ALOPECIA AREATA
INTRODUCTION
The hair loss disorder known as alopecia areata (AA) differs from androgenetic alopecia (AGA) aka common pattern hair loss in several crucial ways. First, unlike AGA, AA can affect anyone at any age whereas AGA typically manifests as a progressive disorder beginning in a male’s mid to late 20s and a female’s mid to late 30s. Second, AA presents as discrete zones of complete hair loss and in some cases the affected scalp resembling a moth-eaten appearance. AGA in males begins with bitemporal recession and a thinning of the vertex scalp. In females, AGA manifests as gradual thinning of hair density, however the anterior hairline is usually preserved. Far more prevalent than AA, AGA affects forty percent of males by age 35 and fifty percent of females by age 50. Both males and females stand a lifetime risk of developing AA of approximately 2%.
MECHANISM OF DISEASE ACTION
Here, the underlying genetic, biochemical and epigenetic factors governing AA vs AGA are markedly different. While both are polygenic, complex trait disorders, AA is driven by substantially different triggers. In contrast to androgenetic alopecia where follicle miniaturization leads to thinner and finer hairs over time, alopecia areata is a disorder of hair follicle-cycling, where inflammatory cells attack the hair follicle matrix epithelium when it is undergoing early cortical differentiation (anagen growth cycle), which are then prematurely induced into the catagen phase. Thus, the visible hair in the affected zone is essentially ablated en masse and all at once. Also of note, unlike AGA, AA does afflict other mammals and thus widely utilized animal models of AA have proven instrumental in uncovering the operative factors leading to effective treatments and potential cure. AA is most commonly inherited as a dominant trait but may also occur due to a recessive gene. It often occurs in association with other ectodermal defects. One specific gene, known as ULBP3, is known to act as a homing beacon for cytotoxic cells that can invade and quickly destroy an organ. In unaffected individuals, ULBP3 is not present in hair follicles, but the ULBP3 proteins are abundant in hair follicles of those affected by AA.
CURRENT TREATMENT OPTIONS
Until very recently, the treatment options for AA were primarily limited to corticosteroids, delivered via topical application, injection or oral bolus. These include Methotrexate, Anthralin & Hydrocortisone. The use of photochemotherapy is supported by some studies and may present a potential alternative for patients unable or unwilling to use systemic or potentially deleterious steroid-based therapies. Some data appears to suggest that the use of amino acids, caffeine, capsaicin, curcumin, garlic gel, marine proteins, melatonin, onion juice, procyanidin, pumpkin seed oil, rosemary oil, saw palmetto, vitamin B7 (biotin), vitamin D, vitamin E, and zinc may perhaps modulate the onset and progression of AA. However, well-controlled, peer-reviewed studies of these natural compounds are not as yet readily apparent.
FUTURE & POSSIBLE OPTIONS TO CURE
Recent breakthrough studies at Columbia University have demonstrated a remarkable rescue of phenotype, both in animal model experiments and subsequent human trials. The operative therapy has been based around a set of gene markers in a pathway known as JAK-STAT. JAK inhibitors block the T-cell mediated inflammatory response thought to be a key driving factor behind AA pathogenesis. By inhibiting the janus kinase (JAK) signal transducer and activator of transcription (STAT) signaling pathway, a reversal of hair loss has been observed in AA patients undergoing therapy test trials. Treatment with three JAK inhibitors, ruxolitinib, baricitinib and tofacitinib, led to robust hair regrowth in AA patients, and similar effects have also been demonstrated in animal models of AA. The discovery of JAK inhibition represents a major breakthrough in the treatment of AA. Positive results in early phase 1 and phase 2 clinical trials have enabled the commencement of phase 3 clinical trials and there is now a growing sense of optimism among patients with long-standing, treatment-refractory AA. Further work is planned to determine the optimal dose and treatment duration and whether or not maintenance therapy to preserve the newly regrown hair may be required.