Most reports on serious MTX toxicity have focused on hepatic abnormalities, while other effects, including hematologic reactions, have not been emphasized. We experienced a case of pancytopenia secondary to MTX therapy in a patient with RA and renal insufficiency. A 67-year-old woman with a 12-year history of active seropositive RA that was a response to non-steroidal anti-inflammatory drugs, hydroxychloroquinine and intra-articular steroid injections, had been followed up and was diagnosed as early chronic renal failure in October, 1993. Recently, because of significant morning stiffness and polyarthralgia, the decision was made to institute MTX treatment. This was begun as a single oral dose of 5mg/week. After 2 doses, the patient was admitted to the hospital with general weakness. Laboratory tests showed a hemoglobin level of 7.9 g/dl, WBC count 1800/mm3 and platelet count of 64000/mm3. The serum creatinine level was 6.1 mEq/dl and the BUN level was 82 mEq/dl. Liver function test results were normal, but the serum albumin level was 2.7 g/dl. The patient subsequently developed fever and blood transfusions, granulocyte colony stimulating factor (G-CSF) and intravenous prophylactic antibiotic therapy were required. Her condition was improved. In summary, Low-dose MTX-related adverse hematologic side effects, including fatal pancytopenia, are rare but are a cause of increasing concern in patients with RA and renal insufficiency. Close monitoring of associated risk factors, particularly impaired renal function, should be mandatory for all patients who are receiving MTX therapy.
Aged ; Antirheumatic Agents/adverse effects* ; Antirheumatic Agents/administration & dosage ; Arthritis, Rheumatoid/drug therapy ; Arthritis, Rheumatoid/complications ; Case Report ; Female ; Human ; Kidney Failure, Chronic/complications ; Methotrexate/adverse effects* ; Methotrexate/administration & dosage ; Pancytopenia/chemically induced* ; Risk Factors

Bucillamine is a disease modifying anti-rheumatic drug, structurally similar to D-penicillamine. Although D-penicillamine-induced pemphigus has been not infrequently demonstrated, pemphigus associated with bucillamine was rarely reported. We describe a patient complicating pemphigus vulgaris after bucillamine treatment in rheumatoid arthritis (RA) and polymyositis (PM) overlap syndrome. PM and RA overlap syndrome was diagnosed three years ago and bucillamine was administrated for 20 months. Skin lesions including erythematous flaccid blisters on her chest, axillae, and back were occurred and were compatible with pemphigus vulgaris by typical pathology. Withdrawal from bucillamine and prednisolone treatment made rapid improvement of pemphigus lesions.
Syndrome ; Skin/pathology ; Polymyositis/*complications/*drug therapy ; Pemphigus/*chemically induced/*pathology ; Middle Aged ; Humans ; Female ; Cysteine/adverse effects/*analogs & derivatives ; Biopsy ; Arthritis, Rheumatoid/*complications/*drug therapy ; Arthritis ; Antioxidants/*adverse effects

Antirheumatic Agents ; therapeutic use ; Arthritis, Rheumatoid ; complications ; drug therapy ; Atlanto-Axial Joint ; injuries ; Humans ; Joint Dislocations ; etiology ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Syringomyelia ; diagnosis ; etiology ; physiopathology

OBJECTIVETo investigate the effects of methanol extract of Celastrus orbiculatu (MECO) on synovial hyperplasia and cartilage erosion and degradation in rheumatoid arthritis (RA), and explore the possible mechanisms to provide clues for new drug development for RA treatment.

METHODSThe articular synovium from patients with RA and normal articular cartilage were co-implanted into the back of severe combined immunodeficient (SCID)mice to establish the chimeric model SCID- HuRAg. Four weeks later, the mice were given MECO intragastrically at 30 mg/day, leflunomide at 500 microg/day or distilled water, respectively, for 4 consecutive weeks. After completion of the treatments, the histological scores of the grafts for synovial hyperplasia, cartilage invasion by synoviocyte and cartilage degradation around the chondrocytes were evaluated, and serum level of tumor necrosis factor-alpha (TNF-alpha) was measured with radioimmunoassay. The expression of TNF-alpha mRNA and the cell apoptosis in the synovium were detected with in situ hybridization (ISH) and TUNEL, respectively, and the results were analyzed with the image analysis system.

RESULTSThe grafts survived in the mice till the end of experiment. MECO and leflunomide, in comparison with distilled water, significantly lowered the scores for synovial hyperlasia (2.00+/-0.76 and 2.25+/-0.89 vs 3.63+/-0.52), cartilage erosion (1.69+/-0.80 and 2.00+/-1.36 vs 3.75+/-0.53), cartilage degradation (1.88+/-0.83 and 2.13+/-0.83 vs 3.63+/-0.74) and serum TNF-alpha level (0.84+/-0.09 and 0.83+/-0.12 vs 0.99+/-0.11 ng/ml). Cell apoptosis of the synovium increased significantly with MECO and leflunomide treatments, but the expression of TNF-alpha mRNA in the synovium decreased significantly in MECO group.

CONCLUSIONMECO can effectively suppress synovial hyperplasia and cartilage erosion and degradation SCID-HuRAg mice by reducing TNF-alpha production in the synovium and promoting synovial apoptosis. MECO can be comparable with leflunomide in their effect, but the former is more effective in suppressing TNF-alpha expression in the synovium.

Animals ; Apoptosis ; drug effects ; Arthritis, Rheumatoid ; complications ; drug therapy ; metabolism ; pathology ; Cartilage Diseases ; complications ; drug therapy ; metabolism ; pathology ; Celastrus ; chemistry ; Cell Transplantation ; Female ; Gene Expression Regulation ; drug effects ; Humans ; Hyperplasia ; complications ; drug therapy ; Male ; Methanol ; chemistry ; Mice ; Plant Extracts ; isolation & purification ; pharmacology ; therapeutic use ; RNA, Messenger ; genetics ; metabolism ; Synovial Membrane ; drug effects ; pathology ; transplantation ; Tumor Necrosis Factor-alpha ; blood ; genetics

No abstract available.
Anti-Inflammatory Agents/administration & dosage ; Arthritis, Rheumatoid/*complications/diagnosis/drug therapy ; Cervical Vertebrae/*pathology ; Female ; Humans ; Infusions, Intravenous ; Magnetic Resonance Imaging ; Medulla Oblongata/drug effects/*pathology ; Methylprednisolone/administration & dosage ; Middle Aged ; Treatment Outcome

Tumor necrosis factor (TNF) is essential for host defense against Mycobacterium tuberculosis, and the risk of reactivation of latent tuberculosis infection (LTBI) increases with anti-TNF therapy. This study estimated the prevalence of LTBI and evaluated the safety and completion rate of short-course therapy with isoniazid plus rifampin for 3 months to treat LTBI in a cohort of Korean arthritis patients before initiating anti-TNF therapy. We retrospectively studied the files of 112 consecutive patients to evaluate LTBI before starting anti-TNF drugs. Screening tests were performed, including a tuberculin skin test and chest radiography. LTBI treatment was indicated in 41 patients (37%). Of these, three patients refused the LTBI treatment. Of the 38 patients who underwent LTBI treatment, 36 (95%) took isoniazid plus rifampin for 3 months. Six patients (16%) showed transient elevations of liver enzymes during the LTBI treatment. Overall, 35 patients (92%) completed the LTBI treatment as planned. In conclusion, LTBI was diagnosed in one-third of Korean arthritis patients before initiating anti-TNF therapy. A high percentage of these patients completed 3 months of LTBI treatment with isoniazid plus rifampin without serious complications.
Adult ; Antibiotics, Antitubercular/pharmacology ; Arthritis, Rheumatoid/*complications/*diagnosis/*drug therapy ; Female ; Humans ; Korea ; Male ; Middle Aged ; Retrospective Studies ; Rifampin/pharmacology ; Spondylitis/metabolism ; Spondylitis, Ankylosing/complications/diagnosis/drug therapy ; Tuberculin Test ; Tuberculosis/*complications/*diagnosis/*drug therapy ; Tumor Necrosis Factor-alpha/*antagonists & inhibitors

No abstract available.
Antirheumatic Agents/therapeutic use ; Arthritis, Rheumatoid/blood/*complications/diagnosis/drug therapy/physiopathology ; Biological Markers/blood ; Drug Therapy, Combination ; Facial Dermatoses/complications/diagnosis ; Female ; Hand Joints/physiopathology/radiography ; Humans ; Immunosuppressive Agents/therapeutic use ; Inflammation Mediators/blood ; Knee Joint/physiopathology/radiography ; Lupus Erythematosus, Systemic/blood/*complications/diagnosis/drug therapy ; Middle Aged ; Syndrome ; Treatment Outcome

Adult ; Aggressive Periodontitis ; complications ; drug therapy ; therapy ; Anti-Infective Agents ; therapeutic use ; Antirheumatic Agents ; therapeutic use ; Arthritis, Rheumatoid ; complications ; drug therapy ; Dental Scaling ; Female ; Follow-Up Studies ; Humans ; Isoxazoles ; therapeutic use ; Methotrexate ; therapeutic use ; Metronidazole ; therapeutic use ; Periodontal Splints ; Root Canal Therapy ; Spiramycin ; therapeutic use

Anti-Inflammatory Agents ; administration & dosage ; Arthritis ; diagnosis ; drug therapy ; etiology ; physiopathology ; Arthritis, Rheumatoid ; diagnosis ; Clofazimine ; administration & dosage ; Dapsone ; administration & dosage ; Delayed Diagnosis ; Diagnosis, Differential ; Humans ; Leprostatic Agents ; administration & dosage ; Leprosy ; complications ; diagnosis ; drug therapy ; physiopathology ; Male ; Middle Aged ; Prednisolone ; administration & dosage ; Rifampin ; administration & dosage ; Treatment Outcome

Treatment of interstitial lung disease (ILD) in rheumatoid arthritis (RA) has been controversial. Although there have been several anecdotal reports on the efficacies of corticosteroids or cytotoxic agents such as methotrexate, cyclophosphamide, azathioprine, and D-penicillamine for the treatment of ILD associated with RA, no controlled studies have been performed. To date, corticosteroids have been a central agent for the treatment of this disease, but their effects are partial and temporary in most cases. In addition, the adverse effects of these agents are considerable. On the other hand, limited information is available on the cyclosporine use in ILD associated with RA. We describe a 49-yr old female patient with RA and ILD that had initially responded to high dose prednisolone and cyclophosphamide intravenous pulse therapy, and the lung disease was aggravated with the tapering of prednisolone. After 10 months of follow-up loss, the patient was successfully treated with low dose cyclosporine without high dose corticosteroids.
Anti-Inflammatory Agents/therapeutic use ; Antirheumatic Agents/*therapeutic use ; Arthritis, Rheumatoid/complications/*drug therapy/radiography ; Cyclophosphamide/therapeutic use ; Cyclosporine/*therapeutic use ; Disease Progression ; Female ; Glucocorticoids/therapeutic use ; Humans ; Lung Diseases, Interstitial/complications/*drug therapy/radiography ; Middle Aged ; Prednisolone/therapeutic use ; Treatment Outcome