Use of Isotretinoin for Facial papules in FFA

Facial papules in FFA

Facial papules occur in a subset of patients with frontal fibrosing alopecia. Its’ been difficult to ascertain what exactly these facial papules represent. Some of the difficulty comes from the limited number of biopsy specimens that have been obtained from such pappules. Some investigators have found small vellus hairs in the biopsies of facial papules, whereas others have only found hypertrophic sebaceous glands. 

Dr. Aline Donati and her colleagues were among the first to rigorously study facial papules in patients with FFA. She proposed that these papules contained vellus hairs and these vellus hairs showed typical LPP findings with perifollicular inflammation and fibrosis. 

In 2017, Pedrosa and colleagues from Portugal set out to further examine the features of these facial papules. The researchers showed that papules were present in 62 of 108 patients. 10 patients with facial papules underwent biopsy.  All 10 of these patients had similar histological findings, namely hypertrophic sebaceous glands but no evidence of a hair follicle in the biopsy and no evidence of lichenoid inflammation. Interestingly the skin was soft and thin which allowed for easy visualization of the sebaceous glands. 

Oral isotretinoin was reported helpful for these patients. The dose was 10 mg every other day and this was typically added to standard therapies that the patients was already on (such as anti-androgen therapies). Improvement was rapid – most patients saw changes with 2-4 months. 

Conclusion:

This study is interesting for two reasons.

1) It confirms that some biopsies for facial papules in patients with FFA will not contain hairs nor inflammation. Whether these sampled areas once contained hairs is unknown but presumably they did. The hypothesis then is that the vellus hairs were destroyed by the inflammation.

SEE: CURRENT HYPOTHESIS FOR FACIAL PAPULES IN FFA

2) The study is also interesting because it draws attention to the fact that low dose isotretinoin may in fact be helpful as a treatment for these facial papules.

 

Reference

Pedros et al. Yellow facial papules associated with frontal fibrosing alopecia: A distinct histologic pattern and response to isotretinoin. Journal of the American Academy of Dermatology 2017; 77:754-765

Donati et al. Facial papules in frontal fibrosing alopecia: evidence of vellus follicle involvement. Arch Dermatol 2011; 147: 424-1427.

Hydroxychloroquine: 10% stop from side effects

10% Stop from Side Effects

How often do patients stop hydroxychloroquine treatment because of side effects?

Hydroxychloroquine (also known by the name Plaquenil and generics) is an oral anti-inflammatory medication frequently used in the treatment of a variety of autoimmune diseases. For autoimmune hair loss, hydroxychloroquine is used in the treatment of lichen planopilaris, frontal fibrosing alopecia, discoid lupus, and pseudopelade of Brocq.

Side effects include irritation of the liver, pigment changes on the skin, reduced blood counts and retinopathy. The eye side effects are among the more worrisome side effects.

It’s helpful when prescribing a medication to have a sense of how common a side effect might be an how commonly a patient will discontinue a given medication.

Tetu and colleagues performed a retrospective study between January 2013 and June 2014 of patients receiving hydroxychloroquine for a variety of skin issues (not limited to hair). The study included 102 patients (93 of whom were women, with a median age of 44.5; range: 22-90 years). At least one adverse event was reported for 55 patients (ie 54%). 11 patients (10.75%) discontinued hydroxychloroquine due to a side effect that was thought to be directly attributable to the use of hydroxychloroquine.
 

Conclusion

It’s nice to have this kind of information when prescribing medications. Although the study did not solely focus on the use of hydroxychloroquine for hair loss, it’s reasonable that a similar proportion of hair loss patients would be expected to stop their hydroxychloroquine due to a side effect. Other oral options include doxycycline and tetracyclines, mycophenolate, cyclosporine, methotrexate and other anti-lymphocytic agents.
 

Reference

Tétu P, et al. Ann Dermatol Venereol. 2018.

Is topical clobetasol safe for the scalp?

On the Safety of Topical Clobetasol 

I've often asked if applying topical clobetsol steroid cream, lotion, foam or shampoo to the scalp is safe. Before we answer that, it's important to understand what clobetasol is and why it's used. 

Clobetasol is a class I steroid. Hydrocortisone is Class 7.

There are seven classes of steroid strengths. Class 1 steroids are the strongest and class 7 are the weakest. Clobetasol is a class 1 steroid and requires a prescription (in most countries). Hydrocortisone is a class 7 steroid that can often be bought 'over the counter' at the local drug store.  In simple terms, clobetasol is about 600 times stronger than hydrocortisone.  That does not simply equate to dangerous. It simply equates to stronger. A common steroid potency chart is found in the list below

TOPICAL STEROID POTENCY COMPARISON

Frequency, Duration, Amount

When someone tells me they are are using clobetasol, the first thing I want to know is how much are they using and how often are they using it? It comes as a surprise to some that how much steroid a patient is using is usually more important to me that the how often.  A patient who used clobetasol every day but it takes them 5 months to use up their bottle has a very different safety risk profile than someone who is using clobeetasol every day but goes through a bottle every two weeks.  Similarly, a patient who uses clobetsol twice per week could be using more than a patient using it everyday. The amount matters!

On the Fear of Topical steroids

There is quite a bit of inappropriate and misguided fear about topical steroids. I'm not saying topical steroids don't deserve respect, because they do. However, the fear that permeates society mainly comes form poor knowledge and also from the misuse of these products among the general population. Sadly, sometimes this misdirected fear comes from unethical practice and misguided motives. It's tough to change that but I can give at least 1000 examples from my own practice over the years of these situations:

A clinic wanting to sell product A for a child advising a parent "Oh you wouldn't want to put a steroid on your child would you?"

A clinic wanting to sell treatment B to there patient saying "Steroids are not safe. This treatment I am recommending is drug-free and natural."

A clinic wanting to establish 'trust' with a client and advises them "You need to stay away from that other clinic recommending you that steroid treatment. What was recommended is very unsafe. I can't believe they wanted to give you that. They should be reported."

It's difficult in the short term to change how hair medicine gets practiced throughout the world and it's difficult to regulate clinics and practitioners that prey on the vulnerability of their clients and patients. However, we can first and foremost recognize these patterns and spread accurate information as a starting point. I can assure you it's not always a popular view. Topical steroids can be quite safe when used appropriately.  Of course, they are unsafe when used inappropriately.

Logic, Practicality and other Forgotten Issues

When it comes to topical steroids, we need to be logical and practical.  Practical thinking does us good as humans, and we should not forget these principles:

A. It's safe to walk to your across the parking lot to your car on a blazing hot summer day, but it would not be appropriate to walk for hours across the entire city on the same hot day.

B. It's safe to add a bit of hot chili pepper to dish that one is preparing for dinner, but adding the entire chili pepper bottle would just not make sense.

C. It's safe to add a dab of toothpaste to one's toothbrush, but squeezing out the whole tube onto the brush would just be bizarre. 

D. It's generally safe to use a bit of topical steroid for short periods of time to calm down an inflammatory scalp disorder that is causing a patient extreme discomfort, itching and burning. 

E. It's generally safe to use a bit of topical steroid for short periods of time to reduce scalp inflammation that is preventing hair growth.

Safety Monitoring

Anyone using topical steroids needs to be monitored by an expert who knows how to use these prescriptions and what side effects they carry.  

First, patients using the steroid must understand how much to use and for how long. They should carefully record the amount of steroid they are using on a monthly basis and carefully record how long it takes them to go through their tube or bottle. 

Excessive use of topical steroids does lead to thinning of the skin, and even side effects from absorption into the body. These side effects are relatively uncommon with proper doses. 

Use of Topical Clobetasol in Hair Loss

In hair dermatology, we use topical steroids for many reasons. Topical clobetsol is commonly used to treat alopecia areata, and scarring alopecias such as lichen planopilaris (LPP). When used, these should be used for a short of time as needed and always under supervision. Frequent breaks from the steroid use ("steroid holidays")  are frequently helpful. For children with inflammatory scalp conditions that require topical steroids, we often prescribe topical steroids for 4-6 weeks straight and then give a 2-4 week steroid-free holiday period. This cycle is often repeated.

Summary 

Topical steroids can be both safe and effective when used appropriately. Of course, the don't help everyone and may not be enough of an immunosuppressive type treatment for certain kinds of hair loss. For example, some patients with alopecia areata and some patients with lichen planopilaris find that topical steroids help but not enough and hair loss still occurs despite using them.  In such as case the physician needs to decide whether to continue the topical steroid and add other immunosuppressive treatments or whether to stop the topical steroids altogether in place of the new immunosuppressive treatments. 

Stopping Birth Control: Will My Hair Come Back?

Will My Hair Come Back?

Stopping birth control can be associated with hair shedding. For many individuals the shedding occurs with 4-8 weeks after stopping birth control and eventually shedding returns to normal within 9-12 months and hair density returns to normal as well.

One of the most misunderstood topics when it comes to hair loss and birth control, is the array of considerations when hair density and shedding do not return to normal as one would anticipate. 
Situation “A” and “B” are common when birth control is stopped. In “A”, there is an initial shed followed by a cessation of shedding at month 7-10 and hair density returns to normal by month 12. In situation “B” there is no real perceived increased in shedding at all and the patient notices no real change in her hair at all. These situations typically occur in a patient with no underlying androgenetic alopecia and no strong predisposition to it as well.

Situation “C” and “D” are different. In situation “C” the patient starts out with good hair density but notices at 9-12 month later that her hair density has not returned and is a bit thinner. In situation “D” the patient notices the hair density is quite a bit thinner. In these two situations, the patient often has an underlying predisposition to androgenetic hair loss. In “C” there may have not been any degree of androgenetic hair loss to begin with but the shedding has accelerated the arrival of the patient’s genetic hair loss. In situation “D” there was some genetic hair loss to begin with but it was so mild it was unnoticed by the patient. The birth control pill in this situation was often helping as a treatment to stop the balding process even though the patient was not using it for this reason. By stopping the birth control pill, a helpful treatment actually gets stopped without the patient knowing and the patient’s hair loss is accelerated to a greater degree than in “C”

Patients and physicians should be aware of the array of different possibilities that exist when birth control is stopped.

Hair loss in Kidney Transplant Patients

Hair loss is among the top distressing symptoms

Nearly 30,000 kidney transplants are performed every year in North America. Patients receiving kidney transplants require lifelong immunosuppressive medications to help them avoid graft rejection and loss of the transplanted kidney.  The symptoms that patients experience after their transplant have the potential to affect quality of life. These include excess hair loss on the scalp, hair growth on the face (hirsutism), gingival hyperplasia, weight gain, cushingoid facies, hand tremors, and skin disorders. These are consistently among the most bothersome to patients and may have serious psychosocial implications.

Several studies have examined factors affecting quality of life in patients receiving kidney transplants. Hair loss In a recent study of 231 kidney transplant patients, high blood pressure, tiredness and hair loss were the three most distressing symptoms in both men and women. For women, hair loss was the most distressing symptoms.  A 2010 study in adolescents showed that hair loss was among the most distressing of the symptoms in adolescent kidney transplant patients.  

Conclusion

Hair loss can occur for a variety of reasons in patients with organ transplants. This study, as well as others, indicate that patients experiencing side effects are most likely to be non adherent to various aspects of their immunosuppressive treatment recommendations. This can result in more serious complications, such as acute rejection, graft loss, rehospitalization, and even mortality. Strategies for minimizing side effects of immunosuppressive therapy and improving medication adherence are key to the long-term management of kidney transplant recipients. It is important to properly diagnose and treat hair loss in organ transplant patients to limit the effects on quality of life. 

Reference

Teng S, et al. Symptom Experience Associated With Immunosuppressive Medications in Chinese Kidney Transplant Recipients.  J Nurs Scholarsh. 2015.

Dobbels F, et al. Health-related quality of life, treatment adherence, symptom experience and depression in adolescent renal transplant patients. Pediatr Transplant. 2010.

Methotrexate for Hair Loss:

A closer look at MTX for Autoimmune Hair Loss

Methotrexate (MTX) is an immunosuppressive medication that can both be used to treat some forms of hair loss as well as cause hair loss. Methotrexate is a medication the has been used for over 60 years. It was initially developed as a cancer treatment (and continues to be used in oncology) but is also used to treat a variety of autoimmune conditions including lupus, rheumatoid arthritis, psoriasis and vasculitis.

When treating hair loss, MTX has a role in treating both scarring and non scarring conditions. Evidence supports a role of weekly oral methotrexate in treatment of lichen planopilaris, frontal fibrosing alopecia, discoid lupus and alopecia areata. In the treatment of alopecia areata, methotrexate has been used in both children and adults, often in combination with systemic corticosteroids (like dexamethasone and prednisone).

Hair Loss as a side effect of MTX

In addition to its use in treating hair loss, methotrexate can sometimes also cause hair loss. About 5-10 % of users experience hair loss and the type of hair loss includes both increased hair breakage as well as increased shedding.  Hair color changes can also occur.

MTX side effects

Anyone considering MTX needs to speak to their physician about the risks and benefits. Side effects from methotrexate include reduced blood counts, liver damage, ulcers, cough, lung irritation (rarely fibrosis or scarring in the lung), nausea and abdominal pain, fatigue, kidney damage and memory problems. Methotrexate can not be used by women trying to become pregnant or who are pregnant. 

Because methotrexate interferes with how folic acid is metabolized, the drug needs to be taken with folic acid supplements. Generally methotrexate is given only one day per week and folic acid is given the other 6 days of the week (on the days methotrexate is not taken).

Download MTX Handout for Patients. 

Classic studies from the Past: A Look at the Early Dutasteride Studies

Dutasteride vs Finasteride: Suppression of DHT

In the world of hair loss, we often quote numbers and statistics. We frequently throw around information without a good idea of where that information actually came from. An important study is a 2004 study by Dr. Clark and colleagues. It is one of the the classic studies examining how DHT changes with use of finasteride and dutasateride. 

The researchers studied 399 men with prostate enlargement (BPH) and randomized them to once-daily dosing for dutasteride (0.01, 0.05, 0.5, 2.5, or 5.0 mg), or 5 mg finasteride, or placebo for a total of 24 weeks. The percent decrease in DHT was 98% with 5.0 mg dutasteride and 95% with 0.5 mg dutasteride. This was found to be significantly lower than the 71% suppression observed with 5 mg finasteride.  Moreover there was less variability in DHT changes with dutasteride than finasteride. 

Clark et al. Marked suppression of dihydrotestosterone in men with benign prostatic hyperplasia by dutasteride, a dual 5alpha-reductase inhibitor. J Clin Endocrinol Metab. 2004

The other important part of their studies was the increased in DHT that follows stopping the medication. The graph above shows that DHT levels rise much more slowly when dutasteride is stopped than when finasteride is stopped. This is on account of the long half life of dutasteride compared to finasteride (6 hours for finasteride and 4-5 weeks for dutasteride).

Reference

Clark RV, et al. Marked suppression of dihydrotestosterone in men with benign prostatic hyperplasia by dutasteride, a dual 5alpha-reductase inhibitor. Randomized controlled trial. J Clin Endocrinol Metab. 2004.

Topical JAK inhibitors for Hair Loss

The Future of JAKs

The janus kinase pathway is a signaling pathway inside cells and continues to be explored in terms of its relevancy to hair disorders. Accumulating research suggests that blockade of this pathway with so called JAK inhibitors can benefit a number of hair loss conditions including alopecia areata. Both topical and oral JAK inhibitor have shown promise.  JAK inhibition may also be relevant to the treatment of androgenetic alopecia.   Another trial is evaluating the effect of two concentrations of ATI-502 on the regrowth of hair in a randomized, double-blinded, parallel-group, vehicle-controlled trial in a larger study of AA.  

Aclaris is a company which has secured the rights to study and develop the use JAK inhibitors for the treatment of alopecia areata (AA) as well as androgenetic alopecia (AGA). They have a number of JAK inhibitors they are studying and several are currently in clinical trials. This includes ATI-502 and ATI-501. Press releases from the company indicate that a number of studies are underway. This includes a trial to evaluate the effect of ATI-502 on the regrowth of scalp and eyebrow alopecia areata.  In addition to AA, it is interesting to note that trials are underway to evaluate the effect of ATI-502 on the regrowth in androgenetic alopecia (AGA). 

Comment

It's an exciting time for many new potential treatments in hair loss. The JAK inhibitors have already shown benefit in AA and additional studies will determine whether these agents receive approval and ultimately come to market. 

Steroid Injections: Atrophy (dents, depressions, holes)

Atrophy (dents, depressions, holes)

Steroid injections are a relatively common treatment for many inflammatory and autoimmune scalp conditions. There is rarely a day in the office that I don’t perform steroid injections. These are very valuable treatments for many patients with alopecia areata, scarring alopecias and even some forms of traction alopecia.

One of the side effects of steroid injections is atrophy. Atrophy appears as an indentation in the skin at the site of injection. The patient may refer to it as a “dimple” or a “depression.” Others may call it a “dent” or even a “hole” The indentation can often be better felt than seen.

The chance of developing indentations (atrophy) depends on the concentration of steroid the doctor uses. Higher concentrations (10 mg/mL) give a greater risk of causing atrophy than lower concentrations (2.5 or 5 mg/mL). Some studies suggested that the risk may be as high as 3 in 10 patients when a dose of 10 mg/mL is used. 
The indentations occur because the steroid affects collagen and elastin underneath the skin. The steroids inhibit the growth of fibroblasts, which are the cells that collagen and elastin. Studies have shown there is less collagen made and it’s degraded more quickly. There is a reduction in diameter of collagen fibrils. The collagen bindles become atrophic snd separated. Similar to collagen, elastin fibers become thin and fragmented.

Atrophy typically is seen by 3 weeks if it’s going to occur. An important point to be made is that the atrophy is generally reversible provided more injections aren’t given to an area already showing atrophy. The skin usually returns to normal in 3-4 months. Steroid injections should not be readministered too soon to an area that has not “recovered” as further atrophy can occur - some of which can be very long lasting.

Treatment for steroid atrophy is mainly to wait for the body to start making more collagen and elastin again in a few months. If this does not happen, saline injections, dermal fillers and fat injections can be considered.

Treating alopecia areata: More than shots?

Options for treating alopecia areata

Alopecia areata is an autoimmune condition that affects nearly 2 % of the world's population. The condition is autoimmune in nature, which means that the patient's own immune system is attacking the hairs. Treatments that reduce inflammation can often be helpful - although spontaneous regrowth can occur in some patients even without treatment. 

 

Options for Treating AA:

Steroid injections, also known as "steroid shots" are  helpful treatment for many patients with several patches of alopecia. Steroid injections are less effective for wide spread alopecia areata - and other options need to be considered in these situation. Too often I hear patients say "Is there anything else besides shots?"

Beyond Shots

Steroid injections are extremely important for many patients and if done properly present a treatment option with reasonably good efficacy and quite good safety. I think alot of people are suprised when I say there are at least 25 different treatment options for alopecia areata other than 'shots.'  Here I've listed the treatment options for alopecia areata

Topical Treatments
Topical steroids
Topical bimatoprost
Essential oils
Anthralin
Squaric acid
Diphencyprone
Minoxidil
Topical tofacitinib
Topical ruxolitinib
Onion juice
Garlic gel

Topical retinoids

Topical capsaicin 

Topical liquid nitrogen

Injection Treatments
Steroid injections
Platelet rich plasma

Dupilumab (DUPIXENT)
 

Intramuscular Treatments
Intramuscular triamcinolone 

Oral Treatments
Prednisone
Dexamethasone
Antihistamines
Simvastatin & Ezitimibe
Methotrexate
Tofacitinib, Ruxolitinib, Baricitinib
Azathioprine
Cyclosporine
Sulfasalazine
Oral minoxidil

Zinc supplements

Light and Laser Treatments
Psoralen UVA (PUVA)
308 nm Excimer Lasers

Conclusion:

There are many treatments that can be considered for patients with alopecia areata.  Steroid injections are helpful for many patients and should never be discounted. But patients who find that steroid injections did not help have numerous other options available to discuss with their dermatologists.

Using Finasteride with Pre-existing Gynecomastia

Does finasteride make gynecomastia worse?

I'm often asked if finasteride could make gynecomastia worse if one has gynecomastia to begin with.  The short answer is that it could. There are a large number of  anecdotal reports of finasteride worsening pre-existing gynecomastia. The challenge in giving good hard facts to the question is that a good clinical trial has not been done in men who have gynecomastia and start finasteride. 

Most studies have looked at the risk of gynecomastia in men starting finasteride who don’t have gynecomastia to begin with. Most men with gynecomastia to begin with are excluded from these trials so we don’t have good data on how gynecomastia worsens in finasteride users. Finasteride raises estrogen levels and it would make sense from a mechanistic and pathophysiological point of view that that small increase in estrogen could trigger hyperplasia of breast tissue in susceptible men. I encourage all males with concerns about gynecomastia to discuss these issues with their physicians. Serial photography of breast tissue is essential although frequently not done.

Biologic Agents and LPP: What do they teach us?

Biologic Agents in Lymphocytic Scarring Alopecia

The field of dermatology has changed dramatically with the introduction of a variety of monoclonal antibodies, fusion proteins and growth factors to the list of treatment options. These agents are used to treat a wide range of disorders including psoriasis, hidradenitis suppurativa, atopic dermatitis, pyoderma gangrenosum, and various blistering diseases. This is by no means the full list.

The use of these agents in lymphocytic scarring alopecias like lichen planopilaris has been studied to a very limited degree. However their benefits are not entirely clear and many agents may actually worsen the disease. Here, we very briefly review some of the existing literature about the use of various biologic agents in treating LPP, including the monoclonal antibodies, fusion proteins and growth factors.

 

CATEGORY 1: Monoclonal Antibodies

Monoclonal antibodies are antibodies that target specific cell-surface receptors. These antibodies may be chimeric, humanized or human depending on how much murine and human proteins they contain. 

a) Anti-TNF Antibodies: Adalimumab, Infliximab, Certolizumab, Golimumab

TNF-α antagonists have been associated with paradoxical psoriasiform, lichenoid, eczematous, granulomatous, and acneiform eruptions.  Lichenoid reactions specifically are uncommon but are an emerging cutaneous adverse effect.   In 2010, Fernandez-Torres reported the development of lichen planopilaris in with infliximab treatment. The patient in the case was a 37-year-old man with recalcitrant plaque psoriasis who was being treated with infliximab at a dosage of 5 mg/kg every 8 weeks. However, 11 months into treatment he presented with follicular keratotic papulo-pustules, perifollicular erythema, and scaling, with progressive hair loss of the frontal and parietal regions of the scalp and eyebrows. In 2016, Jayasekera and colleagues reported the development of lichen planopilaris in a 12 year old girl treated with adalimumab for oliogarthritis. Her lesions cleared with discontinuation of the clobetasol.

b) Anti-CD20: Rituximab

Rituximab is a chimeric monoclonal antibody against the protein CD20, which is primarily found on the surface of immune system B cells. In 2011, Erras and colleagues published a report in the European Journal of Dermatology of a patient with juvenile arthritis treated with rituximab who experienced complete resolution of co-existening lichen planopilaris.

c) Anti-IL-12 and anti-IL-23 monoclonal antibody: Ustekinumab

In 2015, Weber published a report of a patient with LPP treated with ustekinumab over a 10 months period without evidence of any benefit 

d) Anti-LFA1: Efalizumab

To the best of my knowledge, there are no reports of lichen planopilaris with this group of agents no evidence of a treatment benefit with these agents. 

e) Anti-CD2 antibody: Siplizumab

To the best of my knowledge, there are no reports of lichen planopilaris with this group of agents no evidence of a treatment benefit with these agents. 

f) Anti-CD4 antibody: Orthoclone (OKTcdr4a)

To the best of my knowledge, there are no reports of lichen planopilaris with this group of agents no evidence of a treatment benefit with these agents. 

g) Anti-CD25 antibodies: Basiliximab, Daclizumab

To the best of my knowledge, there are no reports of lichen planopilaris with this group of agents no evidence of a treatment benefit with these agents. 

h) Anti-CD80r: Galiximab (IDEC 114)

To the best of my knowledge, there are no reports of lichen planopilaris with this group of agents no evidence of a treatment benefit with these agents. 

i) Anti-IgE: Omalizumab

To the best of my knowledge, there are no reports of lichen planopilaris with this group of agents no evidence of a treatment benefit with these agents. 

 

CATEGORY 2: Fusion Antibody Proteins

Fusion proteins, also known as 'chimeric proteins', are proteins which are created by the fusion of the receptor domain of a human protein with the constant region of human IgG. The resultant fusion protein then attaches (binds) specifically to a ligand or co-receptor. Recombinant fusion proteins have also been produced by combining human proteins with bacterial toxins. The fusion proteins most commonly used in dermatology are Etanercept, Alefacept, Abatacept, and Denileukin Diftitox. Of these four agents, only Etanercept has been studied in relationship to lichen planopilaris.

a) Etanercept

In 2009, Abbasi and colleagues reported the development of lichen planopilaris in a patient with psoriasis who was treated with etanercept.  Just the year before, Garovich reported a case of LPP with etanercept in the British Journal of Dermatology. 

b) Alefacept

To the best of my knowledge, there are no reports of lichen planopilaris with this group of agents no evidence of a treatment benefit with these agents. 

c) Abatacept

To the best of my knowledge, there are no reports of lichen planopilaris with this group of agents no evidence of a treatment benefit with these agents. 

d) Denileukin Diftitox

To the best of my knowledge, there are no reports of lichen planopilaris with this group of agents no evidence of a treatment benefit with these agents. 

 

CATEGORY 3: Recombinant human cytokines and growth factors

This category consists of water soluble non-immunoglobulin proteins and glycoproteins produced by a wide variety of cells. A variety of immune stimuli lead to their production and release.   Recombinant cytokines or cytokine antagonists are manufactured by recombinant DNA technology have been used as immunomodulators for malignant and inflammatory skin conditions.  The principal recombinant cytokines used in dermatology are interferon α (IFNα), Interferon γ (IFNγ), Interleukin 1 Receptor antagonist (IL1Ra), Interleukin 2 (IL-2), Interleukin 4 (rhIL-4), Interleukin 10 (rhIL-10), Interleukin 11 (rhIL-11), Granulocyte macrophage colony stimulating factor (GM-CSF), Platelet derived growth factor (PDGF). 

To the best of my knowledge, there are no reports of lichen planopilaris with this group of agents no evidence of a treatment benefit with these agents. 

REFERENCE

Abbasi NR, et al. Lichen planopilaris noted during etanercept therapy in a child with severe psoriasis. Pediatr Dermatol. 2009

Fernández-Torres R, et al. Infliximab-induced lichen planopilaris. Ann Pharmacother. 2010. 

Garcovich S, et al. Onset of lichen planopilaris during treatment with etanercept. Br J Dermatol. 2008

Jayasekera PS, et al. Case Report of Lichen Planopilaris Occurring in a Pediatric Patient Receiving a Tumor Necrosis Factor α Inhibitor and a Review of the Literature. Pediatr Dermatol. 2016 Mar-Apr.

McCarty M, et al. Lichenoid Reactions in Association with Tumor Necrosis Factor Alpha Inhibitors: A Review of the Literature and Addition of a Fourth Lichenoid Reaction. J Clin Aesthet Dermatol. 2015Erras S, et al. Rapid and complete resolution of lichen planopilaris in juvenile chronic arthritis treated with rituximab. Eur J Dermatol. 2011 Jan-Feb.

Webster G. Failure of lichen planopilaris to respond to ustekinumab.  Dermatol Online J. 2015.

What are the side effects of Low Dose Naltrexone (LDN)?

Low dose naltrexone: What side effects are possible?

Low dose naltrexone is increasingly studied in the field of hair loss, mainly in the areas of scarring alopecia and alopecia areata. To date, there remains only limited evidence that these drugs have a role. We continue to study them in our clinic. 

DOWNLOAD LDN HANDOUT

Side effects: What side effects are possible?

Dr. Donovan generally counsels patients about the top side effects including 

1. Difficultly sleeping.

This is usually just for the first week. If trouble sleeping go beyond this, one can reduce the dose to 3 mg or 1.5 mg

2. More vivid dreams.

This is seen in approximately 37 % of LDN users and can decrease over time.

3. Reduced need for thyroid medication.

Patients with autoimmune thyroid disease who take thyroid medications may want to start with a 1.5 mg dose and monitor their TSH every 2-4 weeks. This is to prevent a change from a hypothyroid/euthyroid state to a hyperthyroid state. Many patients with LDN require less thyroid supplementation while on LDN.

4.  Headaches.

Headaches have been noted to be increased compared to placebo. 

5. Anxiety (rare).

To date, there is not a consistent increase in headaches in the frequency of anxiety in LDN users compared to placebo.

6. Tachycardia (increased heart rate)

Although tachycardia is something we watch for, to date, there is not a consistent increase in headaches in the frequency of abnormal heart rhythms in LDN users compared to placebo in studies conducted to date.

7.   Rare - Fatigue, Loss of appetite, nausea, mood swings, mild disorientation

Side effects in the clinical studies

There are only a limited number of well conducted studies examining side effects of low dose naltrexone. By well conducted studies, one is specifically referring to studies that compared side effects of LDN to placebo. Here are some studies that guide our understanding of side effects of LDN

1.  Younger and colleagues, 2013. 

A study of 31 patients with fibromyalgia by Younger and colleagues showed that headaches and vivid dreams were by far the most important of the side effects of LDN compared to those using placebo.  Other side effects did not appear statistically different in LDN users vs placebo (at least based on the small numbers). 

SOURCE: Younger and colleagues. Arthritis Rheumatism 2013. 

 

2. Mischoulon et al, 2017

A randomized trial of 1 mg twice daily low dose naltrexone (LDN) was studied by Mischoulon and colleagues in 12 patients with depression. Their study was small but differences in side effects between the treatment (NTX) and placebo (PBO) groups were not appreciable. 

Mischoulon D, et al. J Affect Disord. 2017.

 

3. Laser Sharafaddinzadeh et al, 2010

In a randomized study study of 106 patients with multiple sclerosis, the main side effects were nausea, epigastric pain, mood alteration, mild irritability, headache, and joint pain.

4. Mohammad Ali Seifrabiei et al, 2008

A randomized study of low dose naltrexone in 89 hematologic patients showed that LDN was associated with better appetite, reduced nausea and vomiting compared to users of placebo. There were no differences in insomnia in this study. 

Mohammad Ali Seifrabiei et al. Am J Applied Sciences 2008

5. Smith et al, 2013

Small studies in children receiving low dose naltrexone for inflammation bowel disease (Crohn's disease) showed no differences in sleep, dreams, twitching, headaches, appetite, nausea, or double vision. 

References

Younger J, et al. Low-dose naltrexone for the treatment of fibromyalgia: findings of a small, randomized, double-blind, placebo-controlled, counterbalanced, crossover trial assessing daily pain levels. Randomized controlled trial. Arthritis Rheum. 2013.

Mischoulon D, et al. Randomized, proof-of-concept trial of low dose naltrexone for patients with breakthrough symptoms of major depressive disorder on antidepressants. Randomized controlled trial.  J Affect Disord. 2017.

Smith JP, et al. Safety and tolerability of low-dose naltrexone therapy in children with moderate to severe Crohn's disease: a pilot study. Randomized controlled trial.  J Clin Gastroenterol. 2013.

David Mischoulon et al. Randomized, proof-of-concept trial of low dose naltrexone for patients with breakthrough symptoms of major depressive disorder on antidepressants. Journal of Affective Disorders 2013. 

Laser Sharafaddinzadeh et al. The effect of low-dose naltrexone on quality of life of patients with multiple sclerosis: a randomized placebo-controlled trial. Multiple sclerosis 2010. 

Treatment of Androgenetic Alopecia During Pregnancy

Treating AGA in Pregnancy:

Most treatments for AGA are either not safe or not recommended during pregnancy. This includes minoxidil, anti androgens, various supplements, over the counter products and topical agents. The cardinal rule of treating any conditions during pregnancy or using any treatment during pregnancy is simple: ask a physician. 

Low Level Laser: Generally Safe for Most

 Low level laser treatments (LLLT) are the only safe treatments during pregnancy for women with AGA. This applies to most of the standard at home devices. Everything else needs stopping and some treatments need stopping well in advance. For some women, treatments during pregnancy are not necessary because it is possible due to hormonal surges during pregnancy stopping treatment may potentially not have a huge effect while pregnant and one can start many treatment again after giving birth. However, it should be noted that some women do experience hair loss during pregnancy as well.

WHICH HAIR LOSS MEDICATIONS ARE SAFE TO USE WHILE BREASTFEEDING?

Although I often ask my patients to discontinue most hair loss medications during pregnancy, the question frequently arises as to whether some medications can be restarted while moms are breastfeeding.  Breastfeeding has many benefits for babies.  For some drugs, the answer is yes. For others, the answer is no.

In 2001, the American Academy of Pediatrics published a helpful guide as to the safety of medications during breastfeeding. It's important to always check with your physician before starting any medication during breastfeeding. However, the following medications (used in hair loss) are felt to be safe for women who are breastfeeding.  For a full list of medications which are safe during breastfeeding, click here.

I generally do not recommend restarting treatments until month 1 after delivery if the baby is breastfed although many studies and reports show no harm in use if minoxidil and antiandrogens by women who are breastfeeding.

Does Finasteride Help All Causes of Hair Loss?

Finasteride: FDA approved for Male Balding

Finasteride is FDA approved for androgenetic alopecia in males but may also help hair loss from other conditions.

Finasteride for Male Balding

Finasteride was approved in 1997 for male balding at a dose of 1 mg. This approval came 5 years after finasteride was approved for treating prostate enlargement at a dose of 5 mg. Although generics are now available, the finasteride pills was initially marketed only as Propecia. For males with balding, it helps all areas that are thinning with the crown helped somewhat more than the front. Young males under 40 seems to get more benefit in the frontal areas of hair loss than men over 40.  Side effects of finasteride should always be reviewed before starting. 

Finasteride Side Effects - Donovan Hair Clinic

What conditions does finasteride help?

Finasteride is approve for male balding but may help several other conditions. These conditions include frontal fibrosing alopecia, some types of female patterned hair loss and very rare cases of lichen planopilaris including fibrosing alopecia in a pattern distribution (FAPD). Such uses are "off-label" and prescribed only in select cases.

What conditions does finasteride not help?

Finasteride does not help other types of hair loss. It does not appear to have benefit in alopecia areata, trichotillomania, telogen effluvium,  infectious causes of hair loss, and scarring alopecias such as folliculitis decalvans.  

Cortisone Injections - Only for Inflammatory Conditions

What are steroid injections used for? 

Cortisone injections are commonly used for many hair loss conditions but are not effective in all conditions. The most well known use of cortisone injections is for alopecia areata followed by scarring alopecias such as lichen planopilaris, frontal fibrosing alopecia, central centrifugal cicatricial alopecia amd even some cases of traction alopecia. Steroid injections are not helpful in androgenetic alopecia and most cases of telogen effluvium.

Are steroid injections safe?

Monthly steroid injections are generally fairly safe for a few months and this is commonly done for small patches of alopecia areata with very good effect. However one needs to sit down with a physician to review all potential side effects even with short term use. Our Handout on Steroid Injections in shown in the link below

Donovan Hair Clinic - STEROID INJECTIONS

Side effects with short term use include temporary indentations in the scalp, tenderness with the injections, rarely fatigue, mood changes. Some female patients will notice that they might even miss a period. Complications such as adrenal suppression, diabetes, blood pressure changes, are rare but need to be considered. With longer term use beyong 4-5 months one needs to consider all the short term changes mentioned above plus changes in bone density, mood changes, fatigue, stretch marks, diabetes, cholesterol issues, cataracts, high blood pressure and a few other issues as well.  Alot of the real magnitude of risk depends on the concentration of the steroid that is being injected and the actual volume. If concerned, please be sure to have a discussion with your physician. Steroid injections can be highly highly effective for many conditions but need to be respected.

Permanent Chemotherapy Induced Alopecia (PCIA)

A New type of Hair loss in Patients Undergoing Chemotherapy: PCIA

Every year about 650,000 patients undergo chemotherapy in the United States. Hair loss is a common side effect of chemotherapy and occurs in about 65 % of patients who receive chemotherapy. There are two main types of hair loss that can occur in patients undergoing chemotherapy. The first is hair loss that happens within weeks of starting the chemotherapy and then lasts several months before growing back.  This is known as temporary chemotherapy induced alopecia ("TCIA"). The second type is uncommon and occurs when patients fail to regroth their hair back to the level it was before undergoing chemotherapy. If hair has not grown back after chemotherapy by the 6 month after chemotherapy, we call this permanent chemotherapy induced alopecia (PCIA) and it is sometimes also called Chemotherapy Induced Permanent Alopecia (CIPAL).

Permanent Chemotherapy Induced Alopecia (PCIA) 

The failure of the hair to grow back fully 6 months post chemotherapy raises concerns about a phenomenon known as permanent chemotherapy induced alopecia (PCIA).     In recent years a number of studies have highlighted the possibility of PCIA in women with breast cancer treated with various chemotherapeutic agents, especially drugs known as taxanes. Docetaxel and paclitaxel are part of this group of drugs. The exact mechanisms are unclear although injury to the bulb as well as follicular stem cells are thought to be relevant. Adjuvant anti-estrogen hormonal therapy may be an important cofactor in many women with PCIA. A similar PCIA presentation has been reported in patients undergoing bone marrow transplantation. The scalp is predominantly affected in women with PCIA although a minority may have eyebrow, eyelash and body hair loss as well.

Different Clinical Presentations of PCIA

PCIA doesn't appear similar in all patients. In fact, three main types appear to exist including a diffuse type, a diffuse type with vertex accentuation (mimicking androgenetic alopecia) and a patchy type mimicking alopecia areata.   

Examination under the Microscope: Biopsies of PCIA

Histopathology of biopsy specimens shows a non-scarring alopecia with preservation of sebaceous glands, miniaturization, decreased anagen hairs, increased telogen hairs and end stage avascular fibrous tracts. There may be several histological presentations and the exact features remains to be defined although a high proportion show dysmorphic telogen germinal units. Some biopsies show peribulbar type inflammation.

How do we treat PCIA?

We don't really know yet how to best treat PCIA. The most common treatments described in the medical literature are oral and topical minoxidil. Both seem to provide benefit to at least a proportion of patients.  Other treatments are not known to provide benefit. 

Dr. Donovan's Articles for Further Reading

Preventing Hair Loss from Chemotherapy

Does hair always grow back after chemotherapy?

REFERENCES

Miteva M, Misciali C, Fanti PA et al. Permanent alopecia after systemic chemotherapy: a clinicopathological study of 10 cases. Am J Dermatopathol. 2011 Jun;33(4):345-50.  

Fonia A, Cota C, Setterfield JF et al. Permanent alopecia in patients with breast cancer after taxane chemotherapy and adjuvant hormonal therapy: Clinicopathologic findings in a cohort of 10 patients. J Am Acad Dermatol. 2017 May;76(5):948-957.

Rugo HS.  Real-world use of scalp cooling to reduce chemotherapy-related hair loss.  Clin Adv Hematol Oncol. 2017

 

DHT LEVELS AND FINASTERIDE

How do DHT levels change with one dose of finasteride?

Understanding how DHT levels change with finasteride is important in order to best counsel patients - especially those experiencing side effects. 

After taking 1 pills of finasteride, the drug itself is largely eliminated from the body in 1-2 days given that the half life of finasteride is about 4-6 hours (after five half lives a drug is significantly reduced in the body). However the same is not true of DHT levels. After a single dose of finasteride, DHT levels are reduced by 60 % (ie from 65 ng/dL to 25 ng/dL). However, the DHT levels don't rise back up quickly even though the drug is out of the body. Rather, DHT levels rise slowly increasingly just 15-20 % after the second day (ie from 25-30 ng/dL up to 30-35 ng/dL). Now back to the original question.

Of the two lines in the diagram, red or yellow, which best depicts how finasteride levels change with a single pill?

The answer is the yellow line! This concept is important since patients who are experiencing finasteride related side effects may still benefit from dosing every second or third day. It may not be quite as effective but as we can see from the graph, DHT levels are still being suppressed by this dosing schedule.
 

Reference

Vermeulen et al. Eur Urol 1991.

Challenging Cases of Hair Loss: Practical Tips When Nothing Seems to Help

What to do when a patient's hair loss refuses to improve? 

Every now and then there are some unusually challenging cases of hair loss that cause me to sit quietly at the end of the day and rethink the best means to treat me it. I'm talking about patients with alopecia unversalis who do not improve with any treatment, including the most potent of oral immunosuppressives. I'm talking about patients with scarring alopecia who continue to have symptoms and lose hair despite the most aggressive treatments. I'm talking about patients with early onset androgenetic alopecia who progress despite anti-androgens, minoxidil, laser and more. Is there anything we can do in these situations? Fortunately there usually is. Here are some practical tips.

Practical Tips

1. If the diagnosis is at all in question, a scalp biopsy should be done and possibly two. Blood tests should have been checked prior to the appointment but if not, basic screens are appropriate.

2. If a patient's diet is poor, one might look at ways to improve it. 

3. If stress and emotional issues are high, it might be worthwhile to address these. Stress is clearly relevant for some people.

4. Consideration needs to be given to whether a current treatment is actually causing the hair loss to worsen. Stopping treatment for a period may be useful in some situations.

5. A complete health check should be done by the patient's regular physician. Routine screening exams (mammograms, colonoscopies) should be up to date according to age appropriate screening.

6. One should always at least ask if patients are using their recommended treatment. Every now and then there are some incredible surprises.

7. If a different route of administration is possible this should be considered. Some oral drugs might be compounded topically. Some topicals may be available in oral form.
 

Conclusion

If a physician sees enough patients with hair loss, he or she will encounter cases of hair loss that don't seem to respond to anything. An organized approach in these situations is needed. Every so often some surprising improvements can finally occur!

Low dose Naltrexone: The Potential Uses are Many

LDN in Scalp Dermatology

Low dose naltrexone (LDN) is a relatively inexpensive medication that may have benefit in many aspects of dermatology including hair dermatology. I have prescribed it to patients with lichen planopilaris, alopecia areata and even the so called scalp dysesthesias (scalp pain syndromes). It is believed that our internal opioid and endorphins have an important effect on the immune system.

It is now understood that various immune system cells also have opioid receptors on their surface. It is the ability to block opioid receptors in the body between 2 am and 4 am that is proposed to give the beneficial effects. Blockade in this manner lead to changes in the immune system and increase in the body’s endorphin and encephalin levels. These are powerful modulators of the immune system.