M. Joyce Rico

Vancomycin-associated linear IgA dermatosis: A report of three cases

BACKGROUND Linear IgA dermatosis is an autoantibody-mediated, subepidermal blistering disease that is rarely associated with drug exposure. OBJECTIVE We report the development of linear IgA dermatosis in three patients associated with the administration of vancomycin and further characterize the immunopathology. METHODS Direct and indirect immunofluorescence assays were performed to characterize the immunoreactants, determine the subclass of the IgA deposits, and map the site of antibody deposition. RESULTS A subepidermal blistering disease developed in all patients shortly after vancomycin was initiated, which resolved on discontinuation of the drug. Immunofluorescence studies revealed linear deposits of IgA1 only at the basement membrane zone, below the lamina lucida. Circulating IgA anti-basement membrane zone antibodies were not detected. CONCLUSION Three patients had linear IgA dermatosis in association with the administration of vancomycin. All patients had linear deposits of IgA1 localized to the sublamina densa zone. Immunophenotypically, the disease in these patients mimics the pattern of IgA deposits seen in the majority of patients with idiopathic linear IgA dermatosis.

Multicenter Randomized, Double-blind, Placebo-Controlled, Clinical Trial of Dapsone as a Glucocorticoid-Sparing Agent in Maintenance-Phase Pemphigus Vulgaris

OBJECTIVE To determine the efficacy of dapsone as a glucocorticoid-sparing agent in maintenance-phase pemphigus vulgaris (PV). DESIGN A randomized, double-blind, placebo-controlled study with a crossover arm for those who failed treatment. SETTING A US multicenter outpatient study. Patients A total of 19 subjects enrolled among 5 centers, 9 randomized to receive dapsone and 10 to receive placebo. Inclusion criteria were biopsy and direct immunofluorescence-proven PV controlled with glucocorticoids and/or cytotoxic agents, disease in maintenance phase, and aged 18 to 80 years. Physicians had tried at least 2 tapers of glucocorticoids unsuccessfully and had 30 days of stable steroid dosage. Treatment for any patient unable to taper glucocorticoids by more than 25% within 4 months was declared a failure, and the patient was allowed to switch to the opposite medication while maintaining the double-blind. Main Outcome Measure The ability of patients to taper to 7.5 mg/d or less within 1 year of reaching the maximum dosage of the study drug. RESULTS Of the 9 patients receiving dapsone, 5 were successfully treated, 3 failed treatment, and 1 dropped out of the study. Of the 10 patients receiving placebo, 3 were successfully treated, and 7 failed treatment. This primary end point favored the dapsone-treated group but was not statistically significant (P = .37). Four patients who failed treatment while receiving placebo were switched to treatment with dapsone. Of these, 3 were successfully treated after switching to dapsone treatment, and 1 failed treatment. We found that, overall, 8 of 11 patients (73%) receiving dapsone vs 3 of 10 (30%) receiving placebo reached the primary outcome of a prednisone dosage of 7.5 mg/d or less. CONCLUSION This trial demonstrates a trend to efficacy of dapsone as a steroid-sparing drug in maintenance-phase PV.

Neonatal pemphigus vulgaris in a child born to a woman in remission

We describe the tenth reported case of neonatal pemphigus that mimicked Barts syndrome and review previously published cases. Unlike previous cases, the child was born with significant blistering to a mother who was in complete remission throughout the pregnancy. High antepartum maternal titers of anti-intercellular space antibodies, increased maternal disease activity, and maternal disease that requires high doses of corticosteroids or use of combined therapy correlate with poor fetal outcome, including intrauterine death.

Systemic plasmacytosis with cutaneous manifestations in a white man: Successful therapy with cyclophosphamide/prednisone

Plasmacytosis is a rare disorder that occurs mainly in the Asian population; it is characterized by a polyclonal proliferation of plasma cells and hypergammaglobulinemia. There are two variants: cutaneous plasmacytosis with involvement limited to the skin and systemic plasmacytosis described by Watanabe et al.1 defined as involvement of two or more organ systems. In the Caucasian population, there has been one patient with cutaneous plasmacytosis reported from Spain2 and a patient from Switzerland of unknown race that conforms to the description of Watanabe et al. of systemic plasmacytosis.3 We describe what we believe to be the second case of systemic plasmacytosis in a white patient.

Guidelines of care for dermatologic conditions in patients infected with HIV

Abstract This report reflects the best data available at the time the report was prepared, but caution should be exercised in interpreting the data; the results of future studies may require alteration of the conclusions or recommendations set forth in this report.

Treatment of autoimmune blistering diseases.

This review highlights some of the recent advances and controversies in the treatment of autoimmune blistering diseases, with an emphasis on the practical management of these patients for the clinician. The indications, dosages, and side effects of drugs commonly used to treat these conditions are reviewed. Corticosteroids, administered either topically or systemically, are commonly used in the management of these disorders. Agents that may act as anti-inflammatory agents may offer some benefit, including gold, dapsone, antibiotics, and niacinamide. Immunosuppressants, particularly azathioprine or cyclophosphamide, are used as adjuvants in patients whose condition is not controlled on high-dosage corticosteroids or who cannot tolerate the side effects of steroids.

Comparative epitope mapping of sera from United States (US) and Japanese patients with bullous pemphigoid (BP) to fusion proteins encoded by BPAG1.

Sera from patients with bullous pemphigoid (BP) from the United States (US), Japan, and Britain demonstrate similar reactivity to the major target antigens BPAG1 and BPAG2. The purpose of the present study was to determine if the epitope specificity of circulating autoantibodies in patients with BP from the US and Japan is similar as mapped by binding to fusion proteins encoded by BPAG1. Sera from patients and controls with BP from the US and Japan were assayed for reactivity to intact BPAG1 and BPAG2 by immunoblot, and to fusion proteins encoded by BPAG1 by immunoblot and enzyme-linked immunosorbant assay (ELISA). Significant reactivity to fusion proteins encoded by the carboxyl region (FP 16-8) and coiled-coil region (FP3) was seen in sera from the US and Japanese patients, but not from normal controls from the US or Japan. Sera from US and Japanese patients differed in their response to FP7; namely, the reactivity of sera from US patients but not from Japanese patients to FP7 was significantly different from the reactivity of their respective control sera. The reasons for this difference in reactivity are unknown but may reflect genetic or environmental factors relevant in the generation of an autoantibody response to these target antigens.

Idiotypes, anti-idiotypes, and autoimmunity

Over the past two decades it has become clear that the ability of a host to generate antibodies against a wide variety of potential antigens is due to structural diversity in the antibody molecule within the variable region. This diversity results in sites within the molecule that are themselves immunogenic. These immunogenic sites are called idiotopes, and the collection of idiotopes on a single antibody molecule determines that antibodys idiotype. The idiotype of an antibody molecule is defined serologically by a second antibody termed an anti-idiotype. Anti-idiotypic antibodies can recognize antibody molecules bearing similar or identical structures within the variable regions, which are often on or near sites of antigen binding. Investigation into the nature of idiotype and anti-idiotype interactions has increased our knowledge of antibody structure, antigen-antibody interactions, the regulation of antibody production, and the nature of autoimmune disorders. This review will discuss the nature of idiotypes and anti-idiotypes and their potential role in the diagnosis, management, and treatment of autoimmune, infectious, and malignant diseases.

Composite keratohyaline granules in striate keratoderma.

The gross, light microscopic, and ultrastructural findings in a 55 year old man was striate keratoderma are presented. There was no family history of the disease. The lesions developed in his late teens and early adult years, and consisted of progressively worsening, raised, hyperkeratotic, linear plaques on the palm and volar surface of the third and fifth fingers bilaterally. There were also painful callosities on both heels, and thick, raised plaques on the heels and lateral plantar surfaces. The epidermis was papillomatous and acanthotic, with marked orthokeratosis, minimal parakeratosis, and a very thickened granular layer. No epidermolysis was seen. Electron microscopy showed increased tonofibrils in the stratum spinosum arranged in wavy, parallel bundles and a granular layer in which normal Odland bodies were present. However, the keratohyaline granules were large, with rounded borders and a striped, alternating, dark and light content characteristic of composite granules. There was diminished contact of the granules with tonofibrils. The transition to the stratum corneum was abrupt. The ultrastructural and genetic features of keratodermas, with special emphasis on the striate type, are reviewed.The gross, light microscopic, and ultrastructural findings in a 55 year old man was striate keratoderma are presented. There was no family history of the disease. The lesions developed in his late teens and early adult years, and consisted of progressively worsening, raised, hyperkeratotic, linear plaques on the palm and volar surface of the third and fifth fingers bilaterally. There were also painful callositieson both heels, and thick, raised plaques on the heels and lateral plantar surfaces. The epidermis was papillomatous and acanthotic, with marked orthokeratosis, minimal parakeratosis, and a very thickened granular layer. No epidermolysis was seen. Electron microscopy showed increased tonofibrils in the stratum spinosum arranged in wavy, parallel bundles and a granular layer in which normal Odland bodies were present. However, the keratohyaline granules were large, with rounded bordersand a striped, alternating, dark and light content characteristic of composite granules. There was diminished contact of the granules with tonofibrils. The transition to the stratum corneum was abrupt. The ultrastructural and genetic features of keratodermas, with special emphasis on the striate type, are reviewed.