4.2.1 Alopecia Areata

A reversible, non-scarring, usually localised but occasionally generalised form of autoimmune hair loss involving sometimes the nails.

It is caused by an autoimmune process with lymphocytic (T-helper and T-cytotoxic cell subsets) infiltrate around anagen hair bulb causing (initially) reversible hair loss. A breakdown of immune privilege of the hair follicle is thought to be an important driver of alopecia areata. Many studies have discovered a deficiency of Tregs in AA lesions showing with disease progression a further decrease of the regulating T cell subset. Dysregulation of interferon-gamma (IFN-g) and interleukin (IL)-15 are additional key factors. There is an association with other autoimmune diseases (atopic syndrome, vitiligo, thyroid diseases, rheumatic arthritis) and Down’s syndrome.

Usually there are no symptoms reported by the patient apart from a noticeable loss of hair. Itch, pain or erythema are missing. There is no visible inflammation, but local minor oedema can occur and the loss of hair is a non-scarring loss type, typically in circular shapes with solitary, multiple or diffuse patterns. Pull test from the margin is in active disease positive. Sometimes there are associated nail changes (pitting, or roughness, termed trachyonychia, or even nail loss at a late stage, termed onychomadesis). Exclamation mark hairs may be seen on careful examination, but are not pathognomonic.

It may occur in any part of the body, but is most easily identified in hairy areas such as the scalp or beard region, brows and eye lashes.

Classification is according to extent of hair loss:

• alopecia areata (AA) (patchy alopecia),

• ophiasis type (occipito-temporal alopecia),

• alopecia totalis (AT; complete scalp alopecia), and

• alopecia universalis (AU; complete scalp and body alopecia).

Recently a new scoring system has been introduced: AA-spectrum disease should simply be classified as AA with two additional qualifiers, a SALT score (Severity of Alopecia Tool (SALT)), used to calculate an AA severity score (0-100%, no hair loss to complete scalp hair loss) and the presence or absence of body involvement (complete or incomplete loss of body hair).

An association with atopy (e.g. with increased IgE) conveys a worse prognosis. Sometimes an associated autoimmune thyroiditis is present and may be screened for (e.g. microsomal thyroid antibodies, antibodies against thyroglobulin). Syphilis serology (where there are multiple small patches clinically) should be considered to exclude moth-eaten alopecia of secondary syphilis. A fungal culture should be performed if there is diagnostic doubt or scaling present incl. M. furfur and trichophytes.

A biopsy is not usually required but would show a heavy perifollicular lymphocytic infiltrate around stage III and IV anagen follicles with apoptosis of follicular keratinocytes and formation of dystrophic hair shafts. No destruction of the permanent part of the hair follicle.

Focal lesions have a high spontaneous remission rate (30% within 6 months, 50% with 1 year, 80% within 3 years). Widespread disease has low spontaneous remission rate (<10%).

Factors conveying a poor prognosis include involvement of occipital scalp hairline (ophiasis type), widespread disease, recurrent disease, longer duration (onset in childhood), atopy, vitiligo, thyroid disease and familial occurrence.

The differential diagnosis includes secondary syphilis, trichotillomania, trichotemnopmania, early stage of scarring alopecias (such as deep trichophyton infections) and chronic telogen effluvium.

Spontaneous regrowth most commonly occurs so treatment is not always required. Unpigmented hairs can occur at the beginning until bulb melanocytes recover. Small lesions can be treated with high-potency topical corticosteroids or intralesional corticosteroids. More widespread forms may respond to topical immunotherapy with diphenylcyclopropenone or short-term high dose systemic corticosteroids. Third line treatments include methotrexate, zinc and phototherapy. Wigs, permanent make-up for eyebrows and self-help groups can be helpful, especially those with psychosocial problems due to the hair loss. Currently, there are ongoing studies with the CTLA4-Ig fusion protein abatacept, anti-IL15Rβ monoclonal antibodies and the Janus kinase inhibitors baricitinib, ritlecitinib (also an inhibitor of tyrosine kinase), and deuruxolitinib are launched already. Upadacitinib and bempikibart are in clinical trials. Another new approach is to deliver directly T-reg cells by microneedling into the hair loss lesions.