Therapeutic Elimination of the Type 1 Interferon Receptor for Treating Psoriatic Skin Inflammation.

Phototherapy with UV light is a standard treatment for psoriasis, yet the mechanisms underlying the therapeutic effects are not well understood. Studies in human and mouse keratinocytes and in the skin tissues from human patients and mice showed that UV treatment triggers ubiquitination and downregulation of the type I IFN receptor chain IFNAR1, leading to suppression of IFN signaling and an ensuing decrease in the expression of inflammatory cytokines and chemokines. The severity of imiquimod-induced psoriasiform inflammation was greatly exacerbated in skin of mice deficient in IFNAR1 ubiquitination (Ifnar1(SA)). Furthermore, these mice did not benefit from UV phototherapy. Pharmacologic induction of IFNAR1 ubiquitination and degradation by an antiprotozoal agent halofuginone also relieved psoriasiform inflammation in wild-type but not in Ifnar1(SA) mice. These data identify downregulation of IFNAR1 by UV as a major mechanism of the UV therapeutic effects against the psoriatic inflammation and provide a proof of principle for future development of agents capable of inducing IFNAR1 ubiquitination and downregulation for the treatment of psoriasis.

Renbok phenomenon and contact sensitization in a patient with alopecia universalis.

BACKGROUND: Immune responses are largely regulated by cytokines that are secreted by activated T cells. Interactions among these cells are complex, and the interaction between 2 responses may alter the effect of either response alone. It has been established that contact sensitization-induced inflammation can reverse hair loss due to alopecia areata. In parallel, the Renbök phenomenon demonstrates how 2 distinct autoimmune diseases--psoriasis and alopecia areata--interact to result in clinically active psoriasis suppressing alopecia areata. OBSERVATIONS: We describe a patient with concurrent psoriasis and alopecia universalis with terminal hairs within plaques on his extremities, representing the only normal hair growth on his body. Adjacent biopsy specimens confirmed our clinical suspicion of plaque psoriasis with normal hair follicles and alopecia universalis with a peribulbar lymphocytic infiltrate. Our patient's psoriatic plaques cleared rapidly with narrow-band UV-B phototherapy, but hair growth at the site was maintained. His scalp alopecia responded to squaric acid dibutylester contact sensitization therapy. CONCLUSIONS: This case represents a natural experiment in which 3 distinct but overlapping immune responses favored psoriasis or contact dermatitis over alopecia areata. The precise mechanism responsible for these effects remains unclear; however, based on recent reports, we speculate that cytokine cross-regulation plays a role in competition among these distinct immune responses.

Oral curcumin in the treatment of moderate to severe psoriasis vulgaris: A prospective clinical trial.

BACKGROUND: There is a need for safe, inexpensive, and effective psoriasis therapies. Many anecdotal accounts of patients' successful treatment with the alternative medicine curcumin exist. OBJECTIVE: We sought to determine the safety and efficacy of oral curcumin in patients with psoriasis. METHODS: We conducted a phase II, open-label, Simon's two-stage trial of 4.5 g/d of oral curcuminoid C3 complex in patients with plaque psoriasis. End points included improvement in Physicians Global Assessment score, Psoriasis Area and Severity Index score, and safety end points throughout the study. RESULTS: The intention-to-treat analysis response rate was 16.7% (95% confidence interval: 2%, 48%) and both responders achieved a Psoriasis Area and Severity Index 75 score. There were no study-related adverse events that necessitated participant withdrawal. LIMITATIONS: Small sample size and lack of placebo group are limitations. CONCLUSION: The response rate was low and possibly caused by a placebo effect or the natural history of psoriasis. Large placebo-controlled studies are necessary before recommending oral curcumin as a psoriasis treatment.

Clinicopathologic correlation of cutaneous metastases: experience from a cancer center.

OBJECTIVE: To analyze the clinical, histopathologic, and immunohistochemical characteristics of skin metastases. DESIGN: Retrospective analysis (January 1, 1990, to December 31, 2005). SETTING: Comprehensive cancer center. PATIENTS: Fifty-one patients (21 men and 30 women) with biopsy-proven skin metastases and correlative clinical data. INTERVENTIONS: Four dermatopathologists reviewed a random mixture of metastases and primary skin tumors. Immunohistochemical studies for 12 markers were performed on the metastases, with skin adnexal tumors as controls. MAIN OUTCOME MEASURES: Clinical characteristics of cutaneous lesions, clinical outcomes, histologic features, and immunohistochemical markers. RESULTS: Eighty-six percent (43 of 50) of the patients had known stage IV cancer, and skin metastasis was the presenting sign in 12% (6 of 50). In 45% (21 of 47) of the biopsies, the lesions were not suspected of being metastases owing to unusual clinical presentations. Seventy-six percent of the patients died of disease (median survival, 5 months). On pathologic review, many metastases from adenocarcinomas were either recognized or suspected, but the primary site was not easily identified based on histologic findings alone. Metastases from small cell carcinomas and sarcomas were histologically misinterpreted as primary skin tumors. Immunohistochemical analysis using a panel including p63, B72.3, calretinin, and CK5/6 differentiated metastatic carcinoma from primary skin adnexal tumors. CONCLUSIONS: Cutaneous metastases can have variable clinical appearances and can mimic benign skin lesions. They are usually seen in patients with advanced disease, but they can be the presenting lesion. Although many metastatic adenocarcinomas can be recognized based on histologic findings alone, immunohistochemical analysis is an important diagnostic adjunct in some cases.