Tor Pettersson

Pancytopenia induced by low‐dose methotrexate. A study of the cases reported to the Finnish Adverse Drug Reaction Register from 1991 to 1999

Objective: To study cases of low‐dose methotrexate‐induced pancytopenia with special reference to clinical outcome and factors predisposing to bone marrow suppression. Methods: Patient files of 14 cases of methotrexate‐induced pancytopenia reported to the National Agency for Medicines in Finland from 1991 to 1999 were reviewed. A review of four additional cases was included. Results: Of the 18 patients (median age 72 years), 12 had rheumatoid arthritis, one psoriatic arthritis, five psoriasis without arthritis, and one pemphigus erythematosus. Major co‐morbidity was recorded in 12 patients, and 16 patients used significant concomitant drugs. Eight patients had a mildly or moderately elevated serum creatinine concentration. In every patient the occurrence of cytopenia was abrupt. Eight patients (44%) died, and the most frequent cause of death was infection. Conclusions: Our data show that methotrexate‐induced pancytopenia is associated with high mortality especially in cases with significant co‐morbidity and concomitant medications.

Biopsy Diagnosis of Amyloidosis in Rheumatoid Arthritis: Malabsorption caused by intestinal amyloid deposits

Fifteen patients with severe rheumatoid arthritis and known amyloidosis have been studied with respect to the occurrence of amyloid deposits in the gingiva, small intestine, rectum, and kidney. The findings from these organs have been compared. The occurrence of malabsorption has been studied. The findings suggest that small intestinal biopsy is a valuable method for the diagnosis of amyloidosis, and that malabsorption, especially of lactose, is more frequent in these cases than hitherto believed. Eight of the patients were seronegative.

Adenosine Deaminase Activity in Joint Effusions

The activity of adenosine deaminase (ADA) was determined in serum and synovial fluid of 98 patients with joint effusions of various causes. Compared with osteoarthritis, there were significantly higher mean synovial fluid ADA activities in seropositive rheumatoid arthritis (p less than 0.01), chronic seronegative polyarthritis (p less than 0.001), juvenile chronic arthritis (p less than 0.001) and reactive arthritis (p less than 0.001). In inflammatory joint diseases higher mean ADA activities in synovial fluid than in serum were observed, indicating a local release of ADA by cells within the joints. ADA activity in synovial fluid correlated with general disease activity as measured by haemoglobin concentration and erythrocyte sedimentation rate, and may provide an additional measure of the degree of inflammation in joint diseases.

Successful Treatment of the Anemia of Rheumatoid Arthritis with Subcutaneously Administered Recombinant Human Erythropoietin: Slower response in patients with more severe inflammation

We performed a 24-week open clinical study in which 12 patients with rheumatoid arthritis (RA) and anemia (mean hemoglobin (Hb) value 102 g/l, range 90-109 g/l) were treated with recombinant human erythropoietin (rHuEPO). rHuEPO was given as a subcutaneous injection twice weekly with an initial dose of 300 U/kg/week. Nine of the 11 patients who completed the study responded with an increase in Hb value of 15 g/l or more within 3 to 17 weeks. Three months after treatment the Hb levels were significantly lower than the highest Hb levels (p < 0.0001). There was an inverse correlation between the response rate and the mean serum concentrations of C-reactive protein and serum amyloid A protein (p < 0.001 and p < 0.003, respectively). We conclude that rHuEPO can correct anemia in patients with RA, but the response seems to be adversely influenced by the inflammatory activity of the disease.

Platelet Values In Amyloidosis

Platelet counts have been recorded in respect of 41 amyloidosis patients. Persistently-elevated platelet counts were observable in 22 patients; 19 of them had amyloidosis secondary to rheumatoid arthritis (RA). In patients with amyloidosis secondary to RA, a positive correlation was noted between platelet counts and high Waler-Rose titres. No significant correlations were observable either between platelet counts and haemoglobin or leukocyte values, or between platelet counts and serum protein fractions, nephrotic syndrome or renal insufficiency. As far as is known, the amyloid deposit does not represent any immunological activity. The conclusion is drawn that in amyloidosis, elevated platelet counts are attributable to the underlying disease and its activity.Dr Olof Selroos, M.D. IV Medicinska kliniken Unionsgatan 38 00170 Helsingfors 17 Finland

Lysozyme Concentrations in Synovial Fluid, Pleural Fluid and Thoracic Duct Lymph in Rheumatoid Arthritis

Lysozyme (LZM) concentrations in synovial fluid were determined in patients with seropositive and seronegative rheumatoid arthritis (RA) and in patients whose arthritic exudates had been caused by Reiters disease, a Yersinia enterocolitica infection, osteoarthritis, or trauma. Patients with rheumatoid disease had significantly higher levels of lysozyme in synovial fluid than patients with non-rheumatic diseases. The concentration of lysozyme correlated with the number of polymorphonuclear leukocytes in synovial fluid in seronegative--but not in seropositive--rheumatoid arthritis. In patients with rheumatic arthritis the lysozyme level correlated inversely with the concentration of glucose in synovial fluid. In patients with rheumatoid pleural effusion, lysozyme levels in pleural fluid were comparable to those in serum. The concentration of LZM in thoracic duct lymph was roughly the same as in serum. During drainage of thoracic duct lymph, the lysozyme level in serum decreased.

Immunization and Arthritis

Arthritis has been reported as a rare complication after immunization with various vaccines. After the administration of rubella virus vaccine, arthritis has been a relatively frequent complication, particularly in adolescent girls and young women. In connection with intensive immunization, rheumatoid factor has been transiently observed in both animals and human beings. The immunopathological implications of this phenomenon are poorly understood. Caution is indicated as regards intensive immunization which may be connected with unknown hazards.

Thrombocytosis in Experimental Amyloidosis in Rabbits

Rabbit platelets bave been counted during the development of amyloidosis induced by twice-weekly injections of sodium caseinate. A rapid increase in platelet numbers was noted after commencement of the injection regimen. During injection periods of from 11 to 15 weeks, the platelet count remained at a higher level than that in the control animals. These results are in agreement with the clinical observations, which indicate that thrombocytosis in amyloidosis patients occurs in situations of prolonged antigenic stimulation concomitant with an intact immune system, as is observable in amyloidosis secondary to chronic infections and active rheumatoid arthritis, and which is independent of the amyloid deposit itself.