Manuka Honey for Treating Folliculitis Decalvans

Antibacterial Properties of Manuka Honey May Provide Benefits in Treating Folliculitis Decalvans

Folliculitis decalvans (FD) is a scarring alopecia that affects both men and women. FD is less common than some of the other  scarring alopecias like lichen  planopilaris and central centrifugal cicatricial  alopecia. The cause of FD is not completely know although a  role for bacteria has been postulated.   Bacteria such as Staphylococcus aureus frequently are found in the scalp of patients with folliculitis decalvans. Eradication  of bacteria with antibiotics, isotretinoin and other treatments frequently is associated with improvement of the disease.

A preliminary report proposes that Manuka honey may have benefits in the treatment of folliculitis decalvans

In 2019, a dermatology group in  Boston reported a patient with folliculitis decalvans whose disease improved with use of topical Manuka honey applied to the scalp. Manuka honeyis well known to wound care professionals. In fact, 17 clinical trial s involving  almost 2000 patients have suggested Manuka honey helps wounds heal.  Manuka honey has antibacterial properties – perhaps  due to its low pH, and other  plant  based and hydrogen peroxide based ingredients. A 1999 paper by Cooper and  colleagues showed that  Manuka honey killed  Staph aureus bacteria in wounds. 

The patient in the 2019 paper was a 20 year old male who had used a considerable number of  treatment before he started applying manuka honey to his scalp. These treatments included steroid injections,  clobetasol lotion, prednisone, minocycline, doxycycline and isotretinoin. Some of these treatments were actually  quite helpful for the young man – however he had to  stop because of some side effects of these treatment.  

The  patient decided to start applying Manuka honey  to his scalp after about 1 month into a course of the oral antibiotic cephalexin. As he continued on both cephalexin and topical honey and found that after an additional 4 weeks of both treatments the scalp had improved considerably. 6 months later he stopped cephalexin. His disease eventually flared again and the man used honey alone to settle down his disease. 

Summary/Conclusion

This is an interesting paper. It doesn’t definitively prove Manuka honey helps FD but it hints that it might have a role. We also can’t rule out that the patients long term use of antibiotics and other treatments (like steroids) and isotretinoin have reduced disease activity that makes Manuka honey more likely to help. Nevertheless, this is an interesting paper that hopefully fuel more research in manuka honey.

Reference

Yeh et al. Resolution of folliculitis decalvans with medical honey. Dermatology Online Journal 2019;. 25(8); 

Cicatricial Marginal Alopecia: Your traction alopecia patients will thank you!

Not all ‘Traction Alopecia’ is Actually Traction Alopecia

Traction alopecia is a form of hair loss that occurs due to pulling of hair. Diagnosing traction alopecia sounds easy but surprisingly there are a great number of mimicking conditions that can fool the hair specialist.

Frontal traction alopecia refers to hair loss in the frontal hairline that is due to traction. Often the temples are affected but any part of the frontal hairline, temples and area around the ears can be affected. Often the hairs in the very frontal hairline are unaffected leading to the appearance of a so called “fringe” sign:

Classic ‘fringe’ sign in a patient with traction alopecia. The fringe refers to the fringe of hair in the frontal hairline.

Cicatricial Marginal Alopecia (CMA)

There are times when patients who present with what seems to be traction alopecia tell us that they couldn’t possibly have traction alopecia. These are the patients who tell us that they have worn their hair fairly natural for years and that a diagnosis of traction alopecia just makes no sense to them. These are the patients that politely stare at us when we tell them to be careful how they style their hair and to be carefully to avoid heat or chemicals. When a hair specialist wants to make a diagnosis of traction alopecia but realizes the patient’s story just does not add up to give a convincing story of traction alopecia - the diagnosis of cicatricial marginal alopecia (CMA) must be considered.

The Differential Diagnosis of Frontal Hair Loss: What’s a specialist to consider anyways?

Of course, the diligent hair specialist considers many things in the differential of frontal traction alopecia like presentations including

1. Traction alopecia

2. Cicatricial Marginal Alopecia

3. Frontal fibrosing alopecia

4. Discoid lupus

5. Androgenetic alopecia

6. Telogen effluvium

7. Alopecia Areata

8. Trichotillomania

Cicatricial Marginal Alopecia: A Traction Alopecia Like Alopecia Without A Traction History

It was Dr Lynn Goldberg in Boston who put forth the notion of cicatricial marginal alopecia. She described 15 patients who presented with hair loss in a typical traction alopecia like pattern. Information pertaining to whether or not the patient relaxed or straightened the hair was available In 12 patients. 6 of the 12 patients gave a history of relaxing the hair or straightening the hair. For the other 6 other patients there was no such history. In other words, in 50 % of patients with frontal 'traction alopecia-like” hair loss a history of true traction styling practices were not present. These patients still had some degree of scarring on their biopsies indicating that this too could be a scarring type of hair loss. 

Treatment of CMA involves topical or oral minoxidil combined with topical and/or intralesional steroids. In some patients use of agents like oral doxycycline or topical tacrolimus can be helpful.

Summary and Key Lessons

As soon as we let open our mouths to pronounce the words traction alopecia, we must say in the same breath “or a traction alopecia like mimickers.” Could my patient have traction alopecia or a “traction alopecia like mimicker.”

Cicatricial Marginal Alopecia is one of these closely related mimickers. I like to refer to it as cicatrical marginal alopecia to honour my great colleague Dr Goldberg and so this is what I write in all my letters and consultation notes to other physicians. In my mind, I say the patient has a Traction Alopecia Like Alopecia Without a Traction History because it helps me remember the key elements of this presentation.

Reference

Goldberg L. Cicatricial Marginal Alopecia: Is It All Traction? Br J Dermatol 2009 Jan;160(1):62-8.

Can I Use Minoxidil When My Lichen Planopilaris (LPP) is Active?

Using Minoxidil in Cases of Active Lichen Planopilaris (LPP)

I’m often asked if minoxidil can be used for patients who have active scarring alopecia. The answer really depends on the patient and other specific details. Before we tackle the question, we need to take a look at what constitutes ‘active’ scarring alopecia.

What is active scarring alopecia?

Active scarring alopecia refers to hair loss caused by an overactive immune system process. The patient may have scalp itching, have increased scalp burning and may be shedding more and more hair. All of these things point to active scarring alopecia. What do we do when scarring alopecia is deemed active? Well, we increased the amount of immunosuppressive and immunomodulatory treatments we are using.

Here are just come examples of how we change treatment is we feel LPP is active

Example 1: instead of using steroid injections, we might use steroid injections AND topical steroids.

Example 2: Instead of using topical steroids, we might ADD oral doxycycline.

Example 3: Instead of using oral doxycycline, and topical steroids, a patient might be started on oral doxycycline PLUS oral hydroxychoroquine

In other words, once the LPP is determined to be active (or still active) we are going to make some pretty important decisions about increasing treatment. These are indeed big decisions because treatments have potential side effects, cost money

What is are the potential side effects of minoxidil?

Now , let’s focus on minoxidil and the potential side effects. In addition to side effects like headaches, dizziness and heart palpitations and hair growth on the face, minoxidil can cause two important side effects for patients with scarring alopecia: 1) Minoxidil can cause increased hair shedding and 2) Minoxidil can cause scalp itching for some people. These two side effects can make it difficult to figure out if the itching and shedding are coming from the active LPP or coming from the minoxidil.

So can I use minoxidil if I have LPP or not?

I always advise that patients review use of any medication with their dermatologist. In general, if a patient was using minoxidil for a very long time (without any problem) before the LPP even started, it’s usually fine to continue. In these situations, it’s unlikely any increased shedding or scalp symptoms the patient experiences is going to be attributable to the minoxidil. But starting up or initiating the use of minoxidil when one has active LPP is active is not usually a good idea. If the patient gets more shedding or more scalp symptoms, it will impossible to tell if they are coming from active LPP or coming from the minoxidil. In the worse case scenario, one can imagine a situation where the doctor increases the dose of medications thinking that the change in clinical symptoms or signs was due to increased activity of the LPP when really it was just the minoxidil. Imagine if the patient developed a side effect of the new mediation - and it never needed to be started in the first place.

Trichoscopy of Folliculitis Decalvans

Key Trichoscopic Signs of Folliculitis Decalvans

Folliculitis decalvans (FD) is a scarring alopecia which causes permanent hair loss. Patients develop red, itchy scalps that often contains pimples. Bacteria such as Staphylococcus aureus can sometimes be isolated when swabs are taken from these pimples.

A number of “trichoscopic” or “dermatoscopic” signs are suggestive of folliculitis decalvans including some I have shown here: (1) perifollicular “tubular” scaling, (2) compound follicles containing 6 or more hairs, (3) linear fibrotic bands and the (4) red “strawberry ice cream” color.

(1) Perifollicular “tubular” scaling

Trichoscopy (Scalp Dermoscopy) of Folliculitis Decalvans, Image 1. tubular scaling. The scale rides up higher on the hair shaft in folliculitis decalvans than in lichen planopilaris.

(2) Compound Follicles (Containing 6 or more Hairs)

Trichoscopy (Scalp Dermoscopy) of Folliculitis Decalvans, Image 2. “Compound follicles” are follicles containing more than 6 hairs emerging from a single pore.

(3) Linear fibrotic bands

Trichoscopy (Scalp Dermoscopy) of Folliculitis Decalvans, Image 3. Linear Fibrotic bands indicate a pattern of scarring associated with the typical starburst scaling.

(4) Red “Strawberry ice cream” Color.

Trichoscopy (Scalp Dermoscopy) of Folliculitis Decalvans, Image 4. Strawberry Red Color.

Folliculitis decalvans (FD) vs Lichen planopilaris (LPP).

Folliculitis decalvans can resemble lichen planopilaris at first glance. However, it does have many differences. Compared to LPP, FD is more likely to have pustules, is more likely to bleed, is more likely to showing compound follicles or “tufting” and is more likely to have tubular scaling the climbs up the follicles (as in this image) and more likely to have these linear fibrotic bands too. Treatment for FD has been discussed in other posts but includes antibiotics, isotretinoin as well as other treatments. 

Lichen planopilaris: Classic trichoscopic findings

Classic trichoscopic findings of LPP

Classic trichoscopy of active lichen planopilaris, an immune mediated scarring alopecia is shown below.

Classic trichoscopic image from a patient with active lichen planopilaris (LPP)

There is redness and scale around hairs (called perifollicular erythema and perifollicular scale). Some hairs are twisted (called pili torti). The areas of scalp devoid of hairs are no longer red as the immune system has destroyed hairs in that area and has since left the area. Treatments discussed in other posts as in the following link.

Treatments for LPP: What is available?

Challenge Case of Compound Follicles - Final Diagnosis Lichen planopilaris

The Case of Compound Follicles

“Compound follicles” are follicles with 6 or more hairs coming out of a single pore. Occasionally, follicles with 4,5 and rarely 6 hairs coming out of a single pore can be found as an isolated finding- especially towards the more posterior regions of the scalp. But large groupings of hairs like this are rare with advancing age and in fact - the presence of many areas containing compound follicles should prompt the clinician to consider that the patient might have a scarring alopecia. Compounding occurs when 2 or more adjacent follicles “fuse” together. They do not occur because a hair follicle suddenly makes more hairs. Compound follicles are more common in neutrophilic scarring alopecias like folliculitis decalvans (FD) than in lymphocytic scarring alopecias like lichen planopilaris (LPP). Nevertheless, occasional follicles with 5 and 6 hairs can be found in LPP…. as we’ll see in the case below.

I’ve included below a schematic diagram showing the typical findings in lichen planopilaris (LPP) and folliculitis decalvans (FD). Lichen planopilaris typically has no compounding although rarely it’s true that we can see it ….as we’ll seen in the case below. Compounding is more common in folliculitis decalvans.

Generally speaking, the tendency in LPP is for hairs to be destroyed and follicles to contain fewer and fewer hairs over time rather than to contain more follicles in them.

Case


The case was a patient who presented with redness in the scalp and a loss of hair density. Trichosocpy of the scalp is shown in the photo above. The arrow points to a follicle with 6 hairs coming out of a single pore. There were not many other features in this photos that suggested LPP such as perifollicular scale or perifollicular erythema or pili torti or scarring.

Below is a more typical photo of lichen planoplaris. As you’ll likely agree, the above photo doesn’t quite look like the only below. The typical photo of LPP has scale around hairs. Furthermore, most of the hairs either come out of the pores in groups of 2 or just one hair or no hair at all !

Typical trichoscopic image of lichen planopilaris. Perifollicular scale (white scare around hairs) is evident.

Occasional hairs in our patient’s case had a thicker scale than expected in LPP which prompted me to also consider whether this could be “starburst” scaling of FD. A “hint” of crusting is present but there are no pustules. Redness is interfollicular. A typical trichoscopic image of FD is shown below:

Typical trichoscopic image of folliculitis decalvans. Starburst scale is seen around hairs and compound hairs (hairs with more than 6 hairs coming out of a single follicular opening) are clearly evident.

A biopsy was be done to evaluate for the possibility of scarring alopecia. The biopsy returned showing lichen planopilaris with no features of folliculitis decalvans. The biopsy also showed that there was a perifollicular inflammatory infiltrate of lymphocytes together with lichenoid change (death of keratinocytes) in the outer root sheath. Perifollicular fibrosis was seen along with loss of sebaceous glands.

FINAL DIAGNOSIS: LICHEN PLANOPILARIS. 

Comment on Case

This was a nice example of a case that was atypical. Not all patients with lichen planopilaris have a typical presentation. Most however have scalp symptoms (like itching or burning or tenderness). Most have redness of some sort in the scalp. Most of scale around hairs. This patient had a bit of subtle redness and not really that much in the way of symptoms. The patient had some unusual compounding by trichoscopy which was the tip off that something might not be right. The biopsy confirmed the diagnosis of lichen planopilaris. Compounding is not a typical feature of LPP but certainly can be seen from time to time. It’s usually not a feature seen in all regions of the scalp and usually the compounding is limited to less than 7 hairs. Compound hairs containing 10, 15 our 20 hairs are almost never seen in lichen planopilaris (LPP) but can be seen very commonly in folliculitis decalvans (FD).

The patient was started on topical steroids and steroid injections together with hydroxychloroquine. The patient will be seen back in 3 months to review response to treatment. Blood tests will be needed monthly for three straight months for CBC, AST, ALT while starting hydroxychloroquine. An eye examination will be needed within 6 months. Clinical photos and trichoscopic photos were taken at the first visit and wil be compared to photos taken a the 3 months follow up. The hope is that redness will be reduced and that that patient’s perception of increased shedding will be reduced. I will monitor over time if more hair loss occurs. Regrowth may or may not occur in scarring Alopecias and this is not a main goal. The goal of treatment is to stop it from getting worse.

Hydroxychloroquine (Plaquenil) and Hair Loss: Is my Plaquenil causing me to lose hair?

Losing Hair on Plaquenil: The 5 Possibilities

Hydroxychloroquine (also known by its popular brand name Plaquenil) is an oral medication that is commonly used to treat a variety of autoimmune diseases including systemic lupus, dermatomyositis, rheumatoid arthritis, Sjogren’s and many other conditions as well. In the field of hair loss, conditions such as lichen planopilaris, frontal fibrosing alopecia and discoid lupus are frequently treated with hydroxychloroquine.

Can hydroxychloroquine cause hair loss?

It’s possible for any medication to cause hair loss, but for some medications it’s quite rare and for others it’s much more common. Whenever a patient using hydroxychloroquine reports hair loss there are 5 possibilities to consider.

1. The Plaquenil is Causing Hair Loss

One needs to always consider the possibility that Plaquenil is causing the hair loss. Usually Plaquenil related hair loss starts 2-6 months after the Plaquenil was started. We call this a drug induced telogen effluvium. If the Plaquenil was started 10 years ago and a patient reports hair loss last month, it’s not very likely that the Plaquenil is the culprit. That is often forgotten.

2. The Autoimmune Disease the Plaquenil is Used for is Causing Hair loss

Autoimmune disease can cause inflammation in the body and this type of inflammation itself can trigger hair loss in the form of a hair shedding or ‘telogen effluvium.’ When rheumatoid arthritis flares patients can shed hair. When lupus flares, patients can lose hair. If it’s not clear if the disease itself is contributing to hair loss, the specialist (ie rheumatologist) can help chart the activity of the patient’s disease over the past 1-2 years. It this correlates with hair shedding episodes experienced by the patient, then disease activity is likely involved in the patient’s hair loss.

3. A New Autoimmune Disease is Causing Hair Loss

It's well known that once a patient develops one autoimmune disease that he or she is more likely to develop a second autoimmune disease. One must always keep this in mind. Autoimmune scarring alopecias and autoimmune alopecia areata must always be considered when a patient with one autoimmune disease reports hair loss.

4. A New and Unrelated Hair Loss Condition has Developed

Hair loss is common and other conditions can develop. A 37 year old female with systemic lupus who uses Plaquenil for many years and now reports hair loss may have a number of possible hair loss conditions including telogen effluvium, female pattern (androgenetic alopecia), traction alopecia, or scarring alopecia. 40 % of women by age 50 will develop female pattern hair loss. This means that 40 % of female patients who use Plaquenil will develop female genetic hair loss - not from the drug itself but because that is the expected frequency in the population.

5. A New Treatment that was Introduced is Causing the Hair loss

For any patient who is currently using Plaquenil and develops new hair loss one must keep a very open mind as to the possibilities for the hair loss. In addition to the discussion points above, one must review whether new medication have been started. Was another medication introduced to treat the autoimmune disease? Was another mediation introduced to treat some other health condition. I recently saw patient with lupus who developed hair loss from an antacid type medication. We reviewed the precise course of the hair loss, pinpointed that it must have been the antacid medication and changed the medication. 2 months later the shedding had slowly considerably and 8 months later the patient’s hair has returned.

Conclusion

There are many reasons for hair loss in patients who use Plaquenil. One must always consider the possibility that the drug itself is triggering the hair loss but at the same time keep an open mind to other possibilities.

Steroid Injections for Hair Loss - A Look at Triamcinolone Acetonide

Steroid Injections with Triamcinolone Acetonide

Steroid injections are extremely helpful for many hair loss conditions - particularly some forms of localized alopecia areata (AA) some patients with lichen planopilaris (LPP), frontal fibrosing alopecia (FFA), central centrifugal cicatricial alopecia (CCCA) and folliculitis decalvans. I sometimes even use in the early stages of traction alopecia when I feel the condition is in its earliest stages.

Triacminolone acetonide is a common medication used for steroid injections for inflammatory related causes of hair loss. Kenalog is a popular brand name and available in 10 mg and 40 mg bottles. The final dose the physician uses is typically 2.5 to 5 mg per mL.

There are two common doses of triamcinolone acetonide that one orders from the manufacturer - 10 mg per mL and 40 mg per mL. Either is fine to order provided one keeps in mind that when using the 40 mg per mL dose one is going to need to use 4 times less than if using the 10 mg per mL dose. Every few months I get calls from physicians who call me in a panic because they have prepared their injections using a 40 mg per mL bottle but they thought it was a 10 mg per mL bottle. (the correct way to deal with this is to 1) admit one’s error to the patient, and then 2) flood the scalp generously with saline injections to dilute out the steroid and see the patient back in 4 weeks and 8 weeks to see if any atrophy developed). There are many brands of triamcinolone acetonide one can order. Kenalog is one brand (shown here) but there are others. I have used many over the years and find some do get clogged up when using tiny 30 gauge needles. I don’t find this happens with Kenalog.

As reviewed in other posts, I believe in starting steroid injections at 2.5 mg per mL and only going to 5 mg per mL if needed. The low dose can be helpful and allows more injections to be performed as the maximum dose is 4 mL if one uses a 5 mg/mL concentration or 8 mL if one uses a 2.5 mg per mL concentration.

Cetirizine (Zyrtec) in Lichen Planopilaris: Best Viewed as an Adjunct not Main Treatment

Cetirizine (Zyrtec) for Treating Lichen Planopilaris: Where does it fit in?

Antihistamines are increasingly being studied for the treatment for various types of hair loss. For the autoimmune disease known as alopecia areata for example, use of antihistamines like fexofenadine (Allegra) as well as others (i.e. ebastine) may have some treatment related benefits. In scarring alopecia. the use of antihistamines has only received a limited amount of study. Today, we will discuss the use of the antihistamine cetirizine for treating lichen planopilaris.

Lichen planopilaris is an immune medicated disease. There are a number of proposed mechanisms that lead ultimately to the disease. Cetirizine is an antihistamine medication and widely used for various types of allergy related symptoms. However, the medication may have a number of general and wide reaching effects on the immune system.

How does cetirizine work and how does it affect the immune response ?

Cetirizine is an H1 receptor antagonist. The drug minimally crosses the so called ‘blood brain barrier’ and so limited amounts actually get into the brain. This results in less sedation with cetirizine compared to any other traditional antihistamines. The 5 mg and 10 mg doses are unlikely to give sedation for most people. However, the 20 mg and 30 mg doses are much more likely to give sedation. There has been concern in recent years among long term chronic use of high doses of antihistamines on cognitive decline in patients so this needs to be taken into account when discussing high dose cetirizine as chronic therapy with patients with any medical condition.

Cetirizine has a number of potential effects to modify the immune response. These include

1. Inhibit DNA binding activity of NF-kappa B,

2. Inhibit the expression of adhesion molecules on immunocytes and endothelial cells

3. Inhibit the production of IL-8 and LTB4, two potent chemoattractants, by immune cells.

4. Induce the release of PGE2, a suppressor of antigen presentation and MHC class II expression, from monocyte/macrophages

5. Reduces the number of tryptase positive mast cells in inflammation sites.

The 2010 d’Ovidio Lichen Planopilaris Study

In 2010, d’Ovidio and colleagues studied the use of cetirizine at high doses. Rather than using 5 mg to 10 mg daily that is commonly use over the counter, the authors studied the benefits of 30 mg/daily. Twenty-one patients with lichen planopilaris (LPP) were treated with cetirizine as well as their topical steroids. in 18 or 21 patients (85.7 %) there was a reduction in redness, scaling and a reduction in extractable anagen hairs by the pull test. The authors reported that one patient developed cardiac arrhythmia after 3 months of successful treatment and dropped out of the study.

Cetirizine is an antihistamine and functions as an H1 receptor antagonist. In 2010, d’Ovidio showed that cetirizine at high doses (30 mg) could benefit some patients with lichen planopilaris. Over the counter antihistamine dosing like shown in the phone is 10 mg.

What are the side effects of cetirizine?

Side effects of cetirizine and other information can be found in our Handout.

Cetirizine Handout for LPP

Rare side effects including heart failure, angioedema and tachycardia. These side effects are rare at low doses such as the 5 mg and 10 mg (over the counter doses). Side effects increase as one increased the dose. The 30 mg dose used in the d’OIividio study would be expected to have a greater degree of side effects than the lower doses.

Conclusion

Cetirizine may have some benefit in treating lichen planopilaris. I sometimes prescribe cetirizine as an adjective treatment in patients with persistent itching and burning who are not fully responding to mainstay topical, intralesional and oral treatments. Generally I use 5 mg or 10 mg and only rarely do I prescribe 15-20 mg. I do not typically prescribe 30 mg doses as I find side effects increase greatly. One must respect the drug interactions and contraindications for the drug (as outlined in the handout). In many ways, I view cetirizine as a helpful add on - much the same way as I view the use of low level laser therapy in this disease. I do not think in the present day that cetirizine should find itself at the top of the therapeutic ladder but certainly has a place.

Reference

d’Ovidio R et al Therapeutic hotline. Effectiveness of the association of cetirizine and topical steroids in lichen planus pilaris--an open-label clinical trial. Dermatol Ther. 2010 Sep-Oct;23(5):547-52.

Namazi MR et al. Cetirizine and allopurinol as novel weapons against cellular autoimmune disorders.Int Immunopharmacol. 2004 Mar;4(3):349-53.

Is Immunotherapy (DPCP, SADBE) Effective for Lichen Planopilaris or Frontal Fibrosing Alopecia ?

Immunotherapy (DPCP, SADBE) Does NOT Help Scarring Alopecia

Diphencyprone (DPCP) and Squaric Acid Dibutyl Ester (SADBE) are long standing treatments for the autoimmune hair loss condition alopecia areata. The cause itching and burning in the scalp and essentially trigger an allergic contact dermatitis. The inflammation that these chemicals create can trigger hair growth in some patients with alopecia areata. It’s quite remarkable.

FIGURE 1. Diphenycyprone (DPCP) is a liquid that is applied to the scalp to treat alopecia areata. It causes an allergic reaction but can stimulate hair growth in some users.

FIGURE 2: Hair Regrowth in a patient with ‘ophiasis” type of alopecia areata who was treated with diphenyprone.

Does DPCP and Squaric Acid Help Lichen Planopilaris or Frontal Fibrosing Alopecia (FFA)?

DPCP and Squaric acid are not effective in these scarring alopecias. It’s not that large studies have been done - it’s just that I’ve seen patients many patients over the years with scarring alopecias who have come to see my after having DPCP. These patients were all mistakenly diagnosed as having alopecia areata when really they had frontal fibrosing alopecia or lichen planopilaris. Hair regrowth did not occur and many experiencing a significant worsening.

FIGURE 3: Patient with frontal fibrosing alopecia who was first thought to have the ophiasis form of alopecia areata and was treated with DCPC for many months. The patient did not experience regrowth.

There is absolutely no reason to believe that DPCP or squaric acid are effective in LPP or FFA. The pathogenesis of these two conditions is very different than alopecia areata. While it’s true that some treatments overlap - many do not. The following table summarizes some of these important differences. DPCP is effective for some patients with alopecia areata but is not effective in LPP. Doxycycline is effective for some patients withLPP but not helpful in treating alopecia areata.

Table 1: Treatments in Alopecia Areata vs Lichen Planopilaris

Reference

[1] DPCP for Hair Loss: Can I Apply it at Home?

Patient-Doctor Conference Focused on Scarring Alopecia

CARF’s Patient-Doctor Conference All Set For Nashville, TN

I’m looking forward to another great meeting of the Cicatricial Alopecia Research Foundation (CARF). Every 2 years, CARF hosts a wonderful meeting that brings together patients and physicians. I’ve attended for several years now and always enjoy it. I’ll be speaking again at this year’s meeting and look forward to seeing everyone there. The two and a half day meeting is packed with lots of great information, support, and good fun.

Information on the meeting can be found on the CARF website and is also highlighted here:

CARF 2020 Patient Doctor Conference

The conference brochure can be downloaded here:

CARF 2020 in Nashville, TN: April 24-26, 2020



The Use Metformin in Lupus: How does this apply to our Discoid LE (DLE) Patients?

Metformin for Lupus: Will it help discoid lupus?

Metformin is a well known diabetes drug. Recent evidence has suggested that metformin may have a positive impact on the treatment of some autoimmune diseases.

Metformin is well understood to reduce glucose production by the liver and to reduce absorption of glucose in the gastrointestinal tract and to increase insulin sensitivity. However, metformin may also reduce production of reactive oxygen species (ROS) which help create inflammation in lupus. The possible benefits of metformin in lupus was demonstrated in 2015 where Wang and colleagues in the journal Arthritis and Rheumatolgy showed that metformin reduce the risk of disease flares by 51 % compared to conventional treatment.

In a 2018 poster by McLeod and colleagues presented at the 2018 meeting of the American College of Rheumatology, authors showed that metformin helps patients with lupus improve control of their disease. The researchers studied 15 patients with lupus using metformin and compared to 1331 patients not using metformin. The authors found there ws a difference in disease activity in patients using metformin.

Metformin for Discoid Lupus: Will it help?

These studies are interesting as they suggest that metformin has the potential to help patients with lupus. What we don’t know yet is whether metformin will help the various types of ‘cutaneous’ lupus including discoid lupus.

Metformin may have an impact not only on autoimmune diseases (including effects on monocytes, macrophages and neutrophils), but improve gut microbiota and have an antifibrotic effect as well. These effects together make them ideal to consider in the study of scarring alopecia. We already know that drugs as pioglitazone may be helpful in lichen planopilaris.

REFERENCES

Wang et al. Neutrophil Extracellular Trap Mitochondrial DNA and Its Autoantibody in Systemic Lupus Erythematosus and a Proof-of-Concept Trial of Metformin.Arthritis Rheumatol. 2015 Dec;67(12):3190-200. doi: 10.1002/art.39296.

McLeod C, Olayemi G, Bhatia N, Migliore F, Quinet R. The Impact of Metformin on Disease Activity in Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/the-impact-of-metformin-on-disease-activity-in-systemic-lupus-erythematosus/. ABSTRACT NUMBER: 2645

Frontal Fibrosing Alopecia: The Early Stages

When FFA First Begins 

Frontal fibrosing alopecia (FFA) is a scarring alopecia that affects women to a greater extent than men. The cause remains unknown although hormonal and immune-based mechanisms are clearly relevant.

The disease causes loss of hairs in the frontal hairline, sides and back of scalp, eyelashes, eyebrows and body hair. What is interesting about FFA is that the very earliest stages are associated with destruction of the tiny “vellus” hairs. This destruction leaves behind the thicker terminal hairs. 

In the earliest stages of FFA, the hair loss can be completely unnoticeable. There are frequently no symptoms and there is simply a subtle thinning in the area rather than complete loss. 

This photo of a patient with FFA shows a relatively normal looking scalp that is easily mistaken for androgenetic alopecia. (In fact this photo could easily be a picture of androgenetic alopecia were it not for the loss of all vellus hairs in this area over a 3 month period). In androgenetic alopecia, there is a gradual (slow!) conversion of thick hairs to thin hairs (a process called miniaturization). In FFA, we often do not see the miniaturized and vellus hairs as they are preferentially destroyed by the immune system. We see mainly single terminal hairs in FFA. Over time (without treatment) there may be some redness that develops in this area and even some scaling. About 40 % of women with FFA have androgenetic alopecia as well, so the two conditions frequently co-exist.

It is often not a decision “is this FFA or AGA ...but rather is it FFA, AGA or both.” The goal of treatment however is to stop that from occurring and the patient was started on topical fluocinonide gel, pimecrolimus cream, steroid injections and oral finasteride.

Characteristics of FFA in Men

 Characteristics of FFA in Men

Frontal fibrosing alopecia is a type of scarring alopecia that causes hair loss along the frontal hairline and sideburns but can also affect the back of the scalp, eyebrows, eyelashes and body hair.  For every 100 patients I see with a diagnosis of FFA, 99 patients are women and 1 patent is   male.

Tolkachjov and colleagues performed a study of 7 male patients with frontal fibrosing alopecia to gain a better understanding of how these patients present and what type of hormonal or endocrine abnormalities might be present. 

Of the 7 patients, 4 showed loss of the sideburns, 3 showed loss of eyebrows, 2 showed loss of  hair in the occipital scalp.  1 patient had hair loss on the legs, 1 had hair loss on the arms and 1 had loss of hair from the upper lip. None of the 7 patients had facial papules and only 1 had androgenetic alopecia.  Interestingly, none have evidence of thyroid disease and none had low total testosterone levels (although  2 had evidence of low free testosterone).  All patients were ANA negative or only weakly positive. 

Of the 7 patients, 4 started systemic therapy with oral hydroxychloroquine and 3 of these patients were able to achieve disease stabilization with use of this drug.  

Comment

FFA is rare in men but we are seeing an increasing number of males affected. This study is small and so it’s difficult to get a good sense about how FFA in men differs from women.  Hypothyroid disease occurs  in 15-23 % of female patients with FFA. Although the data in this study would suggest that hypothyroidism is uncommon in men with FFA, the study is too small to really get a sense of that information.

Reference

Tolkachjov et al. Frontal fibrosing alopecia among men: A clinicopathologic study of 7 cases. Journal of the American Academy of Dermatology 2017; 77:683-90 

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.

Facial Papules in FFA: What is our current understanding?

What is our current understanding?

Facial papules are present in a significant proportion of patients with FFA. The papules appear as small yellowish colored bumps that may cause the patient’s face, forehead and chin to feel “rough.” For years, it’s been confusing as to what these papules really are. Early studies by Dr. Aline Donati et al showed that these papules contain inflamed vellus hair follicles.  More recent studies, including those by Pedros and colleagues showed that biopsies of facial papules contained no inflammation … and no hairs!

The following diagram is a diagram that I use when teaching about the facial papules in FFA. It’s a schematic cartoon of the current hypothesis about what these hairs represent and why they disappear.

It appears that early in the course of the facial papules, inflammation is present in the vellus hairs. Over time, the hairs disappear and what is left is a dome shaped papule containing hypertrophic sebaceous (SG) glands.

Over time, some papules do flatten and some even disappear. This can take a long time. Studies by Pedros and colleagues have shown that use of oral isotretinoin can help reduce the appearance of 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.

Pathology of Lichen Planopilaris: Lichenoid Change

Lichenoid Change

There’s a few key things about scalp biopsies of lichen planopilaris (LPP) that are really is helpful to evaluate when looking under the microscope. These include the cell death of hair follicle keratinocytes (so called “lichenoid change” in the earliest stages as well as loss of sebaceous glands (oil glands) over time.

There are, of course, many other changes that can be seen and that a pathologist or dermatopathologist may offer comments. These include reductions in hair density, perifollicular fibrosis, and inflammation in the upper parts of the hair follicle. Changes in the skin layer (lichen planus-like changes) and dilated eccrine glands can also be a part of the pathology.

Unfortunately, there tends to be an extreme focus at times on documentation of perifollicular fibrosis and perifollicular inflammation when evaluating LPP. Certainly these are important and present in LPP. The problem is that they are not diagnostic of LPP as these findings are common in androgenetic alopecia too. In fact, up to 3/4 of patients with AGA have some degree of perifollicular fibrosis and about 1/3 or more have significant perifollicular inflammation.

The photo here shows typical features of the “lichenoid” change that accompanies LPP. There is inflammation in the root sheath and some hair follicle keratinocytes are showing vacuolar change and cell death. 

Scalp Biopsies For LPP: Wonderful Tool When Used Properly

Scalp biopsies are wonderful tools but they must be interpreted properly. Getting a scalp biopsy “just because” it sounds like a good idea is rarely every never a good idea. One needs to have a purpose of doing a biopsy - to rule in a disease or rule out a disease.

There is much confusion when it comes to diagnosing LPP and AGA. Every year I see at least 30 patients who come into through my office with a diagnosis of LPP and leave my office with a diagnosis of AGA. It's not some treatment I did that changed the diagnosis, it's the diagnosis that changed. It’s a pretty remarkable and sometimes emotional consult.

How’s this even possible? How can a diagnosis be wrong?

First off, let me say that most people who come into the office with a diagnosis of LPP actually have LPP. So what we are talking about here is something specific.

There is, however, tendency to overcall or overdiagnose LPP on account of a failure to recognize a few points. First, perifollicular inflammation and fibrosis is common in AGA. In fact, nearly 75 % of patients with AGA have perifollicular fibrosis and 30-40 % have perifollicular inflammation. So these alone are certainly not criteria for LPP! What needs to be properly recognized is that LPP is associated with “lichenoid change” in the outer root sheath and death of hair follicles keratinocytes.

The other cardinal feature of scarring alopecia is loss of the sebaceous glands. These latter two features need to be the focus of the pathologist’s attention and not solely the perifollicular fibrosis and inflammation. As simple as it sounds, many lives can be altered be understanding these principles.

 

 

 

 

REFERENCES

Evaluation of Perifollicular Inflammation of Donor Area during Hair Transplantation in Androgenetic Alopecia and its Comparison with Controls.
Nirmal B, et al. Int J Trichology. 2013.

Diagnostic and predictive value of horizontal sections of scalp biopsy specimens in male pattern androgenetic alopecia.
Whiting DA. J Am Acad Dermatol. 1993.
 

Hair Transplant Test Sessions for Scarring Alopecia

Common Errors in Performing 'Test Sesssions'  

Hair transplants can be an option for patients with scarring alopecia but only if certain criteria are met. First and foremost, the disease should ideally be completely 'inactive' for at least 2 years and the patient should be off all types of immunosuppressive medications. Unless these minimal criteria are met, we can't be sure the scarring alopecia is truly quiet (inactive).

Sometimes a hair transplant “test session” is performed 8-12 month prior to proceeding to the ultimate full hair transplant session. The purpose of the “test session” is to better estimate the chances of success of a larger transplant session. Patients with a successful test session are given the green light to proceed to a full session. Patients with a poor outcome on the tests session may be advised not to proceed with hair restoration in the near future. 

I think there is a lot of misunderstanding about how to perform a test grafting session for a patient with scarring alopecia. Below I outline some common errors. But first, let me begin with an analogy. 

Hair Transplant Test Sessions: An Analogy

I often use the following analogy when explaining the concepts I believe are important in  a hair transplant tes session. As an analogy. imagine yourself offered an exciting job position. 9 months of the year you’ll be travelling to the world's most exotic destinations. The only catch is that 12 weeks of the year, you'll need to be in the arctic circle during the middle of winter. Each day, you’ll need to walk 20 miles through ice and snow collecting various samples. You’ll sleep in a tent each night and you need to carry all your belongings with you. 

You are really not sure if you’ll be able to withstand the cold and all your friends think you’ll crazy for thinking about accepting the position as they think you are far to soft of a person to withstand the cold and extremes of the artic circles. To test whether you can really survive an article winter,  you decide to make a “test visit” for 1 month to see if you’ll really like living there or not. You figure if you can survive 4 weeks, 12 weeks should not be so bad. 

As you are deciding when to go, a friend advises you to go in the summer since she’s heard it’s lovely in the summer. Another friend advises you to go in the winter but stay at some luxury accommodations he’s heard good things about.   

In my opinion, neither pieces of advise from these friends is really ideal for a ‘test visit.’  To challenge yourself to see if you are really going to withstand the arctic winter, you need to visit in the winter - and you need to stay in lodging that best represents how you’ll live if you do decide to move. That lodging is, of course, a tent. It’s reasonable to bring two blankets with you and a few more warm belongings that most people who live in the area normally use – because let’s face it – the whole experience is completely new to you. 

The same is true with a transplant test session. The whole experience of moving from a warm, richly vascularized area into a scarred, poorly vascularized area is a big challenge for a little hair follicle. During a 'test session, I believe one needs to challenge these little hairs and see if they really can make it. One needs to make the scalp suitable to growing but not too perfect and luxurious that it falsely misrepresents the challenges that will ultimately be present if a real transplant is performed. Newly transplanted hairs are not really used to growing in scar tissue and not used to growing in between the little bits of inflammation that are often there – so it’s reasonable to help them out a bit. But my opinion is that a test session should truly be a test session. The hairs need to be tested !

COMMON ERRORS IN "TEST SESSIONS"

1.     Excessive topical corticosteroids and immunosuppressives are used

A test session is really all about testing whether hairs can withstand the challenges of growing in less than ideal conditions. The new grafts need to grow in scarred scalp tissue that may lack ideal blood supply. The skin itself may be too thick or too thin.

As part of the test session, I believe on should use minimal corticosteroids (and minimal other immunosuppressives if at all possible). It's still okay to use them but just not excessively.  I typically recommend steroids a few times per week before the test transplant with steroids stopped one month before. Steroids are started again 1 month after the test session but only twice weekly for two months and then once weekly thereafter.  A mid potency topical steroid should be sufficient.

One needs to challenge these little hairs and see if they really can make it. One needs to make the scalp suitable to growing but not too perfect and luxurious that it falsely misrepresents the challenges that will ultimately be present if a real transplant is performed. The analogy is similar to the arctic circle analogy I used above. 

2.     The grafts are spaced too far apart

Ideally, 100-200 grafts should be put in an area at a density of 25-30 follicular units per cm2 and this area carefully followed over time. The problem with placing grafts at a lesser density is that it does not adequately ‘stress’ the hair follicles during the test session. When it comes to growing in scar tissue, it’s easier for hairs to grow when they are far apart rather than close together. My view is that during a ‘test session’we need to understand how the hair follicles survive under realistic situations. If the patient ultimately proceed to a full hair transplant session, follicle are going to be transplanted at a density of 20-25 follicular units per square cm AT MINIMUM and so a test session should slightly exceed this. We need to test the follicles!

3.     Too many grafts are put in

I don’t recommend that test sessions be done with more than 200 grafts and 150 is often ideal. The problem with doing more than 200 is that it become difficult to count the grafts. 

I have seen patients who come to see me after have 500-800 grafts ‘peppered’ into the front of the scalp or ‘peppered’ into the crown. Instead of putting 100-150 follicles in to an area the size of a golf ball, 500-800 grafts get put into an area the size of a large melon or small dinner plate. It is easy to count 100-200 grafts (1, 2, 3, 4…) but more difficult to count 500. When it comes to hari transplant test session, I believe we need accurate survival numbers. Knowing that 90% survived is very different than knowing 54 % survived. Knowing that the survival 'seemed ok' is very different than knowing that the survival was 'excellent.'

4.     The grafts are put into an area already containing hair follicles

In my opinion, a test session should be performed in an area with as few hairs as possible, ideally with no hair. Sometimes this is not possible, but if it is –this should be followed. This makes it easier to document “before and after”photographs, count hairs and document clearly the survival of grafts. 

The problem with putting in 500-1000 grafts in area area that already has hair, is that it becomes impossible to really get a sense of the proportion of grafts surviving at a time 9-12 months post op. I saw a patient recently who had 500 grafts placed into his crown. The test session was performed in an area that was thinning but not bald. It was impossible to really get a sense of how many grafts survived, despite the fact that the surgeon estimated survival waspretty good. Photos suggested there were no changes to the density and the patient felt it had worsened! Objective measurements are what is needed in these test session.  

5.     The grafts are put in an area that is not representative of the actual scalp to be transplanted

Hair follicles need to be placed in an area that is representative of the average quality of the skin of the scalp, and possibly even in an area that represents slightly poorer than average quality. If much of the scalp contain thicker areas of scar tissue, this is not unreasonable to perform the test session in there. If most of the scalp is thick pale, poorly vascularized tissue and only a small portion of the scalp is pink normal appearing skin, it is misrepresentative to perform the test tession in the pink, normal appearing area.  

Returning to the analogy above, it is unreasonable (in my opinion) for a person undergoing a test visit to the article circle to stay in a luxury accommodation during the visit when the whole purpose of the visit is to see if one can really withstand the extremes of living in the article circle. In the same way, it is unreasonable to make the test session a wonderful opportunity for hair growth.

A test session should represent a true... test!