Tumour necrosis factor-α inhibition can stabilize disease in progressive vitiligo.

Tumour necrosis factor (TNF)-α, a proinflammatory cytokine central to many autoimmune diseases, has been implicated in the depigmentation process in vitiligo. We review its role in vitiligo by exploring its pro- and anti-inflammatory properties and examine the effects of blocking its actions with TNF-α antagonist therapeutics in reports available in the literature. We found that TNF-α inhibition halts disease progression in patients with progressive vitiligo but that, paradoxically, treatment can be associated with de novo vitiligo development in some patients when used for other autoimmune conditions, particularly when using adalimumab and infliximab. These studies reinforce the importance of stating appropriate outcomes measures, as most pilot trials propose to measure repigmentation, whereas halting depigmentation is commonly overlooked as a measure of success. We conclude that TNF-α inhibition has proven useful for patients with progressive vitiligo, where TNF-α inhibition is able to quash cytotoxic T-cell-mediated melanocyte destruction. However, a lingering concern for initiating de novo disease will likely prevent more widespread application of TNF inhibitors to treat vitiligo.

Pyoderma gangrenosum: a retrospective review of patient characteristics, comorbidities and therapy in 103 patients.

BACKGROUND: Pyoderma gangrenosum (PG) is an uncommon and challenging disease, highly associated with comorbidities, but poorly characterized from a diagnostic and therapeutic perspective. OBJECTIVES: To describe the epidemiology of PG in a hospital-based retrospective review, focusing on demographics, comorbidities and treatments. METHODS: We conducted a retrospective chart review. Patient data were taken from the Research Patient Data Repository of Brigham and Women's Hospital and Massachusetts General Hospital from 1 January 2000 to 31 December 2007. We identified and confirmed 103 cases of PG, and collected data on anatomical location, number and size of the PG lesions, patient demographics, comorbidities, mortality rate and treatments. RESULTS: Of the 103 patients, 78 (76%) were female, and only 7% had a biopsy suggestive of PG. The lower leg was the most common location with 78% of PG ulcers occurring there, and 67 (65% of patients) had two or more ulcers at some point. Thirty-five individuals (34%) had inflammatory bowel disease (IBD), 21 (20%) had haematological disorders, 14 (14%) had major depression, 20 (19%) had seronegative arthritis, 11 (11%) had psoriasis, and nine (9%) had hepatitis. Therapy was generally multimodal. The mortality rate during the 8-year study period was 16%. CONCLUSIONS: We present one of the largest PG case series to date. In our study, we found that biopsy of a PG lesion rarely yielded characteristic features of the disease and tissue pathology should not be used to exclude a PG diagnosis. We also found a female predominance and associations with IBD and haematological disorders. Patients with PG in this series had high rates of depression and hepatitis. Further work is needed to establish the mechanism(s) underlying these findings.

Psoriasis treatment: current and emerging directed therapies.

Quality of life studies in patients with cutaneous psoriasis attest to its significant impact on day to day activities and personal social interactions. Up to 40% of patients with psoriasis may develop psoriatic arthritis, usually within 5-10 years after onset of the cutaneous disease, heightening quality of life issues. These data have prompted an increased awareness and interest in more aggressive management of psoriasis; coupled with a better understanding of immunopathogenesis, this has led to the development of new agents targeting specific cells and molecules involved in the development and maintenance of psoriatic plaques. Although non-biological therapies, including methotrexate and ciclosporin, show significant efficacy their side effect profiles have precluded their long term use for moderate to severe psoriasis. This review concentrates on new biological agents, focusing on the three agents approved for psoriasis within the past 18 months (alefacept, efalizumab, and etanercept). Phase II and III trial data on other agents in development (adalimumab and infliximab) are also presented. Surveys show many patients want to be treated more aggressively. It is hoped that the introduction of new agents that are more targeted and that hold the promise of fewer side effects will cause patients and their physicians to reconsider systemic treatment and, as a consequence, stimulate other patients to reconsider treatment for psoriasis. Close cooperation between dermatologists and rheumatologists, particularly in the area of psoriatic joint disease, will enhance these considerations.