Symmetry and Hair Loss: Which types of hair loss tend to be more symmetrical?

Symmetry and Hair Loss: Which patterns of hair loss are often symmetrical?

They say that nothing in nature is truly symmetrical. But clearly some objects come fairly close. We immediately recognize that there are some planes or axes of symmetry in this plant. In other words, you can draw several lines whereby the right side looks pretty similar to the left side.

Symmetry is something I pay attention to when it comes to hair loss. Many hair loss conditions have what is know as sagittal symmetry- meaning that if you draw a line directly up from the nose through the forehead and back to the back of the scalp you’d find that the hair loss affecting the right side is more or less a mirror image to the left side.

Several of the so called non scarring alopecias have some degree of “sagittal symmetry.” The right side typically looks like the left side. Androgenetic alopecia and telogen effluvium mostly have sagittal symmetry. I use the word “mostly” because even these conditions are not perfectly symmetrical. For example, some males notice one temple recedes faster on one side than the other side (often the right recedes faster than the left). The one non scarring condition that rarely shows sagittal symmetry (unless it is more advanced) is the autoimmune disease alopecia areata. In fact, what makes alopecia areata so unqiue is the random areas it affects the scalp. Symmetry is not usually a part of alopecia areata (except in forms like AA totalis, universalis, ophiasis, diffusa, etc). A circle of alopecia on the left is rarely even matched by a circle of alopecia on the right. Last week I saw a patient who came with a presumed diagnosis of alopecia areata. One sideburn was missing on the right and one side burn was missing on the left. The tip off here for me that something was wrong with the previous diagnosis was the alopecia areata is not usually so symmetrical. The correct diagnosis for this patient turned out to be frontal fibrosing alopecia.

Most scarring alopecias are not so symmetrical. Lichen planopilaris is less symmetrical than pseudopelade. Dissecting cellulitis tends to be less symmetrical than folliculitis decalvans. Frontal fibrosing alopecia often has some degree of sagittal symmetry but of course not perfectly.

The Outer and Inner Root Sheaths of the Hair Follicle

The ORS and IRS of the Hair Follicle

The hair follicle is surrounded by two main structures below the surface of the skin - the inner root sheath and the outer root sheath. The inner root sheath is quite thin and the outer root sheath is quite thick. These two sheaths wrap around the hair follicle like blankets. In the above photo of scalp hematoxylin and eosin stained histology, the IRS and ORS are shown. The hair shaft is often not seen on these standard slides as it gets washed away during processing in the lab. But right in the middle (of the hole in the middle) is normally where the hair shaft is found.

The inner root sheath (IRS) is actually not one structure but rather has several layers - a Henle layer, Huxley layer and cuticle layer. The IRS has several important roles including helping shape and mould the newly developing hair shaft and also helping with proper keratinization. The inner root sheath helps keep the hair fiber firmly glued into the scalp.

The outer root sheath (ORS) is continuous with the skin epidermal layer. The epidermal layer essentially dips down to join up with the ORS in the region where hair follicles come out of the skin. The ORS is thickest about 1/3 of the way to the bottom. This region of the ORS contains a further thickened region know as the “bulge.” The bulge region of the ORS contains the hair follicle “stem cells.” Stem cells are cells which have the potential to become other types of cells including cells of the IRS, ORS and matrix. In essence these stems of the bulge have the potential to forms new hairs.

Frontal Fibrosing Alopecia: A Closer Look at Pregnancy-related issues

Frontal Fibrosing Alopecia (FFA): What do we know so far about pregnancy and fertility-related issues?

FFA is a scarring alopecia which has both a a hormonal and immune basis. The suspected hormonal alterations have promoted evaluation of whether women with FFA have different pregnancy histories or differences in the age of menopause.

Buendia-Castano and colleagues conducted a case control study in 2018 to better assess the factors potentially associated with the development of FFA. The authors assessed responses to questions pertaining to many aspects of patient’s gynaecological history including pregnancy, breastfeeding, and menopausal status.

The authors found that there was no difference between the number of pregnancies, age at first pregnancy and length of time the mothers breastfed in women with FFA compared to women without FFA. It’s important to note that much of this information comes from interviewing women who developed FFA in their 50s - long after they had completed their families.

The main difference in this study however was that women with FFA experienced menopause appropriately two years earlier than women without FFA. Other studies, albeit not all, have suggested that FFA may be associated with early menopause and in some cases even premature menopause (menopause before age 40). The study by Buendia-Castano and colleagues did not find differences in the number of children women with FFA had, or rates of in vitro fertilization (IVF) or rates of fertility treatments compared to controls. This suggests that the genes or factors associated with FFA may not directly impact fertility - at least the genes that drive what I refer to as classical late onset FFA.

A key area for which knowledge is lacking is what are the clinical factors associated with FFA that develops before age 40 and whether fertility is in fact altered in this particular age group. I call this early onset FFA. Is fertility decreased in a woman who develops FFA at age 32 and plans to get pregnant in the future. We don’t really have enough data yet on the clinical features of FFA in women who develop FFA between 25-40.

Reference

Buendia- Castano et al. 2018.

5 things that happen when you shampoo too little or too much

Recent interview with Romper.com

I was recently interviewed by Katie Goldin from romper.com on several of my views on shampooing routines for the hair and scalp. Her article “5 things that happen when you wash your hair too little or too often” can be read by clicking on the photo

Stopping Hair Loss Medications in Pregnancy: Which ones do we need to stop?

Stopping Hair Loss Treatments During Pregnancy.

When I’m asked whether or not treatments for hair loss needs to be stopped during pregnancy, I generally respond with two questions: 1) What is the exact hair loss condition that the person has? and 2) what do we actually expect to happen to the hair and scalp during pregnancy.

Many hair loss related treatments can not be used during pregnancy.

For many hair issues, treatment is not recommended for women trying to conceive or during the pregnancy. The effect of the given treatment on the baby must always be given careful consideration. Some treatments have simply never been studied. Some have been studied and have been found to cause harm. Some appear to be safe.

For androgenetic alopecia, the hormonal changes that occur in pregnancy often help slow or stop hair loss. Many patients actually have an improvement in density. Most formal treatments for androgenetic alopecia can not be used with the exception of low level laser. Minoxidil, antiandrogens, PRP are all not an option.

For scarring alopecias, each patient situation is unique so there is no one guiding principle - with the exception of “less is better.” The occasional use of a mild topical steroid to control itching in patients with lichen planopilaris or other scarring alopecias may be possible and very helpful. For conditions like folliculitis decalvans, additional of a topical antibiotic like topical clindamycin may be helpful and I often prescribe in the second and third trimester. Oral immunosuppressive and immunomodulatory agents are not permitted. The rare exception is Hydroxychloroquine (Plaquenil) which is rarely used is serious and rapidly progressive scarring alopecias and those with systemic autoimmune diseases (lupus). Some studies have suggested an increase risk of fetal malformation in hydroxychloroquine users so the decision to use or not use this medication requires thorough discussion with the treating physician.

The use of doxycycline, methotrexate, mycophenolate are not permitted in pregnancy.

For treatment of seborrheic dermatitis, I often recommend a zinc pyrithione based shampoo or ciclopirox. I don’t advise use of ketoconazole.

There are few good options for treating alopecia areata in pregnancy. A low level laser can be considered but is often ineffective for alopecia areata. Repeated monthly steroid injections is not usually advised in pregnancy.

SEE ALSO

Article 1 - Hair Loss After Pregnancy

Article 2 - Treatment of AGA During Pregnancy

Article 3 - Hair Loss Drugs and Breastfeeding - Which are safe?

Challenges in diagnosing shampoo allergy.

Shampoos for Patients with Irritation and Allergy

 

Of the 10-30 ingredients that are present in modern shampoos, it's possible to be irritated or allergic to one of the components.  Diagnosing a true shampoo allergy is not easy as patients don't necessarily present to clinic with a red scalp immediately after using a shampoo and say that they have a shampoo allergy. Rather patients with sensitivities to an ingredient in shampoos may present with dermatitis of the eyelid, neck, ears, face, back and sometimes the scalp. 

Patients with shampoo allergy are frequently not convinced it's their shampoo that is causing problems. They may change their shampoo brand only to find that at the dermatitis does not clear. Their (incorrect) conclusion is therefore that it can't possibly be a shampoo problem. However, there are so many similar ingredients in shampoos that sometimes a switch form one shampoo to another doesn't actually remove the allergen!

There are several potential allergens in shampoos. Of 179 shampoos analyzed in a study by Zirwas and colleagues, 170 had fragrance, making it the most common allergy. CAPB was second palace allergen (53 %),  MCI/CI was third place (51. 4 %),   formaledye releasers were fourth (48 %) and propylene glycol was fifth (38 %).  Vitamin E and parabens are sixth and seventh. 

About 1-4 % of the population has fragrance allergies and the incidence of fragrance allergy is increasing.  Given the large proportion of shampoos that have fragrance it can be quite difficult to find a shampoo that does not have fragrance. 

Not everyone needs to change their shampoos. The vast majority of people do not have problems with common shampoos. However, if there is any suspicion that an ingredient in a shampoos might be irritating or causing allergy, a switch to an low irritant - low allergen shampoo might be considered. Consultation with a dermatologist who specializes in contact allergy would also be appropriate in many situations. 

Interested individuals may wish to review our website for our handouts on shampoos that don't contain fragrance and shampoos that are devoid of ingredients like CAPB, MCI/MI, formaldehyde releasers and propylene glycol.

On Seeing the Bigger Picture

The Bigger Picture Must Not be Forgotten When Diagnosing Hair Loss

Emily Carr was a Canadian artist and became well know for her landscape paintings - especially of trees and the forest. I like this quote of Emily Carr. It reminds us to always consider the meaning of the the “bigger picture.”

The use of techniques like trichoscopy have really changed how physicians practice hair loss medicine. Seeing the scalp up close increases accuracy to diagnose certains hair loss conditions. But we must always remember to step back and consider the “bigger picture.”

For example, although physicians come to learn that hair follicle “miniaturization” is a feature of androgenetic alopecia (male and female balding), the finding of a small number of miniaturized hairs on the scalp does not necessarily mean that much. The advice about seeing the “bigger picture” is useful for patients too. The occasional thin hair a patient sees in the brush should not necessarily cause alarm. At least not with taken the entire scalp density into context.

Emily Carr’s words are indeed wise .... “In the forest think of the forest, not this tree and that.”

The examples for the scalp could go on and on., The finding of one hair with so called “perifollicular scale” around the hair does not necessarily mean the diagnosis is the scarring alopecia lichen planopilaris if the surrounding areas of the scalp still look normal.   

Every day patients email us with concerns that they found a hair with this change or that change. One hair rarely matters - it’s the bigger picture of what is happening to many hairs that really makes the difference in the diagnosis.

And on we go. The finding of a single scar on the scalp does not necessarily mean scarring alopecia. A single twisted hair does not necessarily mean the “pili torti” of scarring alopecia. A single pustule does not mean much either.  

Just like a forested area may have tens of thousands of trees (or more) depending on whether one is referring to a local neighbourhood forest or the forests of the deep wilderness, the scalp itself has up to 100,000-120,000 hairs. If a patient is suspected to have hormonal issue or immune based issue or genetic issue as the cause of their hair loss but yet only seems to have changes affecting one or two hairs when the scalp is examined we need to at least consider the possibility that we’re not quite barking up the right tree (as the expression goes). Perhaps we don’t quite have the diagnosis. 

It’s certainly true that many hair diseases favour certain areas of the scalp and leave other areas unaffected. So, we might not expect all the hairs to be affected. In addition, every disease has to start somewhere so one could argue that at least one hair up there on the scalp needs to be the very first hair affected in any given disease. The reality is that even when we diagnose diseases in the very earliest of stages, we generally see many hairs affected - not just one

The area that genetic hair loss affects may contain 25,000-40,000 hairs. By the time we’re confidently able to diagnose genetic hair loss clinically some 10-20 % of hairs in a given area are showing “miniaturization.” In other words many thousands of hairs on the scalp show the key diagnostic features. The area that frontal fibrosing alopecia affects may contain 5000 - 10000 hairs. Certainly more than one hair is likely to be affected by the patient’s activated immune system. Similarly the immune system in patients with lichen planopilaris may be patrolling an area containing 30,000-70,000 hairs depending on the extent. A single finding in one hair follicle does not carry much significance. After all, why would the immune system target one hair and not disturb thousands (or tens of thousands) of others nearby?

While the tools we have in trichoscopy are wonderful and have changed how hair dermatology is practiced, we need to always consider the bigger picture. Emily Carr’s quote is a nice reminder that we need to step back and consider what is happening on a bigger scale to hundreds of hairs in an area - of better yet - to tens of thousands of hairs in the area.

The Telemedicine Consultation For Hair Loss: Is it Suitable for Everyone?

Doctor, Don’t You Need to See My Scalp?

A proportion of patients in my practice conduct their visit via telemedicine consultations. I’ve devoted this article to the telemedicine consultation - who are they for? who are they not for? what are the risks?. Telemedicine consultations go by many names, including video conferencing, remote consultations. Telemedicine consultations are defined as a type of consultation whereby the patient and the doctor are not in the same physical space.

Telemedicine consultations are not appropriate for everyone with hair loss. When it comes to telemedicine consultations, I divide discussions into two groups: (1) patients I’ve never met who ask me to help them via a telemedicine consultation and (2) patients who I’ve already seen in the office in the past who now require a telemedicine consultation as part of their follow up care.

The Basic Rules of Telemedicine Consultations

The basic rules of telemedicine consultations are pretty simple:

(1) Provided I have photos, blood tests and a very detailed questionnaire filled out, telemedicine consults are OCCASIONALLY a good idea for a patient I’ve never met before. (Some subtle diagnoses may be missed)

(2) Telemedicine consults are QUITE OFTEN a good idea for patient I’ve never met before if they have had a scalp biopsy in the recent past and send this to me along with photos, blood tests and a very detailed questionnaire. (It’s less likely that a subtle diagnosis will be missed).

(3) Telemedicine consults are VERY OFTEN a good idea for my existing patients provided there is no dramatic worsening of their disease or concerning signs (what I term red flags).

PART A. When is A Telemedicine Consultation Appropriate for the New Hair Loss Patient?

Most “first time” patients benefit from an up close examination in the office. In other words, most first time patients are encouraged to attend an in person visit rather than a telemedicine consultation if possible. This allows me to use trichoscopy (up close examination) and confirm the diagnosis with the greatest certainty. The only time a telemedicine consultation make a lot of sense for a brand new patient is when I’m pretty confident about the diagnosis after reviewing their photos, blood tests and health questionnaire information (pertaining to their hair loss). If after reviewing everything, my feeling is “this could only be diagnosis X” - then a telemedicine consultation is a very reasonable plan. That’s the basic principle that guides all telemedicine consultations.

PART B. A Helpful Algorithm for Deciding on the Appropriateness of a Telemedicine Consultation for a First Time (New) Patient

PART C. When is A Telemedicine Consultation Appropriate for the Existing Hair Loss Patient of the Practice?

Although telemedicine consultations might not be appropriate for every new patient who consults me about their hair loss, it should be noted that telemedicine consultations are often a very reasonable approach for many current, existing patient of the practice who I’ve had the opportunity to evaluate in person in past visits.

The mistake people make is assuming I need to see the scalp ‘up close’ in properly evaluating the scalp every time they have an appointment. That’s true for a first time visit. That’s sometimes true for follow up visits (ie second and third visits) but very often it’s not true for the follow up visit. What matters most in the follow up visit is determining if the hair density has improved or not - and this can be ascertained simply with photos that the patient takes at home. If the hair density has improved, seeing the scalp “up close” adds very little to how I make decisions for most people. In other words, if the patient’s hair is better, seeing the scalp up close is usually not going to change my mind about the bigger treatment plan.

Phrased another way, I might say that while there is no doubt about it that a person should ideally be seen in person for an initial appointment, that’s simply not the reality fo everyone for a follow up appointment. Some patients should be seen in person for a follow up but some patients do not need to be seen in person.

PART D. Deciding on Telemedicine for the Follow up (Existing) Patient.

Two things are important for deciding on the appropriateness of a follow up visit by telemedicine:

QUESTION 1: Is there more hair on the scalp, less hair or the same amount as the last visit ?

QUESTION 2: If the hair density is worse, and the patient has a non scarring alopecia, are there any “red flag signs” that warrant an up close scalp examination by trichoscopy?

PART E. A Helpful Algorithm for Deciding on the Appropriateness of a Telemedicine Consultation for a Follow up (Existing) Patient

PART F. The Most Important Questions to Ask at the Follow up Visit

There are many questions that need to be asked at the follow up visit. The answers to these questions help determine how the patient is responding to treatment and also help determine whether any diagnoses might have been missed in the past. The answers to these questions help guide decisions as to whether or not the patient should come for an up close examination.

PART G. The EIGHT “Red Flags” of the Follow up Consultation

There are several pieces of information that a patient might share during a follow up telemedicine consultation that make it important to consider seeing the patient in person rather than by telemedicine. I refer to these as the red flags. They generally apply to patients who have been diagnosed with non scarring alopecia at a previous visit (androgenetic alopecia, telogen effluvium). Patients who were diagnosed at a last visit with a non scarring hair loss condition but now present with worsening hair loss on the eyebrows or eyelashes or body hair should ideally be seen in person so trichoscopy can be done. The same is true for patients with non scarring alopecia who present with worsening of shedding or worsening of scalp symptoms. Furthermore, if the photos sent in by the patient suggest that a new diagnosis might be present or raise questions as to whether the original diagnosis is correct a telemedicine consultation might not be the best way of conducing the interview. Finally, if the patient was expected to have an improvement in a certain aspect of their symptoms (Like shedding or scalp symptoms) but failed to achieve this sort of improvement, a follow up should be considered in person so that trichsocopy may be performed.

PART H. The Follow up Visit

In my practice, I use a standard follow up template for every telemedicine consultation I conduct. It allows me to ensure that I have properly reviewed all the key things that I need to review with the patent. It also helps me determine if there are any red flags - and not miss any. For any patient with non scarring alopecia who answers yes to any of the red flags, consideration should be given to possibly having an in person examination so that the scalp may be examined.

The FOLLOW Up Visit Intake Sheet

SUMMARY

Telemedicine consultations can be a wonderful means of assisting patients with concerns about hair loss. The telemedicine consultation is often appropriate for the existing patient in the practice whose scalp has been properly examined in the past. In many cases, I do not require the patient to have an up close (trichoscopy) examination because that is not how treatment decisions are going to be made. This type of consultation is also frequently appropriate for new patients who have already had a scalp biopsy. Telemedicine consultations may be appropriate for a new patient even if they have never had a biopsy but one must exercise a good deal of caution. Not every new patient can be properly evaluated via telemedicine. Subtle diagnoses may be missed in some cases. One must carefully review photos, blood tests and patient historical details (questionnaires or a carefully obtained history). If there remains a reasonable possibility that a subtle diagnosis might be missed an in person visit should be encouraged. Hair specialists who are new to the practice of hair loss medicine should be extremely cautious with offering consultations for new patients via telemedicine - as these are the most challenging of the telemedicine consultation scenarios discussed. A newer hair specialist may not appreciate what they are missing and may not be able to determined the chances or likelihood that they might be missing a diagnosis.



Why treat scarring alopecia if it can't regrow hair?

Treating Scarring Alopecia: What’ s the point?

The scarring alopecias are a group of hair loss conditions whereby patient’s lose hair in a manner that has the potential to be permanent. The reason the hair loss may be permanent is that these conditions are associated with the depositing of tiny bits of scar tissue beneath the scalp that make it difficult for hair to regrow. Treatments are often used to help stop the process, although sometimes regrowth is possible. Regrowth is more of an option when treatments are used in the earliest stages of the disease. In more advanced stages, regrowth generally does not occur.

Why treat if I’m not going to regrow anything back?

Patients often ask me why they should bother treating if they can’t grow back any hair. Sometimes this is said in frustration but other times after much thought about the whole process. Here are some important considerations as to why some patients decide to try to treat their scarring alopecia despite the fact that that hair is not going to come back for many people:

1. I want to save whatever hair I have now. Some patients choose to begin treatment to save the hair that they have. They understand that getting more hair back is not likely to occur but want to hold on to whatever they have. They want to have the ability to style the hair they have now and use the existing hair to camouflage thinning areas.

2. I want to stop my symptoms of itching and burning. Scarring alopecias can be associated iwth troublesome scalp symptoms like itching, burning and tenderness. Some patients choose to begin treatment to stop their symptoms regardless of what effect it will have on hair growth or loss. Not all patients with scarring alopecia have symptoms but for some patients the intensity of symptoms can be quite high. it’s not uncommon for itching, burning for some patients to reach levels of 6-10 out of 10 (with 10 being maximal itching and burning that one can imagine).

3. I would like to keep the hair they have now so my hairpeice, wig or system fits better on the scalp. Some patients want to hold on to their hair so that their current wig or hairpeice has something to attach to or so that it blends in better with their existing hair. Consider the middle age male with lichen planopilaris that I saw last week. He is wearing a hair system and it looks terrific. The top of the scalp is shaved and the system is attached to the top of the scalp with use of adhesive. It blends in quite unnoticeable with this hair around the sides and the back. The main issue for him is that he also has lichen planopilaris (scarring alopecia) affecting the sides and the back and this area is at great risk for being lost too. If this area were lost the current system might not camouflage as effectively. We are doing everything we can to save the hairs around the sides and back. Regrowth of hair is not a point of discussion here.

Summary and conclusion

The early and aggressive treatment of scarring alopecia can sometimes lead to a bit of improvement in hair density - but not always. Many patients with scarring alopecia chose to begin treatment even though getting back hair is not one of the goals. For some the decision to start treatment centers around the hope to hold on to whatever they have. For others, it’s centered around setting or stopping troublesome scalp symptoms like itching or burning.

Risk of Alopecia areata and Lichen planopilaris increased in Patients with Hidradenitis Suppurativa

New study Identifies Increased Risk of Autoimmune Hair Loss in Hidradenitis Suppurativa

Hidradenitis suppurativa (HS) is a dermatological condition that is associated with painful draining lumps in the underarm area (axillae), groin area and buttocks and under the breast. The lay public often refers to such lumps as boils - and patients affected by hidradenitis often describe their disease as one of multiple draining boils in the armpits, groin and buttocks regions. The condition can be emotionally and physically disabling.

Association of HS with Several Hair Loss Conditions

For years, it has been appreciated that there is a close relationship between HS and the scarring alopecia dissecting cellulitis. A new study points out that patients with HS are also at risk to develop alopecia areata and lichen planopilaris.

Researchers at Penn Sate Milton S Hershey Medical Center in Hershey, Pennsylvania studied 3645 patients with HS and compared the findings to 36, 450 matched controls. The researchers showed that patients with HS were at increased risk (relative risk 2.22) to develop alopecia areata (including totalis and universalis) compared to the control group. Interestingly, there was also an increased risk of lichen planopilaris (relative risk 1.54).

Comment

This was an interesting study and helps us to understand that alopecia, LPP dissecting cellulitis and hidradenitis share more in common than perhaps we once realized. This data would suggest that these diseases all share in common a central role of the hair follicle as an target of the initial inciting event. These disease probably have some common inflammatory pathways shared.

This data is an important as research in hidradenitis is at an all time high and the condition is being studied and discussed by dermatologists at a rate never seen before. Advances in treatments for HS may provide some help to how we go about treating alopecia areata and lichen planopilaris. Confirmation of this awaits further studies.

Reference

Horissian M et al. Increased risk of alopecia areata for people with hidradenitis suppurativa in a cross-sectional study. J Am Acad Dermatol 2019

Topical Treatments are Safer - but Humans Generally Dislike them

Topical Treatments: Unless the Treatment is Amazing People Generally Dislike Topical Treatments

There is a major push to develop better and better and safer and safer treatments for hair loss. There is a move from using oral treatments (ie oral finasteride) to using topical ones (ie topical finasteride). At the same time, there is ongoing recognition that many patients don’t like topical treatments. Critics can relax - of course some people don’t mind topical treatments. Yes, there are countless patients the apply topical treatments every day. Yes, not a day goes by that a patient doesn’t say to me how they are using their topical product “religiously.” But most people don’t like them. The strategists and big thinkers of the hair world understand this. Most don’t.

Men, Minoxidil and the Mapar Study: Do most men use minoxidil as they should?

I’d like to introduce you to a study that is often forgotten. I think it’s as much a study of behavioural psychology as it is a study of hair loss treatment.

A 2007 study by Mapar examined the proportion of men that stopped using minoxidil. As we go about reviewing this study it’s important to keep in mind that minoxidil doesn’t do all that much for about 75 % of men. It helps 25 % to various degrees and the rest aren’t helped all that much. So, in any study looking at use and disuse of minoxidil, we expect a good amount to eventually stop using - but we also expect a good proportion to carry on!

Mapar studied 1495 men aged 20-40 years who started treatment with 5% topical minoxidil solution. Remarkably, almost all the patients gradually avoided continuing the treatment. Only in a few patients was the cessation of medication due to adverse effects. The causes of discontinuation in the majority of patients were the low effect of medication and an aversion to this topical treatment method.

Conclusion

There are flaws to any study and granted this one has them too. But this study has important lessons. Humans are more likely to apply topical treatments if the treatment works fast and has good effect. We’re less likely to commit to a topical plan if outcomes are slow and mediocre.

It would be a mistake to conclude from this study that minoxidil has no role in male balding. Not at all. The take home message form this study is that most men left to their own will - are going to stop using. It’s the role of the specialist to help manage expectations and to encourage use for the appropriate amount of time to determine if it’s working or not.

Reference

Mapar et al. Is topical minoxidil solution effective on androgenetic alopecia in routine daily practice?J Dermatolog Treat. 2007;18(5):268-70.

Lichen planopilaris: An Inflammatory Disease

Lichen planopilaris is associated with Inflammation Around Hairs

Lichen planopilaris (LPP) is a type of scarring hair loss that gives permanent hair loss. Scalp biopsies are performed if the diagnosis is still not clear after the physician has examined the scalp.

This photo shows a scalp biopsy from a patient with lichen planopilaris. The skin surface is shown at the top of the picture. Four hair follicles can be seen below that. Inflammation is seen surrounding these hairs. This inflammation promotes the progressive destruction of hair follicles.

Histopathology of lichen planopilaris: Inflammation is seen around the hairs

Treatments for LPP

Treatments for LPP are reviewed in other articles. Treatments that stop inflammation are often helpful in LPP including topical steroids, steroid injections, topical calcineurin inhibitors, oral doxycycline, oral hydroxychloroquine (Plaquneil), methotrexate, cyclosporine, isotretinoin, mycophenolate ... and others. The goal of treatment is typically to help stop the disease rather than prompt regrowth. That said, the aggressive treatment of LPP in the early stages may help with some amount of regrowth.

Acne necrotica of the scalp: What is it?

Acne necrotica varioliformis and acne necrotica miliaris

Acne necrotica varioliformis (ANV) - DEEP SCARRING FORM

Acne necrotica varioliformis is thought to be rare but it’s probably way more common than we realize. We just don’t speak of this entity much anymore. Patients with acne necrotic varioliformis develop crops of 1-2 mm papules (bumps) or pustules (“pimples” - except they don’t have pus) that end of healing over with formation of a pitted scar. (varioloform means resembling chicken pox or variola).

When the lesions on ANM first start they look like a red bump but soon form an umbilicated lesions that then goes on to form a pustules and then a crust and then scar. Patients affected by ANV are typically middle aged women (although men can be affected as well) and develop these lesions most often on the face (frontal hairline), scalp, nape but also can develop them on the chest and nose, eyebrows (interestingly in a seborrheic distribution). They can however be more widespead in the scalp, face and trunk. The condition can come and go for years (i.e. a recurrent process) with outbreaks of just a few such bumps or several hundreds. Some of the literature (mainly a 1988 article by Dr David Fisher) cites that affected patients are more likely to be anxious, or under great pressure - but this has not be firmly established. 

The diagnosis of ANV is usually made clinically - meaning that an experienced physician can make this diagnosis by looking carefully at the frontal hairline, scalp, forehead/face and nose and chest and eyebrows.   Pitted scars is the key finding that I look for. This an often be found on the back of the scalp but really anywhere where the disease has affected including the lateral eyebrow. A biopsy can be helpful if there is uncertainty. Biopsy of an umbilicated papule typically shows a lymphocytic infiltrate around the hair follicle and this results in massive death (necrosis) of the keratinocytes in the follicular sheath. Rather than the focal inflammation in the outer portion of the follicle in lichen planopilaris, the inflammation in ANV is widespread throughout the keratinocytes in the sheath. The inflammation may spread into the epidermis with so called lymphocytic exocytosis and there may be necrosis of the epidermis too. In addition to what is happening in the follicle itself, there is also surrounding fluid accumulation (subepidermal edema) and lymphocytic inflammation as well. 

In recent years, there has been a trend to call the condition lymphocytic necrotizing folliculitis. Terms such as acne frontalis are still used. 

Treatment of Acne Necrotica Varioliformis

The treatment of ANV generally begins once the lesions have been cultured. I generally recommend starting with cultures before any type of antibiotic is given. If the culture comes back with an organisms, one can determine the appropriate antibiotic as this information is typically provided by the microbiology lab. If the cultures come back negative, one can begin empirical therapy with topical options like topical clindamycin lotion, topical erythromycin gel and possibly a steroid as well. If ineffective, the dermatologist will generally prescribe an oral agent such as doxycycline (50-100 mg twice daily) or isotretinoin (at a dose of 0.5 mg per kg). Options such as cephalexin or trimethoprim-sulfamethoxasole can be considered as well. I do believe, as do others, that it is imperative to stop the itch scratch itch cycle in this condition. Antihistamines can be considered as can low dose SSRI or SNRI antidepressants. If these antidepressants do not help, doxepin or tricylic antidepressants (amitriptyline 10-25 mg at night can be considered). 

In order to reduce the bacterial load on the body and scalp, topical antibiotics (mupirocin) can be applied to the nares, axillae, and groin. The nails should be trimmed very short. The use of an antibacterial wash can also be considered in resistant cases. 

Acne necrotica miliaris (ANM) - SUPERFICIAL FORM

The diagnosis of acne necrotica “miliaris” must also be considered in all patients with acne necrotica “varioliformis”. However, patients with ANM usually ONLY have a few lesions on the scalp at any one time -although frontal hairline, face and chest can be affected in some patients). By ‘few’ I mean 8-10. The back of the scalp can particularly be affected. The scalp is the main site compared to ANV where the chest and face, eyebrows are also affected. The lesions appear as superficial exocoriated crusts and papules that are extremely itchy. They can resemble pimples although it’s difficult to actually squeeze anything out of them. In fact, it’s usually difficult to find the actual pimple lesions because they have crusted over. The lesions in ANM do NOT heal with scars - and that’s the key differentiating factor from ANV. A link between bacteria such as Propionibacterium acnes or Staphylococcus aureus and ANM has been proposed. Many researchers feel that ANM is simply a form of P acnes folliculitis of the scalp

Treatment of Acne necrotica miliaris (ANM)

Treatment of ANM is similar to ANV with topical steroids, topical antibiotics, and oral tetracyclines being helpful.

FINAL COMMENTS

ANV is more common than we all realize. We just don’t talk about this condition anymore. The dermatologists Plewig and Kligman summarized it best in their 1993 textbook when the stated "Awareness of this bizarre disease is a prerequisite for an accurate diagnosis."

Reference

Fisher DA. Acne necroticans (varioliformis) and Staphylococcus aureus. J Am Acad Dermatol. 1988;18:1136-1138.

Kossard S, Collins A, McCrossin I (1987) Necrotizing lymphocytic folliculitis: the early lesion of acne necrotica (varioliformis). J Am Acad Dermatol 16:1007–1014.

Pitney et al. Acne necrotica (necrotizing lymphocytic folliculitis): An enigmatic and under-recognised dermatosis. Australas J Dermatol. 2018 Feb;59(1):e53-e58.

Plewig G and Kligman AM, eds. Acne and Rosacea. 2nd ed. New York,NY: Springer Verlag NY Inc; 1993:500-505.

Aclaris Shares Some New Research Data on ATI-502 in Androgenetic Alopecia

Small Study of ATI-502 Shows Three Times the Benefits in Women than Men

Aclaris is a US pharmaceutical company that has an interest in determining if their JAK inhibitor technologies can help grow hair in various types of hair loss conditions. They have been studying the use of their JAK inhibitors in various hair loss conditions such as alopecia areata and andrognetic alopecia. Recent studies of the Aclaris topical JAK inhibitor was disappointing for those with alopecia areata. Interestingy, the companies 6 month data with the same drug for treating androgenetic alopecia has shown some positive results. Equally surprising as well was the finding that women seem to have repsonded to the treatment much better than men.

This data comes from a press release that the company has shared on their website.

Small Study of AT-502 Indicates Potential Benfits for Women’s Hair Loss

The Aclaris company is just getting going with its look at the use of JAK inhibitors in androgenetic alopecia. The interest in using the JAK inhibitors to treat androgenetic alopecia dates back to findings by Columbia University researcher Dr. Angela Christiano.

Although Dr. Christiano’s hypothesis has been that inhibiting JAK pathways could help the balding process by blocking inflammation that otherwise keeps hairs dormant, this has not always seemed to be the case so far. Patients with alopecia areata and androgenetic aloepcia who are treated with JAK inhibitors often grow back their hair from the alopecia areata component but don’t really grow back the androgenetic alopecia component. In other words, much of the information we have to date would seem to suggest that JAK inhibitors like tofacitinib and ruxolitinib don’t help the balding process. So, to consider treating androgenetic alopecia with a JAK inhibitor might seem like a bit of a stretch.

The Aclaris study shared in this press release was a very small study of AT 502 in about 23 participants. The study subjects applied the topical JAK inhibitor twice daily for 26 weeks. 14 men and 6 women with androgenetic aloepcia were able to complete the study in a manner that allowed hairs to be counted “before and after”. 22 participants were able to give their opinions on the treatment and also have have their study doctors evaluate the benefits.

What came out as interesting to me in this preliminary study was just how much better the topical drug was in helping women with androgenetic alopecia than men. In fact, it appears the topical JAK had three times the growth promoting benefits in women than men. It is important to keep in mind that the study is small and further evaluation will be needed. Nevertheless, in women using the AT 502 there was an increase in the number of thick hairs (so called non vellus target hairs) by 15.3 hairs per square cm in women and 5.6 hairs per sq cm in men. 82 % of study subjects felt that they actually had some kind of improvement with the drug. According to the study doctors, about 73 % of patients in the study improved with AT 502.

Comment

This is interesting preliminary data. It’s pretty clear now that inflammation has a role in androgenetic alopecia, ‘Microinflammation’ is now the buzz word in the field and we’re slowly coming to all realize that the inflammation hiding under the scalps in patients with androgenetic alopecia is probably not a good thing.

See previous article: Inflammation in AGA:

It’s intriguing that these JAK inhibitors would have so much better of an effect in women than men. The improvements in 15 hairs per sq cm is quite significant and we’ll need to wait to see if the women in the study can hold on to this improvement through the 1 year time point and whether this can be confirmed in bigger studies (there were only 6 women in this particular study!)

Whether getting rid of this scalp “microinflammation” is best done with a JAK inhibitor or best done with some other type of treatment will await further studies. For now, we’ll all await the 1 year update on results from Aclaris.

The Oral JAK Inhibitor Race

The JAK Inhibitors in Alopecia Areata: A Look at Pfizer and Concert Pharmaceuticals

The last 5 years have witnessed some exiting progress in the field of alopecia areata research. Although not yet FDA approved, we now have several JAK inhibitors that are used “off label” in treating this disease - tofacitinib, ruxolitinib and baricitinib. These continue to be studied and they have become an important part of my practice is resistant forms of alopecia areata.

SEE PREVIOUS ARTICLES:

How long do we use tofacitinib for? Can we taper?

Tofacitinib for Alopecia Areata: How soon does regrowth occur?

New Clinical Trials For JAK Inhibitors Underway

A number of clinical trials have been completed and additional ones are in progress.

Furthermore, we are now seeing several clinical trials underway with new drugs. Companies like Pfizer, Aclaris and Concert Pharmaeuticals are studying various new JAK inhibitors.

Pfizer: PF-06651600 And PF-06700841

Pfizer has taken interest in understanding the potential benefits of its JAK inhibitors. Centers in the US, Canada, and Australia are involved in studies of Pfizer created JAK inhibitors:

Pfizer Trials: PF 06651600

Concert Pharmaceuticals: CTP-543

Concert Pharmaceuticals has recently expanded it’s clinical trials. The company studies a specific form of ruxolitinib known as “deuterated ruxolitinib.” The JAK inhibitor is also known as CTP-543. Clincial trials are now underway comparing the tolerability of once-daily versus twice-daily dosing of CTP-543, in adult patients with chronic, moderate to severe alopecia areata.

Concert Pharmaeutics: trials with CTP-543

Comments

It’s an exciting time in the clinical and research world of alopecia areata. The JAK inhibitors have brought to the clinic what we have long hoped for - treatments that specifically target pathways that are abnormal in alopecia areata. The ongoing studies of topical JAK inhibitors have been somewhat disappointing to date - but the studies of the oral JAK inhibitors continue to show promise. Of course, additional studies in both area are important as this field moves foward.

Patients interested in understanding what clinical trials may be available in their area should visit the clinical trials website of the US National Library of Medicine:

Is there a clinical trial in my geographical area?

Results of Topical JAK Inhibitor Study for Alopecia Areata Does not Show Benefit

ATI-502 Topical JAK Inhibitor for Alopecia Areata Did Not Show Benefit

The JAK inhibitors are a group of medications that have been shown to benefit patients with alopecia areata when taking in the oral form. Tofacitinib, Ruxolitinib and Baricitinib are pills that have shown benefit in alopecia areata and are frequently used ‘off label’ in more advanced forms of the disease. By off label, we simply mean that the drugs have not yet received formal FDA or Health Canada approval.

There has been a massive surge in interest in studying whether topical JAK inhibitors could provide benefit. Companies such as Aclaris are studying various JAK inhibitors for alopecia areata. I was interested to note this week the final results that were published by Aclaris Therapeutrics regarding their Phase 2 clinical trial of ATI-502 (also known as AA-201) a ‘topical’ JAK inhibitor for alopecia areata. The study showed that the topical JAK inhibitor treatment did not prove more effective than the placebo.

The study was a double blinded placebo controlled trial which evaluated two concentrations of AT-502, namely 0.12 % and 0.46 %. Participants applied the treatment twice daily for 24 weeks.

READ ACLARIS NEWS RELEASE SHOWS NO BENEFITS FOR ATI-502

COMMENT

These studies of topical JAK inhibitors are very important (and so are the studies with the oral JAK inhibitors). While it would seem that topical JAK inhibitors should help if the oral forms help, that needs to be proven in well conducted trials. The way that a topical JAK inhibitor is made up by the pharmacist is clearly important as previous studies showed the some formulations - like ointments - are quite ineffective for treating alopecia areata. For example, a 2018 study by Liu, Craiglow and King did not find the 2 % ointment to be all that helpful.

TOPICAL TOFACITINIB OINTMENT NOT VERY HELPFUL FOR ALOPECIA AREATA

It will be interesting to see if other topical JAK inhibitors have positive results in ongoing studies.

Twice daily use of bimatoprost 0.03 % for eyebrow frontal fibrosing alopecia

Bimatoprost (Lumigan, Latisse) for Eyebrow FFA

Bimatroprost is a prostaglandin F2 alpha analogue that is helpful in stimulating hair growth for some types of hairs. It is FDA approved for treating poor eyelash brow (eyelash hypotrichosis) with a once daily application. A recent report supports the use of bimatoprost twice daily in the treatment of eyebrow frontal fibrosing alopecia.

Murad and Bergfeld from the Cleveland Clinic reported a 48 year old female with eyebrow FFA along with scalp FFA. She was intiially treated wtih hydroxychloroqine (200 mg twice daily), clobetasol scalp lotion and tacrolimus 0.01% ointment. Although her scalp FFA improved somewhat, her eyebrow FFA did not improve with the hydroxychlorouqine and the patient was therefore started on an off label use of bimatoprost 0.03 % twice daily. Within 6 months the patient reported improved eyebrows. She did not experience any side effects.

Comment

This is a nice study to have on hand. There are only three things that can really the used on the eyebrows topically in FFA - minoxidil, topical steroids and bimatoprost. We’ve been using bimatoprost (as Latisse) for many eyebrow hair loss conditions - including alopecia areata, frontal fibrosing alopecia, trichotillomania, and other hypotrichotic disorders. While growth does not occur in all patients and the chances of growth depend on the specific condition being treated and its activity, bimatoprost is one of the tools in the toolbox for getting eyebrows to grow.

Reference

Murad A et al. Prostaglandin analogue for eyebrow loss in frontal fibrosing alopecia: a case report.J Eur Acad Dermatol Venereol. 2019 May 22. doi: 10.1111/jdv.15704. [Epub ahead of print]

Changes in the Scalp Microbiome in Alopecia Areata

Different Organisms Found on the Skin in Alopecia Areata

It has been estimated that every square centimeter of human skin normally has about 1 billion organisms. This includes bacteria, viruses and fungi. There is nothing abnormal about this - it’s simply part of being human. We share our skin with many microorganisms in the world around us. We call this normal population of organisms the “skin microbiome.” When the constitution of these organisms change, we say that there has been ‘microbial dysbiosis.

Microbial Dysbiosis in Alopecia Areata

The topic of microbial dysbiosis has become increasingly popular. In many fields of medicine, experts are examining changes in bacteria as a means to explain disease pathophysiology. The two most common areas of exploration are the gut and skin. Changes in the normal populations of organisms in the gut and skin are believed to play a role in certain diseases.

Whether or not “microbial dysbiosis” plays a role in scalp disease is actively being researched. A recent study from Milan showed that patients with alopecia areata indeed had a change in their scalp microbiome. The study showed an increase in Propionibacterium, a decrease in Staphylococcus epidermidis and no change in Staphylococcus aureus. The analysis specifically showed an increase of Propionibacterium from 45.6% to 55.1% in AA subjects. Alongside data showed a general decrease of Staphylococcus epidermidis from 32.6% to 27.4% .

Conclusion

This is one of the first studies to now focus on changes in the skin microbiome and how this relates to skin disease. The precise significance of the information is not clear. However, it should be noted that P. acnes is able to synthesize many enzymes involved in the metabolism of porphyrins that, once activated, may contribute to oxidation and follicular inflammation.

Reference

Pinto D et al. Scalp bacterial shift in Alopecia areata. PLoS One. 2019 Apr 11;14(4):e0215206. doi: 10.1371/journal.pone.0215206. eCollection 2019.

Are we seeing more young males with balding ?

Is Early Onset Androgenetic Alopecia Increasing in Males?

Early onset balding is important to recognize and important to understand all the health issues surrounding it. I define early onset male balding as a form of androgenetic alopecia happening before age 30. Men with early balding have an increased risk of high blood pressure, high cholesterol, and metabolic syndrome later in life - so proper counselling is essential for these males.

Is the incidence of male balding increasing?

I am often asked if more young men are balding nowadays. I was interested to read results of a survey of 41 dermatologists whereby 88% felt there indeed was an increase in incidence of AGA in men younger than 30 years.

I was also interested to read a theory by Goren and colleagues as to why more and more young men might be experiencing balding. The argument was that there are increasing social pressures for women to conceive later in life and women who are actually able to conceive in their late 30s and 40s may have genetics that leads them to have a lower risk for premature ovarian failure, higher antral follicle counts in the ovary and ovulation at a later age. These same genetics (ie the length of the CAG repeat on the androgen receptor gene) is associated with increased balding in their male children.

More study is needed of this interesting hypothesis.

Reference

Goren A et al. Social selection favours offspring prone to the development of androgenetic alopecia. J Biol Regul Homeost Agents. 2017 Oct-Dec;31(4):1013-1016.

Antidepressants in alopecia areata: Could they help the hair if depression is also present?

Is there a role for antidepressants in alopecia areata patients?

Antidepressants may not only benefit some patients with depression but may have an anti-inflammatory effects as well. inflammation is increasingly understood to have some type of role in the mechanisms that lead to depression. It has been proposed that the anti-inflammatory actions of antidepressants maybe relevant to their anti-depressive effects. Decreases in TNF -alpha levels and increases in IL-10 levels may be among the effects observed with antidepressants.

Studies of Antidepressants in Alopecia Areata

To date, there have been three controlled trials of antidepressants in pateins with alopecia and several case reports. These include studies of using the following antidepressants:

1) Imipramine 75 mg daily

2) Paroxetine 20 mg daily

3) Citalopram 20 mg daily

4) Trimipramine 100 mg daily

Three Controlled Antidepressant Trials of Note

Three controlled trials have reported beneficial effects of antidepressants in treating alopecia areata. Patients with alopecia areata that were part of these studies had either anxiety or a depressive disorder.

STUDY 1: Perini et al, 1994

Perini and colleauges conducted one of the earliest studies looking at the potential benefits of antidepressants. Here they studied the tricyclic antidepressant antidepressant imipramine. The authors conducted a placebo-controlled study with imipramine 75 mg once daily as the sole therapy for alopecia areata. At 6 months, hair regrowth was reported in 5 out of 7 patients treated with imipramine, with no regrowth noted in the placebo group of 6 patients.

STUDY 2: Cipriani et al, 2001

In 2001, a small randomized controlled study was conducted by Cipriani and colleagues. The study involved a total of 13 patients with alopecia areata who were randomized to receive either paroxetine 20 mg (8 patients) or placebo (5 patients). The authors reported a better outcome with paroxetine than placebo.

Unlike other studies this study also includes more severe and resistant types of AA: alopecia totalis in 3 patients and alopecia universalis in one patient. Paroxetine was given for 3 months, with a follow-up at 4 and 6 months after treatment was discontinued. Complete regrowth of hair was observed in 2 patients treated with paroxetine, and 4 patients showed partial regrowth.. In comparison, only one patient from the placebo group had an almost complete regrowth of hair.

STUDY 3: Abedini and colleauges, 2014

In a 2014 study by Abedini et al. 60 individuals with recent onset AA were treated with triamcinolone injections in alopecic patches, and one half of these (i.e. 30 indivdiuals) were randomized to also receive the open-label supplement of citalopram 20 mg orally once daily. At 6 months of treatment there was significantly more hair regrowth, as measured by reduced mean diameter of the alopecic patch, in the citalopram patients compared with the triamcinolone injection only patients. Citalopram was then stopped at the 6 month mark, and patients were reassessed after another 6 months. Relapse of AA was noted in 20% of patients who had previously received citalopram compared with 66.7% of patients who had only received triamcinolone injections.

Reference

Abedini H, Farshi S, Mirabzadeh A, Keshavarz S. Antidepressant effects of citalopram on treatment of alopecia areata inpatients with major depressive disorder. J Dermatol Treatm 2014; 25: 153–155.

Cipriani R, Perini GI, Rampinelli S. Paroxetine in alopecia areata. Inter J Dermatol 2001; 40: 600–601

Perini G, Zara M, Cipriani R, Carraro C, Preti A, Gava F, et al. Imipramine in alopecia areata. A double-blind, placebo-controlled study. Psychother Psychosom 1994; 61: 195–198. 56.

Ricciardi A, Ruberto A, Garcia-Hernandez MJ, Kotzalidis GD, Trevisi M, Persechino S, et al. Alopecia areata with comorbid depression: early resolution with combined paroxetine- triamcinolone treatment. J Eur Acad Dermatol Venereol 2006; 20: 1000–1001.

Ruiz-Doblado S, Carrizosa A, Garcia-Hernandez MJ, Rodrigu-ez-Pichardo A. Selective serotonin re-uptake inhibitors (SS-RIs) and alopecia areata. Int J Dermatol 1999; 38: 798–799.