A case of lupus-like syndrome in a patient receiving adalimumab and a brief review of the literature on drug-induced lupus erythematosus.

WHAT IS KNOWN AND OBJECTIVE: Drug-induced lupus erythematosus occurs with some drugs and resolves with their withdrawal. Anti-TNF therapies have been found to be associated with a lupus-like syndrome, which is clinically distinct from classical drug-induced as well as idiopathic lupus erythematosus. CASE DESCRIPTION: We describe a case of a patient with severe psoriasis, who developed muscle pain with paraesthesia accompanied by ANA titres elevation with adalimumab treatment. The condition resolved after adalimumab cessation, and the patient was started on ustekinumab with good results. WHAT IS NEW AND CONCLUSION: Ustekinumab might be a useful treatment option for patients with a history of TNF-induced lupus-like syndrome.

Downregulation of toll-like receptor 4 and IL-6 following irradiation of the rat urinary bladder.

The pathophysiology behind radiation cystitis is poorly understood. Here we investigated whether bladder irradiation affects the immune system of the rat urinary bladder. Female rats were sedated and exposed to one single radiation dose of 20 Gy or only sedated (controls) and killed 16 h to 14 days later. Rats were placed in a metabolic cage at 16 h, 3 days, 7 days and 14 days following bladder irradiation. The urinary bladders were harvested and analysed with qPCR, immunohistochemistry and/or Western blot for the expression of interferon (IFN)-γ, interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-10, IL-13, nitric oxide synthases (eNOS, iNOS and nNOS), tumour necrosis factor (TNF)-α and toll-like receptor 4 (TLR4). Urine was collected and analysed for IL-6 and nitrite (reflecting nitric oxide activity) with ELISA and the Griess reaction, respectively. Irradiation increased bladder frequency and decreased voiding volumes 14 days following bladder irradiation. Bladder irradiation increased the expression of IL-10 and collagen in the bladder, while TLR4 and IL-6 expressions were decreased in the urothelium concomitantly with a decrease in mast cells in the submucosa and urine levels of IL-6 and nitrite. The present findings show that bladder irradiation leads to urodynamic changes in the bladder and may suppress important immunoregulatory pathways in the urinary bladder.

Cyclosporine A area-under-time-concentration-curve in rheumatologic patients after the first dose. Which of the sparse sampling strategies will predict the best?

OBJECTIVE: The aim of the present study was to validate the limited sampling strategies (LSS:s) for prediction of AUC of cyclosporine A (CsA) after the first dose in rheumatologic patients. METHODS: 22 patients suffering from rheumathoid arthritis, systemic lupus erythematodus, ankylosing spondylitis dermato(poly)myositis or seronegative spondylarthritis were treated with Neoral® (female/male: 11/3, mean ± SD: age 49 ± 14 y, body weight 75 ± 12 kg, height 166 ± 7 cm, dose 71 ± 25 mg, dose per kg 1.0 ± 0.3 mg/kg), or Consupren® (7/1, 78 ± 36, 175 ± 8, 82 ± 22, 1.1 ± 0.3). Two patients whose C12h were missing were excluded from the AUC0-12 calculation. Whole blood levels of CsA were analyzed with HPLC. Blood samples were collected at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours after taking the first dose. Altogether 115 LSS:s obtained from the literature were validated. A linear trapezoidal rule was used as a reference method. Mean percentage prediction error (%PE) < ± 15% and maximal one value of absolute %PE > 30% were considered to be acceptable. The root mean squared error (RMSE) was evaluated for equations that passed the criteria. RESULTS: The best performance with all values of the absolute %PE < 30% was found in three LSS:s for AUC0-12 and two for AUC0-8: AUC0-12 = 123.792 + 1.165 × C1h + 3.021 × C3h + 7.33 × C8h; 97.6 + 1.27 × C1h + 3.14 × C3h + 4.06 × C6h; or 124.3 + 1.34 × C1h - 0.16 × C2h + 3.27 × C3h + 3.96 × C6h; AUC0-8 = -19.8 + 1.99 × C2h + 2.38 × C4h + 3.15 × C6h or -22.4 + 2.51 × C2h + 5.49 × C6h. Validation criteria were further fulfilled in AUC0-12 = 24 + 3.66 × C0h + 2.11 × C1.5h + 4.54 × C4h or 0.2 + 2 × C2h + 10.2 × C6h; AUC0-8 = 55.37 + 2.89 × C0h + 1.08 × C1 + 0.9 × C2h + 2.23 × C3h; and AUC0-4 = -41 + 1.17 × C1h + 1.85 × C2h. Only one equation proposed for AUC0-6 did not pass the validation criteria. CONCLUSIONS: Equations validated for prediction of AUC0-12, AUC0-8 and AUC0-4 might be used for LSS:s of CsA independently of the length of treatment, indication, dosage or galenic formulation.

Increasing the infliximab dose in rheumatoid arthritis patients: a randomised, double blind study failed to confirm its efficacy.

OBJECTIVE: To evaluate the effect of infliximab dose escalation in incomplete responders in a randomised controlled trial. METHODS: 141 rheumatoid arthritis (RA) patients treated with infliximab for 12 months (3 mg/kg; intervals 0, 2, 6 and then 8 weeks) who responded to the drug (disease activity score in 28 joints (DAS28) decrease >1.2) but who were not in remission (DAS28 >2.6) were enrolled into the study. Patients were randomly assigned into arm A, 3 mg/kg, and arm B, 5 mg/kg infliximab every 8 weeks. Outcome measures included the DAS28, its components and C-reactive protein (CRP). RESULTS: There were no significant differences in changes in the DAS28, its components, or CRP in patients in arms A and B during the 12 months of treatment. All patients showed a DAS28 decrease greater than 0.6 after 28 weeks. Eleven patients interrupted therapy in arm A and 14 in arm B. Infusion reactions and non-serious adverse events were observed in 4.2% and 28.2% of arm A patients and in 7.2% and 47.8% of arm B patients. The frequency of serious adverse events was comparable between arms A and B (16.9% and 15.9%, respectively), and the frequency of serious infections was not significantly greater in the higher dose group (5.8%) than in the lower dose group (5.6%). CONCLUSIONS: In this setting, increasing the infliximab dose from 3 mg/kg to 5 mg/kg in RA patients with residual disease activity did not improve efficacy but moderately increased toxicity. These data indicate that a switch to another biological treatment would be a more appropriate strategy in incomplete responders.

[Recommendations of Czech Rheumatological Society for the treatment of rheumatoid arthritis. Efficacy and treatment strategies]. / Doporucení Ceské revmatologické spolecnosti pro lécbu revmatoidní artritidy. Ucinnost a strategie lécby.

Rheumatoid arthritis (RA) is an autoimmune disease of unknown aetiology characterized by presence of chronic symmetric synovitis, which leads to the formation of joint erosions. Generally recommended method for activity assessment of RA is so called Disease Activity Score (DAS). In early RA when low disease activity is present with oligo- or monoarthritis antimalarials are drugs of choice, while sulfasalazine (SAS) is recommended in cases with medium activity without erosions. Initial treatment with methotrexate (MTX) or leflunomide (LEF) should be applied in a very active polyarthritis with a rapid development of erosions. MTX is often combined with other disease modifying drugs (DMARD) and the blockers of tumour necrosis factor alpha (TNF-alpha). LEF is to be administered to the patients in whom the other DMARD are contraindicated or not tolerated. In established RA with oligo- or monoarthritis with permanent low activity SAS is DMARD of choice. In cases with insufficient response and medium activity MTX is used and if it is inefficient LEF or combination of DMARD should be considered. In a very active disease with a rapid evolution of erosions high doses of MTX or LEF are recommended. When extraarticular symptoms of RA are present azathioprine is to be applied and in case of involvement of vital organs cyclophosphamide should be used. When DMARD are failing or contraindicated TNF-alpha blockers are to be applied. When one TNF-alpha blocker is inefficient it should by replaced by another one from the same group or another biological should be used. For indication of biologicals the activity limit is DAS28 5.1 and the decrease of DAS28 more than 1.2 is an efficacy criterion. Nonsteroidal antirheumatic drugs are an important part in the management of RA, and also corticosteroids are often of used in oral or parenteral form. To the complex therapy of RA nonpharmacological means are usually implemented--different physical procedures and various surgeries.

[Long-term drug interaction of warfarin with amiodarone]. / Dlouhotrvající léková interakce warfarinu s amiodaronem.

Authors describe a case of drug interaction between amiodarone and warfarin in 66-year-old man with recurrent atrial fibrillation. In spite of a relatively low dose of warfarin, prothrombin time became extremely prolonged and bleeding manifestations occurred. Effects of the interaction persisted for a long time after the withdrawal of both drugs. Various approaches to oral anticoagulant reversal are discussed. Pharmacokinetics of both drugs is explained, as well as the mechanism of their interaction through cytochrome P450 inhibition in the liver. Authors emphasize the great interindividual variability and long persistence of this interaction. It is necessary to consider carefully the indication of using these drugs together and when the use is inevitable, it is recommended to lower the warfarin dose to 50-70% and to perform thorough and frequent INR monitoring.