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Frontal Fibrosing Alopecia: The Early Stages

When FFA First Begins 

FFA-early

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.


Dr. Jeff Donovan is a Canadian and US board certified dermatologist specializing exclusively in hair loss. To schedule a consultation, please call the Whistler office at 604.283.1887
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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 


Dr. Jeff Donovan is a Canadian and US board certified dermatologist specializing exclusively in hair loss. To schedule a consultation, please call the Whistler office at 604.283.1887
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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.

 

 

 


Dr. Jeff Donovan is a Canadian and US board certified dermatologist specializing exclusively in hair loss. To schedule a consultation, please call the Whistler office at 604.283.1887
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Hydroxychloroquine: 10% stop from side effects

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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.


Dr. Jeff Donovan is a Canadian and US board certified dermatologist specializing exclusively in hair loss. To schedule a consultation, please call the Whistler office at 604.283.1887
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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.

facial papuels.png


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.


Dr. Jeff Donovan is a Canadian and US board certified dermatologist specializing exclusively in hair loss. To schedule a consultation, please call the Whistler office at 604.283.1887
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Pathology of Lichen Planopilaris: Lichenoid Change

Lichenoid Change

lichenoid change.png

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. 


Dr. Jeff Donovan is a Canadian and US board certified dermatologist specializing exclusively in hair loss. To schedule a consultation, please call the Whistler office at 604.283.1887
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Scalp Biopsies For LPP: Wonderful Tool When Used Properly

LPP

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?

AGA

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.

LPP2

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.
 

 

 


Dr. Jeff Donovan is a Canadian and US board certified dermatologist specializing exclusively in hair loss. To schedule a consultation, please call the Whistler office at 604.283.1887
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Why is my scarring alopecia flaring again?

Consideration when scarring alopecias become worse

Scarring alopecias are hair loss conditions which are associated with both inflammation and scarring. A variety of treatments can be used to reduce inflammation and help halt the disease. The precise choice of treatment depends on the exact diagnosis. Generally speaking, treatments include topical steroids, steroid injections, and systemic immunosuppressive medications. For some scarring alopecias, antibiotics are also used. 

flare.jpg

Scarring alopecias may respond well to treatment are the patient will experience a halting of their hair loss and symptoms (if symptoms are present).

In some cases, relatively “inactive” scarring alopecias may become “active” again and cause further symptoms and hair loss. We call such unexpected reactivation a “flare.”

 

 

Reasons for a Flare of Scarring Alopecia

Here we review considerations that must be given for any patient with scarring alopecia who experiences a flare.  When I work with doctors or give lectures, I frequently use the teaching tool or mnemonic "I'M WORSE" to review causes of a flare. Each letters stands for considerations that must be evaluated.

 

I = Injury to the Scalp

Scalp injury can worsen many scarring alopecias and trigger a 'flare' in patients who had otherwise quiet disease. There can be many potential sources of such injury including a direct blow (i.e. something strikes the scalp), a massive sunburn or scalp surgery. In the latter category, a hair transplant is an example of a surgical procedure that can potentially trigger a flare in a patient with a scarring alopecia. For this reason, a hair transplant is never an option for patients with scarring alopecia that is not completed quiet.

 

M = Medications are making it worse

In some patients who are experiencing “flares” of their scarring alopecia, it is sometimes the medication itself that is causing things to worsen. Occasionally patients prescribed steroids injections, steroid shampoos, hydroxychloroquine, methotrexate, minoxidil, or retinoids find their hair loss has worsened on account of a specific drug or topical product. 

This is a challenging category to evaluate but does need careful consideration.  Occasionally for example a patient with relatively stable disease who adds minoxidil in hopes to stimulate more hair growth finds that minoxidil triggers worsening shedding and dryness that seems to flare things overall. Similarly, there are some patients who find that steroid injections similarly trigger a flare.

 

W = Wrong Medication or Dose

It is not common for medication dosing errors to be the main reason for a flare. Nevertheless it needs to be considered. A patient who changes their dose after getting a prescription refill could find that this change triggers a flare. For topical medications that are compounded, one must consider that the method use to compound the drug may changed.

 

O = Other Condition Developed or Worsened

For a scarring alopecia may be perceived to have worsened, one must keep in mind that it could actually be a completely separate medical issue that has triggered the worsening rather than the scarring alopecia itself. A example would be the development of iron deficiency in a patient with lichen planopilaris that triggered a worsening of hair loss. The key treatment in this scenario is to treat the iron deficiency rather than more aggressively treat the scarring alopecia. Similarly, in a patient with stable LPP who develops hyperthyroidism (and hair loss from the thyroid disease) the perception to the patient is likely to be that their scarring alopecia is worse. In reality, their scarring alopecia may be stable but they have a second condition that has developed and it too is causing hair loss. 

 

R = Rejection of Prescribed Medications (Medication Compliance)

For a patient whose scarring alopecia is flaring, one needs to consider the possibility that the patient is not using the medication in the manner that was intended. An example could be a patient who was supposed to use doxycycline for 6 months but stopped it after two months. In such situations it is important to inquire about the exact reason the medication was stopped prematurely. In some cases, it may due to side effects that prompted stopping the medication or other factors such as cost. We know that a very large proportion of patients do not take their medications in the manner prescribed. So a physician should never assume adherence to the treatment protocol

 

S= Stressful life events

For patients with scarring alopecia, stress is a potential trigger of a “flare” of scarring alopecia.  Many patients with scarring alopecias such as lichen planopilaris, pseudopelade, frontal fibrosing alopecia, folliculitis decalvans notice that the scalp can become considerably more itchy around times of intense stress. This may be stress related to work or family, personal relationships, finances or other issues. All have the potential to trigger a flare.


E= Enigma (NO clear reason)

The last category is the most common. Most of the time, the exact cause of a patient's flare is not known. Despite all factors being reviewed, it just does not seem clear why a patient who was stable for so many months is now experiencing worsening of their disease (i.e. a flare). There is much about the immune system in the present day and age that we simply do not understand. The immune system can become active for reasons we do not understand. In this situation, additional treatment is needed to halt inflammation. 

 


Dr. Jeff Donovan is a Canadian and US board certified dermatologist specializing exclusively in hair loss. To schedule a consultation, please call the Whistler office at 604.283.1887
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Compounding of Follicles

Compounding of Follicles

compound follicles.png

Compound follicles are hair follicle units that have more than 6 hairs coming out of a single pore. The tendency to form compound hair follicles is sometimes a feature of so called neutrophil mediated scarring alopecias. Folliculitis decalvans (shown here) frequently shows compounding of hairs. 


Dr. Jeff Donovan is a Canadian and US board certified dermatologist specializing exclusively in hair loss. To schedule a consultation, please call the Whistler office at 604.283.1887
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Perifollicular erythema in FFA

Redness around hair follicles: Perifollicular eythema

Frontal fibrosing alopecia or "FFA" is a scarring alopecia (scarring hair loss condition) that most commonly develops in women 45-65. It causes permanent hair loss. The cause is not know although a mix of immune based mechanisms and hormonal mechanics are likely to contribute. The condition can be asymptomatic - and many patients have no itching, burning or pain.



FFA Disease Activity: How do we know it's' active or not

PFE

How do we know whether a given patient's FFA is active? Undoubtedly, the absolute best way is with a photo. If a patient's photo changes over a period of monitoring (6 months or 12 months) the FFA is active by definition.

However, photographs don't capture subtle changes in activity. To accomplish this examination by "dermoscopy" is helpful. In this photo, slight redness around the hairs can be seen. We call this "perifollicular" erythema. (note peri means "around"). In 2013, Spanish researchers Toledo- Pastrana and colleagues published an article in the International Journal of Trichology examining dematoscopic features of FFA. Of 79 patients examined, 66 % showed perifollicular erythema. In patients with active disease, perifollicular erythema was present in 95 % of patients.


Conclusion


Perifollicular erythema is an important sign to look for in FFA. It indicates disease activity and a high likelihood of further hair loss in the patient.

 


Reference


Toledo- Pastrana et al. Perifollicular erythema as a trichoscopy sign of progression in frontal fibrosing alopecia. Int J Trichoscopy 2013; 5: 151-3.


Dr. Jeff Donovan is a Canadian and US board certified dermatologist specializing exclusively in hair loss. To schedule a consultation, please call the Whistler office at 604.283.1887
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Dissecting Cellulitis: Early Features

Early Stages of DSC

Dissecting Cellulitis (DSC) is a relatively rare scarring alopecia. Men are affected much more than women and affected patients are frequently young males in their 20s.

dsc2

The condition beings with discharge of pus and sometimes blood from the scalp. It can also be quite itchy. The beard, underarm (axilla) and groin can be affected with similar discharge. A key feature of diagnosis is the presence of sinus tracts or "tunnels" underneath the skin. Small thin vellus hairs are also seen in the affect area.

The primary treatment of DSC is isotretinoin although antibiotics, zinc, dapsone, colchicine, and TNF inhibitors can be used.


Dr. Jeff Donovan is a Canadian and US board certified dermatologist specializing exclusively in hair loss. To schedule a consultation, please call the Whistler office at 604.283.1887
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Pseudopelade of Brocq

ppb2.png

Pseudopelade of Brocq

Pseudopelade of Brocq (PPB) is a scarring alopecia. It causes permanent hair loss. The cause is unknown.

In contrast to lichen planopilaris, there is little to no scale around hair follicles. The areas may be pink-colored when active. Treatment is similar to lichen planopilaris including use of topical steroids, steroid injections, topical calcineurin inhibitors, oral methotrexate, oral doxycycline, oral hydroxychloroquine and others.


Dr. Jeff Donovan is a Canadian and US board certified dermatologist specializing exclusively in hair loss. To schedule a consultation, please call the Whistler office at 604.283.1887
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Pseudopelade of Brocq

Pseudopelade of Brocq

ppb.png

Pseudopelade of Brocq (PPB) is a scarring alopecia that affects both women and men. The central scalp is often affected first. This condition causes permanent hair loss - hair does not regrow. The goal of treatment is to stop further loss. The cause is unknown.

The areas of hair loss are usually pale colored in those with PPB although they may be slightly pink. When one feels these areas with a finger it is usually obvious that the area dips down below the level of the skin. We call this phenomenon "atrophy". The condition is frequently misdiagnosed as lichen planopilaris (another scarring hair loss condition). The two conditions are similar but lichen planopilaris has more redness and scaling than PPB and is generally more responsive to treatment. Treatment of PPB is similar to LPP and includes topical steroids, topical calcineurin inhibitors, doxycycline, hydroxychloroquine, steroid injections and similar anti-lymphocytic agents.


Dr. Jeff Donovan is a Canadian and US board certified dermatologist specializing exclusively in hair loss. To schedule a consultation, please call the Whistler office at 604.283.1887
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Biologic Agents and LPP: What do they teach us?

Biologic Agents in Lymphocytic Scarring Alopecia

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

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

 

CATEGORY 1: Monoclonal Antibodies

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

 

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

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

 

b) Anti-CD20: Rituximab

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

 

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

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

 

d) Anti-LFA1: Efalizumab

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

 

e) Anti-CD2 antibody: Siplizumab

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

 

f) Anti-CD4 antibody: Orthoclone (OKTcdr4a)

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

 

g) Anti-CD25 antibodies: Basiliximab, Daclizumab

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

 

h) Anti-CD80r: Galiximab (IDEC 114)

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

 

i) Anti-IgE: Omalizumab

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

 

CATEGORY 2: Fusion Antibody Proteins

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

a) Etanercept

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

 

b) Alefacept

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

 

c) Abatacept

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

 

d) Denileukin Diftitox

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

 

CATEGORY 3: Recombinant human cytokines and growth factors

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

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

 

REFERENCE

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

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

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

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

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

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

 


Dr. Jeff Donovan is a Canadian and US board certified dermatologist specializing exclusively in hair loss. To schedule a consultation, please call the Whistler office at 604.283.1887
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What are the side effects of Low Dose Naltrexone (LDN)?

Low dose naltrexone: What side effects are possible?

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

DOWNLOAD LDN HANDOUT

 

Side effects: What side effects are possible?

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

 

1. Difficultly sleeping.

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

 

2. More vivid dreams.

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

 

3. Reduced need for thyroid medication.

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

4.  Headaches.

Headaches have been noted to be increased compared to placebo. 

 

5. Anxiety (rare).

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

 

6. Tachycardia (increased heart rate)

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

 

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

 

Side effects in the clinical studies

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

 

1.  Younger and colleagues, 2013. 

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

SOURCE: Younger and colleagues. Arthritis Rheumatism 2013. 

SOURCE: Younger and colleagues. Arthritis Rheumatism 2013. 

 

2. Mischoulon et al, 2017

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

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

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

 

3. Laser Sharafaddinzadeh et al, 2010

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

 

4. Mohammad Ali Seifrabiei et al, 2008

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

Mohammad Ali Seifrabiei et al. Am J Applied Sciences 2008

Mohammad Ali Seifrabiei et al. Am J Applied Sciences 2008

 

5. Smith et al, 2013

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

 

References

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

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

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

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

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

 

 


Dr. Jeff Donovan is a Canadian and US board certified dermatologist specializing exclusively in hair loss. To schedule a consultation, please call the Whistler office at 604.283.1887
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Lichen Planopilaris: Beard and Facial Hair

Beard and Facial Hair

lpp-beard:facial.png

Beard hair loss in men can be due to a variety of causes. Alopecia areata is among the more common of these and presents with asymptomatic patches of hair loss. A variety of conditions given hair loss accompanied by redness and even permanent hair loss. Lichen planopilaris, folliculitis decalvans and discoid lupus are three important conditions to consider in males presenting with apparent scarring in the beard region. This photo shows a 68 year old male with beard loss from lichen planopilaris. In my experience, most individials with beard LPP tend to have a more aggressive form of scalp LPP. Treatment of beard LPP is similar to the principles of treating scalp LPP and includes topical steroids, steroid injections, calcineurin inhibitors, and systemic agents such as docycycline, methotrexate, hydroxychloroquine, mycophenolate, cyclosporine and sometimes retinoids.


Dr. Jeff Donovan is a Canadian and US board certified dermatologist specializing exclusively in hair loss. To schedule a consultation, please call the Whistler office at 604.283.1887
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Lichen Planopilaris (LPP): Many different presentations

Many Different Presentations

lpp-presentations.png

Lichen planopilaris (LPP) is one of the more commonly encountered of the approximately one dozen different so called “primary scarring alopecias.” Lichen planopilaris can present very differently in different patients. Some patients have tremendous itching, or burning or scalp tenderness and other patients have none. Some have intense redness in the scalp (like the patient here in this photo) and others have only subtle pinkness. Some have scaling around hairs (such as in the photo here), and others have little to none. Despite these differences, all patients with LPP share in common an inflammatory process directed towards select hair follicles that has the potential to lead to its destruction. Responses to treatment also differs with some responding very well to even limited therapies and others responding poorly to even aggressive systemic immunosuppressive treatments. 


Dr. Jeff Donovan is a Canadian and US board certified dermatologist specializing exclusively in hair loss. To schedule a consultation, please call the Whistler office at 604.283.1887
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Low level laser for Lichen Planopilaris: Early Data

Does low level laser therapy (LLLT) help LPP?

lllt

Lasers are popular nowadays, especially as patents search for drug free alternatives. For patients with scarring alopecia, a variety of lasers are known to help. For patients with lichen planopilaris, treatment with the excimer laser has shown promising results in early studies.   In a new study, Fonda-Pascual and colleagues from Spain set out to examine the benefits of LLLT in 40 patients with lichen planopilaris. 

The study itself was designed as a 6 month prospective interventional study and the goal was to follow the activity of the disease before and after treatment using the so called lichen planopilaris activity index (LPPAI).  Videodermoscopy was used to follow 5 specific areas for perifollcular redness and perifollicular scale and to follow hair thickness. 

The study was small with 8 patients (3 males 5 females). Patient had LPP for an average of 3-4 years (mean 44.25 months). A laser helmet based device with 246 LEDs was used (each with a wavelength of 630 nm and fluency of 4 J/cm2).

Interestingly, all patients had a reduction in symptoms, redness and scaling and there was a decrease in the LPPAI after 6 months. An increase in hair thickness was also measured. 

 

CONCLUSION

This is an interesting preliminary study. More studies are needed on the potential benefits of LLLT. The inflammation in LPP is generally quite high up in the skin and these laser devices only penetrate a short distance into the skin making them potentially effective agents to target the inflammation in these scarring alopecias. This research study is primarily and details about other treatments used by these 8 patients were not given.  Nevertheless, it has prompted interest in further investigations in this important area.

 

REFERENCE

Fonda-Pascual P, et al. Effectiveness Of Low-Level Laser Therapy In Lichen Planopilaris. J Am Acad Dermatol. 2017.


Dr. Jeff Donovan is a Canadian and US board certified dermatologist specializing exclusively in hair loss. To schedule a consultation, please call the Whistler office at 604.283.1887
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Treatment of AKN with Long Pulsed Alexandrite Laser

AKN: Long pulsed Alexandrite as an option

AKN-image

Acne keloidalis nuchae is a scalp condition that commonly affects the back of the scalp. Patients develop what they frequently term 'bumps' at the back of the scalp. These frequently are associated with hair loss and the bumps themselves may stay and enlarge. In advanced cases the areas coalesce to form a large plaque. 

Treatments for AKN include topical steroids, antibiotics, retinoids, steroid injections. A variety of laser treatments may also be possible.  In previous studies the 810-nm diode laser and 1,064-nm Nd:YAG laser have been used for treating AKN with promising results.

Tafnik and colleagues set out to study the benefits of the 755-nm alexandrite laser in 16 male patients with AKN. Their study showed a significant decrease in the mean papule, pustule count, keloidal plaque size, and pliability at the fourth and sixth laser sessions when compared with baseline. The main complication was a temporary reduction in hair density in the treated area in 4 of 16 patients as a result of the laser treatment. This was accepted by the patients because of its reversible course.  No lesional recurrence was detected in the follow-up period.

 

STUDY CONCLUSION

This study provides evidence that the 755-nm alexandrite laser may provide options for treating AKN. The laser appears safe and effective in the condition and recurrence rates are fortunately low. 

 

REFERENCE

Tawfik A, et al. A Novel Treatment of Acne Keloidalis Nuchae by Long-Pulsed Alexandrite Laser. Dermatol Surg. 2018.

 


Dr. Jeff Donovan is a Canadian and US board certified dermatologist specializing exclusively in hair loss. To schedule a consultation, please call the Whistler office at 604.283.1887
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Pulsed Azithromycin for Folliculitis Decalvans

Pulsed therapy for Folliculitis decalvans

Folliculitis decalvans is a type of scarring alopecia and causes permanent hair loss. Affected individuals develop crops of papules, and pustules. The most effective treatment options are antibiotics and isotretinoin. 

 

Pulsed Therapy for FD

In an effort to reduce side effects from the daily use of a drug, "pulsed therapy" is frequently used for some medications. Pulsed therapy refers to delivery of a medication for short periods of time (i.e. the 'pulse') followed by periods of time whereby the patient does not receive any medications at all.  Pulsed therapy is common with oral steroids, oral anti-fungal medications as well as some antibiotics.

A new study has examined the possibility of using pulses of azithromycin to treat folliculitis decalvans.  The researchers studied 19 patients with mean age 27 years. Treatment was with azithromycin 500 mg per day for 3 consecutive days and repeated every 2 weeks. The severity of the disease was evaluated before treatment and after 1, 3 and 6 months.  

The study showed that azithromycin reduced the number of lesions as well as the disease activity. 

 

Conclusion

Pulsed azithromycin is among the antibiotic options for FD. Pulses of azithromycin are sometimes used as treatments for acne so this method of using azithromycin in a pulsed manner is not new. Side effects of azithromycin should be carefully review before starting. 

Download our Azithromycin Handout for Patients

 

REFERENCES

Andre MC et al. Effective Treatment of Folliculitis Decalvans: Azithromycin in Monotherapy. Hair Therapy and Transplantation. 

Antonio JR et al. Azithromycin pulses in the treatment of inflammatory and pustular acne: efficacy, tolerability and safety.J Dermal Treatment 2008;19(4):210-5. doi: 10.1080/09546630701881506.

Parsad D et al. Azithromycin monthly pulse vs daily doxycycline in the treatment of acne vulgaris.J Dermatol. 2001 Jan;28(1):1-4.

 


Dr. Jeff Donovan is a Canadian and US board certified dermatologist specializing exclusively in hair loss. To schedule a consultation, please call the Whistler office at 604.283.1887
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