Drug-induced linear IgA bullous dermatosis in a patient with a vancomycin-impregnated cement spacer.

Linear IgA bullous dermatosis (LABD) is an autoimmune blistering rash caused by IgA autoantibodies against the epidermal basement membrane zone. It commonly is drug induced, often in association with systemic vancomycin. We report a case of a previously healthy 77-year-old man who developed a diffuse macular rash and hemorrhagic bullae on the left leg 10 days after placement of a vancomycin-impregnated cement spacer (VICS) during a revision knee arthroplasty and initiation of postoperative treatment with intravenous (IV) vancomycin. The lesions initially were limited to the leg in which the hardware was placed, but the patient later developed painful palmoplantar and oropharyngeal blisters as well as edematous, erythematous plaques on the back and buttocks. A punch biopsy from a lesion on the left thigh revealed neutrophil-rich subepidermal bullae, and immunofluorescence revealed linear IgA and C3 deposition along the dermoepidermal junction, confirming a diagnosis of LABD. This report illustrates the importance of considering antibiotic-impregnated cement spacers, which frequently are used to manage prosthetic joint infections, as potential culprits in patients with cutaneous eruptions.

Allopregnanolone analogs that positively modulate GABA receptors protect against partial seizures induced by 6-Hz electrical stimulation in mice.

PURPOSE: Low-frequency (6 Hz), long-duration (3 s) electrical stimulation in mice produces seizures characterized by immobility, focal clonus, and automatic behaviors reminiscent of human limbic epilepsy. Renewed interest has been expressed in this seizure model with the recognition that it is sensitive to a broad spectrum of anticonvulsants (AEDs) and may have distinct pharmacologic responsiveness from other in vivo tests of AED efficacy. Here we sought to determine whether the progesterone-derived neuroactive steroid allopregnanolone (5alpha,3alpha-P) and several structural analogues with varying degrees of activity as positive allosteric modulators of gamma-aminobutyric acid (GABA)A receptors are protective in the 6-Hz seizure model. METHODS: Mice were pretreated with neuroactive steroids (15 min before) or clonazepam (CZP; 30 min before) to 6-Hz corneal stimulation (32 mA). Animals that failed to exhibit immobility were considered protected. RESULTS: The neuroactive steroids prevented 6-Hz seizures with rank order of potencies (ED50 values): ganaxolone (6.3 mg/kg) > 5alpha,3alpha-P (14.2 mg/kg) > or = 5beta,3alpha-P (14.4 mg/kg) > 5alpha,3beta-P (>100 mg/kg). CZP also was protective (ED(50) value, 0.075 mg/kg). The potencies of the neuroactive steroids and CZP are similar to their previously reported activities in the pentylenetetrazol (PTZ) seizure model. CONCLUSIONS: Neuroactive steroids have comparable potencies in the 6-Hz and PTZ models. Their structural specificity in both models corresponds with their activities as positive allosteric modulators of GABAA receptors, although ganaxolone is more potent than expected, probably because it has greater bioavailability. The 6-Hz model may be a valuable tool in drug development for the identification of GABAergic AEDs.