Relapsing drug-induced hypersensitivity syndrome.

PURPOSE OF REVIEW: Drug-induced hypersensitivity syndrome (DIHS) is a serious adverse drug reaction with potential morbidity and mortality. 'Flare up' or relapses in DIHS is a rare but important feature. These relapses may occur within days to several weeks, even after discontinuation of the offending drug. In this article, we review the pathogenesis of DIHS, implication of human herpesvirus 6 reactivation, and describe published case reports of patients with relapsing DIHS. RECENT FINDINGS: Common drugs associated with DIHS include (but are not limited to) antiepileptics such as carbamazepine, phenytoin, and valproic acid; antituberculous drugs; sulfasalazine; allopurinol; and antivirals such as abacavir and nevirapine. Relapses may occur even after cessation of the culprit drug and appropriate management with corticosteroids. Studies have suggested that reactivation of herpesvirus, particularly, human herpesvirus 6, is the main cause of relapses. However, other pathomechanisms have been proposed - case reports have described the importance of drug cosensitization. In such cases, the introduction of a second drug (often an antibiotic) induces the relapse of DIHS. DIHS may also cause multiple drug allergies, where a patient develops sensitisation to other drugs which were previously well tolerated. SUMMARY: Large studies are lacking in this heterogeneous condition. More research is needed to further understand the pathogenesis of drug cosensitization and multiple drug allergies, role of genetics, identification of risk factors, and prevention of relapses in DIHS.

Two-year preclinical testing of perfluoropolyether polymer as a corneal inlay.

PURPOSE: To assess the long-term biocompatibility and optical clarity of a perfluoropolyether (PFPE) polymer as a corneal inlay. METHODS: A 4-mm-diameter PFPE inlay was implanted under a microkeratome flap in the corneas of rabbits (n = 16) and maintained for predetermined time points of 6, 12, or 24 months. These were compared with normal (n = 3) and time-matched sham-wounded rabbit corneas (n = 8). All corneas were monitored clinically with a slit lamp. Histology was performed on all eyes on termination to assess the tissue response. RESULTS: Some sham and implanted animals were discontinued from study 1 to 2 days after surgery because of flap dislodgement. Ten animals with PFPE inlays remained in the study, and 7 of these were maintained to their predetermined time point for up to 2 years (3 were discontinued because of peripheral corneal defects). The corneas of these 7 animals remained clear and healthy, tear film remained normal, and there were no signs of inflammation, neovascularization, or increased conjunctival redness. All inlays remained centered and optically clear (clarity 85% or greater). Histology showed PFPE was biostable. The epithelia of operated corneas were stratified but slightly thinned compared with those of normal corneas. Stromal tissue anterior and posterior to each inlay appeared normal. Keratocytes in the vicinity of the inlay were normal in distribution but showed increased vacuolation, indicating tissue repair after the surgery. CONCLUSIONS: The PFPE polymer maintained a high level of optical clarity and showed long-term biocompatibility for up to 2 years when implanted as an inlay in the rabbit cornea.

Approaches to improving the biocompatibility of porous perfluoropolyethers for ophthalmic applications.

Porous perfluoropolyether (PFPE) membranes for ophthalmic applications were prepared with a zwitterion monomer, 3-[[2-(methacryloxy) ethyl](N,N-dimethyl)ammonio]-propane-1-sulphonate, copolymerized in weight ratios of 0-10%. The polymer samples were assessed for a range of physical properties, including equilibrium water content, bovine serum albumin permeability, transparency, refractive index and the ability to support corneal epithelial cell and tissue attachment, growth and migration. In vitro assessment of the polymers using bovine corneal epithelial cells and tissue showed that a zwitterion incorporation level of between 0% and 6% in the PFPE membranes supported the migration of an intact sheet of epithelial tissue without compromising epithelial cell attachment and growth, with 4-6% being the optimal level for these properties. Binding patterns of the cell adhesion glycoprotein fibronectin were also found to reflect the cell and tissue response. Effective nutrient permeability, refractive index and optical transparency were also maintained by the porous PFPE polymers containing this concentration of zwitterionic monomer. The presence of amounts of zwitterion greater than 6% was inhibitory to both tissue migration and cell growth and was associated with increased optical haze. These results demonstrated that it is possible to achieve the potential for increased biocompatibility in zwitterion-containing PFPE polymers without compromising existing beneficial characteristics.