Alopecia areata affects both children and adults and hair of all colours. [1] Up to 66% of patients are younger than 30 years of age, and only 20% are older than 40 years, with no sex predilection. Alopecia areata is further associated with an increased overall risk of other autoimmune disorders: lupus erythematosus in 0.6% of patients, vitiligo in 4% and autoimmune thyroid disease in up to 28% of cases.

• There are two primary option for management: [1]
  • use of an immunosuppressive regimen (preferable for patients with acute and rapidly progressing alopecia areata), or
  • an immune-deviation strategy that manipulates the intracutaneous inflammatory milieu (preferred for patients with the chronic, relapsing form).
• At present, only two approaches reach the level of evidence-based medicine: intralesional injections of glucocorticoids and the induction of contact allergy.

• The possibility to use JAK inhibitors for alopecia areata arose from an unusual case report in which a patient with plaque psoriasis being treated with tofacitinib experienced a reversal in alopecia universalis. [2]
• We now know that Janus kinase-signal transducer and activator of transcription (JAK-STAT) is a signalling pathway that is crucial in maintaining the CD8+ NKG2D+ T cell inflammatory infiltrate which is typical of alopecia areata. [3]
• At present, at least 3 JAK inhibitors are under investigation in alopecia areata: tofacitinib, baricitinib and ruxolitinib. [4]
• In a study with tofacitinib in 66 patients (>50% scalp hair loss, alopecia totalis and universalis) treated with tofacitinib 5 mg twice daily, 32% of patients were intermediate responders (improvement in S ALT score ≥5% and ≤50%) and 32% were strong responders (changes in SALT score ≥50%).[4]
• Patients with chronic alopecia areata were less likely to be good responders; drug cessation resulted in disease relapse in a mean of 8.5 weeks. [4]
• A small study in 12 patients with moderate-to-severe alopecia areata on oral ruxolitinib, 20 mg twice per day, for 3–6 months, followed by 3 months follow-up off drug reported that after 6 months 75% of patients (9 of 12) had a strong response to treatment (defined as >50% hair regrowth). [4]
• At the end of the treatment, shedding started 3 weeks after cessation of ruxolitinib. [4]
• Most recently, the efficacy, side effects and durability of ruxolitinib was compared to tofacitinib in the treatment of severe alopecia areata. [5]
• Both tofacitinib and ruxolitinib induced remarkable hair regrowth, with a mean change in SALT score of 93.8 ± 3.25 in the ruxolitinib group and 95.2 ± 2.69 in the tofacitinib group.
• However, the ruxolitinib group showed a shorter duration for initial hair regrowth.
• Baricitinib is an oral selective inhibitor of JAK1 and JAK2, approved for the treatment of rheumatoid arthritis.
• To date only isolated case reports have been published on baricitinib in alopecia areata, although a placebo-controlled trial involving 725 subjects comparing baricitinib to placebo in moderate to severe alopecia areata is currently recruiting (NCT03570749).

• Apremilast is a disease modifying antirheumatic drugs (DMARD) used in psoriasis; a small retrospective analysis on 15 patients showed that apremilast could be a potential treatment for refractory alopecia areata at doses lower than that approved for psoriasis; however, further study is needed. [6]
• Fumaric acids inhibit T-suppressor cells and T-helper cells by the inhibition of the cytokines INF-γ, IL-2, IL-12 and TNF-α, and block ICAM and the proliferation of keratinocytes.
• A retrospective analysis of 13 patients with various types of alopecia showed that those with alopecia totalis showed no response, while 67% those with alopecia universalis partially responded; 50% of alopecia areata patients had full regrowth of hair after a mean period of treatment of 5.2 months. [7]
• However, relapse was seen after a mean of 3.3 months following cessation of therapy.
• A number of other agents are in the early stages of investigation.
• These include BNZ-1 (a selective and simultaneous inhibitor of cytokines IL-2, IL-9 and IL-15), tralokinumab (an IgG4 humanised monoclonal antibody that specifically binds IL-13) and dupilumab (a Th2 antagonist that blocks IL-4 receptor α, inhibiting IL-4 and IL-13). [4]

• A large number of targeted therapies are currently under investigation for alopecia areata.