Recent advances in the understanding of severe cutaneous adverse reactions.

Severe cutaneous adverse reactions (SCARs) encompass a heterogeneous group of delayed hypersensitivity reactions, which are most frequently caused by drugs. Our understanding of several aspects of SCAR syndromes has evolved considerably over the last decade. This review explores evolving knowledge of the immunopathogenic mechanisms, pharmacogenomic associations, in vivo and ex vivo diagnostics for causality assessment, and medication cross-reactivity data related to SCAR syndromes. Given the rarity and severity of these diseases, multidisciplinary collaboration through large international, national and/or multicentre networks to collect prospective data on patients with SCAR syndromes should be prioritized. This will further enhance a systematized framework for translating epidemiological, clinical and immunopathogenetic advances into preventive efforts and improved outcomes for patients.

Piperacillin-tazobactam-induced linear IgA bullous dermatosis presenting clinically as Stevens-Johnson syndrome/toxic epidermal necrolysis overlap.

Linear IgA bullous dermatosis (LABD) is a subepidermal autoimmune bullous disease characterized by linear IgA deposition at the basement membrane zone, which is visualized by direct immunofluorescence. Patients with LABD typically present with widespread vesicles and bullae; however, this is not necessarily the case, as the clinical presentation of this disease is heterogeneous. LABD clinically presenting as Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) is an infrequent, yet well-described phenomenon. Most cases of LABD are idiopathic, but some cases are drug-induced. Multiple drugs have been implicated in the development of LABD. We report a case of piperacillin-tazobactam-induced LABD presenting clinically as SJS/TEN overlap. This is the first reported case of a strong causal association between piperacillin-tazobactam and the development of LABD.

Rituximab in the adjuvant treatment of pemphigus vulgaris: a prospective open-label pilot study in five patients.

BACKGROUND: Rituximab is a monoclonal antibody directed against the CD20 antigen expressed on B lymphocytes. There are reports of its efficacy in the treatment of autoimmune diseases, including pemphigus. OBJECTIVES: Prospectively to evaluate the efficacy of rituximab as adjuvant treatment for pemphigus vulgaris (PV). METHODS: Patients with PV were treated with intravenous rituximab (375 mg m(-2)) weekly for 4 weeks in this prospective open-label pilot study. Other concurrent immunosuppression was continued. RESULTS: Of five patients, one achieved complete remission and was able to cease all medication, while two achieved clearance of clinical lesions but continued on systemic therapy. Two patients had progressive disease. Time to response was 2-8 months, with a 13- to 18-month response duration. Response was associated with reduction in serum antiepithelial antibodies. Two patients had significant infectious complications (one developed community-acquired pneumonia associated with delayed-onset neutropenia and the other developed cytomegalovirus infection). CONCLUSIONS: Rituximab has shown efficacy in the treatment of PV. Patients on multiple immunosuppressives should be closely monitored for infectious complications.

Orbital decompression in Graves' orbitopathy: efficacy and safety.

BACKGROUND: Vision-threatening compressive optic neuropathy occurs in a minority of patients with Graves' orbitopathy. Surgical orbital decompression, systemic glucocorticoids and orbital irradiation are treatment options. Orbital decompression is being performed on an increasing number of patients for other indications such as corneal exposure and disfiguring proptosis. AIMS: To examine the outcomes of surgical orbital decompression for Graves' orbitopathy by one surgeon. METHODS: An analysis of a retrospective case series of 88 consecutive patients (151 orbits) who underwent orbital decompression for Graves' orbitopathy between April 1991 and November 2002. RESULTS: The indication for surgery was compressive optic neuropathy for 57 orbits; 94 orbits had an indication other than optic neuropathy. Of those with optic neuropathy, 94% had improvement or maintenance of visual acuity and 93% had improvement in colour vision after decompression. The overall mean reduction in proptosis was 4.7 mm. Of all patients, 30% had new or worsened diplopia postdecompression. Patients with optic neuropathy were more likely to develop new or worsened diplopia than those without optic neuropathy. CONCLUSIONS: Orbital decompression is a safe procedure and effective in improving vision in compressive optic neuropathy. It is effective in reducing proptosis, therefore improving exposure keratopathy and cosmesis. However, new or worsened diplopia is a significant postoperative complication, and subsequent strabismus surgery might be required. This is an important consideration, especially for patients undergoing surgery for non-optic neuropathy indications.

Molecular and biochemical analysis of a 105 kDa Mycoplasma gallisepticum cytadhesin (GapA).

The identification of a gene (gapA) from Mycoplasma gallisepticum with homology to the P1 cytadherence gene of Mycoplasma pneumoniae is reported. The gapA gene is a 2895 bp ORF encoding a protein with a molecular mass of 105 kDa. Nucleotide sequence analysis of the gapA gene revealed 45% homology to the M. pneumoniae P1 gene, 46% homology to the Mycoplasma genitalium MgPa gene and 47% homology to the Mycoplasma pirum P1-like protein gene. It has a 64 mol % A+T content compared to 46, 60 and 72 mol % respectively for the P1, MgPa and the P1-like protein genes. As with the P1 and MgPa genes, gapA is a central gene in a multi-gene operon, but unlike the P1 and MgPa genes, there is only a single copy of gapA in the genome. GapA is a trypsin-sensitive surface-exposed protein. Chicken tracheal-ring inhibition-of-attachment assays, using anti-GapA Fab fragments, resulted in 64% inhibition of attachment. These results indicated that GapA plays a role in cytadherence of M. gallisepticum to host cells.

Physical mapping of the Mycoplasma gallisepticum S6 genome with localization of selected genes.

We report the construction of a physical map of the Mycoplasma gallisepticum S6 genome by field-inversion gel electrophoresis of DNA fragments generated by digestion of genomic DNA with rare-cutting restriction endonucleases. The size of the M. gallisepticum S6 genome was calculated to be approximately 1,054 kb. The loci of several genes have been assigned to the map by Southern hybridization utilizing specific gene probes.