Lack of muco-cutaneous signs of toxic shock syndrome when T cells are absent: S. aureus shock in immunodeficient adults with multiple myeloma

Staphylococcal toxic shock syndrome (TSS) is an acute life threatening disease. The diagnosis can be made clinically based on diagnostic criteria. The clinical manifestations are caused in large part by there lease of high levels of T-cell-derived cytokines as a result of potent toxins, also called superantigens (SAg), produced by Staphylococcus aureus, but it is not clear which clinical symptoms/signs are strictly T-cell dependent. Here, we report on three adults with multiple myeloma (MM) presenting with S.aureus sepsis/shock, and two patients with typical TSS. The MM patients had compromised humoral immunity because of depression of normal immunoglobulin (Ig) levels at the expense of the M protein.In addition, their T cells were absent due to high dose chemotherapy initiated for bone marrow trans-plantation. The MM cases lacked mucosal hyperemia, erythroderma and desquamation, but were otherwise indistinguishable from the TSS cases. All patients grew S. aureus and in each case, SAg genes were detected by PCR. In several cases, the plasma contained biological SAg activity resulting in VP specific proliferation of indicator T cells in vitro. The same specific activity was observed with the supernatant fluids of S. aureus broth cultures from the respective bacterial isolates. This confirms the presence of bio-active toxins in the plasma but did not lead to full blown TSS when T cells were lacking.Thus, S. aureus sepsis/shock can be clinically distinguished from typical TSS, and we suggest that mucocutaneous manifestations of TSS are the most telling signs of massive T-cell-dependent cytokine release.     

A Double-masked,Randomized Study to Investigate the Safety and Efficacy of Daclizumab to Treat the Ocular Complications Related to Behçet's Disease

Purpose: To investigate the safety and efficacy of daclizumab (Zenapax, humanized anti-Tac, HAT) in controlling the ocular manifestations of Behçet's disease. Design: Randomized, placebo-controlled, double-masked clinical trial. Participants: Seventeen participants with Behçet's disease experiencing at least two prior ocular attacks and requiring treatment with immunosuppressive agents for the ocular complications of Behçet's disease. Methods: Participants received either intravenous placebo or daclizumab (1 mg/kg) infusions every two weeks for six weeks, then every four weeks while continuing their standard immunosuppressive regimens. If clinically indicated, tapering of the standard immunosuppressive medications was allowed after six months of study enrollment. Complete ocular and physical examinations and an adverse event assessment were performed at baseline and prior to each study infusion. Main Outcome Measures: Primary safety endpoints were the development of a life-threatening complication or a severe opportunistic infection. Primary efficacy outcomes were the number of ocular attacks and an assessment of systemic immunosuppressive medications required during the study, including the ability to taper concomitant immunosuppressive therapy. Results: Nine participants randomized to daclizumab and eight to placebo were followed monthly. Follow-up ranged from one to 34 months, with a median follow-up of 15 months. Two participants randomized to daclizumab discontinued study therapy prior to the end of the study for personal reasons. No participant experienced a safety endpoint, and visual acuity remained stable in all participants during the course of the study. Ten participants (six daclizumab, four placebo) experienced ocular attacks requiring therapy. The median ocular attack rate during the study was greater in the daclizumab arm than the placebo arm (median 1.27 vs. 0.17 attacks/year, respectively). Participants in the placebo arm also experienced a greater reduction in the immunosuppressive medication score compared to participants receiving daclizumab (median –4.0 vs. –1.0, respectively). Conclusions: The observed results in the placebo group demonstrate that careful follow-up and treatment with standard combination immunosuppressive therapy can be effective for the management of the ocular complications of Behçet's disease. In our small study, there was no suggestion that daclizumab was beneficial in comparison with placebo. However, the low observed attack rate limited our ability to make a definitive treatment group comparison.     

Pigmentary tumors of the conjunctiva in children: analysis of surgical decision

Pigmentary tumors of the conjunctiva are rare in children, but they deserve special attention as, under some circumstances, they can question the quo ad vitam prognosis. The management of these tumors is controversial because the clinical diagnosis is uncertain, not reliable for a long term evolution prognosis. In this study, after a short review of the literature, the authors present their own experience in the field (47 cases during the last 10 years, out of which 18 underwent surgery) and they try to develop an algorithm of surgical decision based on age-related factors, clinical appearance, aesthetic factors and on the possibility of establishing a good relationship with the patient and the family.     

Gamma interferon assay as an alternative to PPD skin testing in selected patients with granulomatous intraocular inflammatory disease

BACKGROUND: To evaluate the QuantiFERON-TB test (gamma interferon assay), approved by the Centers for Disease Control and Prevention for the detection of latent tuberculosis (LTB), in patients who potentially may require immunosuppressive therapy for ocular inflammatory disease. METHODS: Blood samples from 12 consecutive patients with granulomatous ocular inflammatory disease were evaluated first with the purified protein derivative (PPD) skin test and then with the QuantiFERON-TB test (11 of 12 patients, 1 declined). The results of the 2 tests in both U.S.- and non-U.S.-born patients were compared with their Bacillus Calmette-Guérin (BCG) vaccination status and chest x-rays. RESULTS: In our small series there was a high degree of concordance between the QuantiFERON-TB assay and the PPD skin test. INTERPRETATION: The QuantiFERON-TB test did not demonstrate intrinsic merit over PPD skin testing for screening for LTB in selected patients when immunosuppressive therapy is considered. The confounding effect of BCG vaccination renders interpretation of both tests difficult. Early reports suggest the second-generation tests that are now available may hold promise for use in the uveitis clinic and should be formally evaluated.     

The effect of cyclosporine A (Restasis) on recovery of visual acuity following LASIK

PURPOSE: To compare the recovery of uncorrected visual acuity (UCVA) following LASIK in patients treated with topical cyclosporine A 0.05% and patients treated with a standard postoperative regimen. METHODS: In this single-center, open-label, retrospective study, a standard refractive workup was performed in 45 patients (85 eyes) who underwent LASIK and did not have preexisting dry eye. In 36 eyes, a standard postoperative eye drop regimen was followed, and in 49 eyes, cyclosporine A 0.05% was added to the standard regimen for 12 weeks. Uncorrected visual acuity was measured 1 week and 1 and 3 months postoperatively. RESULTS: One week postoperatively, 22 (44.9%) eyes in the cyclosporine A group and 8 (22.2%) eyes in the standard treatment group had UCVA of 20/15. Cumulatively, 36 (73.5%) eyes in the cyclosporine A group and 24 (66.7%) eyes in the standard treatment group had UCVA of 20/20 or better. One month postoperatively, 37 (75.5%) in the cyclosporine A group and 23 (63.9%) eyes in the standard treatment group had UCVA of 20/20 or better. Three months postoperatively, 40 (81.6%) eyes in the cyclosporine A group and 25 (69.4%) eyes in the standard treatment group had UCVA of 20/20 or better. Mean UCVA in the cyclosporine A group showed statistically significant improvements compared with the standard treatment group. CONCLUSIONS: Cyclosporine A 0.05%, in the form of Restasis, may be an effective treatment for reducing the time needed for visual recovery after LASIK. Use of cyclosporine A was associated with overall better and faster recovery of UCVA.