Open label trial of alefacept in palmoplantar pustular psoriasis.

BACKGROUND: Palmoplantar pustular psoriasis (PPP) is difficult to treat. We assessed the effectiveness of alefacept in PPP and the safety of a 30 mg/week dose. METHODS: Fifteen individuals with PPP were started on 15 mg/week intramuscularly (IM) alefacept. Efficacy was measured by the PPP severity instrument (PSI). Treatment was continued for 16 weeks, and the alefacept dose was increased to 30 mg/week IM at week 9 if the PSI did not decrease by at least 25%. Other outcomes included physician's global assessment (PGA), reported adverse events and CD4+ T-lymphocyte counts. Clinical response was observed for 12 weeks after the last injection. RESULTS: The severity of PPP improved in both the PSI and the PGA (p<0.0001 and p = 0.0009, respectively). Much of the improvement occurred after 10 weeks of therapy. Nail severity scores improved (p = 0.0003). CD4+ counts decreased, but all remained >250 cells/mm3. There were no severe adverse effects or discontinuations due to adverse events. CONCLUSIONS: Alefacept in doses up to 30 mg/week was well tolerated in patients with PPP and appeared to have some efficacy. The use of concomitant therapy, the lack of a comparator, and the small sample size are limitations of the study.

Lesions resembling malignant atrophic papulosis in a patient with progressive systemic sclerosis.

Malignant atrophic papulosis (MAP), or Degos syndrome, is a rare disorder of unknown etiology. It is characterized by a deep subcutaneous vasculopathy resulting in atrophic, porcelain-white papules. We report the case of a 42-year-old woman with a history of progressive systemic sclerosis who presented with painful subcutaneous nodules on her abdomen along with chronic atrophic papules on her upper and lower limbs. Biopsy results of both types of lesions revealed vascular thrombi without surrounding inflammation. We briefly review the literature on MAP and its association with various connective tissue diseases. To our knowledge, there have been no previous reports of a patient with the clinical and histologic presentations described here. Although the histologic appearance of the subcutaneous nodules was very similar to that of the atrophic papules, the clinical characteristics of the 2 types of lesions were strikingly different. It is fair to theorize that Degos lesions do not start as atrophic porcelain-white papules but rather evolve from a primary lesion. We hypothesize that these lesions start as painful red nodules and may represent part of the disease spectrum in the evolution of MAP.

Alefacept: a novel biologic in the treatment of psoriasis.

Recognition of psoriasis as a T-cell-mediated immune disease has led to the development of various therapeutic approaches directed against the T cell and T-cell processes such as activation, trafficking and cytokine release. The novel and selective biologic agent alefacept, with an effect of selective apoptotic reduction in memory-effector T cells, has been given FDA approval for the treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy. The clinical profile of this novel biologic agent is presented here. Two pivotal multicenter, randomized, placebo-controlled, double-blind studies enrolling 1060 patients were designed to support the efficacy and safety of alefacept in the treatment of moderate to severe chronic plaque psoriasis. With either intramuscular or intravenous administration, well over half of patients treated with a single course of alefacept achieved a 50% reduction in PASI (Psoriasis Area and Severity Index), and a second course of therapy provided further benefit by increasing response rates and providing long-lasting off-treatment responses regardless of the route of administration. In all studies, alefacept was well tolerated. There was no evidence of an increased risk of infections or malignancies and no opportunistic infections were reported. Consistent with its composition as a fully human fusion protein, alefacept had a low incidence of immunogenicity and no evidence of an increased rate of antibody development over time. There was no evidence that primary or secondary responses to a new antigen or memory response to a recall antigen were blunted in patients treated with alefacept. In conclusion, alefacept is the first biologic therapy to demonstrate positive effects in an immune-mediated disease while maintaining immune responses to novel and recall antigens. This selective effect on the immune system distinguishes alefacept from immunosuppressive therapies that are nonselective.

Relapsing polychondritis.

A 43-year-old Chilean man presented with a 5-month history of progressive hypertrophy of the ears bilaterally. He was seen initially by a dermatologist in Chile for complaints of erythema and swelling of the ears, and had been treated unsuccessfully with topical steroids and antimicrobial ointments. On presentation to our clinic, the hypertrophy had stabilized and the erythema had resolved, but he complained of decreased hearing due to narrowing of the external auditory canal. Associated symptoms included occasional pruritus, but he denied any pain. He also denied a history of sinus problems, respiratory symptoms, ocular pain, chest pain, and arthralgias. Physical examination revealed firm hypertrophy of the collagenous areas of both ears, sparing the ear lobes (Fig. 1). No pain was elicited on palpation. No conjunctivitis was noted and the nasal passages were clear. His chest was clear to auscultation. Histologic examination revealed a minimal perivascular infiltrate of lymphocytes and plasma cells in the dermis with fibrosis of the subcutis (Fig. 2). Blood tests showed a normal complete blood count, antinuclear antibody, and rheumatoid factor. Anti-collagen II antibodies were elevated at 29.2 Eu/ml (normal, 0-20 Eu/ml; borderline, 20-25 Eu/ml; elevated, > 25 Eu/ml).