Alopecia areata - probing the deforestation.

Sir,

Alopecia areata (AA) is a chronic inflammatory auto-immune disorder resulting in nonscarring hair loss. It is thought to be triggered by a collapse of immune privilege in hair follicles. The dominant role of Th1 cells is explained by the demonstration of infiltrating chemokine (C-C motif) receptor 5 (CCR5+) CD4+ T lymphocytes around hair follicles. Intralesional injections of both IL-4 and neutralizing anti-IFN-γ antibody have shown to suppress CD8+ T cell infiltrates around the hair follicles and repressed enhanced IFN-γ mRNA expression in the affected alopecic skin. Also Th1 transcription factor T-box21 (T-bet) small interfering RNAs (siRNA) mitigated alopecia and resulted in the restoration of hair shaft elongation.[1]

Peripheral blood gene expression profiling of AA showed upregulation in immune response, cytokine signaling, signal transduction, cell cycle, proteolysis and cell adhesion-related genes. It also revealed the activation of several genes related to natural killer-cell cytotoxicity, apoptosis, mitogen activated protein kinase, Wnt signaling, and B- and T-cell receptor signaling in AA. A study showed that 363 genes (97 upregulated and 266 downregulated) were found to be differentially expressed in AA skin compared to nonlesional skin acting via T-cell mediated (CCL5, CXCL10, CD27, ICAM2, ICAM3, IL7R, and CX3CL1) and humoral mechanisms (IGHG3, IGHM, and CXCR5).[2]

In an experimental model natural killer (NK) cell depletion (tested by injecting anti-asialo GM1 antibodies) significantly increased perifollicular CD49b+T cells in the alopecic skin. The study shows evidence that IFN-c secreting CD49b+ T-cell subsets, by evoking strong Th1 response (cytokines IL-2, IL-12,interferon-γ and IL-1RA), are inappropriately stimulated by the receptor-activating signals released from the hair follicle epithelium and⁄or are inadequately suppressed in AA and that some NK cells are actually protective at least early on.[3]

Genetic variants in the FAS and FASLG genes (FasL or CD95L; a type-II transmembrane protein of TNF family),[4] an immune response to trichohyalin and Keratin-K16, reduced expression of red/IK cytokine (antagonist of IFNγ-induced expression of MHC class II antigens and a regulator of CD34+ cell growth) and indoleamine 2,3-dioxygenase have all been incriminated in the pathogenesis of AA. That AA shares etiology with other autoimmune disorders is suggested by establishing the involvement of the TRAF1/C5 (TNF receptor-associated factor 1, complement component 5) locus in the causation of familial and severe AA.[5]

The characteristic yellow dot pattern seen in reflectance confocal microscopy with round or polycyclic yellow-pink dots with miniaturized or broken hair shafts corresponds to the chronic phase of AA (depicting dilated infundibula of the vellus like anagen and telogen follicles). Increased serum sIL-2R level and lower IL-18 level at baseline are poor prognostic markers in AA. Coudability hairs (normal-looking hairs tapered at the proximal end) are useful in gauging the disease activity in AA and may surrogate the hair-pull test.

A variety of treatment options such as phototoxic psoralen and ultraviolet-A therapy after topical application of 0.1% 8-methoxypsoralen, diphencyprone, dinitrochlorobenzene, squaric acid dibutylester, steroids, minoxidil, anthralin, and bexarotene have shown promise in managing AA.