Risk of skin and soft tissue infections (including shingles) in patients exposed to anti-tumour necrosis factor therapy: results from the British Society for Rheumatology Biologics Register.

INTRODUCTION: Anti-tumour necrosis factor (TNF) therapy is a mainstay of treatment in rheumatoid arthritis (RA). In 2001, BSRBR was established to evaluate the safety of these agents. This paper addresses the safety of anti-TNF therapy in RA with specific reference to serious skin and soft tissue infections (SSSI) and shingles. METHODS: A cohort of anti-TNF-treated patients was recruited alongside a comparator group with active RA treated with non-biological disease-modifying antirheumatic drugs (nbDMARD). 11 881 anti-TNF and 3673 nbDMARD patients were analysed. Follow-up was by 6-monthly questionnaires to patients and clinicians. Analyses considered SSSI and shingles separately. Incidence rates (IR) were calculated and then compared using survival analyses. RESULTS: The crude IR for SSSI were: anti-TNF 1.6/100 patient-years (95% CI 1.4 to 1.8); nbDMARD 0.7/100 patient-years (95% CI 0.5 to 1.0) and shingles: anti-TNF 1.6/100 patient-years (95% CI 1.3 to 2.0); nbDMARD 0.8/100 patient-years (95% CI 0.6 to 1.1). Adjusted HR were SSSI 1.4 (95% CI 0.9 to 2.4), shingles 1.8 (95% CI 1.2 to 2.8). For SSSI, no significant differences were seen between anti-TNF agents. For shingles, the lowest risk was observed for adalimumab (adjusted HR vs nbDMARD) 1.5 (95% CI 1.1 to 2.0) and highest for infliximab (HR 2.2; 95% CI 1.4 to 3.4)). CONCLUSION: A significantly increased risk of shingles was observed in the anti-TNF-treated cohort. The risk of SSSI tended towards being greater with anti-TNF treatment but was not statistically significant. As with any observational dataset cause and effect cannot be established with certainty as residual confounding may remain. This finding would support the evaluation of zoster vaccination in this population.

Anti-TNF therapy is associated with an increased risk of serious infections in patients with rheumatoid arthritis especially in the first 6 months of treatment: updated results from the British Society for Rheumatology Biologics Register with special emphasis on risks in the elderly.

OBJECTIVES: To evaluate the risk of serious infections (SIs) in patients with RA treated with anti-TNF therapy with emphasis on the risk across different ages. METHODS: Using data from the British Society for Rheumatology Biologics Register, a prospective observational study, we compared the risk of SI between 11 798 anti-TNF-treated patients and 3598 non-biologic DMARD (nbDMARD)-treated patients. RESULTS: A total of 1808 patients had at least one SI (anti-TNF: 1512; nbDMARD: 296). Incidence rates were: anti-TNF 42/1000 patient-years of follow-up (95% CI 40, 44) and nbDMARD 32/1000 patient-years of follow-up (95% CI 28, 36). The adjusted hazard ratio (adjHR) for SI in the anti-TNF cohort was 1.2 (95% CI 1.1, 1.5). The risk did not differ significantly between the three agents adalimumab, etanercept and infliximab. The risk was highest during the first 6 months of therapy [adjHR 1.8 (95% CI 1.3, 2.6)]. Although increasing age was an independent risk factor for SI in both cohorts, there was no difference in relative risk of infection in patients on anti-TNF therapy in the older population. There was no difference in hospital stay for SI between cohorts. Mortality within 30 days of SI was 50% lower in the anti-TNF cohort [odds ratio 0.5 (95% CI 0.3, 0.8)]. CONCLUSIONS: These data add to currently available evidence suggesting that anti-TNF therapy is associated with a small but significant overall risk of SI. This must be balanced against the risks associated with poor disease control or alternative treatments.

Interactions between HIV infection and leprosy: a paradox.

Early in the HIV epidemic it was feared that the disease would undermine leprosy control, as has occurred with tuberculosis. It was predicted that patients with leprosy and HIV coinfection would have an increased risk of lepromatous disease and a faster clinical evolution, and that the leprosy would be more difficult to treat. None of these concerns have materialised and the interaction between HIV and Mycobacterium leprae seems to be far more subtle than that between HIV and tuberculosis. We review the epidemiological, clinical, and pathological data relating to leprosy/HIV coinfection. The published epidemiological data are limited in quality but show neither an increased HIV prevalence among leprosy cases nor an alteration in clinical spectrum of leprosy among coinfected patients. Some data suggest that immune-mediated reactions that complicate leprosy occur at a higher frequency in coinfected patients. Leprosy has now been reported presenting as immune reconstitution disease among patients commencing highly active antiretroviral treatment. Histopathological observations reveal a normal spectrum of appearances in biopsies of leprosy lesions from coinfected patients, even among those with advanced immunodeficiency. These observations suggest that cell-mediated immune responses to M leprae are preserved at the site of disease despite evidence that these responses are abrogated systemically, by contrast with tuberculosis, in which the host granulomatous response is impaired by HIV coinfection. We speculate that this paradox may relate to differences between the activation state and rates of cell turnover within leprosy and tuberculosis granulomas that differentially affect the susceptibility of the granulomas to HIV. The interactions between leprosy and HIV have been little studied and further research on the clinical, pathological, and management aspects of this coinfection is warranted.

Penicillium marneffei infection in HIV.

PURPOSE OF REVIEW: Since the start of the HIV pandemic, systemic infection with Penicillium marneffei has developed from a very rare diagnosis to the third most common opportunistic infection in HIV co-infected patients in South East Asia. HIV patients who have travelled to or lived in Asia may present with this infection in nonendemic countries, and it has therefore become important for all those working in the field of HIV to recognize, understand and treat this emerging disease. RECENT FINDINGS: The clinical features, diagnosis and treatment of this infection are reviewed. Recent data exploring antigen-based serodiagnostics, the role of newer antifungals such as voriconazole, and the possibility of discontinuation of secondary prophylaxis after immune restoration from highly active antiretrovirals are discussed. SUMMARY: Large series from endemic areas and case reports from nonendemic regions have been published and provide insights into clinical features and presentation. Novel diagnostics are evolving, with galactomannan and other assays looking promising. Present therapy is largely based on noncontrolled studies, and further research into optimal therapy and the potential to discontinue secondary itraconazole prophylaxis is required.

Leprosy: current diagnostic and treatment approaches.

PURPOSE OF REVIEW: Leprosy remains an important problem globally and leprosy patients may present to physicians outside leprosy endemic areas. We review the recent biological and clinical advances in leprosy. RECENT FINDINGS: Sequencing the genome has been a major biological advance and will open up new possibilities for research. The three cardinal criteria (anaesthetic skin patches, thickened nerves and acid-fast bacilli in skin smears) have not yet been bettered. Multidrug therapy for leprosy is highly effective with low relapse rates though the optimal duration of therapy for multibacillary patients is unclear. Nerve damage remains a significant problem (in some series only 50% responding to steroid therapy). New treatments for leprosy reactions are needed. Stigma remains a problem but is being combated by patient groups. SUMMARY: Far from being eliminated as a public health problem, leprosy still causes a considerable long-term morbidity in both the developing and developed world. New treatments for leprosy reactions are needed and the optimal length of multidrug therapy required further research.