Corticosteroid-sparing effect of etanercept in idiopathic panuveitis resistant to immunosuppressive therapy.

Uveitis, an inflammatory eye disease with varying immunopathogenic mechanisms, may be associated with autoimmune disorders, may be secondary to infection, or may be idiopathic. Response to treatment of uveitis is inconsistent. In this report we describe an adult with idiopathic panuveitis who attempted to lower his oral corticosteroid dose from intolerable levels but was unable to do so because of the reappearance of symptoms. His 8-year course was managed with ocular and systemic corticosteroids, methotrexate, and cyclosporine, which allowed only partially successful control of his ocular inflammation. Complete control was not achieved until the addition of etanercept. With this case report we are the first to describe the complete response of idiopathic panuveitis to etanercept. Our success with this patient strongly supports the critical role of tumor necrosis factor in the immunopathogenesis of some cases of idiopathic panuveitis. Furthermore, etanercept offers a relatively nontoxic, safe option in cases of panuveitis that are unresponsive to traditional immunosuppressive therapy.

Endogenous endophthalmitis due to Salmonella arizonae and Hafnia alvei.

Enteric pathogens rarely involve organs other than those of the gastrointestinal system. We have reported the case of a woman with rheumatoid arthritis who had endogenous endophthalmitis due to Salmonella arizonae and Hafnia alvei. The infection probably resulted from the use of snake powder as a food seasoner. After appropriate intravenous, intraocular, subconjunctival, topical, and oral antibiotic therapy based on laboratory susceptibility studies, the patient's condition clinically improved, but complications resulted in therapeutic enucleation. Because of the ubiquitous nature of these and other potentially pathogenic organisms, great care must be taken in evaluation, management, and education of immunocompromised patients.

Corticosteroid induction of Ig+Ia- B cells in vitro is mediated via interaction with the glucocorticoid cytoplasmic receptor.

Flow microfluorometry was used to examine the effect of dexamethasone on the expression of surface Ia (sIa) on resting and activated murine B cells. Although dexamethasone resulted in a 50% reduction in sIa expression 12 h after injection, it was significantly less suppressive when injected together with B cell activators. In vitro dexamethasone, but not other related steroid hormones, induced a population of cells that were sIg+sIa-. A 20% reduction in the expression of sIa was noted by 4 h of culture with 10 nM dexamethasone, but maximal inhibition of 70% was not reached until 12 h of culture, and this degree of suppression persisted as long as dexamethasone remained in culture. When the dexamethasone was washed out after 8 h of culture, the maximal reduction was still noted at 12 h, but by 24 h there was re-expression of sIa toward base line levels, indicating it did not induce irreversible lethal alterations in the B cell. The inhibition of sIa expression correlated with a specific reduction in the quantity of messenger RNA for sIa as measured by Northern blot analysis, indicating that this is mediated at least in part by suppression of the steady state levels of Ia mRNA. The corticosteroid receptor antagonist RU486 was able to reverse the suppressive effects of dexamethasone on sIa expression, thus demonstrating that its effect is mediated specifically by binding to its intracellular receptor. Furthermore, when protein synthesis was inhibited during the short period of time that cells were preincubated with dexamethasone, minimal suppression of Ia expression was noted, suggesting that the dexamethasone may be stimulating a protein that has suppressive effects on MHC class II expression. The suppressive effects of dexamethasone in vitro were substantially reduced when B cells were simultaneously activated by stimuli that increase the expression of sIa. These data indicate that the suppressive effects of corticosteroids on immune response Ag are corticosteroid specific; are greater in resting than in activated B cells; are induced via the classical steroid mechanism of action, which is receptor mediated; and may result from the induction of an inhibitory protein that suppresses Ia mRNA.

Renal failure with minimal change nephrotic syndrome: reversal with hemodialysis.

A patient with acute renal failure accompanying nephrotic syndrome associated with minimal change nephropathy acutely reversed with hemodialysis and ultrafiltration. This response is felt to support the interstitial edema tubular obstruction theory of renal failure occurring with minimal change disease. Acute hemodialysis with significant fluid removal may dramatically reverse severe degrees of azotemia in this condition independent of corticosteroid therapy. The latter, however, may be necessary for remission of the nephrotic syndrome.