Tolerability and safety of long-term rituximab treatment in systemic inflammatory and autoimmune diseases.

Rituximab, an anti-CD20 monoclonal antibody causing selective B-cell depletion, is used for various systemic inflammatory and autoimmune diseases (SIADs). Long-term safety data on rituximab are limited. The objectives of this study were to evaluate the long-term safety and tolerability of rituximab treatment for SIADs. A retrospective, single-center observational study including all patients ≥ 16 years treated with rituximab for SIADs was performed. The electronic medical records were reviewed, and data concerning indication and duration of rituximab treatment, prior and concurrent immunosuppressive therapy, and adverse events such as infections requiring hospitalization, dysgammaglobulinemia and end organ damage, were collected. A total of 70 patients were included, with a median treatment duration of 54 months, ranging 30-138 months. The most common indications for rituximab treatment were granulomatosis with polyangiitis (22.9%), primary Sjögren's syndrome (20.0%) and systemic lupus erythematosus (14.3%). Infections and persistent dysgammaglobulinemia were the most common adverse events, occurring in 34.3% and 25.7%, respectively. A total of 64 infections were observed in 24 (34.3%) patients, including 1 case of fatal infection. Seventeen patients performed B-cell quantitation during the first 2 years following discontinuation, of which only four (19.0%) demonstrated B-cell reconstitution. End organ damage occurred in two patients, presenting as pyoderma gangrenosum and interstitial pneumonitis. No opportunistic infections were observed. Three patients died during the observational period, of which one was due to lethal infection. This study presents observational data with long treatment duration. It demonstrates that long-term rituximab treatment is relatively well tolerated, and that no cumulative side effects were observed.

Tubulointerstitial nephritis and uveitis syndrome. / Tubulointerstitiell nefritt og uveitt-syndrom.

BACKGROUND: Uveitis and acute renal failure can be seen in various immune-mediated systemic diseases. Here we present a case of a young man with a rare inflammatory oculorenal syndrome. CASE REPORT: A man in his thirties was admitted with a constellation of fatigue, flank pain, weight loss and bilateral acute anterior uveitis. Laboratory tests showed anaemia, leukocytosis with eosinophilia, as well as elevated creatinine and C-reactive protein, and urine analyses demonstrated mild proteinuria. Work-up excluded sarcoidosis, Sjögren's syndrome, systemic lupus erythematosus, ANCA-associated vasculitides, Behçet disease, spondyloarthritis and infection. Renal biopsy showed severe tubulointerstitial nephritis. INTERPRETATION: Following exclusion of the abovementioned disorders, a diagnosis of tubulointerstitial nephritis and uveitis (TINU) syndrome was made. TINU syndrome is a rare inflammatory disorder which can be diagnosed in patients presenting with uveitis and tubulointerstitial nephritis after exclusion of other causes of similar oculorenal involvement.

Development of sarcoidosis following etanercept treatment: a report of three cases.

After over 10 years of use of tumor necrosis factor-alpha (TNF-α) inhibitors, their side effects and complications are reasonably well documented. Recently, however, granulomatous reactions and cases of complete sarcoidosis have been reported, especially in patients treated with the TNF-α receptor protein, etanercept. This is intriguing because the TNF-α antibody drugs infliximab and adalimumab are reportedly used to treat sarcoidosis. We present three patients who developed sarcoidosis while on etanercept treatment, and discuss if possible differences in cytokine profiles and T regulatory cell function in patients taking different TNF-α inhibitors may explain this paradox.

[Mycophenolate mofetil--a new therapeutic agent for chronic autoimmune diseases]. / Mykofenolatmofetil--et nytt medikament ved kronisk autoimmun sykdom.

BACKGROUND: Mycophenolate mofetil is an immunosuppressive agent frequently used in regimens to prevent allograft rejection. In this review we focus on mycophenolate mofetil as a potential drug for chronic autoimmune diseases. MATERIALS AND METHODS: We searched PubMed for relevant literature and present two case histories. RESULTS AND INTERPRETATION: Treatment with mycophenolate mofetil is best documented in lupus nephritis. In this context, some studies have documented an effect equal to cyclophosphamide for induction treatment, and equal to azathioprine, and better than cyclophosphamide for remission maintenance. Mycophenolate mofetil is today an alternative, although experimental, agent for the treatment of certain autoimmune diseases when conventional drugs have failed or are not tolerated; in the future it may become more widely used for immunosuppression. To establish the role for mycophenolate mofetil, more prospective controlled multicentre studies are warranted.