Recovery of Hair in the Psoriatic Plaques of a Patient With Coexistent Alopecia Universalis

Contact immunotherapy, most commonly with diphenylcyclopropenone or SADBE, is reported to have a 50% to 60% success rate in extensive AA, with a broad range of 9% to 87%¹⁷; however, randomized controlled trials testing the efficacy of contact immunotherapy are lacking. Although the mechanism of action of these topical sensitizers is not clearly delineated, it has been postulated that by inducing a new type of inflammatory response in the region, the immunologic milieu is changed, allowing the hair to grow. Some proposed mechanisms include promoting perifollicular lymphocyte apoptosis, preventing new recruitment of autoreactive lymphocytes, and allowing for the correction of aberrant major histocompatibility complex expression on the hair matrix epithelium to regain follicle immune privilege.^18-20

Iatrogenic immunotherapy may work analogously to the natural immune system deviation demonstrated in our patient. Psoriasis and AA are believed to form competing immune cells and cytokine milieus, thus explaining how an individual with AA could regain normal hair growth in areas of psoriasis.^15,16 The Renbök phenomenon, or reverse Köbner phenomenon, coined by Happle et al¹³ can be used to describe both the iatrogenic and natural cases of dermatologic disease improvement in response to secondary insults.¹⁴

A complex cascade of immune cells and cytokines coordinate AA pathogenesis. In the acute stage of AA, an inflammatory infiltrate of CD4⁺ T cells, CD8⁺ T cells, and antigen-presenting cells target anagen phase follicles, with a higher CD4⁺:CD8⁺ ratio in clinically active disease.^21-23 Subcutaneous injections of either CD4⁺ or CD8⁺ lymphocyte subsets from mice with AA into normal-haired mice induces disease. However, CD8⁺ T cell injections rapidly produce apparent hair loss, whereas CD4⁺ T cells cause hair loss after several weeks, suggesting that CD8⁺ T cells directly modulate AA hair loss and CD4⁺ T cells act as an aide.²⁴ The growth, differentiation, and survival of CD8⁺ T cells are stimulated by IL-2 and IFN-γ. Alopecia areata biopsies demonstrate a prevalence of T_H1 cytokines, and patients with localized AA, alopecia totalis, and AU have notably higher serum IFN-γ levels compared to controls.²⁵ In murine models, IL-1α and IL-1β increase during the catagen phase of the hair cycle and peak during the telogen phase.²⁶ Excessive IL-1β expression is detected in the early stages of human disease, and certain IL-1β polymorphisms are associated with severe forms of AA.²⁶ The role of tumor necrosis factor (TNF) α in AA is not well understood. In vitro studies show it inhibits hair growth, suggesting the cytokine may play a role in AA.²⁷ However, anti–TNF-α therapy is not effective in AA, and case reports propose these therapies rarely induce AA.^28-31

The T_H1 response is likewise critical to psoriatic plaque development. IFN-γ and TNF-α are overexpressed in psoriatic plaques.³² IFN-γ has an antiproliferative and differentiation-inducing effect on normal keratinocytes, but psoriatic epithelial cells in vitro respond differently to the cytokine with a notably diminished growth inhibition.^33,34 One explanation for the role of IFN-γ is that it stimulates dendritic cells to produce IL-1 and IL-23.³⁵ IL-23 activates T_H17 cells³⁶; T_H1 and T_H17 conditions produce IL-22 whose serum level correlates with disease severity.^37-39 IL-22 induces keratinocyte proliferation and migration and inhibits keratinocyte differentiation, helping account for hallmarks of the disease.⁴⁰ Patients with psoriasis have increased levels of T_H1, T_H17, and T_H22 cells, as well as their associated cytokines, in the skin and blood compared to controls.^{4,11,32,39,41}

Alopecia areata and psoriasis are regulated by complex and still not entirely understood immune interactions. The fact that many of the same therapies are used to treat both diseases emphasizes both their overlapping characteristics and the lack of targeted therapy. It is unclear if and how the topical or systemic therapies used in our patient to treat one disease affected the natural history of the other condition. It is important to highlight, however, that the patient had not been treated for months when he developed the psoriatic plaques with hair regrowth. Other case reports also document hair regrowth in untreated plaques,^13,16 making it unlikely to be a side effect of the medication regimen. For both psoriasis and AA, the immune cell composition and cytokine levels in the skin or serum vary throughout a patient’s disease course depending on severity of disease or response to treatment.^6,39,42,43 Therefore, we hypothesize that the 2 conditions interact in a similarly distinct manner based on each disease’s stage and intensity in the patient. Both our patient’s course thus far and the various presentations described by other groups support this hypothesis. Our patient had a small region of psoriasis on the scalp that cleared without any terminal hair growth. He also had larger plaques on the forearms that developed hair growth most predominantly within the thicker regions of the plaques. His unique presentation highlights the fluidity of the immune factors driving psoriasis vulgaris and AA.