Alopecia areata

Meet the patient

A 26-year-old woman found a coin-sized bald patch behind her ear three weeks after a stressful exam fortnight. The patch is perfectly smooth, the skin normal in colour, and at its edge are a few short hairs that look narrower at the bottom than the top — broken shafts that pull out easily. Her fingernails show fine geometric pitting. She is frightened it will spread.[1]

That is the classic patchy alopecia areata presentation, and it carries the two questions that run every case: will it regrow? (the follicle survives — regrowth is always possible) and will it spread? (the pattern and prognostic markers decide). The presence of exclamation-mark hairs at the margin is the single bedside finding that earns the diagnosis.[1][12]

The clinical signature — smooth patch, exclamation-mark hairs, preserved ostia

AA produces one or more well-circumscribed, perfectly smooth, completely hairless patches. The skin within the patch is normal in colour, the follicular ostia are preserved (non-scarring), and the patch is typically asymptomatic, sometimes with mild paraesthesia or pruritus. Gentle traction at the active border extracts dystrophic anagen hairs.[1]

The pathognomonic finding is the exclamation-mark (cadaverised) hair — a short broken shaft, narrower proximally and broader distally, sitting at the advancing margin. Nail changes occur in 10 to 30 percent: fine geometric pitting, trachyonychia ("twenty-nail dystrophy"), onycholysis, onychomadesis or leukonychia. Nail disease correlates with more severe scalp disease and can be the presenting feature in children.[1]

Etymology for viva gold: ophiasis comes from the Greek ophis, "snake" — the band of loss encircles the scalp margin like a serpent. Sisaipho is simply ophiasis spelled backwards, because the pattern is the inverse (central loss sparing the periphery). Both names describe what the eye sees, and both predict a stubborn course.[1]

The six patterns — and the ones that predict a bad outcome

The pattern at presentation sets the prognosis and the treatment threshold. The same patient can transition between patterns over time, so document the current pattern in every clinic letter.[1][14]

The poor-prognostic markers to carry into the viva: childhood onset, atopy, ophiasis pattern, alopecia totalis or universalis, long disease duration, positive family history, and associated nail dystrophy. Patchy disease in an adult with no atopy, no nail involvement and short duration regrows spontaneously in 30 to 50 percent within 6 to 12 months.[1]

Why the follicle is attacked — immune-privilege collapse

AA is a collapse of hair-follicle immune privilege followed by autoimmune attack on anagen follicles. Normally the anagen bulb down-regulates MHC class I and secretes immune-privilege molecules (MIF, α-MSH, TGF-β) to hide from the immune system. A triggering event exposes follicular autoantigens — notably melanocyte-derived peptides, which is why AA preferentially targets pigmented hairs and may spare grey ones.[1]

The key effectors are CD8+/NKG2D+ cytotoxic T cells. They recognise follicular antigens and release IFN-γ, which up-regulates MHC class I and II on the follicular epithelium and perpetuates the attack. JAK-STAT amplifies the loop: IFN-γ signals via JAK1/JAK2, and IL-15 and other γc cytokines signal via JAK1/JAK3, together sustaining T-cell survival and cytotoxicity.[5]

This is exactly why JAK inhibition works. Because IFN-γ and γc cytokines depend on JAK-STAT signalling, JAK inhibitors interrupt the central amplification loop — the mechanistic rationale that underpins baricitinib, ritlecitinib and deuruxolitinib. The follicle is shocked into catagen but not destroyed, which is why regrowth remains possible even after years.[5]

How common, who, and what travels with it

The lifetime risk of AA is about 2 percent (roughly 1 in 50), with a community prevalence of 0.1 to 0.2 percent. Onset peaks in the second to fourth decades, and there is no consistent sex predominance. A positive family history is reported in 10 to 25 percent, supporting genetic susceptibility.[1][2]

Genome-wide association studies implicate HLA associations, CTLA4, IL2/IL21, STX17 and the ULBP gene cluster encoding NKG2D ligands, and Down syndrome carries a markedly increased risk. Psychological stress is linked anecdotally, but recent work frames psychological comorbidity more as a consequence requiring management than a sole cause.[1][4]

AA travels with other autoimmune and atopic disease. Screen for and expect autoimmune thyroid disease (Hashimoto, Graves — check TSH in every patient), vitiligo, atopic dermatitis, asthma, type 1 diabetes and inflammatory bowel disease. Prospective cohorts confirm these associations and the added burden of Down syndrome, in which AA is more severe and refractory.[3][4]

The differential — scarring versus non-scarring

The first fork is scarring or non-scarring, and AA is firmly on the non-scarring side. Within non-scarring, the closest mimics are tinea capitis (scaling, black-dot hairs, lymphadenopathy, KOH-positive), trichotillomania (irregular patches, hairs of differing lengths), secondary syphilis ("moth-eaten" loss with systemic symptoms), telogen effluvium (diffuse shedding 2 to 3 months post-trigger, uniform trichoscopy) and early androgenetic alopecia (patterned miniaturisation, hair diameter diversity).[1]

If there is any feature of scarring — perifollicular erythema and scale, loss of follicular ostia, a smooth shiny scalp — biopsy to exclude lichen planopilaris, frontal fibrosing alopecia, central centrifugal cicatricial alopecia or discoid lupus. AA never scars; if it looks like it might, reconsider the diagnosis.[1]

Trichoscopy and the biopsy

Trichoscopy is the first-line bedside investigation. The characteristic findings cluster into a memorable triad: yellow dots (follicular infundibula plugged with keratin and sebum, prominent in severe disease), black dots (cadaverous broken shafts at the surface — a marker of activity), and exclamation-mark hairs (pathognomonic for active AA). Add broken hairs, short vellus regrowth (a sign of remission or response), and tapered "pencil-point" hairs (Pohl-Pinkus constrictions, a sign of ongoing activity).[6][7]

A 4 mm punch biopsy is indicated when the diagnosis is uncertain, scarring is suspected, or systemic therapy requiring histological confirmation is contemplated. Horizontal (transverse) sections are particularly informative. Classic findings are a peribulbar lymphocytic infiltrate around anagen follicles — the "swarm of bees" of active disease — an increased catagen-to-telogen ratio with miniaturisation, and pigment casts and melanin within fibrous tracts. In chronic disease the infiltrate may be subtle or absent.[8][9]

Baseline bloods — FBC, ferritin, TFTs, B12 and folate — screen for anaemia, thyroid dysfunction and nutritional deficiencies that compound hair loss; VDRL or TPPA if syphilis is suspected; KOH, culture or PCR if tinea is suspected. Screen for atopy, vitiligo and autoimmune thyroid disease because of the recognised associations.[3][4]

Severity — the SALT score

The Severity of Alopecia Tool (SALT) score estimates percentage scalp hair loss on a 0 to 100 scale and is the standard outcome measure in practice and trials. The scalp is divided into zones and assessed visually or with computer assistance.[17]

The conventional treatment target in JAK inhibitor trials is a SALT score of 20 or less. The Alopecia Areata Patient Priority Outcomes (AAPPO) scale captures patient-reported scalp hair, eyebrow and eyelash impact, and emotional burden — increasingly used alongside SALT.[23]

Management — the stepwise ladder

Match the treatment to the severity. Limited patchy disease is managed topically or intralesionally; extensive or refractory patchy disease moves to contact immunotherapy; severe disease (SALT at least 50) moves to oral JAK inhibitors. A Cochrane network meta-analysis and subsequent NMAs confirm that systemic steroids, oral JAK inhibitors and contact immunotherapy all outperform placebo, with JAK inhibitors the most effective for severe disease.[1][10][13]

Topical and intralesional corticosteroids — first-line for patchy disease

Intralesional triamcinolone acetonide 2.5 to 10 mg/mL injected into the dermis of active patches every 4 to 6 weeks is first-line for limited patchy AA. Meta-analysis supports efficacy, with higher concentrations more effective but carrying greater risk of dermal atrophy; use lower concentrations (2.5 to 5 mg/mL) on the face, eyebrows and beard, with a maximum of about 20 mg per session. Avoid injecting areas with visible vellus regrowth or atrophic skin.[11]

Potent topical corticosteroids (betamethasone dipropionate, clobetasol propionate) are applied to patches; scalp foam or solution improves adherence. Topical calcineurin inhibitors (tacrolimus, pimecrolimus) are useful on the face or in children where steroid atrophy is a concern, though evidence is mixed. Topical minoxidil hastens cosmetically visible regrowth but does not treat the underlying inflammation — it is an adjunct.[1]

Phototherapy and contact immunotherapy

Excimer laser or light (308 nm) and narrowband UVB are used for patchy or extensive AA when topical therapy fails, with variable but measurable benefit, especially for patchy disease; relapse is common after stopping.[12]

Contact immunotherapy with DPCP (diphenylcyclopropenone), SADBE (squaric acid dibutylester) or DNCB is a mainstay for extensive, recurrent or refractory patchy AA in specialist centres. It is applied weekly in gradually increasing concentrations to produce a mild eczematous reaction, diverting the local immune response and inducing follicular immune privilege. Response rates vary widely (9 to 87 percent); the best evidence supports use in patients with 30 to 80 percent scalp involvement. Adverse effects are local eczema, urticaria, lymphadenopathy and pigmentary change.[1][13]

Systemic non-JAK therapy — limited role

Oral corticosteroids (short courses or pulse regimens) can produce rapid regrowth, but relapse is common and adverse effects forbid long-term use. Methotrexate and ciclosporin are sometimes used as steroid-sparing agents, but robust trial data are lacking and JAK inhibitors have largely displaced chronic prednisolone.[1][13]

JAK inhibitors — the modern revolution

Oral JAK inhibitors have transformed management of moderate-to-severe AA (typically SALT at least 50) refractory to or unsuitable for topical or contact therapy. They are not curative — relapse is typical after withdrawal — so they are chronic maintenance therapies. The British Association of Dermatologists living guideline (2024), the Japanese Dermatological Association guideline (2024) and the Asia-Pacific Delphi consensus (2026) all now place JAK inhibitors centrally for severe disease.[14][15][16]

Baricitinib (JAK1/2) — 2 mg or 4 mg once daily, FDA-approved June 2022 for severe AA in adults. In BRAVE-AA1 and BRAVE-AA2, 38.8 percent and 35.9 percent on 4 mg achieved SALT at most 20 at week 36 versus 6.2 percent and 3.3 percent on placebo; three-year data show sustained benefit with continuous therapy.[17][22]

Ritlecitinib (JAK3/TEC) — 50 mg once daily (with or without a 4-week 200 mg loading dose), approved June 2023 for severe AA in adults and adolescents aged 12 and over — the first JAK inhibitor licensed for adolescents. In ALLEGRO, 23 percent on 50 mg achieved SALT at most 20 at week 24 versus 2 percent on placebo, with patient-reported benefits confirmed by the AAPPO instrument.[18][23]

Deuruxolitinib (selective JAK1/2) — 8 mg or 12 mg twice daily, approved for adults. THRIVE-AA1 showed 29.6 percent (8 mg) and 41.5 percent (12 mg) achieved SALT at most 20 at week 24 versus 0.8 percent on placebo; THRIVE-AA2 confirmed efficacy.[20][21]

Pre-treatment screening and safety

Before any oral JAK inhibitor, screen for tuberculosis (IGRA or Mantoux), hepatitis B and C, and HIV; check FBC, LFTs, renal function and lipids; review cardiovascular risk, thromboembolic history, malignancy risk and current infections; and update inactivated vaccines — live vaccines are contraindicated during therapy.[14][16]

Common adverse effects are upper respiratory tract infections, acne, headache, elevated creatine kinase and lipid abnormalities. The rare but serious class risks are serious infection, herpes zoster reactivation (consider Shingrix beforehand), venous thromboembolism, major adverse cardiovascular events and malignancy — the FDA class warning cautions use in patients over 50 with at least one cardiovascular risk factor. Counsel women of childbearing potential; JAK inhibitors are contraindicated in pregnancy.[17][20]

Special populations

Children and adolescents: limited patchy disease is managed with topical or intralesional corticosteroids first-line, and response is often better than in adults. Ritlecitinib is approved for adolescents aged 12 and over based on the ALLEGRO adolescent cohort. Psychological support and school liaison are essential; a systematic review highlights the need for better paediatric trial data.[19][24]

Pregnancy and breastfeeding: JAK inhibitors, methotrexate and systemic retinoids are contraindicated in pregnancy and conception planning. Topical and intralesional corticosteroids can be used cautiously; avoid extensive treatment with potent agents. Management is multidisciplinary with dermatology and obstetrics.[1]

Comorbidities and psychosocial impact

Screen holistically. AA carries a higher prevalence of atopic disease, autoimmune thyroid disease, vitiligo, type 1 diabetes, inflammatory bowel disease and Down syndrome — a comorbidity screen is part of routine care, not an optional extra.[3][4]

The psychosocial burden is substantial and examinable. A systematic review and meta-analysis found significantly increased odds of depressive and anxiety disorders and symptoms in both children and adults with AA compared with controls. DLQI scores in AA parallel those of severe psoriasis, and in severe disease there is a real risk of suicidal ideation. Screen for depression, anxiety and quality-of-life impairment at every visit, and offer psychological support.[25]

Prognosis and follow-up

Prognosis is highly variable. Limited patchy AA often regrows spontaneously within 6 to 12 months, though recurrence is common. Ophiasis, totalis, universalis, childhood onset, atopy, nail changes, long duration (over a year) and a positive family history predict a more chronic course. JAK inhibitors produce meaningful regrowth, but relapse after withdrawal is typical — roughly 60 percent lose regrowth within months of stopping — so long-term continuous therapy is often needed to maintain response.[1][22]

Follow-up intervals depend on therapy: topical or intralesional, review at 6 to 8 weeks; contact immunotherapy, weekly applications with response assessment every 8 to 12 weeks; JAK inhibitors, baseline and periodic FBC, LFTs and lipids, infection surveillance and vaccination review.[1]

Ward-round test

1. A smooth bald patch with exclamation-mark hairs at the margin, preserved follicular ostia, nail pitting. Name the pathognomonic trichoscopic triad and the cell that drives the disease.[5][7]

2. A patient with 70 percent scalp loss (SALT 70) wants to know about baricitinib. What SALT response target does the trial use, and what result did 4 mg achieve?[17]

3. Name the band-like pattern of loss around the temporal and occipital margins, its etymology, and its prognostic significance.[1]

4. Before starting an oral JAK inhibitor, list the infection screen, the live-vaccine rule, and one serious class risk to counsel on.[14][17]

5. Why does regrowth remain possible in alopecia areata even after extensive loss, and what is the counselling point on stopping a JAK inhibitor?[5][22]