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 Delamere FM, Sladden MJ, Dobbins HM, Leonardi-Bee J. Interventions for alopecia areata. Cochrane Database of Systematic Reviews 2008, Issue 2. Art. No.: CD004413. DOI: 10.1002/14651858.CD004413.pub2. Assessed as up-to-date: 4 DEC 2007. Published Online: 16 JUL 2008. Cochrane Skin Group

Free download 

onlinelibrary.wiley.com/doi/10.1002/14651858.CD004413.pub2/pdf

 onlinelibrary.wiley.com/doi/10.1002/14651858.CD004413.pub2/full

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Petukhova L et al. Genome-wide association study in alopecia areata implicates both innate and adaptive immunity. Nature 2010 Jul 1; 466:113.

A genome-wide association study of AA reveals shared pathways with other autoimmune diseases, as well as a novel mechanism in triggering autoimmunity.

The fundamental mechanisms underlying the autoimmune attack in alopecia areata (AA) are still unknown. To tease apart the genetic causes of AA, investigators undertook a genome-wide association study (GWAS) using a sample of 1054 cases in the National Alopecia Areata Registry and 3278 controls from other studies.

The researchers found 139 single nucleotide polymorphisms that were strongly and significantly associated with AA. They found strong associations in regions linked to other autoimmune diseases — in particular, CTLA4, IL-2/IL-21, IL-2RA and genes critical to T-cell regulation — as well as a strongly associated region in the ULBP gene cluster. The ULBP gene appears to be a stress-induced molecule that serves as a danger signal to alert NK, natural killer T, T, and CD8⁺ T lymphocytes. ULBP was highly upregulated in early active AA follicles (but not in normal follicles) in two patients. The researchers speculate that upregulation of ULBP3 in the dermal sheath of the hair follicle induces activation of CD8⁺NKG2D⁺ cytotoxic T cells, which are likely responsible, at least in part, for the observed hair loss in AA.

Comment: The GWASs just keep coming. This is a nice study that defines a unique disease mechanism for AA but also demonstrates a shared pathway with other autoimmune disorders, validating the "common-cause" hypothesis of autoimmune disease. The GWAS revealed several risk loci that have been implicated in rheumatoid arthritis, type I diabetes, celiac disease, systemic lupus erythematosus, multiple sclerosis, and psoriasis. The common-cause hypothesis is attractive, because it ties together many disparate autoimmune phenomena into a single, central immunologic disorder. How, when, and why select organs are targeted, and why certain autoimmune conditions favor women, are unknown. A central hypothesis raises the possibility of a coordinated search for novel therapies aimed at these phenotypically distinct conditions.

NIH Public Access   www.ncbi.nlm.nih.gov/pmc/articles/PMC2921172/pdf/nihms226472.pdf

A conversation about genes with Dr. Angela Christiano      www.charlierose.com/view/interview/5111

www.youtube.com/watch?v=t2AtNYrg7tM&hd=1

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Quercetani R, Rebora AE, Fedi MC, Carelli G, Mei S, Chelli A, Poli E. Patients with profuse hair shedding may reveal anagen hair dystrophy: a diagnostic clue of alopecia areata incognita.J Eur Acad Dermatol Venereol. 2011 Jul;25(7):808-10.

Several patients, especially women, seek advice because of hair loss. They may be diagnosed clinically as having telogen effluvium (TE) or androgenetic alopecia (AGA), but histopathology may reveal that a proportion of them have in fact alopecia areata incognita (AAI). We studied 1932 patients with hair loss and no signs of classical alopecia areata. They were submitted to the modified wash test (which counts the total number of telogen hairs lost and the percentage of vellus hairs) and divided into patients having pure TE (403), patients with AGA + TE (1235) and patients with pure AGA (294). Dystrophic hairs were detected with a low magnification microscope.  Dystrophic hairs were observed in 13 patients with TE (3.2%), in 54 with AGA + TE (4.4%) and in none with AGA. In addition, 7 patients with TE and 32 with AGA + TE developed small patches of alopecia areata in 6 to 9 weeks. No patches developed in patients with AGA.

Conclusions  The presence of dystrophic hairs and the development of patches of alopecia areata (and their absence in pure AGA) provide a first evidence of the possibility that within the heterogenous condition named TE some patients have in fact AAI.

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The approval of the prostaglandin analog Latisse (bimatoprost ophthalmic solution 0.03 percent) represents a major advance in offering a solution for cosmetic enhancement of eyelashes.In Dr. Glaser's experience with patients, she says they begin to see results from their use of Latisse as soon as four weeks of application of the topical therapy. Patients see the full effect, including the darkening and thickening of eyelashes, after 12 to 16 weeks. Latisse (bimatoprost ophthalmalic solution 0.03 percent, Allergan) described as "user-friendly" Drug is being studied in pediatric cancer patients to determine whether it stimulates faster eyelash growth in children treated with chemotherapy

As a prostaglandin analog, it (Latisse) stimulates the hair follicles to enter and prolong the growing phase or anagen phase. While 90 percent of all scalp hairs are in the growing phase at any time, less than half of eyelash hairs are in the anagen phase at a specific point in time.  Only about 40 percent of hair on the eyelashes are in the growing phase at any one time," she says. "The majority are in the resting (telogen) phase."

"Lashes look longer, darker and fuller, lashes also look darker because the prostaglandin analog stimulates pigment production", she says.

One of the benefits of Latisse is that it is user-friendly, Dr. Glaser says. A single drop is brushed along the eyelid margin like an eyeliner. If used according to the product monograph, one prescription will last a patient about one month.

It is recommended that a physician, either a dermatologist or an ophthalmologist, take a detailed patient history to ensure patients do not have any pre-existing eye problems before they are prescribed Latisse.

The impact of the application of Latisse is transient, Dr. Glaser says. "The problem is that when you stop the medication, the lashes slowly return to their baseline length," she says. "The lashes go back to where they were over three to four months." Patients were monitored for one month in the clinical trial, Dr. Glaser says, and the effect of Latisse was maintained for at least one month.

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 Müller, C. S. and Shabrawi-Caelen, L. E. (2011), ‘Follicular Swiss cheese’ pattern – another histopathologic clue to alopecia areata. Journal of Cutaneous Pathology, 38: 185–189. doi: 10.1111/j.1600-0560.2010.01640.x 

Yellow dots are the most useful dermoscopic criterion in the clinical diagnosis of alopecia areata and correspond histopathologically with dilated follicular infundibula. They are found in about 95% of alopecia areata cases and help to differentiate alopecia areata from trichotillomania, telogen effluvium and from scarring alopecias. Histopathology of alopecia areata differs with disease activity and dermatopathologist, therefore, heavily depends on other diagnostic features. Objective of the study was to determine the frequency of dilated follicular infundibula, peribulbar lymphocytic infiltrate, inflammatory infiltrates of lymphocytes and eosinophils within fibrous streamers and a shift to catagen/telogen follicles in alopecia areata. Histopathologic features of 56 specimens of 33 patients were correlated with clinical findings and alopecia areata subtype.

Results: 57% of all biopsies showed dilated follicular infundibula, regardless of horizontal or vertical sectioning of the slides. Dilated follicular infundibula showed a maximum occurrence of 66% in the recovery stage of alopecia areata and were seen in 33% of alopecia areata incognita.

In conclusion, dilated follicular infundibula, reminiscent of a Swiss cheese in horizontally sectioned slides, is an exceedingly useful criterion in the histopathologic diagnosis of alopecia areata and are of great help in the daily routine to recognize alopecia areata.

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Doyle LA et al. Psoriatic alopecia/alopecia areata–like reactions secondary to anti–tumor necrosis factor-α therapy: A novel cause of noncicatricial alopecia. Am J Dermatopathol 2011 Apr; 33:161.

Anti–tumor necrosis factor (TNF) drugs are an important part of the therapeutic battery for the treatment of autoimmune disease, including psoriasis, inflammatory bowel disease, and rheumatoid arthritis. However, initiation of TNF inhibitor therapy in patients with no history of psoriasis can lead to the development of scaly plaques and alopecia.

The patients had large, scaly patches on the trunk and extremities along with the nonscarring alopecia on the head. Scalp samples revealed epidermal psoriasiform hyperplasia, hypogranulosis, and the presence of neutrophils. Follicular buds in the deep dermis exhibited lymphocytic and plasmacytic infiltrates associated with eosinophils. The researchers also found miniaturization of hairs and increased numbers of catagen/telogen hairs. Non-scalp samples showed psoriasiform epidermal changes, with plasma cells and eosinophils. Topical steroid treatment significantly improved the alopecia in two patients.

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Hordinsky MK. Treatment of alopecia areata: "What is new on the horizon?"  Dermatol Ther. 2011 May;24(3):364-8.

New drug treatment opportunities based on the results of a genome-wide association study, which implicate T cell and natural killer (NK)-cell activation pathways, are leading to new approaches in future clinical trials of alopecia areata. Special attention is being given to the UL 16-binding protein (ULBP3) gene cluster on chromosome 6q25, as these genes make the NKG2D-activating ligand or signal that can trigger the NKG2D receptor, initiating an autoimmune response. A greater expression of ULBP3 has also been found in hair follicles in scalp biopsy specimens from patients with active disease.

It is now postulated that the characteristic T cell "swarm of bees" infiltrate seen in alopecia areata is the result of T cells being attracted to the hair follicle by NKG2D-activating ligands. Future treatment approaches for alopecia areata include use of drugs that: (i) block the NKGD-activating ligand and NKG2D receptor interaction, (ii) halt activated T cells, or (iii) modification of the inflammatory cytokine network. Many drugs currently being used or being evaluated for other autoimmune diseases that work through these mechanisms might prove to be very effective in alopecia areata.

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Szu-Ying Chu, Yi-Ju Chen, Wei-Cheng Tseng,  et al. Comorbidity profiles among patients with alopecia areata: The importance of onset age, a nationwide population-based study. Journal of the American Academy of Dermatology. Volume 65, Issue 5 , Pages 949-956, November 2011.

Alopecia areata (AA) is considered an autoimmune disease with undetermined pathogenesis. Age at onset predicts distinct outcomes. A nationwide study of the relationship of AA with associated diseases stratified by onset age has rarely been reported.

We sought to clarify the role of atopic and autoimmune diseases in AA, thereby better understanding its pathogenesis.

A total of 4334 patients with AA were identified from the National Health Insurance Database in Taiwan from 1996 to 2008. A national representative cohort of 784,158 persons served as control subjects.

Results

Among patients with AA, there were significant associations with vitiligo, lupus erythematosus, psoriasis, atopic dermatitis, autoimmune thyroid disease, and allergic rhinitis. Different ages at onset resulted in disparate comorbidities. Increased risk of atopic dermatitis (odds ratio [OR] 3.82, 95% confidence interval 2.67-5.45) and lupus erythematosus (OR 9.76, 95% confidence interval 3.05-31.21) were found in childhood AA younger than 10 years. Additional diseases including psoriasis (OR 2.43) and rheumatoid arthritis (OR 2.57) appeared at onset age 11 to 20 years. Most atopic and autoimmune diseases were observed at onset ages of 21 to 60 years. With onset age older than 60 years, thyroid disease (OR 2.52) was highly related to AA. Moreover, patients with AA had higher risk for more coexisting diseases than control subjects. AA is related to various atopic and autoimmune diseases. Different associated diseases in each onset age group of AA can allow clinician to efficiently investigate specific comorbidities.

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P. Rubegni, F. Mandato,^* and M. Fimiani. Case Rep Dermatol. 2010 Jan–Apr; 2(1): 40–45.

 Frontal fibrosing alopecia (FFA) is more common in postmenopausal women, but it can occur in younger women. Some authors consider FFA to be a distinct frontal variant of lichen planopilaris.

Dermoscopy can be very useful, as the differential diagnosis between traction alopecia, alopecia areata, FFA and cicatricial marginal alopecia may be difficult. It is not clear whether or not treatment alters the natural history of the disease - the disease stabilized with time in most of the patients with or without continuing treatment. Here we report a case of a 50-year-old woman with FFA and discuss the relevance of dermoscopy in the differential diagnosis of this disease.

Free download  www.ncbi.nlm.nih.gov/pmc/articles/PMC3004211/pdf/cde0002-0040.pdf

DOI: https://dx.doi.org/10.2147/CCID.S22767

Adel Alsantali

Many therapeutic modalities have been used to treat alopecia areata, with variable efficacy and safety profiles. Unfortunately, none of these agents is curative or preventive. Also, many of these therapeutic agents have not been subjected to randomized, controlled trials, and, except for topical immunotherapy, there are few published studies on long-term outcomes. The treatment plan is designed according to the patient's age and extent of disease. In this paper, the therapeutic agents are organized according to their efficacy and safety profiles into first-line, second-line, and third-line options.

Clinical, Cosmetic and Investigational Dermatology 2011:4 107–11

Full article downloads  dovepress.com/alopecia-areata-a-new-treatment-plan-peer-reviewed-article-CCID

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Chew A-L et al. Expanding the spectrum of frontal fibrosing alopecia: A unifying concept. J Am Acad Dermatol 2010 Oct; 63:653. 

Histologic — but not always clinical — evidence of FFA can be found on the eyebrow or extremities as well as on the scalp.

Frontal fibrosing alopecia (FFA) is a scarring alopecia affecting the frontotemporal or frontoparietal hairline that occurs most frequently — but not exclusively — in postmenopausal women. The disease is characterized histologically by a lichenoid inflammation and thus is considered to be a variant of lichen planopilaris.

Identifying the pathogenesis of scarring alopecia can be a daunting task, especially when the process is advanced. Histologic analysis of specimens from different anatomic locations allowed these authors to confirm that FFA is a generalized form of ichenoid dermatitis and demonstrated that searching for clues away from the scalp, such as loss of hair in the eyebrow and decreased density of hair in the extremities and axilla, can help in the diagnosis. However, the clinician should be aware that clinical features of FFA on the scalp — perifollicular erythema, scaliness, or papules — are not reliably present at the peripheral body sites.

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Otberg N. Systemic treatment for alopecia areata. Dermatol Ther. 2011 May;24(3):320-5.

Of the world population, 1.7% is suffering from alopecia areata at some point in their lives. The exact etiology of this disease is still unknown, and the course of the disease is unpredictable. Effective treatments, especially for severe multifocal alopecia areata, alopecia areata totalis, and alopecia areata universalis, are lacking. The present article will discuss side effects and relapse rates of different systemic agents for treatment of severe and rapid progressive alopecia areata.

Pub med link  www.ncbi.nlm.nih.gov/pubmed/21689241

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Steven J. Peckham, Steven B. Sloan, Dirk M. Elston.

Histologic features other than a lymphocytic infiltrate around follicular bulbs are now recognized as helpful clues to the diagnosis of alopecia areata, especially in long-standing lesions where the peribulbar lymphocytic infiltrate may be sparse or absent.

We sought to determine the frequency of peribulbar lymphocytic infiltrates, eosinophils, lymphocytes, and melanin in fibrous tracts, pigment casts in follicles, the presence of catagen/telogen follicles, follicular miniaturization, and dystrophic (“nanogen”) follicles in alopecia areata. Secondly, we sought to compare the diagnostic use of transversely sectioned versus horizontally sectioned specimens in those cases for which both were available (15 of 109 cases). The pathology archives of Geisinger Medical Center (Danville, PA), Wilford Hall US Air Force Medical Center (San Antonio, TX), and Brooke US Army Medical Center (San Antonio, TX) were searched for the term “alopecia areata” in the diagnostic field from the period of 1991 to 2006, which yielded 109 cases with sections suitable for review. Cases from the two military institutions from 1997 or earlier were excluded to avoid any overlap with data previously reported by our group.

Results

A peribulbar lymphocytic infiltrate was present in 92 specimens (84%), eosinophils in fibrous tracts in 48 (44%), lymphocytes in fibrous tracts in 102 (94%), melanin within fibrous tracts in 92 (84%), pigment casts within follicular canals in 46 (44%), catagen follicles in 101 (93%), and miniaturized follicles in 98 (90%). Dystrophic miniaturized follicles were rare (4 cases). In 14 of 15 cases with both vertical and transverse sections, either was diagnostic. One case showed diagnostic features only in vertical sections.

Limitations

Comparable vertical and transverse sections were only available for a limited number of the cases. We did not correlate duration of disease with individual findings. Our results were correlated with the clinical diagnosis but not with serologic tests for syphilis.

Conclusions

Although most specimens showed evidence of a peribulbar lymphocytic infiltrate (84%), a higher percentage showed evidence of follicles in catagen/telogen phase (93%) and evidence of miniaturization of follicles (90%). This could lead to an incorrect diagnosis of trichotillomania or pattern alopecia. Pigment casts within the hair canal were also found in a significant number of follicles, especially in catagen follicles, creating further potential for misdiagnosis as trichotillomania. A significant percentage showed evidence of eosinophils (44%), melanin (84%), and lymphocytes (94%) in fibrous tracts. These features are particularly helpful when a peribulbar lymphocytic infiltrate is lacking. Vertical and transverse sections appear comparable.

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