Alopecia areata (overview) L63.8

Celsus, 30-60 AD; Sauvages, 1706

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

The severity of alopecia areata can be classified with the SALT score. This is calculated from the extent and degree of hair loss on the scalp and can also be used to monitor therapy.

A distinction is made between:

• Alopecia areata localisata
  • Special form: Alopecia areata of the ophiasistype
• Alopecia areata diffusa
• Alopecia areata totalis
• Alopecia areatauniversalis (maligna)
• Alopecia areata unguium.

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.

Alopecia areata is an autoimmune disorder in which hair follicles in the growth phase (anagen) prematurely transition to the non-proliferative regression phase (catagen) and the resting phase (telogen). The mechanisms leading to alopecia areata are not fully understood. The following are under discussion:

• Infection- or allergy-induced triggers!
• Genetic predisposition (e.g., the TRAF1/C5 gene locus); in trisomy 21 (Down syndrome), alopecia areata occurs at an above-average rate in 10% of cases. Furthermore, a link to the PTPN22, CTLA4, and IL2 genes is widely recognized. In addition, advances in genetic research have led to the discovery of an increasing number of specific gene-related loci. For example, genetic analysis of microRNAs can reveal the crucial role of miRNAs in regulating gene expression and thus contribute to our understanding of functional regulatory mechanisms in cells and organisms.
• Autoimmune factors (frequent comorbidity with thyroid disorders; approximately 20% of patients show elevated levels ofanti-TPO antibodies or anti-TG antibodies)
• AA and celiac disease: A link between AA and celiac disease (CD) was first demonstrated in 1995 (Corazza GR et al. 1995) and confirmed in subsequent studies, with prevalence estimates ranging from 1:85 to 1:116 (Mascart-Lemone F et al. 1995; Hallaji Z et al. 2011). A higher prevalence of alopecia areata and vitiligo was observed in patients with dermatitis herpetiformis compared to the general population. An increased prevalence of anti-gliadin antibodies is also associated with severe AA (alopecia universalis) (Mokhtari F et al. 2016). Ertekin et al. found that 41.7% of pediatric AA patients tested positive for IgA anti-tG antibodies. These patients showed total villous atrophy (Marsh type IIIc) on intestinal biopsy (Ertekin V et al. 2014). Hair growth resumed after eliminating gluten from their diet.  These findings suggest that CD screening is warranted for pediatric AA patients. Note:However, in a later study (2016), however, no significant difference in serological CD markers was found between the case and control groups (p=0.35), suggesting the need for alternative CD detection methods (Mokhtari F et al. 2016).
  • Summary: Despite limited evidence, a trial of a gluten-free diet (GFD) is recommended for refractory cases of alopecia areata (Muddasani S et al. 2021/Rusk AM et al. 2021).

• Alopecia Areata and Vitamin D: Patients with alopecia areata often have lower serum vitamin D levels than control groups. The prevalence of vitamin D deficiency is also elevated. The authors therefore recommend checking vitamin D levels in patients with alopecia areata.

• Alopecia Areata and Psoriasis: The risk of developing alopecia areata is approximately 2.71 times higher in patients with psoriasis than in healthy individuals (Jonas C et al. 2024)
• Alopecia Areata andAtopic Diathesis (familial occurrence in 10–25% of cases, frequent concordant occurrence in monozygotic twins, and associations with various HLA markers: DR-4, DR-5, DR-6, DR-7, DR-11, DQ3, DQB-1) 
• AA and psychological factors (possible; scientific evidence lacking)
• AA and environmental factors (e.g., toxins) are under discussion; conclusive evidence is lacking
• Immunology: Affected hair follicles lose their “immune privilege” (Hair follicles are protected from immune system attacks by a lack of MHC and ICAM-1 expression) and, in contrast to healthy hair follicles, express increased levels of MHC- and ICAM-class surface molecules. This enables the presentation of hair follicle antigens. The detection of these autoantigens and the presence of CD4- and CD8-lymphocytes support a T-cell-mediated autoimmune pathogenesis. However, CD8 T cells appear to play a central role in the pathogenesis: depletion of CD8 cells leads to hair regrowth. The Janus kinase (JAK) signaling pathway appears to play an important role in this process. JAK inhibitors (see “Treatment” below) have been used successfully in some patients. Further molecular biological findings, such as increased expression ofcytokines (IL-1 beta, IL-2, and interferon gamma) in the affected scalp, still need to be evaluated.

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 sex preference, although female predominance is noted in some collectives (m:w=3:7).

Familial clustering detectable (about 25-30% of patients; association with trisomy 21 and variations in the TRAF1 gene - Redler S et al. 2010).

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 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".

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.

1. Androgenetic alopecia: characteristic frontoparietal pattern of hair loss. Prolonged course spanning decades
2. Pseudopelade: not a nosological entity; refers to the final stage of nosologically distinct conditions (lichen planus, folliculitis decalvans; chronic discoid lupus erythematosus). Clinical presentation accordingly! 
3. Alopecia specifica diffusa: Diffuse alopecia; positive syphilis serology (an increasingly rare finding)
4. Microsporia: circumscribed, usually inflammatory alopecia; most commonly seen in children and adolescents. Mycological confirmation establishes the diagnosis!
5. Trichotillomania: A circumscribed, usually poorly defined bald patch (tonsure-like); multiple areas of alopecia are less common. The scalp itself is completely normal. The hair follicles are always present within the lesion (upon microscopic examination) (distinguishing it definitively from scarring alopecia). Short hair shafts always remain (a typical sign and distinguishing feature from alopecia areata)
6. Lichen planus: Usually diffuse alopecia; noticeable follicular inflammation; other signs of lichen planus are present (e.g., oral mucosal involvement). 
7. Lupus erythematosus: In the chronic discoid form, circumscribed scarring alopecia. Immunohistological evaluation. 
8. Folliculitis decalvans(severe pyoderma-associated folliculitis): Disseminated, small, follicular, moderately painful, discrete red papules; progressive inflammatory symptoms with follicular pustules, initial patchy, and later extensive, mirror-like skin atrophy with hair loss. Characteristic features include keratotic notches in the hair shafts near the hair follicles at the margins of the lesions. Rice-field-like conglomerate follicles (tufted hair) form.  

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.

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). Treat 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. Caveat. 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) was applied 2 times/day to the lesional areas. Good results are explicitly described in alopecia areata in the context of the atopic group of forms. Currently, calcineurin antagonists are only approved for the treatment of atopic eczema, so that their use in alopecia areata is off-label. Strictest indication because of unclear long-term side effects!

Alternative: Dithranol: Also described is the production of 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: hyperemization with 2% benzyl nicotinate or other substances stimulating blood circulation (e.g. head tincture hyperemizing, 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 areas 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 increased eyelash pigmentation (see below eyelash lengthening by prostaglandin analogues).
• Thymuskin is reported to have shown a beneficial effect on hair growth in small study cohorts.

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!

Systemic glucocorticoids (numerous publications): For rapidly progressive forms of the disease, try methylprednisolone (e.g., Urbason), initially 20–60 mg orally; after 2–3 weeks, reduce the dose below theCushing threshold. Duration of therapy: 6–8 weeks. Only a morbostatic effect is to be expected; the regrown hair will fall out again after discontinuation of therapy; hair is retained in only 20% of cases.

Alternative:Glucocorticoid pulse therapy: In a randomized, placebo-controlled study, significant improvements were demonstrated with glucocorticoid pulse therapy (prednisolone 200 mg orally once weekly for 3 months). An alternative pulse therapy regimen was reported as 5 mg/kg body weight orally every 4 weeks (repeated 9–12 times). 

Alternatively: Dapsone (e.g., Dapson-Fatol): 100 mg/day orally for several months is also reported to have a favorable effect on the course of the disease in adults. The efficacy is controversial.

Alternative: Ciclosporin A (e.g., Sandimmun, Optoral): At high doses (4–6 mg/kg body weight/day), if necessary, in combination with glucocorticoids (prednisolone 4–5 mg orally per day); due to the known side effects of cyclosporine A, treatment is justifiable only in individual cases. High recurrence rate after discontinuation of therapy.

Alternative:Cyclosporine A —low-dose regimen: Low-dose administration (50–100 mg orally per day) is currently being tested in clinical trials (with good results—personal experience).

Alternative: Methotrexate: 10–15 mg p.o./week, if necessary in combination with glucocorticoids (prednisolone 10–20 mg p.o./day).  

Alternatively— JAK inhibitors: 

• Baricitinib (^Olumiant®): For severe alopecia areata, the oral, selective Janus kinase inhibitorbaricitinib (^Olumiant®) may be used. It has been approved for severe alopecia areata since August 1, 2022 (FDA and EMA). Opportunistic infections should be monitored as potential side effects. 
• Ritlecitinib (^Litfulo®): Another JAK inhibitor has been approved in Germany since November 2023. Ritlecitinib (^Litfulo®) has been approved for the treatment of severe alopecia areata in adults and adolescents aged 12 and older. Ritlecitinib selectively inhibits Janus kinase 3 (JAK3). German health insurance plans do not cover the costs of this approved medication: Section 34 of Book V of the Social Code (SGB V) excludes coverage for medications intended to improve hair growth.

  Ritlecitinib and baricitinib showed no differences in efficacy (ritlecitinib 50 mg and baricitinib 4 mg). The comparison was based on SALT ≤10 (odds ratio, OR: 0.96, 95% confidence interval, CrI: 0.18–7.21) and SALT ≤ 20 (OR: 2.16, 95% CrI: 0.48–16.46) at week 24 (Aceituno D et al. 2025).

• The use of theJAK inhibitors ruxolitinib (which was successfully used in some patients) and tofacitinibis classified as experimental (not approved) (tofacitinib was administered at a dose of 2 × 10 mg/day; Jabbari et al. 2018) should be classified as experimental (not approved). 

Adjuvant therapy: Zinc hydrogen aspartate (e.g., Unizink^100®) 50 mg orally twice daily or zinc sulfate (e.g.,^Solvezink®) 200 mg orally twice daily for at least 6–8 weeks. In addition, concomitant use of biotin (vitamin H), e.g.,^Bio-H-Tin®, 1 tablet orally once daily for at least 6–8 weeks, improves hair and nail quality and reduces effluvium. These treatment approaches are the subject of controversy.   

The prognosis depends on the extent, the number of bald patches, the duration (long clinical course means poor prognosis with regard to healing) as well as the clinical types (the ophiasis type has a particularly poor prognosis for healing). Other prognostically unfavorable factors are: first manifestation in childhood before puberty, familial occurrence, associated autoimmune diseases, the presence of atopic dermatitis, nail involvement and alopecia areata totalis/ universalis.

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 center of the balding area and spreads to the periphery. Thin, completely white downy hairs often appear first, which are gradually replaced by longer, often still unpigmented hairs. Only later does the hair begin to change color normally. In older patients, the lesional hair can remain white for a long time.

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

Immunotherapy with diphenylcyclopropenone (alternatively: dibutyl ester of quadric acid), which was previously listed as the standard treatment for alopecia areata, is now obsolete due to its side effects. It is included here solely for historical reasons: 

Diphenylcyclopropenone (DPCP): Immunotherapy with contact allergens for severe, treatment-resistant forms of alopecia areata. Currently the most effective treatment. Caution! There are no commercially available preparations (not a drug as defined by law); the treating physician bears full responsibility for the therapy and its side effects! A single application of a 2% DPCP solution to one side of the scalp to induce contact sensitization: 2–7 days of (desired) burning and itching, eczema reaction. Next application of a highly diluted DPCP solution (0.001%) 14 days after sensitization, followed by once a week. Slowly increase the concentration. Titrate to a dosage (which varies greatly from person to person) that triggers an inflammatory reaction the next day, characterized by redness and itching, and heals with scaling. Treatment once a week for an initial period of 6–12 months, or years if necessary. Onset of effect after approximately 10 applications. Concomitant therapy with steroid-free creams (e.g., Dermatop Base Cream, etc.). Use clothing for sun protection! In a larger study (142 patients), a “complete response” was observed in about 40% of cases, a “partial response” in 15%, a “minimal response” in 20%, and “no response” in about 30%.

Alternative: Dibutyl squarate (SADBE): An alternative to treatment with DPCP; see above.

It is noteworthy that patients with alopecia areata have a higher prevalence of SD (sexual dysfunction) than healthy control subjects (Munoz-Barba D et al. 2024). 

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2. Barrón-Hernández YL et al. (2017) Bimatoprost for the treatment of eyelash, eyebrow and scalp alopecia. Expert Opin Investig Drugs 26:515-522.
3. Camacho FM et al. (1999) Zinc aspartate, biotin, and clobetasol propionate in the treatment of alopecia areata in childhood. Pediatr Dermatol 16: 336-338
4. Celsus AC (50-60 AD) De medicina. Liber VI, Caput IV, De areis
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7. Hallaji Z et al. (2011) Prevalence of anti-gliadin antibody in patients with alopecia areata: a case-control study. Tehran-Univ-Med-J 68:738-742.
8. Jabbari A et al. (2018) An Open-Label Pilot Study to Evaluate the Efficacy of Tofacitinib in Moderate toSevere Patch-Type Alopecia Areata, Totalis, and Universalis. J Invest Dermatol doi:10.1016/j.jid.2018.01.032.

9. Jonas C et al. (2025) Hair regrowth in a patient with alopecia universalis and psoriasis vulgaris during deucravacitinib therapy. J Dtsch Dermatol Ges 23:234-235.

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21. https://www.ema.europa.eu/en/medicines/human/EPAR/olumiant
22. https://www.ema.europa.eu/en/medicines/human/EPAR/litfulo
23. https://www.mdedge.com/dermatology/article/265433/hair-nails/european-commission-grants-approval-ritlecitinib-severe