Alopecia areata (overview) L63.8

Author: Prof. Dr. med. Peter Altmeyer

Co-Autor: Dr. med. Antje Polensky

All authors of this article

Last updated on: 04.11.2021

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Synonym(s)

alopecia areata; Area Celsi; Circular hair loss; Hair Loss; Pélade

History
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Celsus, 30-60 AD; Sauvages, 1706

Definition
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Mostly reversible, sudden onset, symptomless, circular hair loss of varying severity and unknown cause (autoimmunological factors are discussed), histomorphologically based on an anagen effluvium. Rare are foudroyant processes with complete baldness ("balding overnight").

Classification
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A distinction is made between:

Occurrence/Epidemiology
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Incidence unclear; concerns about 1% of the dermatological patients. The lifetime risk for the occurrence of alopecia areata is 1.7%. The prevalence is given as 0.1-0.2%. There is no clear sex preference.

Etiopathogenesis
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Discussed:

  • Infectious allergic triggering!
  • Genetic predisposition (e.g. gene locus TRAF1/C5)
  • Autoimmunological factors (frequent comorbidity with thyroid diseases, about 20% of patients show an increase in anti-TPO antibodies or anti-TG antibodies)
  • AA patients often have lower serum vitamin D levels than control groups. The prevalence of vitamin D deficiency is also increased. Therefore, the authors recommend checking vitamin D levels in patients with circular hair loss.
  • Atopic diathesis (familial occurrence in 10-25% of cases, frequent concordant occurrence in identical twins and associations with various HLA markers: DR-4, DR-5, DR-6, DR-7, DR-11, DQ3, DQB-1).
  • Psychological factors (probable; scientific evidence lacking).
  • Environmental factors (e.g. toxins) are discussed, sustainable evidence is lacking
  • Immunology: Affected hair follicles lose their "immune privilege" (hair follicles are protected from immune system assault by a lack of MHC and ICAM-1 expression) and, in contrast to healthy hair follicles, express more MHC and ICAM class surface molecules. This allows the presentation of hair follicle antigens. The detection of these autoantigens and the detection of CD4- and CD8-lymphocytes speaks for a T-cell mediated autoimmune pathogenesis. However, CD8 T cells seem to play a central role in the pathogenesis: depletion of CD8 cells leads to hair growth. In this process, the Janus kinase (JAK) signaling pathway seems to play an important role. JAK inhibitors (Ruxolitinib) have been successfully used in some patients.
  • Further molecular biological findings such as an increased expression of cytokines (IL-1 beta, IL-2 and interferon gamma) in lesional scalp still need to be evaluated. The initiators of these events are unknown.

Manifestation
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Frequency peaks in the 2nd and 3rd decade of life. According to statistics only about 6% of patients are older than 60 years. The youngest patient described was 2 months old.

No clear gender preference, although in some collectives a female dominance can be observed (m:w=3:7).

Family clustering demonstrable (about 25-30% of patients).

Localization
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In most cases the capillitium is affected (about 70%).

Other sites are:

  • eyebrows and eyelashes (1,5%)
  • Whiskers (1.5%)
  • underarm and pubescent hair
  • Rarely extremities or trunk hairs.

Clinical features
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Clinical course:

  • The clinical picture can be extraordinarily variable. The disease usually begins with a single focus of complete health, so to speak "overnight". Local symptoms are absent.
  • Typically, there are circular, centrifugally spreading, possibly confluent, non-inflammatory, rather pale bald patches (no erythema formation in the affected areas).
  • In the active marginal area, tufts of hair can be painlessly pulled out as telogenic or dystrophic hairs (see hair cycle below).
  • In the active marginal area, pathological stubby hairs are produced (exclamation mark hairs, cadaver hairs - see fig. below).
  • Follicles always remain visibly intact (important differentiation from scarring alopecias, in which the follicles are destroyed).
  • After weeks to months, hair growth starts again; frequently, regrowing hairs are depigmented. The temporal course of a.a. is mostly chronic, accompanied by relapses and remissions. Relapses can lead to extensive infestation or even universal baldness within a few days.
  • A striking observation is that in mottled gray patients, the gray hairs are initially spared. In the case of massive hair loss, this can lead to "greying overnight".

There are 4 degrees of severity:

  • Grade 1: Single foci or multiple foci, < 30% of the capillitium.
  • Grade 2: Multiple foci > 30% of the capillitium
  • Grade 3: Alopecia of the entire capillitium (alopecia areata totalis)
  • Grade 4: Alopecia of the entire integument (alopecia areata universalis).

Prognostically unfavourable sign with regard to the progression of the foci: exclamation mark hairs or comma hairs as well as cadaveric hairs in the form of comedone-like "points noirs".

Histology
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Dense, lymphocytic perifollicular infiltrate with focal follicular infiltration: Only hair follicles of the anagen phase are affected. Pathology: Damage of the follicle by the infiltrate; interruption of the anagen phase; dystrophy of the hair shaft with resulting breakage, incomplete keratinization (exclamation mark hair) or loss. Reduction to a miniature follicle; cyclic renewal of the hair follicle (catagen/telogen) is maintained, while the infiltrate recedes. The new anagen phase leads either to a new infiltrate attack or spontaneous hair growth.

Therapy
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Therapy trials should have proven their effectiveness in controlled studies. They should continue to achieve a cosmetically satisfactory result and have no serious or lasting side effects.

General therapy
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In mild forms, the external therapy options can be exhausted; in rapidly progressive forms, internal therapy can be used directly.

Resistance to therapy: In case of alopecia that cannot be influenced therapeutically, a wig should be prescribed. In extensive cases of alopecia areata this should of course be done at the start of therapy.

External therapy
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Glucocorticoids, topical: Brush single foci 2 times/day, e.g. prednicarbate (Dermatop solution), mometasone furoate (e.g. Ecural solution), triamcinolone acetonide (e.g. Volon A tincture). Treatment up to about 1 cm into the healthy appearing area. Therapy results are unsatisfactory.

Alternative: Intrafocal, strictly intracutaneous injections (use of a dermojet) of triamcinolone crystal suspension (e.g. Volon A 10 diluted 1:3 with LA such as mepivacaine), are therapy of choice for treatment of single foci. Caution. Injections in the temporal and anterior parietal region, risk of crystals spreading into the retinal arteries with subsequent blindness. Hair regrowth approx. 4-6 weeks after start of treatment. Long-term success is questionable.

Alternative: Calcineurin inhibitors: In studies Pimecrolimus (e.g. Elidel, Douglan) was applied 2 times/day to the lesional areas. Good results are explicitly described in the case of alopecia areata within the atopic circle of forms. At present, calcineurin antagonists are exclusively approved for the treatment of the atopical eczema so that the use in alopecia areata is an off-label use. Strictest indication because of unclear long-term side effects!

Alternative: Dithranol: Also described is the production of a toxic contact ec zema by dithranol, initially 0.05%, in increasing concentration. Daily applications. Education about dithranol therapy required (see also under psoriasis vulgaris).

Alternative: benzyl nicotinate: hyperaemia with 2% benzyl nicotinate or other substances stimulating the blood circulation (e.g. head tincture hyperaemia, Rubriment). Application of the essences on the hairless areas. After introduction, the patient can perform this treatment independently if necessary.

Imiquimod (Aldara 5% cream): Casuistry reports good results (off-label use).

Other:

  • External treatments with minoxidil (e.g. Regaine), tretinoin (e.g. Cordes VAS cream, Pigmanorm cream) or ciclosporin A may be tried.
  • Barrón-Hernández YL et al. 2017 reported good results for alopecia areata in the eyebrow and eyelid area using the locally applicable prostaglandin derivative bimatoprost, which has a primary ophthalmologic indication (elevated intraocular pressure). A known "side effect" of this preparation is eyelash growth and an increased eyelash pigmentation (see below eyelash extension by prostaglandin analogues).
  • Thymuskin is reported to have shown a beneficial effect on hair growth in small cohorts of studies.

Radiation therapy
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PUVA therapy locally ( PUVA bath therapy or PUVA cream therapy). Application of methoxaline is also possible in form of a PUVA-turban. Determination of the MPD to determine the initial UVA dose then slow increase of the UVA dose. Informing the patient about increased light sensitivity in the treated areas.

Recommendation: PUVA therapy 3-4 times/week. If resistance to therapy can be proven after 20-30 treatments: discontinue therapy. Proof of effectiveness from placebo-controlled studies is missing. According to our own experience, successes are verifiable, but unfortunately there is a high recurrence rate and no long-term success!

Internal therapy
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  • Glucocorticoids, systemic (numerous publications): In rapidly progressive courses, try methylprednisolone (e.g. Urbason), initially 20-60 mg p.o., after 2-3 weeks reduction below the Cushing's threshold. Duration of therapy: 6-8 weeks. Only morbostatic effect is to be expected, regrown hairs fall out again after discontinuation of therapy, only in 20% of cases hairs remain.
  • Glucocorticoid pulse therapy: In a randomized placebo-controlled trial, significant improvements were demonstrated with glucocorticoid pulse therapy (prednisolone 1 time/week 200 mg p.o. for 3 months). Alternative pulse therapy was reported to be 5mg/kgKG p.o. every 4 weeks (repeat 9-12x).
  • Alternative: Dapsone (e.g. dapsone-fatol ): 100 mg/day p.o. for months has also been reported to favourably influence the course in adults. The effect is controversial.
  • Alternative: Ciclosporin A (e.g. Sandimmun, Optoral): Highly dosed (4-6mg/kgKG/day), if necessary in combination with glucocorticoids (prednisolone 4-5mg/p.o. /day) effective; due to the known side effects of ciclosporin A, the treatment is only justifiable in individual cases. High relapse rate after discontinuation of therapy.
    • Ciclosporin A - low dose application: Low dose application (50-100 mg p.o./day) is currently being clinically tested (with good success - personal experience).
  • Alternative: Methotrexate: 10-15mg p.o./week gfls. in combination with glucocorticoids (prednisolone 10-20mg p.o./day).
  • Experimental: JAK inhibitors(Ruxolitinib) have been successfully used in some patients. Jabbari et al 2018 conducted a study with JAK inhibitor tofacitinib at a dose of 2x10mg/day. With this therapy, there was >50% regrowth in about 66% of affected individuals.
  • Supportive: Zinc hydrogen aspartate (e.g. Unizink 100®) 2 times/day 50mg p.o. or zinc sulfate (e.g. Solvezink®) 2 times/day 200 mg p.o. for at least 6-8 weeks. In addition, biotin (vitamin H), e.g. Bio-H-Tin® 1 tablet p.o. once a day for at least 6-8 weeks, improves hair and nail quality and reduces effluvium. These therapeutic approaches are controversially discussed.

Progression/forecast
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  • The prognosis depends on the extent, the number of bald spots, the duration (long clinical course means poor prognosis regarding healing) as well as on the clinical types (the ophiasis type has a particularly poor prognosis regarding healing).
  • As a rule of thumb, 30% of alopecia areata patients show regrowth or complete healing within the first 6 months. Within one year this figure is 50%, after 5 years 75%.
  • Spontaneous regrowth usually occurs in the centre of the bald spot and spreads to the periphery. Often thin, completely white downy hairs appear first, which are gradually replaced by longer, often still unpigmented hairs. It is only later that the hair begins to change colour normally. In older patients, the lesional hairs can remain white for a long time.

Tables
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Possible forms of treatment of alopecia areata depending on the degree of the disease

Therapy

disease severity

External

Hyperemic substances

Grade 1

vitamin A acid

Grade 1

Glucocorticoid tinctures or solutions

Grade 1

Diphenylcyclopropenone

grades 1-2

Dithranol

grades 1-3

PUVA local

grades 1-3

UV irradiation (SUP)

grades 1-4

Internal

Zinc

grades 1-4

Biotin (vitamin H)

grades 1-4

PUVA systemic

grades 2-4

Glucocorticoids

grades 3-4

Dapsone

grades 2-4

Note(s)
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The immunotherapy with diphenylcyclopropenone (alternatively: dibutyl squarate), formerly listed as standard therapy for alopecia areata, is obsolete today because of its side effects. It is only listed here for historical reasons:

Diphenylcyclopropenone (DPCP): Immunotherapy with contact allergens for severe, refractory forms of alopecia areata. Currently the most effective treatment modality. Caution. There are no commercial preparations (no drug in the sense of the law), the treating physician bears the full responsibility for the therapy and its NW! Single half-sided application of a 2% DPCP solution to the head to produce contact sensitization: 2-7 days of (desirable) burning and itching, eczema reaction. Next application of a highly diluted DPCP solution (0.001%) 14 days after sensitization, then 1 time/week. Slow increase of concentration. Titration to a dosage (individually very different) that causes an inflammatory reaction with redness and itching the next day and heals with scaling. Treatment 1 time/week initially for 6-12 months, possibly for years. Onset of action after approx. 10 applications. Accompanying therapy with steroid-free creams (e.g. Dermatop base cream etc.). Textile sun protection! In a larger study (142 patients) a "complete response" was observed in about 40% of the cases, a "partial response" in 15%, a "minimal response" in 20% and "no response" in about 30%.

Alternative: Square acid dibutyl ester (SADBE): Alternative to treatment with DPCP, see above.

Literature
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  1. Barrón-Hernández YL et al (2017) Bimatoprost for the treatment of eyelash, eyebrow and scalp alopecia. Expert Opinion Investig Drugs 26:515-522.
  2. Camacho FM et al (1999) Zinc aspartate, biotin, and clobetasol propionate in the treatment of alopecia areata in childhood. Pediatric Dermatol 16: 336-338
  3. Celsus AC (50-60 AD) De medicina. Liber VI, Caput IV, De areis
  4. Haneke E (2013) Nail diseases. dermatologist 64: 519-532
  5. Harrison S et al (2003) Optimal management of hair loss (alopecia) in children. At J Clin Dermatol 4: 757-770
  6. Jabbari A et al (2018) An Open-Label Pilot Study to Evaluate the Efficacy of Tofacitinib in Moderate to
  7. Severe Patch-Type Alopecia Areata, Totalis, and Universalis. J Invest Dermatol doi:10,1016/y.y.y.i.e. 2018.01.032.
  8. Kolde G et al. (2007) Successful treatment of the alopecia areata with Efalizumab. JDDG 9: 834
  9. Lutz G (2015) Thyroid diseases in alopecia areata - a critical review. JDDG 13 (Suppl 1) 18
  10. Ohlmeier MC et al (2012) Topical immunotherapy with diphenylcyclopropenone of patients with alopecia areata - a large retrospective study on 142 patients with a self-controlled design. JEADV 26: 503-507
  11. Safavi KH et al (1989) Incidence of alopecia areata in Olmsted County, Minnessota, 1975 through 1989 Mayo Clin Proc 70: 628-633
  12. Wiseman MC et al (2001) Predictive model for immunotherapy of alopecia areata with diphencyprone. Arch Dermatol 137: 1063-1068
  13. Xing L et al (2014) Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition. Nat Med 20:1043-1049

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Last updated on: 04.11.2021