Topical Tofacitinib for Alopecia Areata: How much does it really help?

2% Ointment Helped 1 of 10 Patients 

Oral tofacifitinb belongs to a group of medications known as JAK inhibitors and represents an off-label treatment for alopecia areata.  Its use is limited by cost but also by potential side effects associated with its immunosuppressive effects. An increasing interest is mounting regarding the potential use of topical JAK inhibitors in treating alopecia areata.

The optimal formulation (liposomal vs ointment) has yet to be definitively proven. Previous studies have suggested a benefit of both topical ruxolitinib and topical tofacitinib in at least some patients with alopecia areata. 

New Study Examines Topical Tofacitinib

Researchers from Yale set out to examine the benefit of tofacitinib ointment in adults with alopecia areata. In their report, the authors described the results of a 24-week, open-label, single-center pilot study of 10 patients with AA treated with tofacitinib 2% ointment applied twice daily.  Patents were eligible for the study if they were 18-years-old or older, had at least 2 patches of alopecia areata, had  stable or worsening disease for 6 months, and have received no treatment for AA for at least 1 month prior enrolment. Tofacitinib was applied to half of the involved scalp and, if and when evidence of hair regrowth was observed, tofacitinib was subsequently applied to the entire involved scalp. 

 

What were the results?

The authors showed that 3 of 10 subjects experienced hair regrowth with topical tofacitinib with a mean decrease of 34.6% in SALT score (standard deviation 23.2%).  Of these three patients, only one had excellent regrowth. 2 others had partial growth. Skin irritation was reported by 40 % of patient and folliculitis in 10 %. Both of theses side effects resolved even without treatment. 40 % of patients had a minor increase in cholesterol levels. Despite these minor side effects there were no serious side effects. 

Conclusion and Summary

This is an interesting study by these Yale researchers who are leaders in this area of JAK inhibitors. It was disappointing that only 1 of 10 patients had significant improvement.  Whether a differential topical vehicle (such as a liposomal vehicle) could have different results awaits further study.  The main message of all of the topical JAK inhibitors studies to date is that they could help some patients with alopecia areata, but for many they do not. 

REFERENCE

1. Liu L et al. Tofacitinib 2% ointment, a topical janus kinase inhibitor, for the treatment of alopecia areata: a pilot study of 10 patients. Journal of the American Academy of Dermatology.

DOI: http://dx.doi.org/10.1016/j.jaad.2017.10.043

2. Topical Ruxolitinib Promotes Eyebrow Regrowth in Alopecia Universalis  

3. Topical JAK inhibitors for Children and Adolescents with AA  

Tofacitinib for Alopecia Areata: How long do we use it?

How long to continue Tofacitinib in Alopecia Areata?

 

A variety of treatments are available for alopecia areata. For localized (limited) AA topical steroids, steroid injections and minoxidil are still the mainstays of treatment. Treatment of advanced alopecia areata is more challenging. A variety of options are available in such cases including diphencyprone, prednisone, methotrexate and more recently tofacitinib.  

Tofacitinib in AA

We have been prescribing tofacitinib more frequently as an off label treatment for alopecia areata. The drug is surprisingly well tolerated for many, but does have potential side effects relating to long term immunosuppression. These include increased risks of infection, and concerns over possible long term cancer risks. The drug is expensive (1200-1400 USD per month). 

Lowest Dose, Shortest Time Needed

Clearly, in order to limit side effects of tofacitinib (and any drug) one should use the lowest dose possible and use it for the shortest duration possible. However, for many patients with advanced alopecia areata who are responding well tofacitinib and experiencing regrowth, any discussion of lowering the dose raises the possibility that hair loss could once again occur. The decision to taper the drug should always be carefully considered. Losing hair again can be devastating.

Some patients with advanced alopecia areata who start tofacitinib will likely need to use higher doses forever to maintain their hair density. But some patients will be able to eventually taper the dose. Some are able to taper it a bit and some are able to taper it a considerable amount and possibly even stop. However, it is less common to be in the latter group. Most patients who need to use tofacitinib in the first place have a more resistant form of hair loss that is unlikely to regrowth fully without immunosuppression.

Tapering Tofacitinib

There is no standardized formula for how to taper tofacitinib. Generally, my approach is the following.

1. Assuming a patient is using 5 mg twice daily (10 mg daily) go down to 10 mg on Monday, Wednesday and Friday and Sunday and 5 mg on Tuesday, Thursday and Saturday. This can be continued for 3 months. If there is any breakthrough hair loss, the patient returns to 10 mg daily.

2. If hair is growing fully, one can consider going down to 5 mg every day for an additional three months.

3. Thereafter, if hair growth continues to be full, we may consider 5 mg on Monday, Wednesday and Friday and no medication on the other days. A slower taper is possible if there are any concerns and this could include 5 mg daily Monday to Friday with the weekends being 'drug-free' periods.

4. Thereafter, any taper is done on a case by case basis. Many patients are not  able to taper further. However some may taper to 5 mg on Mondays and Thursdays before eventually going to one tablet weekly.

Lab Tests During a Taper

If blood tests have been stable and normal at the higher doses of tofacitinib I am generally less concerned about the patient having frequent monitoring blood tests. Nevertheless, I do feel that tests every 3-6 months is still appropriate even in a patient whose tests have been stable. I generally advise my patients to get tests for CBC, CK, cholesterol, liver function tests, creatinine, urinalysis. A repeat ECG is done every year.

Final Comments

The topic of tapering immunosuppressants is an important one in alopecia areata. Some patients are not able to taper immunosupressants at all without losing some hair. However, some patients can taper and a "go slow" approach is generally the best method. Go slow means not only taper the oral immunosuppressants slowly but given attention to how the patient's alopecia areata is treated topically. As tofacitinb is tapered, one may continue various topical (and even corticosteroid injection-based) treatments that have been performed alongside the immunosuppressive agents.  But eventually they too can be tapered in a stable patient. 

Treating Frontal fibrosing Alopecia (FFA): Are retinoids better than finasteride?

Retinoids in FFA Treatment

Frontal fibrosing alopecia ("FFA") is an autoimmune disease that mostly affects women. It is classified as a "scarring" hair loss condition and hair loss is often permanent for many women. A variety of treatments are available including topical steroids, topical calcineurin inhibitors, steroid injections as well as oral treatments like finasteride, doxycycline, hydroxychloroquine and isotretinoin.

A new study from Poland set out to compare benefits of finasteride and "retinoids" (isotretinoin and acitretin) in women with FFA. The study included 29 women who were treated with a dose of 20 mg isotretinoin, 11 women treated with 20 mg acitretin and 14 treated with oral finasteride at a dose of 5 mg/daily.  Interestingly, 76% of patients treated with isotretinoin, 73% of patients treated with acitretin, and 43% of patients treated with finasteride had their disease halted over a 12 month observation period. 

Comments

This study is small and should be interpreted with caution for this reason. Nevertheless it is interesting and points to a potentially valuable role for retinoids that we really don't seem to see with classic lichen planopilaris (a closely related condition). The data in this present study however do not match other much larger studies of finasteride use in FFA which have suggested that a much higher proportion of FFA benefitted from use of this drug.

For now, this study provides us with evidence that retinoids can benefit some patients and should be at considered. Many women with FFA do have a tendency for increased cholesterol levels and the use of retinoids can significantly worsen this so caution and monitoring are needed.

Reference

Rakowska A, et al. Efficacy of Isotretinoin and Acitretin in Treatment of Frontal Fibrosing Alopecia: Retrospective Analysis of 54 Cases. J Drugs Dermatol. 2017.

Medication induced hair loss

Does Drug Induced Hair Loss Eventually Stop ?

If a patient's hair loss is truly from a medication the hair shedding is likely to continue while the medication is present. If the hair loss does not actually have anything to do with the medication and the timing is coincidental, anything is possible... including an improvement, worsening or continued same-rate shedding.

Hair loss from medications is complex. They have different mechanisms causing the loss and not just one. Some are true telogen effluviums, some are toxic responses and some are hormonal. Some are immune-based. Growth promoters like minoxidil and low level laser therapy are often considered for hair loss due to the true effluviums but is often ineffective or results suboptimal. If hair loss is due to hormone based mechanism, then anti-hormonal treatments may help. If immune-based, then immune modulators may help.

Blogs on Drug Induced Hair Loss

For further review see previous blogs

Drugs and Hair Loss: Is it common?

Drug Induced Hair Color Changes

Drug Induced Hair Loss: A Closer Look at Amphetamines

Hair Loss from Chemotherapeutic Drugs: Does it always grow back fully?

WHAT IS THE MOST EFFECTIVE TREATMENT OF ALOPECIA AREATA ?

What is the most effective treatment for a single patch of alopecia areata? 
 

This is a common question. Corticosteroid ("Steroid") injections remain one of the most consistently effective treatment for so called "patchy" alopecia areata. This involves use of tiny 30 gauge needles connected to a syringe to adminster liquid steroid medications into the skin so that the medication can bathe the hair follicles. Despite the worry and concern, steroid injections when used in low quantity are relatively safe and side effects are uncommon. A small dimple or identation in the scalp can sometimes occur but this is temporary. Thinning of the skin does not occur with a single injection. The most commonly used corticosteroid for injection is known as triamcinolone acetonide (Kenalog) although other steroids may be used too. 
This photo shows significant hair regrowth in a patch alopecia areata about 4 months after injection. 

Saw Palmetto: What are the side effects?

Saw Palmetto Side Effects

Saw palmetto (serenoa repens) is a natural herbal-based product commonly used for prostate problems in men and hair loss in men and women. 

A number of studies have suggested that saw palmetto can help hair loss. These studies are small and few in number. Nevertheless, countless numbers of patients turn to these natural products. Furthermore, because they are natural, most assume they are without side effects. The side effect profile of saw palmetto is not entirely clear. It is however known that saw palmetto affects hormones in the body, and risks of mood changes like depression and sexual dysfunction may be real (albeit low) risk.

A recent report provided additional evidence that this natural product might best be classified among chemicals and molecules that affect the hormone and endocrine system of the body (so called "endocrine disruptors"). A 2015 paper from Italy reported development of hot flashes in a 10-year-old girl using saw palmetto. When she stopped treatment, the hot flashes stopped. When she started back up again ("ie a rechallenge'), the hot flashes returned. However, 4 months after starting saw palmetto, the 10 year old got her first menstrual cycle. 

This report reminds us that use of saw palmetto requires counselling of at least the low possibility of side effects. I advise my own patients of the generally well tolerated nature of saw palmetto but remind them of possible risks of mood changes and even the rare possibilities of sexual side effects. More studies are needed to not only document the successes of saw palmetto in medicine but the incidence of side effects.
 

Reference

Morabito et al. Pharmacology 2015.
 

Things to Consider when Latisse won't work

When Latisse Won't Work

Latisse is an FDA approved and Health Canada approved treatment for improving eyelash length, thickness and darkness in patients with eyelash hypotrichosis (not enough eyelashes). Latisse contains the ingredient bimatoprost.

Clinical studies have shown that Latisse is very effective for many user. Many notice changes as early as 4 weeks and 50 % have changes by the second month.  By 16 weeks, 80 % will have an improvement.

Latisse Non-Responders: When Latisse just doesn't work

Latisse is effective for many individuals. However, about 1 out of every 5 users is not going to find that the medication worked all that well for them.  A large proportion of the patients I see in my office come to see me wanting to know why Latisse did not work as good as the advertising stated it should.  Let's review some of the reasons for poor results.

1. The patient is simply in the "20 % group."

Latisse does not help everyone. By 16 weeks, 80 % will be pleased with the money they spent. 20 % won't. I tell my patients that someone has to be in the "80 % group" and someone has to be in the "20 % group." Not everyone responds to Latisse.

2. The bottle does not contain bimatoprost and so it is not Latisse.

Latisse is available through physician's offices (and some drug stores), but there are many other ways of obtaining Latisse and products that claim to be Latisse. I encourage readers to simply enter phrases such as "buy Latisse online" in their Google search engine to see the array of possibilities. Most of these sites will ultimately lead to a box of Latisse (containing the true ingredient bimatoprost) showing up at the door.  But not all.  Patients need to keep in mind the possibility of counterfeit products. It's rare but most certainly does happen.

3. The method of application is wrong.

One needs to apply Latisse nightly to the lower eyelid margin of the upper eyelid with the brushes provided. I can't tell you how many variations of this simple sentence there actually are. Like any drug, it needs to be used according to instructions.

4. The individual has a medical condition of the hair follicle.

It comes as a surprise to many individuals that there are well over 100 reasons for eyelash loss. Not all lash loss is simply due to "aging" or a "tainted bottle of mascara" that was used in the past or improper use of a heated eyelash curler. These certainly can cause temporary or even permanent lash loss. Rather a variety of inflammatory and autoimmune conditions are associated with eyelash loss. 

Eyelash Loss: What else?
 

A careful review of one's story (called the medical history) and up close examination of the eyelashes is needed to determine the cause. One must also examine the eyebrow and scalp hair at the same time as there is no other way to confidently come to the diagnosis.

Causes of eyelash loss include

1. Inflammatory and Autoimmune Conditions. Inflammation of the hair follicle can cause it to fall out. Alopecia areata, frontal fibrosing alopecia, Scleroderma/ en coupe de sabre and lupus are all potential causes.  A variety of true dermatological conditions can also cause lash loss including various eczemas, seborrheic dermatitis and psoriasis. In such cases it is scratching and rubbing that often leads to lash loss.

2. Trichotillomania. 3-5 % of the world will purposefully pull out one or more of their hair follicles somewhere on the body during their lifetime. When repeated, the diagnosis of trichotillomania needs to be considered. Plucking of the lashes is quite common and may even be one sided. 

3. Endocrine disorders. Isolated eyelash loss is uncommon in patients presenting with endocrine disorders. However, one needs to consider thyroid, parathyroid and pituitary disorders.

4. Infections. Infections with fungus, bacteria, viruses all have the potential to cause lash loss. Isolated lash loss is uncommon but can be seen with conditions such as leprosy and syphilis. 

5. Drugs. There are many drugs now implicated in lash loss ranging from cancer drugs to antidepressants (escitalopram) to diabetes medications (sitagliptin and metformin) to methylphenidate. Other drugs include blood thinners, cholesterol meds, propranolol, valproic acid. Even cocaine vapour can cause lash loss.

6.  Infiltrative Conditions. Eyelashes can fall out when cells enter the hair loss that normally don't reside there. Lymphomas are a good example. Eyelash loss can also occur with a variety of local tumors including basal cell carcinoma, squamous cell carcinomas, sebaceous carcinomas and many others.

7.  Nutritional Issues. Poor diets and specific deficiencies can all cause lash loss. This ranges from severe illness with marasmus, to deficiencies of protein, zinc and iron.

8. Congenital and genetic conditions. Many many genetic syndromes are associated with less than normal eyelash density. Well over 50 conditions fall in this category from KID syndrome, Rothmund Thompson syndrome, Incontinentia Pigmenti, Keratosis follicularis spinulosa decalvans, Progeria, Bloom syndrome, Menke's syndrome, Monilethrix to Trichothiodystrophy. Many many others are on this list as well.

Conclusion

There are many causes of eyelash loss. Not every cause of eyelash loss responds to Latisse.

 

Can drugs cause or exacerbate seborrheic dermatitis?

Can drugs cause or exacerbate seborrheic dermatitis? 

Seborrheic dermatitis is red, scaly and sometimes itchy scalp and skin condition that closely resembles dandruff. The condition is extremely common and affects 5 % or more of the population.

There are a variety of well known factors that increase the risk of seborrheic dermatitis including depression, neurological conditions, alcoholism, stress, HIV/AIDS, organ transplantation and advanced age (over 60). 

Drugs are also potential causes of either worsening or inducing seborrheic dermatitis. The anti-cancer drugs are well known causes of seborrheic dermatitis like eruptions. Examples include dasatinib, gefitinib, sorafenib, sunitinib, vemurafenib, 5-FU, Erlotinib, cetuximab, IL-2, and interferon-α. I often advise a scalp biopsy in many of these cancer drug associated seborrheic dermatitis-like presentations as many are actually forms of scarring alopecia (ie EGFR inhibitors). 

Other drugs causing a seborrheic dermatitis-like eruption include griseofulvin, cimetidine, lithium, buspirone, haloperidol, lithium, methyldopa, gold, ethionamide, methoxsalen, methyldopa, phenothiazines, psoralens, stanozolol, and thiothixene.

Bimatoprost for Androgenetic Alopecia: An intensely researched area

Bimatoprost for Male Balding

Bimatoprost is a prostaglandin F2 alpha analogue that stimulates hair growth. Bimatoprost at 0.03 % is a well known eyelash growth stimulatory compound and marketed under the name Latisse. 

Bimatoprost has been studied for use in androgenetic alopecia. At low concentrations, it is not particularly effective. Allergan is currently studying higher concentrations (1 and 3%). Data released by Allergan and available to the public online suggest that these higher concentrations may be beneficial in treating hair loss. This is an exciting area to watch out for in the near future.

The graph shows how bimatoprost compares to minoxidil in these Allergan led studies. In their preliminary results, higher concentrations of bimatoprost was similarly or even slightly more effective that minoxidil (the gold standard FDA approved topical treatment for androgenetic alopecia).

Androgen Blockade For FPHL: Can I use more than I medication?

Androgen blockade has the potential to be help female pattern hair loss. Caution is needed with any hormone blocker due to significant harm that can come to a developing baby were a woman to become pregnant on any hormone blocker. For this reason they are frequently used with various strict contraceptive methods.

Hormone Blocking Medications for FPHL

Female Pattern Hair Loss (also called female androgenetic alopecia) affects 40 % of women by age 50. There are a variety of treatment options including minxodil, anti-androgens, laser and PRP. 

Anti-androgens can help some women with female pattern hair loss. A long list of anti-androgens exist including spironolactone, finasteride, cyproterone acetate, flutamide, dutasteride. The combination of anti-androgens can sometimes work even better than one alone provided the patient actually has a truly androgen responsive hair loss condition. Most men do. But not all women have a form of FPHL that is truly responsive to anti-androgens.

Anti-androgen Side Effects

The decision to use two or more anti-androgens must always be weighed against potential side effects. The combination of androgen blocking pills has the potential to be associated with side effects such as depression, worsening fatigue, breast tenderness, breast enlargement, weight gain, decreased libido.

Alopecia Areata and Oral Contraceptives: 50 Years of Wondering

Do birth control pills cause alopecia areata? Can they be used to treat alopecia areata?

Alopecia areata is an autoimmune conditions that is not uncommon in the population. In fact, about 1 in 50 women will develop alopecia areata and usually before 30.  Oral contractive use is also common in women 18-40 years of age with 15-18 % of women in this age group using birth control. Given these relatively high frequency of alopecia areata and birth control there will be individuals who will develop alopecia areata fairly close in time to the start of an oral contraceptive pill. The question then arises :

Did starting the birth control pill cause the alopecia areata?

 

50 years of wondering

The question as to whether or not oral contraceptives can trigger a patch of alopecia areata has been with us since oral contraceptives first came to market.  In fact, oral contraceptives were first FDA approved in 1960. Reports questioning whether a possible connection could exist between alopecia areata and oral contraceptives surfaced in 1965 with studies published in the British Medical Journal in an article "Alopecia areata and Oral Contraceptives".

No good evidence

For most people, there is no good evidence that alopecia areata is triggered by oral contraceptives. That does not rule out the possibility that there are a proportion of individuals who do have this as a trigger - but for the most part medical studies can't conclusively pinpoint a link. 

Oral contraceptive and Autoimmune diseases

A compressive review by Willams in 2017 examined whether there was any link between hormonal type contraceptives and any of the known autoimmune diseases. The article indicated that ere was in fact substantial evidence exists linking the use of combined oral contraceptives to an increase in multiple sclerosis, ulcerative colitis, Crohn's disease, Systemic Lupus Erythematosus, and interstitial cystitis.  Oral contraceptives were associated with a lower incidence of hyperthyroidism. Alopecia areata was not on this list.

Alopecia areata and estrogen

We do know that the inflammation that is seen in alopecia areata can be influenced in some manner by estrogen.  One study has suggested that alopecia areata can actually be treated with a combination of oral contraceptives (especially those containing norethindrone) and metformin. 

Reisz et al 2013

In 2013, Dr Colleen Reisz from Kansas City evaluated the benefits of one or a combination of birth control pills, metformin and vitamin D in treating alopecia areata. She noted in the background leading up to the study that women of reproductive age experience variation in hormones like estrogens during different phases of the menstrual cycle.  What is so relevant to this study – and alopecia areata in general is that these changes in hormone levels during the menstrual cycle are accompanied by changes in immune function.  Dr Reisz wished to better understand how medical interventions that reduce hormone production and lower aromatase behavior can help alopecia areata. The authors evaluated 14 patients with alopecia areata. 13 had recent hair loss within the past 1 year. About 50 % had moderate to severe hair loss at baseline.

The patients were then offered norethindrone containing oral contraceptive pills (1/20 or 1.5/30) or metformin (500-850mg/day) or both, along with vitamin D (1000-2000IU/day). There were four patients treated with metformin, 9 with metformin and birth control and one with birth control. Some patients (N=5) requested intralesional corticosteroids along with hormonal therapy

Seven of the 14 (50%) had complete regrowth of hair within 3 months of treatment. Another 4 patients regrew their hair fully but the time to reach that state of full regrowth was much longer (about 1 year or more). Of the four other patients, 2 continued to have hair loss, one converted from minor degrees of alopecia to complete hair loss in one week. One patient did not respond at all. 

 

Norethindrone containing oral contraceptives

The following oral contraceptives may contain norethindrone and ethinyl estradiol:  

Norethindrone & Ethinyl Estradiol Containing OCPs

 

CONCLUSION

It's clear that estrogen affect the immune system and at least for some immune based diseases (like multiple sclerosis, ulcerative colitis, Crohn's disease, Systemic Lupus Erythematosus, and interstitial cystitis) there is good evidence that oral contraceptive use increases the risk of developing these conditions. 

We don't have good evidence yet for alopecia areata and to date it would appear for the vast majority of patients there is no link. However, this does not exclude a small subset of individuals that in fact develop alopecia areata after starting a birth control pill. Detailed studies have not examined this and whether there are certain types of birth control pills that are protective against AA and some that are contributory.  The study by Reisz and colleagues discussed above would certainly cause us to give pause and consider that some oral contraceptives may actually be helpful.  For my patients who clearly feel that their OCP is a trigger, I may consider stopping if the alopecia areata is not responding to treatment as one might expect. If an oral contraceptive is restarted in the future, a different one might be considered with close monitoring of whether the OCP gives a flare of the alopecia areata.

REFERENCES

1) Williams WV.  Hormonal contraception and the development of autoimmunity: A review of the literature. Linacre Q. 2017.

2) Oral contraceptives and alopecia. 1968 Mar 9; 1(5592): 593. 

3) Oral contraceptives and alopecia areata. Br Med J. 1965 Oct 23; 2(5468): 1005. 

4) Wallace ML, et al. Estrogen and progesterone receptors in androgenic alopecia versus alopecia areata. Am J Dermatopathol. 1998.

5) Reisz, CM. “Reinstitution of Immune Privilege in Alopecia Areata: norethindrone and metformin” International Journal of Immunology 2013

 

 

Androgenetic Alopecia: Should I start two treatments at once?

 Androgenetic Alopecia: Should I start two treatments at once?

There are many treatments available for any particular hair loss condition. Let’s take androgenetic alopecia as an example. Individuals with androgenetic alopecia might consider topical minoxidil, oral hormone blocking medications, low level laser or even platelet rich plasma.  For some types of hair loss there may be an even greater array of choices.   

I’m often asked if patients should start more than one treatment at the same time. My personal view is not necessarily the right answer or the only view on the subject. However, my personal view is my view. My personal view is that whenever possible medications should not be started at the same times but rather staggered.  The intervals of staggering the treatments will depend on the specific situation and the urgency of treatment.

Example

Consider the 34 year old female patient with androgenetic alopecia who is considering topical minoxidil and oral spironolactone.  After a careful review of the patient’s medical history, blood tests, and examining the scalp, it is determined that both are good options for the patient.  I am faced with two options: Start both or start one at a time (stagger the treatments). Let’s look at the implications of both.

Treatment Option 1: Start Minoxidil and Spironolactone at the Same Time

Both Spironolactone and Minoxidil are recommended for the patient in this situation. What needs to be considered is that minoxidil has about a  30 % chance of helping the patient. It has a 70 % chance of not being all that helpful. Spironolactone has a 40 % chance of improving hair growth. If both are started at the same time and the patient experiences and improvement it will be difficult if not impossible to know which treatment was responsible for the improvement.

Was it the minoxidil?

Was it the spironolactone?

Was it both?

Treatment Option 2: Start Minoxidil First and Introduce Spironolactone in 6-9 months.

My personal preference in this situation was to start minoxidil first. After 6-9 months of treatment (once I determine if the minoxidil is working or not), I can make a decision to add spironolactone. In this case I can have a clear sense for the entire lifetime of the patient what helps and what does not.

Comment and Conclusions  

Treatments for some hair loss conditions (such as androgenetic alopecia) are life-long. A 33 year old woman who lives to 93 could potentially have 60 years of use of a given medication.   From a cost perspective alone, once can potentially save a patient $ 36,000 over their lifetime by confirming that a medication does not work and should be abandoned.

DPCP for alopecia areata: Why do we use acetone to make it up?

Dissolving DPCP in Acetone

Diphencyprone or "DPCP" is a chemical that causes allergic reactions. It is used as an off-label (non FDA approved) treatment for patients with alopecia areata whereby the DPCP is applied directly to the scalp and left on for 24-48 hours. After 48 hours the DPCP is washed off.

DPCP is not soluble in water so it is typically made up in acetone. Acetone is an organic solvent best known as the ingredient in nail polish remover. DPCP may also be soluble in other ingredients such as isopropanol.

What is often forgotten is that DPCP degrades in light and at room temperature. DPCP should be ideally stored at 4 degrees ceclius and protected from light. Usually DPCP is dispensed in brown light proof bottles but I recommend wrapping in aluminum foil to further protect from light.

Am I taking the right amount of hydroxychloroquine (Plaquenil)?

Hydroxychloroquine (Plaquenil): Am I taking too much?

Hydroxychloroquine is an oral medication used in a variety of autoimmune conditions. Side effects have been discussed previously but today we will focus on eye side effects. A number of side effects are possible ranging from vision changes to double vision to asymptomatic changes in various parts of the eye.

The Risk of Retinopathy with Hydroxychloroquine

"Retinopathy" is one of the more worrisome side effects of Hydroxychloroquine. At appropriate doses, studies show that the risk appears to be about 1 % of patients at 5 years of use and 2 % at 10 years. After 20 years, the risk may rise to 20 %. Once the retinal toxicity from hydroxychloroquine occurs, it is believed that the changes in the retina are permanent. Furthermore, the disease can even progress even if hydroxychloroquine is stopped.  

 

Risk Factor for Retinal Toxicity

Retinal damage can occur in anyone. However, the risk may be increased if the following risk factors are present

• Longer Duration of use (cumulative dose)
• Renal or hepatic functional impairment. Compromised kidney and/or liver function can lead to increased accumulation of hydroxychloroquine in the tissues.
• Age over 60 years.
• Preexisting retinal disease
• Concurrent tamoxifen therapy

What dose should I take?

It's clear that taking the appropriate dose reduces (but does not eliminate) the chance of side effects. The optimal dose is 6.5 mg for every kg of lean body weight (not simply what the patient weighs). "Lean body weight" is essentially the patients expected weight for their height and gender - it does not include the "extra" weight that some might carry. Instead of calculating lean body weight, some clinicians advocate simply using the patient's true body weight and multiplying by 5 (instead of 6.5).  In our clinic we typically dose hydroxychloroquine according to the following grid:

Hydroxychloroquine Dosing

Conclusion

The risk of eye related toxicity is low in the first 5-10 years of hydroxychloroquine use provided the dosing is respected. This study has had great importance as it has further helped to define risk and has encouraged changes in screening guidelines. These guidelines now include an initial examination but dedicated yearly screening to begin only after 5 years in otherwise healthy individuals deemed at low risk for eye problems.

Reference

(1) Melles & Marmor. The Risk of Toxic Retinopathy in Patients on Long-term Hydroxychloroquine Therapy. JAMA Ophthalmolol. 2014;132(12):1453–1460.

Can we predict if minoxidil will work or not?

Predicting the chance of benefit before starting

Minoxidil is the only topically approved agent that is approved but the FDA for treating androgenetic alopecia. The drug does not help everyone but does help 25-30 % of users. I've written in previous articles about the future of minoxidil pre-testing kits. It is well known that in order for minoxidil to have a chance to work, the body needs to convert the minoxidil to minoxidil sulphate. Some people have the enzyme (known as minoxidil sulphotransferase) to do this; other people simply do not. Those who lack the enzyme are more likely to be non-responders.

I was interested to read today in a press release that kits to test minoxidil sulphotransferase activity are moving forward in the FDA approval process.  The FDA journey can be lengthy, but the possibility exists that we might see these kits in the clinic in the near future. These will help physicians to predict if it's a good idea to prescribe minoxidil or not. 

Read the press release here: Press Release

Has my minoxidil stopped working?

Has my minoxidil stopped working?

Minoxidil is FDA approved for the treatment of male balding and female thinning. After using it for a period of time, some patients find that it no longer seems to be working the way that it once did. This leads many to ask :

"Has my minoxidil stopped working?"

The most likely explanation is that the minoxidil is, in fact, still working but the machinery that controls balding is working harder. It is likely that more and more genes are being expressed inside the scalp and hair follicles that are accelerating the balding process forward. 

Genetic hair loss has many genes

A recent study from the UK, however, has shown that male balding is far more complicated and many hundreds of genes contribute to balding in men. It identified 287 genetic regions linked to male pattern baldness. This large study examined data from over 52,000 men.

Consider the 30 year old male who started noticing balding at 21 and started minoxidil. At age 16 - 18 he might have had 4-6 genes expressed at the start of balding (before he even noticed) and 21 there may have been a dozen or so distinct genes pushing the balding process. At age 30, there could be dozens and dozens of genes expressed. For many users of Minoxidil, it is usually working the same - and while it was pretty good at stopping 4 genes, it can't fully hold back the genetic changes associated with 60 or 70 genes. These numbers are different for everyone - but it illustrates an important point. The scalp environment and hair follicle milieu changes drastically over time.

Reference

Hagenaars SP, Hill WD, Harris SE, Ritchie SJ, Davies G, Liewald DC, et al. (2017) Genetic prediction of male pattern baldness. PLoS Genet 13(2): e1006594

Doxycycline and Headaches: What everyone needs to know.

Doxycycline and Headaches: Caution Needed

Doxycycline is an oral antibiotic belonging to the so called "tetracycline" class of antibiotic medications. Other members of the family include tetracycline itself as well as minocycline and a few others. I frequently prescribe doxycycline on account of its "anti-inflammatory" effects. I may use doxycycline for treating lichen planopilaris, pseudopelade, frontal fibrosing alopecia, dissecting cellulitis and folliculitis decalvans.

Side effects of doxycycline

Doxycycline is fairly well tolerated but anyone prescribed this medication must understand how to use it as well as the more common side effects. I always counsel patients about nausea - and on account of this the medication should be taken with food. Unlike some of the other tetracycline members, absorption of doxycycline is not significantly worsened by food. I recommend taking doxycycline with a large glass of water and to remain upright for 1-2 hours afterwards. One shoukd never take doxycycline and go to bed (which some people often do in order to sleep through undesirable side effects. 

In some cases vomiting can occur. Other side effects include increasing sensitivity to the sun, weight gain, rash, yeast infections, diarrhea and headaches (see commentary on headaches below). For a more complete list please see our Doxycycline - Handout For Patients.

Headaches in Patients Using Doxycycline:  A closer look at benign intracranial hypertension

Headaches are not common in patients using doxycycline. However, any headache that lasts more than a day or two needs to be given serious attention in users of doxycycline. This is because of a phenomenon called "benign intracranial hypertension."

Benign Intracranial Hypertension

Tetracyclines can rarely cause a condition known as benign intracranial hypertension. Patients affected develop headaches, vision problems and double vision. This occurs from increased cerebrospinal fluid pressure. Despite the name, the condition is not truly "benign" as loss of vision is one serious consequence. Some refer to this condition as "pseduotumor cerebri."

It is not clear why doxycycline causes this phenomenon in some users. It can occur with tetracycline, minocycline and doxycycline. Most research has focused on minocycline.  Intracranial hypertension from doxycycline can occur at any age, males and females and regardless of whether a patient is thin or obese. Some have proposed that venous occlusion is responsible for the increased pressures in the brain. 

Urgent medical attention needed if headaches persist

Anyone with persistent headaches on doxycycline needs to consider immediately stopping and to see a physician for evaluation of benign intracranial hypertension.  Visual acuity needs to be tested urgently and the pupils need to be dilated by a physician to determine if there is "papilloedema" (a serious condition involving swelling of the optic nerve). This condition can even occur in users who have been on doxycycline more than 1 year so one must always be attuned to the importance of seeking medical attention if headaches persist. Treatment of benign intracranial hypertension due to doxycycline involves first and foremost stopping the drug. Medical therapy including acetazolamide, methazolamide or furosemide are often used to lower pressures. Other treatments may also be recommended by the ophthalmologist, neurologist or neurosurgeon.

Clobetasol for Hair Loss

Clobetasol for Hair Loss: What's that all about?

Clobetasol is the  name give to a potent topical corticosteroid. It is also known by its longer proper  name "clobetasol proprionate." Corticosteroids are medications which reduce inflammation. Clobetasol is available as a cream, ointment, lotion, foam and shampoo.

I often prescribe clobetasol for patients with hair loss conditions that are associated with inflammation. In fact, rarely does a day go by that I have not written a prescription for clobetasol. Alopecia areata, scarring alopecias, psoriasis, eczemas, dermatitis, all have the potential to benefit in some way with use of topical clobetasol. 

Clobetasol is never 'just because'

Clobetasol is not a good option for hair and scalp conditions that are not associated with inflammation. One should not use clobetasol "just because" and one should not use clobetasol or any topical steroid unless there is evidence of inflammation either clinically (the patient has symptoms) or histologically (the biopsy shows inflammation).  While the statement "my friend used clobetasol and it helped her- should I use it?" is understandable, it is simply not helpful when deciding if this medication is appropriate for a given person.

Clobetasol is a strong steroid

Clobetasol is among the most potent of topical steroids.  I can't emphasize enough the need to respect these medications. Despite what I hear everyday, these medications simply can't be dumped on the scalp and the scalp simply cannot be "soaked completely." That increases the chances of side effects. Unless you see a lot of patients with hair loss, it's challenging to appreciate the side effects that really can happen.

Long term side effects of potent topical steroids are well known but often ignored because side effects happen so infrequently. But potential side effects include: adrenal suppression, acne, hair loss, cataracts, bone loss, stretch marks, diabetes, persistent red scalp and "rebound" when trying to taper these medications.  I'll agree with anyone who says these are fairly uncommon. But I would challenge anyone who says they don't occur.

In modern medicine, we see side effects more commonly with oral steroids (like Prednisone and dexamethasone) followed by steroid injections (like triamcinone acetonide) followed by topical steroids. Even topical steroids have a range of safety with weak steroids like hydrocortisone being much safer overall than strong steroids like clobetasol.

Conclusion

Without clobetasol and similar potent topical steroids, I would not be able to fight inflammation the way I need to. These medications are extremely valuable. Nevertheless, these medications need to be respected.

Spironolactone Shortages in US and Canada: Update

Spironolactone Back Order Mainly Affects Canada

There is currently a shortage of spironolactone (Aldactone) in Canada. I have spoken with representatives from Pfizer Canada and USA this morning again and the following are updates.

1. Spironolactone in Canada (1 866 532 8608)

There is a shortage of both 25 mg and 100 mg supplies Canada due to a backorder. The pills are not being discontinued according to the company. These are currently being preferentially released to hospitals as the drugs are used at low doses in heart failure and other medical issues.

By the end of October 2017, the 25 mg pills should be available for shipment to pharmacies in Canada. By early November, the 100 mg pills should again be available as well. For now, it is somewhat hit and miss. Some pharmacies have abundant supplies and others have none. Trial and error can often lead one to find a pharmacy with supply. 

2. Spironolactone in the United States (1 800 438 1985)

According to Pfizer USA, the generic spironolactone is being discontinued but the trade name Aldactone pills are still being produced and are currently widely available. 

My team or I will update as any further updates become available. 

Atrophy in FFA: Is it from my topical steroids?

Atrophy in FFA is often from the disease itself 

A common concern from patients with FFA is that their steroids caused atrophy. By atrophy we mean thinning of the skin. Patients with atrophy have thin skin, visible veins. In FFA atrophy leads to blue veins becoming easy to see throughout the frontal scalp and especially at the temples. Patients want new options for treating the disease because they are worried about the atrophy.

FFA Causes Atrophy

There is one assumption that is often wrong here - and that is that steroids are the sole cause of atrophy in FFA. MOST of the time the steroids are not the main cause of the atrophy ! It is very important to keep in mind that the disease itself causes atrophy and visible veins. It is certainly very true that the steroids can cause atrophy too. But FFA itself is usually the leading cause of atrophy in patients with FFA. Many many patients with FFA who have never used steroids can have atrophy - some severe. In fact, severe atrophy is one of the so called poor prognosis signs in FFA. 

Treatment Considerations for Patients with Marked Atrophy

When patients show a considerable amount of atrophy, I usually try to limit this by using non steroids instead of steroid. Non steroids such as pimecrolimus (Elidel) and tacrolimus (Protopic) do not cause atrophy. They seem equivalent although no comparison studies have been done.  My previous research has also shown that finasteride and dutasteride may actually reverse atrophy in a proportion of patients.