Patch testing and sensitization to multiple drugs.

BACKGROUND: Adverse drug reactions pose an increasing diagnostic challenge in hospitals and in outpatient clinics. When consecutive or repeated allergic drug eruptions are suspected, patch testing is a useful diagnostic tool for determining the causative drugs. OBJECTIVES: The aim of the study was to identify patient cases with multiple delayed-type drug sensitizations by using patch testing. METHODS: Eight hundred and eleven patients with suspected drug allergy were patch tested during a 9-year period. RESULTS: Multiple delayed drug sensitizations were found in 12% of those patients with positive results in drug patch testing. CONCLUSIONS: Drug patch testing is useful in cutaneous adverse drug reactions where multiple drugs are suspected. Multiple drug sensitizations can be found in a proportion of patients who have delayed drug allergies. In addition to drug reactions with eosinophilia and systemic symptoms, these patients may have repeated exanthemas or contact dermatitis.

Tight junction proteins in human Schwann cell autotypic junctions.

Tight junctions (TJs) form physical barriers in various tissues and regulate paracellular transport of ions, water, and molecules. Myelinating Schwann cells form highly organized structures, including compact myelin, nodes of Ranvier, paranodal regions, Schmidt-Lanterman incisures, periaxonal cytoplasmic collars, and mesaxons. Autotypic TJs are formed in non-compacted myelin compartments between adjacent membrane lamellae of the same Schwann cell. Using indirect immunofluorescence and RT-PCR, we analyzed the expression of adherens junction (E-cadherin) and TJ [claudins, zonula occludens (ZO)-1, occludin] components in human peripheral nerve endoneurium, showing clear differences with published rodent profiles. Adult nerve paranodal regions contained E-cadherin, claudin-1, claudin-2, and ZO-1. Schmidt-Lanterman incisures contained E-cadherin, claudin-1, claudin-2, claudin-3, claudin-5, ZO-1, and occludin. Mesaxons contained E-cadherin, claudin-1, claudin-2, claudin-3, ZO-1, and occludin. None of the proteins studied were associated with nodal inter-Schwann cell junctions. Fetal nerve expression of claudin-1, claudin-3, ZO-1, and occludin was predominantly punctate, with a mesaxonal labeling pattern, but paranodal (ZO-1, claudin-3) and Schmidt-Lanterman incisure (claudins-1 and -3) expression profiles typical of compact myelin were visible by gestational week 37. The clear differences observed between human and published rodent nerve profiles emphasize the importance of human studies when translating the results of animal models to human diseases.

Tight junction proteins and perineurial cells in neurofibromas.

Cutaneous neurofibromas consist of axonal processes, Schwann cells, fibroblasts, perineurial cells, mast cells, and abundant extracellular matrix. The distribution and role of perineurial cells in neurofibromas has been uncertain, partly because there has not been a specific immunohistochemical marker for perineurial cells. In this study, tight junctions (TJs) of 16 neurofibromas from 12 patients with neurofibromatosis type 1 (NF1) were analyzed using electron microscopy, immunohistochemistry, and Western transfer analysis. Cell-cell contacts with typical ultrastructural morphology of TJs were seen between adjacent perineurial cells surrounding the small nerves and between contacting perineurial cell processes embedded in tumor stroma. Immunohistochemistry showed expression of claudin-1, claudin-3, and ZO-1 in the intercellular junctions of a subpopulation of tumor cells. Occludin was present mainly in perineurium and claudin-5 localized to the blood vessels. Double immunolabelings were used to identify the cell types expressing claudin-1. The results showed that claudin-1 positive cells were also positive for type IV collagen and epithelial membrane antigen but not for S-100 protein. This labeling pattern is consistent with perineurial cell phenotype. Using claudin-1 as a marker, our results showed that clusters of perineurial cells are distributed around the rudimentary nerves within cutaneous neurofibromas and at the periphery of some neurofibromas.

Tight junction proteins ZO-1, occludin, and claudins in developing and adult human perineurium.

In peripheral nerves, groups of Schwann cell-axon units are isolated from the adjacent tissues by the perineurium, which creates a diffusion barrier responsible for the maintenance of endoneurial homeostasis. The perineurium is formed by concentric layers of overlapping, polygonal perineurial cells that form tight junctions at their interdigitating cell borders. In this study, employing indirect immunofluorescence and immunoelectron microscopy, we demonstrate that claudin-1 and -3, ZO-1, and occludin, but not claudin-2, -4, and -5, are expressed in the perineurium of adult human peripheral nerve. We also describe the expression of occludin, ZO-1, claudin-1, -3, and -5 in the developing human perineurium, showing that the expressions of claudin-1 and -3, ZO-1, and occludin follow similar spatial developmental expression patterns but follow different timetables in achieving their respective adult distributions. Specifically, claudin-1 is already largely restricted to perineurium-derived structures at 11 fetal weeks, whereas claudin-3 and occludin are weakly expressed in the perineurial structures at this age and acquire a well-defined perineurial distribution only between 22 and 35 fetal weeks. ZO-1 appears to acquire its mature profile even later during the third trimester. The results of the present and previous studies show that the perineurial diffusion barrier matures relatively late during human peripheral nerve development.