topical minoxidil and topical fluocinonide gel may prompt me to consider twice daily topical JAK inhibitors and abandon other treatments.

 

Options if Topical Steroids, Steroid Injections, Topical Bimatoprost and Topical Tofacitinib Don’t Work:

If hair does not respond to topical options or steroid injections, strong consideration can be given to oral steroid pulses, oral methotrexate or oral JAK inhibitors provided there are no contraindications. These may or may not be covered (reimbursed) by drug plans depending on the amount of scalp hair loss. (Many insurers look to the amount of scalp hair loss when deciding on whether to reimburse for medications). A decision to use these therapies should be done with the understanding that treatment may be needed long term, and possibly lifelong.

Finally, I want to tell you one of the greatest secrets ever for helping patients to avoid passing out. It involves drinking an entire 300 mL bottle of cold water quickly 1 minute before getting injections done. It has to be consumed fast and it has to be cold (ideally). I would say that it has reduced fainting in fainters by 80 %. It works incredible. Consider it before you get your blood tests and if you do go for injections - before your injections too.

Conclusion

I thank you for your question. I hope this helps you in your discussions with your own doctors. There are many options to consider so be sure to review them all thoroughly with your doctors. It’s okay to feel one of the options is not right for you but be open to revisiting the options over time. It could be that one option does not feel right now but could feel right in the future.

Do we need 2 scalp biopsies or just one for diagnosing hair loss?

How many scalp biopsies should I be getting?

I’ve selected this question below for this week’s question of the week. It allows us to review some concepts in scalp biopsies for hair loss.

Question

Hi Dr. Donovan. I am confused about how many scalp biopsies a person should get to diagnose hair loss. Some people say one biopsy is needed and some people say two is better. So I ask you - how many biopsies does a person with hair loss really need?

Answer

Great question. Thank you!

Well, the short answer is that one should have as many biopsies as it needs to figure out the diagnosis. That ranges from zero biopsies to somewhere around four or five. Most commonly, it’s zero and the runner up choice is one or two. Only rarely are three or four or five biopsies ever needed.

But let’s dive into this great question.

Let me begin by saying that I don’t perform a scalp biopsy with every single patient I evaluate. Maybe 1 in 20 or 1 in 25 patients will need a scalp biopsy. Most of the time, I can confirm the diagnosis (or diagnoses) by listening to the patient’s story, and fully examining the patient’s scalp. A full examination of the scalp means I’ve examined the patterns of hair loss PLUS made use of trichoscopy or a type of magnification. With trichoscopy, we can diagnose many hair loss conditions that we use to struggle with before trichoscopy.

So, the more and more skills that clinicians develop in the use of trichoscopy, the fewer and fewer scalp biopsies they end up doing. Trichoscopy is powerful tool!

So, if I’m 100 % confident in the diagnosis after listening to the patient’s full story and examining his or her scalp, we don’t need a biopsy. That’s straightforward.

So guess what? In 95% of patients that come into the office, I’m 100 % confident in the diagnosis after listening to the patient’s full story and examining his or her scalp. So in 95 % of cases, we don’t need a biopsy.

What about the other 5 %?

The other 5 % of patients, we need a biopsy! I perform a biopsy if the diagnosis is not clear. Generally speaking, I take a biopsy when I’m trying to differentiate between two or three different scalp conditions that look the same. I might be trying to differentiate between a patient who has either discoid lupus or lichen planopilaris. I might be trying to differentiate between androgenetic alopecia and fibrosing alopecia in a pattern distribution. I might be trying to differentiate between alopecia areata incognita and telogen effluvium or androgenetic alopecia. Generally speaking I’ll take a single biopsy when I need the pathologist’s help to distinguish between two of three hair conditions that might look similar.

If the scalp looks all the same in all areas of the hair loss, then generally I will take only one biopsy. If there are different areas that look somewhat different, I may take two biopsies. For example, if one area of the scalp has pustules and another area is scaly or has comedones or scales, I might consider two biopsies. If there is concern for infection, I may take a third biopsy and send a piece of the biopsy off to the microbiology lab to try to grow up any organism. (Sometimes I just cut a little piece from one of the other biopsies to send off to the microbiology lab rather than take a whole new piece). But you can quickly see how two biopsies can become three.

In some cases, I may take a few biopsies because I know the disease has different stages and I’m trying to capture different stages. Some of the autoimmune blistering diseases are like this.

In addition, sometimes I’ll need a fresh piece of biopsy for a special staining technique called direct immunofluorescence (DIF). Most biopsies of the scalp get dropped into a preservative called formalin. We can’t drop biopsies that will be processed for DIF in formalin or the procedure won’t work. Therefore, we need another piece. This piece of tissue floats off to the pathology lab in a completely different bath water. Instead of formalin, we use a liquid called Michel’s media.

Finally, sometimes I need many biopsies to try to really capture hair cycle dynamics and the proportion of terminal and vellus hairs. In some cases of chronic telogen effluvium, having several biopsies capturing a T:V ratio of 8:1 or more really helps solidify that diagnosis. Sometimes we can’t get this kind of accuracy with just one biopsy.

Generally speaking though, I usually take a single biopsy. Our lab will cut this single biopsy into both vertical and horizontal sections using a technique called the HoVert technique. Our pathologists don’t need one piece for horizontal sectioning and one separate piece for vertical sectioning.

There are situations where a biopsy comes back somewhat helpful but not nearly as helpful as you might have first imagined. In many cases, I did the biopsy myself so I know it was in a good spot. In this case, I may want to do another biopsy.

In summary, you can easily see how the plan to do one biopsy can turn into two or three or four different samples if there is different morphology on the scalp or we need different analyses done (like culture for infection) or direct immunofluorescence). In general, if I am going to do a biopsy, I usually do one biopsy 85% of the time and two biopsies 15 % of the time. I don't just to two biopsies routinely because it sounds like a good plan. Studies show it often does not add much to the diagnosis.

Thanks again for the wonderful question!

Tinnitus from Hydroxychloroquine (Plaquenil): A Rare but Possible Side Effect

Can Tinnitus Occur from Hydroxychlorouine (Plaquenil)?

I’ve selected this question below for this week’s question of the week. It allows us to review some concepts in the side effects of hydroxychloroquine on the ear and auditory system in general.

Question

I am using hydroxychloroquine for lichen planopilaris and have now develop tinnitus. Is it related to me using hydroxychloroquine? Should I stop the drug? Any information is appreciated! I can’t get answers!

Answer

Thanks for the question. I would ideally want to know more information including your age, how soon it developed after starting hydroxychloroquine, what other medical issues you have (high blood pressure), whether you have hearing loss or vertigo too, what other medications you take and what your baseline level of hearing was before starting hydroxychloroquine. Let’s come back to all this in a moment.

The first thing is to see your doctor. Tinnitus is very very very common and so the first thing is for you and your doctor to figure out if it is likely to be coming from the hydroxychloroquine or not. If you just starting hydroxychloroquine therapy and developed tinnitus, it’s less likely to be related than if you’ve been on the drug many years.

15-20 % of the population will develop tinnitus. Tinnitus refers to the subjective perception of sound such as hearing ringing, buzzing, hissing, chirping, whistling when these sounds don’t actually exist.

This happens to people regardless of whether or not they use hydroxychloroquine. So many many people will conincidentally develop tinnitus on hydroxychloroquine - simply because tinnitus is so incredibly common in the population. For some it will be related to the use of hydroxychlorouine…. and for others it will have nothing to do with the drug at all. So you and your doctors need to figure this out. The odds are stacked in favour of hydroxychloroqouine not being related to the tinnitus for most people

Generally speaking, I stop the drug in most of my hair loss patients reporting tinnitus until we sort things out. A hearing test is mandatory and some other tests might be arranged too.

With tinnitus, a good history is needed to evaluate hearing, other drugs, thyroid diseases, high blood pressure, caffeine, other ear diseases, TMj disease and other issues. . It sometimes takes alot of deep investigation to figure out whether hydroxychloroquine could be a cause or not. As mentioned above, I usually pause treatment and change to something else while the work up for tinnitus is being done.

Ototoxicity with Hydroxychlorouqine

Ototoxicity is less well known by many practitioners. Ototoxicity refers to drug-related injury causing damage to the inner ear structures, which then result in hearing loss and/or tinnitus and/or imbalance (vertigo).

It is thought that the deposition of hydroxychloroquine in the ear structures leads to many of these ear related side effects. It an occur with hydroxychoroquine and the closely related drug chloroquine.

Ototoxicity is a rare side effect with hydroxychloroquine. The ototoxicity is thought to be related to the destruction of the stereocilia (tiny hair cells) in varying degrees, reducing the neuron population, altering the support structures, causing atrophy of the stria vascularis and potentially leading to ischemia.

Is is thought that the binding of hydroxychloroquine to melanocytes in the ear contributes to the ototoxicitiy. This ability of hydroxychloroquine to bind melanocytes leads to damage to cochlear sensory hair cells, a decrease neurons and atrophy of the stria vascularis. All this is thought to be due to damage to blood vessels and a resulting ischemic process.

The main ear symptoms with hydroxychloroquine are tinnitus, neurosensory hearing loss (both from cochlear involvement) and vertigo (from involvement of the vestibular system). The tinnitus and the vertigo are often reversible once the drug is stopped. The hearing loss may not be. We’ll review some key studied in a moment.

Most cases of ototoxicty in the medical literature pertain to chloroquine with fewer reports from hydroxychloroquine. Nevertheless, it is known the hydroxychlroqouine can have ototoxic effects.

Let’s take a look at some key studies from the past.

STUDY 1: Jourde-Chiche N et al 2012

The authors conducted this study to evaluate audiovestibular side-effects in patients treated with antimalarial drugs.

All spontaneous reports of audiovestibular adverse events attributed to antimalarial drugs in the French Pharmacovigilance Network database, between January 1986 and December 2010, were identified. This included all entries into the database for such issues as ‘ototoxicity’, including ‘tinnitus, vertigo, hearing loss, deafness, vestibular or cochlea dysfunction, vestibular nerve injury, tinnitus, ear buzzing and hearing impairment.

During the study period mentioned above, 2339 antimalarial drug-associated side effects were reported, including 61 (2.6%) related to audiovestibular complications. There were 24 reports between 1986 and 1997, and 37 between 1998 and 2010, with hydroxychloroquine and chloroquine equally involved.

Audiovestibular complications attributed to antimalarial drugs included hearing loss, tinnitus and vestibular dysfunction. Symptoms occurred within 24 h after antimalarial drug initiation in four patients. However, 53% of complications were reported after more than 1 month of antimalarial drug use. Doses of hydroxychloroquine and chloroquine were given within recommended ranges to all except one patient. Two patients had serious adverse effects with significant and irreversible functional sequelae (deafness for one, deafness and vertigo for the other).

STUDY 2: Prayuenyong  P et al 2020

Prayuenyong P and colleagues reviewed the published literature on cases of ototoxicity with hydroxychloroquine. They identified six case reports, describing ototoxic effects associated with hydroxychloroquine, were identified. The publication year ranged from 1998 to 2018. Sensorineural hearing loss was identified in five adults and two children. The sensorineural hearing loss was found to be both reversible and irreversible depending on the specific report examined. The onset of hearing loss after hydroxychloroquine treatment varied from 1 month to several years. Tinnitus was also reported concomitantly with hearing loss in 2 cases.

In this study, the authors also evaluated data relating to chloroquine. It appears that ototoxicity after chloroquine use tends to be more sudden, while hydroxychloroquine is more likely to cause ototoxicity after prolonged use.

STUDY 3: De Luca P et al. 2021

in 2021, De Luca performed a review of the literature regarding prior cases of hydroxychloroquine ototoxicity. As expected, their data are similar to the data from the Prayuenyong  P et al study. They found six cases of HCQ ototoxicity, from 1998 to 2018. Tinnitus was reported in 2 cases - one happening in 6 months (Seckin et al 2000) and one happening in three years (de Novaes Fernandes et al 2018) after commencing the drug. In Seckin et al 2000 it was reversible and in the de Novaes Fernandes et al 2018 study it was irreversible.

The authors found that sensorineural hearing loss after HCQ use was reported in 7 patients (three males, four females; five adults, two children). The onset of hearing loss after HCQ treatment varied from 1 month in the Khalili H et al 2014 study to several years in other studies. Hearing loss was found to be irreversible or partially reversible after discontinuation of HCQ in 6 cases. The most common diseases for which patients took HCQ were systemic Lupus Erythematosus (three patients) and Rheumatoid Arthritis (two patients). There were no patients with scarring alopecia using these drugs.

Summary

Ototoxicity can occur with hydroxychlorqouine. This can present as sensorineural hearing loss and/or tinnitus and/or imbalance after using hydroxychloroquine and can be either temporary or permanent.

It’s not clear exactly how common this side effect is but it could be in the order of 1:500 to 1:1000. The authors the Jourde-Chiche N et al 2012 study point out that there were 61 reports from an estimated 41 000 and 47 000 patients were exposed to hydroxychloroquine.

I generally recommend expert referral for patients with tinnitus, hearing loss and vertigo. Brain evoked response audiometry and other audiometry tests (like an audiogram) are important to consider in patients with tinnitus and hearing loss while on hydroxychloroquine. Brain-evoked response audiometry seems to be the most sensitive test in detecting early manifestations of cochlear injury.

There are no formal guidelines for basline screening oor evaluation as is done with hydroxychloroquine related retinal screening. Nevertheless, all hair loss patients with hearing loss, tinnitus and vertigo associated with hydroxychloroqouine therapy should undergo expert evaluation to determine the best course of action.

In some cases, treatment with prednisone may be indicated for some patients but this is left to the ENT specialists. There are reports of hearing loss due to chloroquine being successfully managed with prednisolone (Mukherjee DK. 1979).

It can sometimes be difficult to determine if a drug was the cause or not. For hydroxychloroquine, most cases of tinnitus occur many months after starting as opposed to days or weeks.

A full review is essential for all patients with tinnitus including proper audiology assessment.

REFERENCES

Bortoli R, Santiago M. Chloroquine ototoxicity. Clin Rheumatol. 2007;26:1809–181

Coutinho MB, Duarte I. Hydroxychloroquine ototoxicity in a child with idiopathic pulmonary haemosiderosis. Int J Pediatr Otorhinolaryngol. (2002) 62:53–7. 10.1016/S0165-5876(01)00592-4

de Novaes Fernandes M.R., Soares D.B.R., Thien C.I., et al. Hydroxychloroquine ototoxicity in a patient with systemic lupus erythematosus. An Bras Dermatol. 2018;93(3):469–470. doi: 10.1590/abd1806-4841.20187615. Jun.

De Luca P et al. Chloroquine and hydroxychloroquine ototoxicity; potential implications for SARS-CoV-2 treatment. A brief review of the literature. Am J Otolaryngol. 2021 Sep-Oct;42(5):102640.

Fernandes MRN, Soares DBR, Thien CI, Carneiro S. Hydroxychloroquine ototoxicity in a patient with systemic lupus erythematosus. An Bras Dermatol. (2018) 93:469–70. 10.1590/abd1806-4841.20187615

Johansen PB, Gran JT (1998) Otoxicity due to hydroxychloroquine: report of two cases. Clin Exp Rheumatol 16:472–474

Jourde-Chiche N, Mancini J, Dagher N, Taugourdeau S, Thomas G, Brunet C, et al. Antimalarial ototoxicity: an underdiagnosed complication? A study of spontaneous reports to the French Pharmacovigilance Network. Ann Rheum Dis. 2012;71:1586–1586.

Khalili H, Dastan F, Dehghan Manshadi SA. A case report of hearing loss post use of hydroxychloroquine in a HIV-infected patient. Daru. (2014) 22:20–20. 10.1186/2008-2231-22-20

Lim SC, Tang SP. Hydroxychloroquine-induced ototoxicity in a child with systemic lupus erythematosus. Int J Rheum Dis. (2011) 14:e1–2. 10.1111/j.1756-185X.2010.01582.x

Mukherjee DK. Chloroquine ototoxicity–a reversible phenomenon? J Laryngol Otol. (1979) 93:809–15. 10.1017/S0022215100087740

Prayuenyong  P et al. Clinical Implications of Chloroquine and Hydroxychloroquine Ototoxicity for COVID-19 Treatment: A Mini-Review. Front Public Health. 2020 May 29;8:252

Seckin U, Ozoran K, Ikinciogullari A et al (2000) Hydroxychloroquine ototoxicity in a patient with rheumatoid arthritis. Rheumatol Int 19(5):203–204 9.

JAK Inhibitors for Alopecia Areata: Are they a good option for all patients?

Tofacitinib and JAK Inhibitors : Are they good options for alopecia areata?

I’ve selected this question below for this week’s question of the week. It allows us to review some concepts in management of various forms of alopecia areata.

Question

I have alopecia areata and I’m reading a a lot about the JAK inhibitors lately. I’ve been thinking about whether I should start tofacitinib. I hear it is a pretty good option.

I would appreciate to know your thoughts!

Thank you!

Answer

Thanks for the question. JAK inhibitors have certainly become more a part of the treatment plans for patients with alopecia areata.

For advanced alopecia areata, it could be a great answer. Generally speaking, JAK inhibitors are very seriously considered for patients with 50 % of more of the scalp hair missing but can be considered in other situations including:

a) patients with less than 50% hair loss on the scalp but not responding to the standard treatments

b) patients with less than 50% hair loss on the scalp who don’t wish to use or are not able to use other standard treatments

Now, I don’t know enough about your story to really get a sense of what is right for you. You’ll want to sit down with your dermatologist to discuss all these options. For some patients with small patches of alopecia areata, JAK inhibitors are not the best option at all. Steroid injections, topical steroids and minoxidil might provide just as good outcomes. Generally speaking we reserve JAK inhibitors for those with more advanced forms of alopecia areata.

Here are some of my more typical algorithms for patients with limited forms of alopecia areata as well as those with more advanced forms

REASONS WE MIGHT NOT PRESCRIBE A JAK INHIBITOR

There are many reasons why a JAK inhibitor might not be prescribed for a patient - even if they do have advanced hair loss. Generally speaking, if a certain patient is more likely than another patient to have side effects from using a JAK inhibitor, the drug might not be started.

Some of the reasons I don’t prescribe a JAK inhibitor are shown in the list below. This list is not a complete list, but a list of the more common reasonsL

Final Points

Thanks again for the great question.

JAK inhbitors are really exciting options for helping patients with advanced alopecia areata. They are not right for everyone ! They may not be the right option for patients with limited amounts of hair loss. They are not the right option for someone with a prior history of cancer, blood clots, heart attacks, strokes, patients with certain active infections, female patients who wish to become pregnant soon, patients who smoke, and patients with other reasons too. They are definitely good options for many patients with advanced alopecia areata - assuming the patient understands the risks and the doctor understands the risks and uncertainties to tell the patient.

If the patient has limited alopecia areata (like a few patches), then no, taking tofacitinib would not be a good idea at all. There are options that can deliver similar chances of regrowth including steroid injections, topical steroids, minoxidil.

In general though, there are no standard templates for treating hair loss. There are risks and benefits to everything. JAK inhibitors are a great option for advanced AA provided patients understand the risks and uncertainties. 

How fast does Lichen planopilaris progress?

How Fast Does Lichen Planopilaris (LPP) Progress?

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

QUESTION

I was diagnosed with lichen planopilaris and am wondering a few things. How fast does LPP progress? I’m trying to decide if I should go look for a wig or shave my head? I can’t seem to get anyone to give me a straight answer on how this condition exactly behaves. I'm confused !

ANSWER

Thanks for the question. The speed varies greatly between people. Some people have very very very very very mild and slowly slowly slowly progressive  LPP.  In fact, there are thousands and thousands and thousand of people walking in the world around with very mild form of LPP who don't even know they have the disease and probably never ever will because of how slow it changes. That means that the hair density is the same year after year - and if any hair loss does occur in that patient’s it’s not due to the scarring alopecia but due to other issues like androgenetic alopecia. (SEE FORMER ARTICLE: HOW FAST DOES HAIR LOSS PROGRESS?)

Typically a patient with mildly active, UNTREATED, scarring alopecia will have changes in their hair density that can be captured by a camera every 6 months. In most patients, the hair loss does not change week by week (but of course can in more active cases).

Treatment can stop the disease process for many patients, and some can even get a bit of hair back depending on the individual treatment responsiveness of the patient, the treatment used and the amount of hair loss the patient experienced so far.

There are some forms of LPP that do progressive quite fast. Aggressive treatments are needed to stop it. Aggressive forms that cause rapid hair loss are not common but may affected 2-3 % of patients. Most patients have either a moderately slow process or slow process. Of course, it may seem fast to the patient.

So, the answer to your question is that it's a spectrum. There is no one story of LPP. There are many different stories you’ll hear when you ask 100 patients “how fast did your hair loss occur?”

How soon do indents from steroid injections go away?

Atrophy from Steroid Injections

I’ve selected this question below for this week’s question of the week. It allows us to review some concepts in management of atrophy from steroid injections to the scalp.

QUESTION

How long does it take for indents to go away? I have had steroid injections for what my doctor believed was alopecia areata and my head is now covered in indents now. I mean covered! There has also been way more hair loss!!! It’s very distressing! Will the hair grow back? Will the idents be permanent?

ANSWER

Thanks for the question! This is so important and this is an issue that needs more discussion for sure! Steroid injections can cause atrophy or “indents.” it’s due to collagen production being shut off by the steroids. Atrophy does not happen to everyone. It is more likely to happen at higher doses of steroids (like 10 mg per mL of triamcinolone acetonide) but can happen at 5 mg per mL and even 2.5 mg per mL. It’s also more likely to happen if more injections are done in an area (even with a low concentration). A wonderful study by Yee et al found that there is a 3.3 % chance of atrophy at doses 5 mg per mL and 20 % at 10 mg per mL. So the dose matters! If one wants to reduce the chances of indents… use lower concentrations!

Chances of atrophy with different doses of steroid. From: Yee et al. Efficacy of different concentrations of intralesional triamcinolone acetonide for alopecia areata: A systematic review and meta-analysis. J Am Acad Dermatol. 2020 Apr;82(4):1018-1021.

Generally speaking, indents will return to normal but it can take 2-6 months.

If the indents and hair loss are from the steroid injections (and not from a mimicking condition that causes idents), the chances are 95 % - 99% that atrophy will resolve. It will take time - and sometimes a long time.

But —- a return back to normal is assuming that NO MORE steroid injections are placed there until the time it resolves and no more topical steroids are used there until it resolves.

Those are the key steps now: No more injections for a while in the areas that need to build back collagen again.

The speed and completeness of resolution depends on several factors including 1) if injections were performed in areas that already had atrophy as well as 2) how much “topical” steroid is being used while the atrophy is trying to improve as well as 3) the exact concentration and volume of steroid injected and 4) intrinsic characteristics of the disease itself and the skin of the patient. Not all patients experience total resolution but most do if steroids are reduced or abandoned during the process.

As far as hair regrowth and getting hair back, it depends on what underlying condition is being treated. If there is active alopecia areata underneath and it's not being treated then hair may or may not grow back on its own (that area may need treatment in order to grow). But generally speaking most patients get hair back and atrophy resolves in 3-6 months provided appropriate steps are taken. If there is active alopecia areata underneath, then that hair disease needs treating!

If injections continue month after month after month with no care or concern given by the doctor to the indentations that are cropping up all over the scalp, then it's a completely different story.  Repeated injections into atrophic areas can lead to permanent idents.

Saline Injections to Help Indents

I often advise doctors to consider injection saline salt water into the indents as it helps the idents improve quicker.

Here’s a simple approach I often taken when I meet with patient with indents in some areas but not in others. For example, a patient with alopecia areata and indents in some areas and brand new patches in other areas where there are not yet any idents. It may or may not be right for you but be sure to discussion options with your doctors. It’s an approach that gives a plan for patiently waiting and a plan to get back on injections if it’s felt they were helpful.

Final Summary

Generally speaking, the news is good for patients with idents from injections. But one has to be patient - very patient! One needs to really avoid injecting more and more and more steroid into these areas. That’s when problems really occur! It’s sometimes okay to inject in other areas of the scalp while waiting for the idents to return to normal in a completely different area…..but that is discussed on a case by case basis. If there are too many idents, I advise just waiting. Three is my own cut off. Nice final outcomes can happen … if one is patient !!!!! For some people, that means no injections for 2 months and for others, that means no injections for 6 months. It will depend on the scalp itself and how much steroid was injected.

Thanks again!

Here are some helpful articles too:

Atrophy From Steroid Injections

Saline Injections to Address Atrophy from Steroid Scalp Injections

Reference

Yee et al. Efficacy of different concentrations of intralesional triamcinolone acetonide for alopecia areata: A systematic review and meta-analysis. J Am Acad Dermatol. 2020 Apr;82(4):1018-1021.