Testosterone Replacement in Androgen Deficient Women: What are the effects on the hair?

Testosterone Replacement for Women with Androgen Deficiency: Good or Bad for Hair?

Androgens can both help hair growth and block hair from growing. In males, androgens help hair on the beard grow thicker. In genetically susceptible males, it’s clear that androgens cause balding in males that have the right set of genes.

In women, androgens can also contribute to hair loss. Women with hormonal issues that give high androgens such as polycystic ovarian syndrome (PCOS) and congenital adrenal hyperplasia (CAH), higher than normall androgen drive the balding process. Furthermore, reducing the levels of androgens with drugs such as spironolactone can help slow or stop hair loss.

Does taking androgens cause hair loss in women who are very low in androgens?

Supplementing with androgens (i.e. anabolic steroids and testosterone) can cause hair loss in some men and women. For example, men who take androgens for body building can develop hair loss if they have the right balding genes to begin with.

Androgen deficiency can occur in women and often leads to changes in mental health, loss of libido, reduced bone mass - among other symptoms. A proper evaluation is needed to determine the precise reason for the androgen deficiency as pathological processes affecting the ovary, hypothalamus and pituitary gland can all affect circulating androgen levels.

An important question is whether taking androgens can cause hair loss if women have androgen deficiency to begin with. If women with androgen deficiency are given androgen replacement…. will their hair become even worse? A 2012 study by Glasner and colleagues set out to answer that very question

TESTOSTERONE REPLACEMENT: EFFECTS ON 285 ANDROGEN DEFICIENT WOMEN

The authors studied a total of 285 women with androgen deficiency who were treated with androgen replacement therapy for at least one year. The women in this study had used subcutaneous testosterone implants.

About one quarter of women (27%) had hair thinning prior to starting treatment. Women with thinning hair had the lowest levels of testosterone to begin with compared to women who did not mention problems with their hair.

Interestingly, a majority of these women (63%) actually went on to have some amount of hair regrowth on testosterone treatment. Some women did not have any improvement of their hair on therapy - and these women tended to be of higher body weight (higher BMI).

An important finding of the study was that none of the 285 women reported hair loss on the testosterone replacement. The treatment was otherwise well tolerated although 92 % did develop increased facial hair.

Conclusion

This is an important study and one that I refer to often in my practice. It is appropriate for women who are androgen deficiency and have symptoms and signs that seem to be related to the androgen deficiency to begin an open discussion about androgen replacement with their doctors. This may not be appropriate for everyone and when to offer androgen replacement (and when not to) …. is still a bit controversial. Women with low libido and low blood androgen levels may be the best candidates for replacement based on current evidence. These are important discussions for patients to have with their endocrinologists, gynecologists or primary care physicians. There is no good evidence that androgen replacement for women who are truly deficient compromises the hair and cause hair loss. In fact, it may help many of these women with their hair.

Reference

Glaser RL et al Improvement in scalp hair growth in androgen-deficient women treated with testosterone: a questionnaire study. British Journal of Dermatology 2012. READ ARTICLE

Telogen Hairs: Terminal, Miniaturizing and Vellus

Telogen Hairs: More than a Single Type!

Hair that are firmly rooted in thr scalp and don’t seem to want to come out are mostly “anagen hairs.” In contrast, hairs that can be pulled out and hairs that are going to fall out today, tomorrow or this month are called “telogen hairs.”

There are many types of telogen hairs rather than just one. Long thick hairs are called terminal telogen hairs and they are typically 70 micrometers or more in diameter. Miniaturizing hairs are a type of so called intermediate hair are thinner and are most commonly seen as part of the spectrum of changes seen in androgenetic alopecia (but other conditions like alopecia areata, traction may give some degree of miniaturization).

Telogen hairs that are short, pale and thin are called telogen vellus hairs. They too are commonly found in males and females with androgenetic alopecia but are difficult to see because they are so short and pale in color. This photo shows a 37 micrometer telogen “miniaturizing” hair from a patient with androgenetic alopeca. A relatively unaffected hairs (telogen terminal hair) is seen in the upper left. The precise cut off values for normal hair thickness differ somewhat according to the ethnic background of the patient.

Dermatology Review 2019

Dermatology Review 2019

Looking forward to speaking again at this year’s University of British Columbia (UBC) Spring Dermatology Review in Vancouver. I’ll be speaking on the topic of alopecia areata. 

The Treatment Plan with too Much "SAHLT" - Common, Confounding and Confusing

When treatment plans are too “SAHLTy”?

A common problem I see with many treatment plans nowadays is that too many treatments are started at the same time and the end result is that nobody knows what helped and what did not. The patient leaves the office will plan to start this pill or that, this laser, this treatment and this supplement.

When I teach doctors about hair loss, I tell them to be careful of prescribing a treatment plan with too much SAHLT. SAHLT is my mnemonic or teaching tool to remember the words

SIMULTANEOUS ADMINISTRATION OF HAIR LOSS TREATMENTS (SAHLT)

THE SAHLTy PLAN: What is it?

Unless you’ve stepped foot in my office, you may have never heard of the SAHLTy plan, so let me give you some examples.

Example 1. A 42 year old female patient with androgenetic alopecia is seen in clinic and prescribed minoxidil, spironolactone and PRP sessions every 3 months. (3 simultaneous treatments)

Example 2: A 25 year old male with male balding is seen in the office and prescribed finasteride 1 mg, oral minoxidil 0.5 mg and low level laser therapy three times weekly. (3 simultaneous treatments)

Example 3: A 52 year old female with lichen planopilaris is seen in clinic with massive itching, burning and tenderness and started on prednisone, hydroxychloroquine and doxycycline along with clobetasol lotion daily. A laser device is added too. (5 simultaneous treatments)

What’s common with all three of these plans? There are pretty high in SAHLT. They all involve the SIMULTANEOUS administration of hair loss treatments. They involve multiple treatment plans which leaves the patient and the physician having no good sense of what is ultimately helping and what is not.

Are SAHLTy Plans Ever Helpful?

Sometimes, a SAHLTy treatment plan is necessary such as in a rapidly progressive disease state. However, the patient and the physician need to be aware (….and tell each other!) that they are really not going to have a clue what helped and what did not.

You might be surprised to hear that sometimes a SAHLTy plan is wonderful too. Sometimes when I see a patient in clinic, I’m happy they used a SAHLTy plan. For example, consider a 38 year old female with androgenetic alopecia who started topical minoxidil 5 % foam, laser, PRP and a hair and nail supplement one year ago and comes in to see me with ongoing hair loss. She tells me she used these treatments religiously but feels these treatments did absolutely nothing to stop the loss. In this case, her SAHLTy treatment plan helps me out alot becasue I know immediately that minoxidil, laser, PRP and hair and nail supplements don’t help her. I now don’t need to spend time evaluating their effects - they are all unhelpful for her and we can now move on to other treatments. In her case, we started oral spironolactone and I’ll see her back in 6 months.

Do I ever use SAHLT?

Sure. Sometimes there are reasons to start two treatments at the same time because there is a feeling that timing is important. However, I tell patients that we are not going to know what is helping. If I do start treatments, I observe carefully if there are periods where one of the treatments was stopped.

For example, consider the 27 year old female who comes to see me having started topical minoxidil and low level laser at the same time. She has used these treatments for 18 months. However, she has not been able to use her laser for a period of 1 full month back 5 months ago because she was traveling abroad and could not take the laser with her. Upon her return she noted that her hair is shedding more than it ever had been in the last 12 months. The conclusion here is that even though both treatments (minoxidil and laser) were started at the same time, I now have at least some evidence that the laser actually was helping her based on her story of worsening loss when it was stopped.

I don’t generally recommend stopping any treatment to figure out if it was working or not because most of the time patients do not catch up to the same level of success they once had.

Reducing SAHLT in the Treatment Plan

Let me be the first to say that SAHLTy treatment plans often give the happiest patients - at least short term. If you your patients to be happy quickly, adding the SAHLT works well. (Most physicians want their patients to be happy quickly). Start 4 treatments and once and you massively increase the odds something will work! But when you consider that treatments are LIFELONG for many conditions, COST money, and have potential SIDE EFFECTS, it is simply not a rationale plan in my opinion.

Consider the 42 year old male using minoxidil, finasteride, laser and PRP - all started at the same time 5 years ago. He feels happy that he has been able to keep his hair. Le't’s suppose for the sake of argument that it’s only the finasteride that is actually helping him.

Is it great he’s happy? Sure. I”m happy he’s happy!

But consider this for a moment

a) 30 years of using minoxidil that is not working could adds up to $ 15,000 over 30 years.

b) 30 years of using PRP that is not working could adds up to $ 100,000 over 30 years.

I can assure you that this happy patient would be happier with $115,000 in his pocket and it would have only taken a bit longer to figure out what helps and what doesn’t. Imagine what he might do with $115,000! I can’t even start because this is all too common. My recommendation is that we seek to always know what is helping and what is not. There are times when simultaneous treatments are needed. There are times when it simply is not.

Turmeric (Curmumin) as a Cause of Iron Deficiency

Turmeric as an iron Chelator

Turmeric is increasingly studied for its role in multiple aspects of health. It has been touted to have anti-inflammatory and anti-neoplastic properties. It also is known to bind iron in the gastrointestinal system and may contribute to iron deficiency at very high doses. These properties of turmeric have been shown in animal models

A recent study reported the case of a 66 year old male who developed iron deficiency anemia while using high doses of turmeric to treat his osteoarthritis. He had multiple investigations including upper and lower endoscopy and Hemoccult™ studies - all of which were negative/normal. Interestingly, two weeks after stopping the turmeric and continuing his usual iron supplement, his hemoglobin returned back to normal.

Conclusion.

This was a nice reminder that tumeric may be associated with  iron deficiency anemia. One must give consideration to the iron status of patients using high doses of turmeric/curcum supplements.

Reference

Smith TJ et al. Iron Deficiency Anemia Due to High-dose Turmeric. Cureus. 2019 Jan 9;11(1):e3858. doi: 10.7759/cureus.3858.

Taking Turmeric and Curcumin: What are the considerations?

Things to Think about when Taking Turmeric and Curcumin

Turmeric continues to be studied for its anti inflammatory properties. Studies have suggested it may reduce a variety of inflammatory markers like ESR, CRP and IL-6. We have had an interest in understanding its benefits in a variety of hair disorders.

Turmeric is not particularly “bioavailable” meaning alot of what goes into the body does not actually get absorbed. A variety of strategies are used to increase the amount that ultimately does get absorbed including taking with a fat source and taking with black pepper.

Anyone who takes turmeric supplements will note that they are frequently combined with “lipid-based” absorption-enhancers and by combining turmeric with other natural substances, including various black pepper derivatives (ie piperine) which may increase its bioavailability. The ideal dose of curcumin or turmeric is not known. Many studies have examined the role of 1500 mg as a typical dose. 1 tablespoon of turmeric has about 200-500 mg curcumin although some sources may have a bit less. Many turmeric based supplements indicate the amount of “curcuminoids” in the product. Individuals need to be aware that turmeric and related supplements may increase bleeding tendencies and so any such use should be discussed with a health care professional especially before surgery.

Curcumin and Turmeric: A Closer Look at their Anti-inflammatory and Anti-oxidant Properties

Curcumin and Turmeric Reduce Systemic Inflammatory Markers

“Curcumin” is the naturally occurring polyphenol found in “turmeric” and is postulated to have important anti-inflammatory and anti-oxidant effects and well as have important effects on metabolic functions including effects on lipids.

I’ve been interested in understanding the potential role of turmeric and curcumin for some type of hair issues simply because many of the hair disorders I treat are inflammatory and oxidant based problems. Given that many scarring alopecias arise from issues in lipid and metabolic pathways, I have been interested in understanding if turmeric too might have a role here.

Good research studies of turmeric and curcumin are quite rare. A recent study by Adibian and colleagues further supported an anti inflammatory role. The authors studies the potential effects of curcumin in patients with diabetes. The authors conducted a double-blind randomized clinical trial of 44 patients with type 2 diabetes and they were randomly assigned to curcumin or placebo for 10 weeks. Patients consumed either 1,500-mg curcumin or placebo daily for 10 weeks.

The antiinflammatory and antioxidant properties of turmeric and curcumin are increasingly catching the attention of the research community.

Curcumin Reduces C-reative Protein (CRP) Levels

Results showed that the mean serum level of triglycerides decreased in curcumin group compared with baseline (109 vs. 124, p < 0.05). In addition, the mean concentration of high-sensitivity C-reactive protein (“CRP”) decreased in the curcumin group compared to the control (2.9  vs. 3.4 p < 0.05). Although this study should only be classified as preliminary, these results support continued research into the anti inflammatory and metabolic effects of curcumin - at least at high doses.

1500 mg of curcumin as used in this study is hard to get in the diet and the amount of turmeric this would require from turmeric powder is enormous. For this reason, supplements with curcumin or turmeric are frequently used. 1 tablespoon of turmeric has about 200-500 mg curcumin although some sources may have a bit less.

Reference 

Adibian M et al. Phytother Res. 2019 Mar 12

Telogen Effluvuim from NSAIDS: Are they really potential culprits?

NSAID Induced Telogen Effluvium

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used around the world to treat inflammation, fever, and pain. In rare cases (probably less than 1% of users), they may also cause hair loss in the form of a telogen effluvium.

Common over-the-counter NSAIDs include ibuprofen and naproxen. Prescription NSAIDs include: celecoxib (Celebrex), diclofenac (Voltaren), etodolac (Lodine), fenoprofen (Nalfon), indomethacin (Indocin), ketoprofen (Orudis, Oruvail), oxaprozin (Daypro), nabumetone (Relafen), and sulindac (Clinoril). Barter in 1989 reported to the British Medical Journal a young 2 year old who developed hair shedding within 2 months of using naproxen for an arthritis. Hair regrew when naproxen was stopped. The author also shared data on 85 patients with naproxen related hair loss.

Meyer reported hair loss associated with ibuprofen use in an elderly patient which in turn prompted a larger study of ibuprofen related hair loss.

NSAID related hair loss probably occurs in less than 1 -2% of users. Litt’s Drug Manual reports the risk from celocoxib at less than 2 % and diclofenac at 1-3 %. Naproxen is thought to affect 1% of less of all users.

Confidently diagnosing drug related hair loss is challenging. A history of hair loss a) within 2 months of starting a drug, b) cessation of shedding with stoppage of the drug AND c) recurrence of shedding with “rechallenge” (readministration) of the drug provides the best evidence of a potential link between the drug and shedding. Criteria “d” is rarely pursued but involves d) documenting that higher doses of the drug cause higher degrees of shedding. This happens for some but not all drugs.

Diagnosing drug related hair shedding is among the toughest challenges. Many people who think their hair loss is from a drug end up being wrong. A variety of drugs can cause hair shedding other the NSAIDS including beta blockers, lithium, some antidepressants, heparin, retinoids and blood thinners and some blood pressure medications. This list is by no means complete and thousands of drugs are implicated to various degrees.

Reference 

Barter DA. BMJ. 1989.

Meyer HC. JAMA 1979.

End-stage scarring alopecia (ESSA): Can we get rid of the term?

“End stage” is not always end stage for the patient

Every day I sit and read over pathology reports that arrive to the office. I quickly figure out if the pathologist thinks we’re dealing with a scarring alopecia or a non scarring alopecia. For patients with suspected scarring alopecia, I like to read in the report if all the features of a true scarring alopecia are present such as loss of sebaceous glands.

For time to time, my eye comes across the term ‘end stage’ scarring alopecia in the report. Of all the words in the report, I can confidently say that few words in a biopsy cause more confusion and potential harm to the patient that these two words.

What is meant by the term “end stage”?

We all feel we sort of know what is meant by the term end stage. It doesn’t seem like a positive thing to have for the most part. In medicine, we have terms like end stage kidney disease, end stage liver disease, end stage dementia, end stage heart failure and end stage cancer.

End stage implies that there is some permanency and finality to what is being observed and that there is no returning back to previous states of health. End stage also sometimes implies that what has been done has been done and there may not be much that can be done to alter the situation.

End stage scarring alopecia (ESSA)

The term end stage scarring alopecia is often tacked onto the report when the pathologist sees lots of scarring and little in the way of inflammation. To the pathologist, the finding of ESSA implies that hairs in the biopsy have been destroyed and there is not much left anymore to destroy. In other words, what’s been done has been done- there’s not much that can be done to alter the situation.

End stage may not be end stage to the Patient.

Too often I receive consultations from patients with scarring alopecia who are told they have a biopsy showing “end stage scarring alopecia”. They are told that because they have end stage scarring alopecia there is no need to treat it because it’s pretty much done.

Makes sense?

It would seen to make sense except when I simply ask the patient one question, it seems that something does not quite add up.

MY QUESTION: “Do you think that you have lost more hair in the last 6-12 months?”

PATIENT ANSWER: “For sure. I’ve lost alot more hair”

It would seem strange that a patient end stage disease should have more hair loss. Shouldn’t everything be done? Shouldn’t the inflammatory reaction be done? Shouldn’t the hair loss be done? The answer here is no. By definition a patient with scarring alopecia who is still losing hair has active disease.

The reality of the situation is that there is a big difference between end stage scarring alopecia on a biopsy specimen and end stage in real life. End stage on a biopsy does not necessarily imply that the patient’s disease is inactive. End stage under the microscope does not mean that the patient is not going to lose more hair. End stage does not mean that the patient does not need treatment if he or she wishes to keep what hair they have left. End stage does not mean we discharge the patient from the clinic.

ESSA: Can we do away with the term?

The term end stage is clearly not ideal. It causes some patients to forgo treatment. It gives some patients false hope that their disease is now quiet. It causes some patients to go on to lose more hair that will never come back.

A more appropriate term would simply be ‘advanced scarring alopecia’. I would encourage all pathologists to consider using a phrase like

“The histological findings here support a diagnosis of advanced scarring alopecia. Clininopathological correlation is needed to accurately determine if these histological findings actually imply inactive disease (ie. so called burnt out scarring aloepcia) or whether the patient may in fact have ongoing and progressive hair loss in this or other areas of the scalp.”

For now, I hope that we can do away with the term end stage scarring alopecia.

4 Genes Identified in Frontal Fibrosing Alopecia (FFA)

Frontal Fibrosing Alopecia : The First Four Genes

Frontal fibrosing alopecia (FFA) is a scarring alopecia that affects women to a much greater extent than men. It is increasing in frequency around the world - for reasons that are not clear.

The cause of FFA has been quite a mystery since it was first reported in 1994. Now for the first ever, researchers from the UK and Spain have uncovered 4 new genes that appear to be relevant to FFA. The group studied 844 FFA cases and 3,760 unaffected controls from the UK, identifying three genetic regions (FFA-associated loci) that were subsequently validated using data from Spain in 172 women with FFA and 385 without. A fourth genetic was uncovered in a meta-analysis of data from both cohorts. Taken together these data suggested that significant FFA contributors fall at chromosomes 2, 6, 8, and 15. These four regions are believed to be strongly associated with the onset of Frontal fibrosing alopecia (FFA). 

HLA-B*07:02 on chromosome 6

Of the 4 genetic areas, a location within the HLA-B gene was found to be the most strongly associated with the occurrence of FFA. More specifically, the researchers’ fine-mapping analyses led to the human leukocyte antigen locus HLA-B*07:02 on chromosome 6, which is part of the major histocompatibility complex (MHC).
This appears to be highly relevant because the HLA-B is an important so called “immune recognition gene.” A variation in these genetic coding in these immune recognition genes is thought to contribute to autoimmunity - which in the case of FFA would lead to autoimmune destruction of the hair follicle. What was remarkable in this study was the observation that specific mutations in the HLA B gene carried a 4.73 fold increased risk of developing FFA. When I look at the data, this points to a really significant association. It is this gene that might influence how autoantigens get presented to the immune system.

Other genes potentially relevant to FFA

The other genes were less directly associated with FFA (increased risk of about 1.5 fold) but nevertheless thought to also have a role. The group found a second genetic location of importance, CYP1B1 which is a gene that codes for a metabolic enzyme that is involved in xenobiotic and sex hormone degradation. The gene on chromosome 2 is known by several names including Cytochrome
P450 1B1 microsomal enzyme as well as by the second name “xenobiotic mono-oxygenase and aryl hydrocarbon hydroxylase.” This gene is responsible for how estrogen gets metabolized in the body. FFA is thought to be influenced to some degree by hormonal and environmental factors. I have no doubt that these findings will continue to fuel interest in better understanding the role of environmental factors. ST3GAL1 on chromosome 8 encodes a membrane bound sialotransferase. It is now understood that changes in glycans on the surface of T cells can influence the activity of these T cells.

Additional data from FFA-affected scalp tissue indicated a very significant rise in innate and adaptive immune response genes. Individuals with FFA had an increase in transcripts in genes encoding the interferon pathway - a pathway that is also involved in diseases like alopecia areata. This information may be relevant to how treatments are designed in the future. The involvement of the interferon pathway also calls in question the possibility that drugs blocking interferon (ie jak inhibitors) could have an important role in treatment.

Conclusion

Taken together, this is an important study. This is the first study to point to potential genes that could be relevant to frontal fibrosing alopecia. It reminds us that continued focus on inflammatory and hormonal factors is likely going to lead us to improved understanding of this complex disease.

Reference

Christos Tziotzios et al. Genome-wide association study in frontal fibrosing alopecia identifies four susceptibility loci including HLA-B*07:02. Nature 2019. Online March 8, 2019

 https://doi.org/10.1038/s41467-019-09117-w

https://www.nature.com/articles/s41467-019-09117-w.pdf

Frontal Hairline Loss in a 48 Year Old Black Woman: Is this CCCA?

Diagnosis of Frontal Hairline Loss in Black Women

I just posted a new answer to our “Question of the Week.” I was asked to comment on the best treatment strategy based on a scenario I as given.

The full answer to this week’s question can be read here:

Frontal Hairline Loss in a 48 Year old Black Female

To submit a new question for consideration of our Question of the Week, simply visit complete our online form

Can one see scaling arounds hairs in LPP/FFA without trichoscopy?

Perifollicular Scaling in Lichen Planopilaris & Frontal Fibrosing Alopecia may or may not be easy to see

Lichen planopilaris (LPP) and Frontal Fiborsing Alopecia (FFA) are both types of scarring alopecias. Clinically, patients with FFA and LPP typically give different stories about their hair loss. LPP typcially starts with increased shedding as well as symptoms likely ithcing and burning in the middle of the scalp. Of course, there’s about 50 variations on what patients with LPP report as the first signs and symptoms of the disease so this is not the only way it presents. Patients with FFA, on the other hand, often notice eyebrow or body hair loss month to years ahead of their scalp hair changes. Again, there are many variations on this too. The point is that LPP and FFA are recognized as being clinically distinct. To make matters even more confusing, many patients with FFA have LPP in the middle of the scalp too. The two conditions certainly have their overlap.

Trichoscopy of LPP and FFA are similar - and so is the histology

There’s no doubt that FFA and LPP have their similarities. In fact, when one looks up close with a dermatoscope (trichoscopy), it can be difficult to tell LPP and FFA apart. They can look the same up close. One needs to stand back and think about where the patient is losing hair to make a decision whether the patient has a) FFA or b) LPP or c) both FFA and LPP. The main point here is that dermatoscopic image of classic LPP and FFA can be similar and that includes perifollicular erythema, (redness around hairs) and perifollicular scale (scale around hairs) and many single hairs (rather than hairs in groups of 2 and 3.

The histology of LPP and FFA is also the same. If you give a dermatopathology a biopsy fo FFA and LPP to examine under the microscopy they look the same. One can’t tell them apart. Again, the actual diagnosis of LPP and FFA comes from examining the scalp and the trichoscopic findings and then stepping back and asking “so does this best fit with LPP of FFA?” If only the frontal hairline, eyebrows, body hair involved without any involvement in the mid scalp and crown, in probably fits best with FFA. If the findings are localized more to the mid scalp and crown, the diagnosis may be more likely to be LPP

Do we need a dermatoscope to diagnose LPP and FFA? Are these findings alway present?

Redness and scaling around hairs are imprortant signs of FFA and LPP. They can sometimes be seen simply by looking at the scalp - but not always. Typically, if one can see scale around many hairs without magnification or without a dermatoscope, it’s like the patient has very active disease.

A dermatoscope or trichoscope really enhances the ability to detect these findings of LPP and FFA. In my opinion, trichoscopy can greatly enhancee the ability to diagnose FFA and LPP. The classic scaling, redness and changes around hairs are not always seen from simple visual inspection.

EXAMPLES

Here are some example of perifollicular scale in LPP and FFA.

Perifolliclar scale in LPP. This case is subtle and would not be possible to identify without a dermatoscope.

Perifollicular redness in FFA. This redness is seen even without a dermatoscope.

Perifollicular scale in FFA. The scale in this case is subtle and would only be seen with a dermatoscope. The diagnosis however might still be possible to make by an astute clinician without a dermatoscope. But there is not doubt a dermatoscope makes it easier and enhances the confidence in making the diagnosis. Such confidence can even help patients avoid the need for a biopsy in some cases.

Perfiollicular scale in LPP; This scale would be visible visually by simply looking at the scalp as well as with a dermatoscope.

Perifollicular scale in FFA. The scale here is subtle and would only be seen with a trichoscopic examination.

Perifollicular scale in LPP. The scale here is thick and intensity of redness is quite high. This scale would even be seen without a dermatoscope/trichoscope.

Perifollicular scale in LPP. The scale here is quite thick and is visible simply by examining the scalp.

Perifollicular scale in LPP. The scale here is subtle and only a proper dermatoscopic examination would pick this up.

Perifollicular scale in LPP. The scale here is thick and visible even without a dermatoscope.

Conclusion

A dermatoscope greatly enhances the ability to diagnosis lichen planopilaris and frontal fibrosing alopecia. In extremely active forms, the redness and scale may be visible even without a dermatoscopic examination. By definition, these patients have active disease and are at risk for further loss.

The American Academy of Dermatology Annual Meeting

2019 AAD Meeting

The AAD Annual meeting is among my favourite meeting. It’s a wonderful opportunity to catch up with colleagues across the globe and an opportunity to get caught up what’s happening both in an outside of te hair world. I’m always pleasantly surprised at how fast various aspects of dermatology are progressing.

I particularly enjoyed leading a session last Friday afternoon at the American Academy of Dermatology Meeting Friday in Washington, DC. I guided attendees through a series of high yield self-assessment questions in the field of hair loss - and explained answers to these questions. Attendees had the opportunity to answer some pretty difficult questions in the areas of pathology, scalp dermoscopy, diagnosis, treatment and side effects.

There were several highlights of the session. I reviewed with attendees the link between male balding and an increased risk of skin cancer, prostate cancer and metabolic syndrome. We reviewed that isotretinoin was the most effective treatment for dissecting cellulitis as well as for the facial papules of frontal fibrosing alopecia. We reviewed the value of the scalp biopsy in giving an accurate assessment of terminal to vellus ratios, as well as the density of sebaceous glands. We discussed the benefit of oral minoxidil in the treatment of chronic telogen effluvium and reviewed the role of topical minoxidil in endocrine therapy induced alopecia (ETIA). We discussed the dose dependent side effects of tofacitinib including hyperlipidema, elevated creatine, infection risks, shingles, and possibly pulmonary embolism. We reviewed that newer proposed pathology of the facial papules in FFA as being secondary to destruction of elastic tissue that in turn causes dilation of sebaceous glands and dilated sebaceous ducts. We reviewed the pathology of CCCA and how loss of sebaceous glands might not in fact be such an early step in CCCA (as it is thought to be for scarring alopecias like LPP). We reviewed together the important clinical pearl that bilateral loss of the sideburns in males and eyebrow loss in peri menopausal females is highly suggestive of a diagnosis of FFA. I even challenged participants with questions about the best methods of managing tooth discolouration from iron supplementation in children! (... brushing with baking soda does the trick).

Congratulations to all attendees for their hard work answering some pretty tough questions!

More JAKs in the Box: New Janus Kinase Inhibitors in Clinical Trial stages

JAK Inhibitors: Many Different Compounds Being Trialled For Alopecia Areata

It’s a pretty exciting time in the world of alopecia areata research. 

Although tofacitinib, ruxolitinib and baricitinib are FDA approved for various indications and now used off label for treating alopecia areata, other JAK inhibitor drugs are in the clinical trial stages.

This past weekend, I had the opportunity to hear my colleague dermatologist Dr Brett King of Yale University deliver a very nice first hand account of his work with medications known as the janus kinase (JAK) inhibitors over the past 5 years or so. Dr King described how his patient with alopecia areata back in 2013 lead ultimately to him using tofacitinib as a treatment and how that patient’s successful hair regrowth lead ultimately to an expansion of his work in this area. Dr King shared that there are now at least 7 clinical trials with various JAK inhibitors happening and so we should be hearing a lot more about newer JAK inhibitors in the years to come.

Scalp Cooling for Prevention of Chemotherapy Induced Alopecia: Does it really impact Quality of Life Measures?

Scalp Cooling and Quality of Life: What does the research tell us?

Hair loss from chemotherapy a distressing part of the treatment. Scalp cooling procedures have emerged worldwide as means to reduce the chances that patients get hair loss after chemotherapy. These devices are worn before, during and after chemotherapy. Scalp cooling devices themselves may be as cold as -25 to -30 Celsius and help achieve hair follicle temperatures under 22 C (from their normal 37 C) and by doing so help limit the drug from getting into the scalp (on account of vasoconstriction) and also limit metabolism of the drug by hair follicles. These cold temperatures may provide discomfort.

It’s clear that scalp cooling reduces hair loss but what is less clear is whether it makes peoples lives better.
Marks and colleagues in a new 2019 study set out to evaluate the use of scalp cooling for prevention of chemotherapy induced alopecia and looked at how these treatments affect quality of life.

Of all the studies they examined, 13 met strict criteria for inclusion including 4 randomized clinical trials (RCT), 8 cohort studies, and 1 cross-sectional study with 1282 unique patients. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-C30: 46%) and Breast Cancer Module (QLQ-BR23: 46%) represented the most commonly used QoL assessments. 
Not all studies showed that scalp cooling led to better quality of life measures (“QoL measures”)in cancer patients. In fact, only 4 (31%) of the 13 studies concluded that scalp cooling was associated with significant improvements in QoL measures as assessed by EORTC QLQ-C30 and -BR23s; 8 of 13 studies (62%) determined that there was either non-significant or no improvements; and 1 (7.7%) provided a mixed conclusion. 
This is an interesting study. Now that we have good data to back up the benefit of these devices in preventing hair loss we need to understand who benefits the most from these devices and who is likely to find that the discomfort and other factors (cost, inconvenience) outweigh the benefits. More studies in this important area are needed.

Reference

Marks DH et al. Breast Cancer Res Treat. 2019.

Hydroxychloroquine and Retinal Safety: New Guidelines

Eye Checks for Hydroxychloroquine Users: Second Exam for Most is at Year 5

Hydroxychloroquine (Plaquenil, etc) is an oral immunomodulating medication that is used in the field of hair loss for a range of immunological conditions including lichen planopilaris, discoid lupus, frontal fibrosing alopecia and pseudopelade.

One of the most worrisome side effects of hydroxychloroquine is eye damage in the form of “retinopathy”. The risk overall is still low. A recent review in 2016 by the American Academy of Ophthalmology stated that the risk of retinopathy was 1 % after 5 years of use and 2 % after 10 years of use. At 20 years the risk rises to 20 % but if a person has shown no evidence of retinopathy by that time the risk of conversion increases by only 4 % per year after that.The risk of retinopathy is dependent on dose and duration of treatment. Other factors like renal disease and use of tamoxifen increase the risk as well.

New Guidelines from the American Academy of Ophthalmology indicate that a second examination 5 years after the initial baseline examination is appropriate for most hydroxychloroquine users.

The recommended dose of Plaquenil has decreased slightly in recent years and is currently recommended not to exceed 5 mg per kg daily of actual (real) body weight. Many people I see in my practice come in on the wrong dose and 200 mg twice daily may not be right for everyone. It is important to note that the American Academy of Ophthalmology no longer supports follow up eye examinations every 6-12 months as were done in the past. This has been deemed far too often. 
The actual recommendations from the AAO are for a baseline fundus examination to be performed to rule out preexisting maculopathy. Thereafter, the AAO recommends to begin annual screening after 5 years for patients on acceptable doses and without major risk factors.

Reference

American Academy of Ophthalmology. Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy - 2016

When An Evidence Based Approach is Just not Enough

Keeping the Patient’s Concerns Central in Evidence Based Medicine: Evidence Based Patient Centered (EB-PC) Decision Making

In the early days of medicine, physicians made recommendations to their patients based on their own previous experiences treating other patients. Over time, by witnessing which patients had their diseases improve and which did not, physicians would change their standard recommendations.  Nowadays, the new way of doctoring relies less on one’s previous experiences as a whole and more on the collective experiences of all health care providers around the world. If treatment X has proven itself in several countries or several good studies to be highly effective in treating disease Y, it quickly rises to the top of the list of the top treatment to be considered for any patient with disease Y.  We call this new era the era of ‘evidence based medicine.’

Every student of medicine now develops their entire problem solving skills as a doctor based on this type of evidence based medicine (EBM).  When thinking about what treatment to recommend, one asks the question as to what treatment has proven itself time and time again in clinical studies to be the most effective in treating the given disease. That treatment is then placed at the top of the list in treatment options presented to the patient. 

From Evidence Based Medicine to EvidenceBased Patient Centered Medicine

Evidence Based Medicine has revolutionized how diseases are treated. For every medical condition, we decide on the best treatment to offer the patient by scouring the medical journals for current and past studies.  This does not however always mean that this will be the treatment that the patient goes home with. Although the first step in deciding on treatment is figuring out what has proven effective in other studies, the second step in deciding on treatment is deciding on what makes the most sense to the patient.  The most effective treatment is not always the treatment the patient begins. This is the concept behind evidence based patient centered medicine (EBPCM).

In the world of hair loss, we practice EBPCM each and every day. Some patients leave the office with the most effective treatment. Some leave the office with treatment prescriptions that are potentially less effective. At first glance, it seems incomprehensible – why wouldn’t the patient want the best treatment? The following descriptions help clarify this.

Table 1: Patient comments that Might influence the Type of Treatment Recommended

When discussing treatments with patients, we need to take into account several aspects including the health of the patient, their risk tolerance, cost, goals, lifestyle and how they have responded to treatments in the past. 

Example 1

Consider the 21 year old female with alopecia areata affecting 70 % of her scalp.  Given her history, the physician determines that current evidence would suggest that the best treatment for her is a JAK inhibitor such as tofacitinib. However, using a patient centered approach, further discussion reveals that the patient does not have insurance coverage for the medication. Even if she did, she does not like the sound of taking a systemic medication and does not want to consider the medication. For her the best option to consider are options such as diphencyprone.

 

Example 2

Consider as a second example the 24 year old male who has been recommended to consider finasteride for treatment of his male balding. Further discussion reveals that the patient has depression and together the patient and the physician discuss that finasteride can rarely cause or worsen depression.  Together the patient and doctor feel that now is not the time to risk worsening the depression with finasteride. He decides then to start topical minxoidil and re-evaluate the situation again in 6 months.

 Conclusion and Final Comments

Evidence based algorithms help the physician decide how to rank treatments from most effective to least effective. However, patient centered approaches allow the evidence based algorithm to re-ordered according to what will fit best with the patient. We need evidence based approaches to give us the proper framework. The art of medicine is making sure that the best interest of our patients are always held to the highest level

Changing the Natural Course of Alopecia Areata (AA): Yes or No?

Can we change the “natural history” of alopecia areata?

 When it comes to education surrounding the topic of alopecia areata, the classic teaching that any medical student, intern, dermatology resident, registrar and dermatologist learns – is that alopecia areata mainly governs itself and that no treatment actually changes its so called ‘natural course’. The term ‘natural course’ refers to the course the AA takes if the patient does not treat his or her hair loss. If alopecia wants to go away, it will go away. Yes, treatment might help it go away faster and sooner and treatment might help the hair stay on the scalp longer, but if hair wants to regrow it will regrow. If alopecia wants to come back in the future after the patient is done treatment, it will come back.  No treatment is going to alter this. At least that’s the classic teaching we’re all taught. 

Can treatment today alter the course of AA in the future?

It was about 1 year ago that I remember distinctly hearing a comment by a trusted and respected colleague about his view that treatment today could potentially change how a patient’s alopecia areata behaves down the road. In other words, treatment now could potentially change what alopecia does in the future. In other words, the treatment that I administer today could potentially affect the degree of hair loss a patient has not only in one month and also whether or not the patient is getting flares of their disease in 10 years.  The argument of my colleague was that we should be aggressive in our treatment always – because it affects how the patient’s alopecia acts in the future. And so, when I heard the comment I assumed that somehow my colleague had missed the ‘classic’ teaching. Perhaps my colleague did not know that supposedly no treatment could really change the natural course of alopecia areata. 

Fast forward March 2, 2019 when another colleague Dr Rodney Sinclair in a lecture presentation at the American Academy of Dermatology Annual meeting announced his own hypothesis that treatment of alopecia could potentially alter the course of alopecia areata. He admitted he hadn’t proved it – but it was his strong hunch. As I heard his words, and saw his slides, I was reminded of the conversation I had with another world expert in alopecia areata just one year earlier. And the concept was now obvious to me: there is a clear interest in exploring whether the treatments we administer affects how the alopecia areata acts way down the road. 

The hypothesis of Dr Sinclair was that we might consider aggressively treating our patients with alopecia. We should be aggressive not only so the patient can have more hair in the next few months but so that he or she might be less likely to have a flare of the disease next year or well into the future. 

The hypothesis also has important implications for children with alopecia areata. We currently have the view that if a child’s alopecia areata wants to be aggressive in its course and hair loss wants to come back again in the future – it’s simply going to do so. Sinclair’s views, however, offer a different view and a different hope. His views are that by considering offering the patient aggressive treatments before the child walks out the door that same day – that we might drastically affect the course of his or her alopecia.  

 Conclusion

We’ve had many paradigm shifts in how we think about alopecia areata in recent years and quite possibly we could be onto yet another one. More studies are needed to determine if treatment of alopecia affects the patterns of hair loss the patient has years down the road.

Permanent chemotherapy induced alopecia : How common is it?

Permanent chemotherapy induced alopecia: 4 in 10 Patients Affected

There are two types of hair loss that follow receipt of a chemotherapeutic agent: temporary chemotherapy induced alopecia (TCIA) and permanent chemotherapy induced alopecia (PCIA) The first type is somewhat expected and most people are aware of the possibility of losing hair with chemotherapy. The second type is thought to be rare and is largely considered an unexpected occurence. PCIA is defined as the failure of the hair to grow back fully by 6 months following the end of chemotherapy.

A Closer Look at PCIA: How common is it really?

Kang et al recently set out to perform a prospective cohort study of 61 consecutive patients ≥18 years of age with postoperative diagnosis of stage I-III breast cancer expected to receive adjuvant chemotherapy at an outpatient breast cancer clinic in Seoul, Korea. The proportion of participants who had PCIA at 6 months and 3 years was 39.5% and 42.3%, respectively. Patients who received a taxane-based regimen were more likely to experience PCIA compared with patients with other types of chemotherapy.

Conclusion:

This is a really important study because it teaches us that PCIA may not be anywhere near as rare as we once believed it to be. So many patients who I see are told by their oncology teams that permanent types of hair loss are infrequent and some are not even told of the possibility. If PCIA truly has a frequency as high as 40 %, then counselling about this side effects becomes an even higher priority for oncology teams.

Reference

Kang D et al. Permanent Chemotherapy-Induced Alopecia in Patients with Breast Cancer: A 3-Year Prospective Cohort Study. Oncologist. 2018.

A Closer Look at the Safety of Lysine

is Lysine safe at 1000 mg Dosing?

L-lysine (or “lysine”) is a supplement that is sometimes used in the clinic for helping patients with hair shedding disorders. It’s also used sometimes for patients with low iron or zinc levels that just won’t budge with typical supplements. At doses typically used in our clinic (ie 1000-1500 mg daily), L-lysine can be considered quite safe.

I was interested to recently read a review of 12 relatively high quality studies on lysine. The observed adverse events were mainly subjective symptoms related to the gastrointestinal tract such as nausea, stomachache, and diarrhea. These were observed typically only for individuals using very high doses (above 6000 mg daily) and not for the typical 1000-1500 mg doses used in the hair clinic.

In general, L-lysine has a good safety profile for most people.

Reference

Hayamizu K et al. Safety assessment of L-lysine oral intake: a systematic review. Amino Acids. 2019