Old wine in new bottles: reviving old therapies for alopecia areata using rodent models

Alopecia areata is regarded as a tissue-restricted autoimmune disease of hair follicles in which follicular activity is arrested because of the continued activity of lymphocytic infiltrates. Actual loss of hair follicles does not occur, even in hairless lesions. A variety of immunomodulating therapies, including contact sensitizers and immunomodulators, are part of the usual armamentarium for this disorder. None of these treatments have been consistent in their efficacy, and many have untoward side effects. Nevertheless, their uses in valid animal models provide a tool to dissect out molecular mechanisms of therapeutic effects. For several decades, both mechlorethamine (for the treatment of cutaneous T cell lymphoma) and anthralin (for the treatment of psoriasis) have been used successfully. When these therapies were tested in rat and mouse alopecia areata models, we found anthralin and mechlorethamine to be the most effective topical modalities, respectively. The underlying cellular mechanisms may act through targeting infiltrative lymphocytes, and the molecular mechanisms may involve specific cytokine expression changes. These visible, accessible, and unilaterally treated animal model systems are ideal for studying novel alopecia areata therapies, particularly in terms of their in vivo molecular mechanisms of action.