Pneumocystis carinii pneumonia following methotrexate therapy for rheumatoid arthritis

Abstract

Methotrexate has been used to treat several rheumatic diseases when conventional therapy has failed (1,2). Recently, several articles have extolled the efficacy of this agent in refractory definite or classic rheumatoid arthritis (RA) (3)(4)(5). Response rates in excess of 50% have been noted in uncontrolled series (3-5). A great deal of enthusiasm has been generated by this high response rate, especially in view of the minimal side effects which have accrued with lowdose methotrexate regimens used in the treatment of RA and other disorders (1,(3)(4)(5)(6)(7)(8)(9). We report a case of Pneirmocystis curinii pneumonia occurring in a patient with RA who was receiving low-dose methotrexate. To our knowledge this complication has not been previously reported.A 74-year-old white woman with a 10-year history of seropositive RA presented with fever, chills, and a productive cough of 2 weeks' duration. Gold and penicillamine had been discontinued previously due to lack of efficacy. Her current regimen consisted of therapeutic doses of salicylates, 5 mg prednisone daily (continuous low-dose prednisone for the preceding 6 years), and 15 mg methotrexate weekly, given orally at 12-hour intervals over a 24-hour period. Methotrexate had been well tolerated since initiation 8 months earlier.Physical examination revealed a slightly cushingoid 74-year-old woman in moderate respiratory distress. Temperature was 38.8"C, respiratory rate 44, pulse 112, and blood pressure 110/70. She was agitated and mildly confused; cyanosis was absent. Cardiac examination results were remarkable only for a grade I/IV systolic ejection murmur along the left sternal border. There was no neck vein distention. Bibasilar rales and end inspiratory wheezes were heard diffusely throughout the lung fields. Her examination findings were otherwise unremarkable except for synovitis of the ankles, wrists, and metacarpophalangeal joints.Chest roentgenogram revealed mild cardiomegaly and heavy interstitial markings throughout both lung fields. The white blood cell count was 8,200/mm3 with 80% neutrophils and 2% bands. Arterial blood gas on 2 liters oxygen per minute showed a pH of 7.42, Pcoz of 36, and Po2 of 64. Sputum Gram stain and culture failed to reveal any pathogens.A regimen of erythromycin, tobramycin, and trimethoprim/sulfamethoxazole was started. Results of routine cultures, stains for acid-fast bacilli and fungi, and direct fluorescent antibody test for Legionella pneirmoplzilia on specimens obtained at bronchoscopy on the second hospital day were negative. Transbronchial biopsy revealed nonspecific inflammation in interstitial areas. Progressive respira-1291 tory insufficiency ensued, necessitating mechanical ventilation. Open lung biopsy, on hospital day 3, showed active interstitial pneumonitis with some alveolitis. Grocott stains were positive for sparse P curinii organisms compatible with a partially treated pneumocystis pneumonia. All antibiotics were discontinued except for trimethoprim/sulfamethoxazole, which was given for 3 weeks. Serum pneu...

Treatment for rheumatoid arthritis and the risk of hospitalization for pneumonia: Associations with prednisone, disease‐modifying antirheumatic drugs, and anti–tumor necrosis factor therapy

“…Methotrexate is suspected of conferring susceptibility to infectious pathogens (14)(15)(16)(17)(18)(19)(20), although most reports concern methotrexate pneumonitis, a hypersensitivity reaction (21). Low-dose prednisone is another commonly used treatment for RA, but there are no reported studies determining whether it is a risk factor for pneumonia in RA.…”

Pneumocystis jiroveci pneumonia associated with low-dose methotrexate treatment for rheumatoid arthritis: report of two cases and review of the literature

“…a Chest radiographs revealed bilateral ground-glass infiltrates and reticular shadows. b The shadows disappeared after treatment with prednisolone and trimethopurim/ sulfamethoxazole a b MTX is effective for RA are still unclear, many antiinflammatory and immunosuppressive actions, such as the inhibition of cellular proliferation, alterations in the lymphocyte subsets, a decreased cytokine production, the suppression of T-cell activation, and cell adhesion molecules, [1][2][3][4][5][6][7][8][9][10][11][12] have all been hypothesized to play a role. The concomitant use of nonsteroidal anti-inflammatory drugs, which can raise the plasma concentration of MTX by displacing it from albumin binding sites and impairing its renal excretion, could also have potentiated the MTX toxicity.…”

“…In 1983 PCP complicating low-dose MTX therapy for RA was reported. 2 Due to the wide diversity for the options for the treatment of RA including biological agents, we should take greater care of PCP. We herein describe two patients who developed PCP during low-dose MTX therapy and discuss the importance of appropriate prophylaxis.…”

Local infectious complications following large joint replacement in rheumatoid arthritis patients treated with methotrexate versus those not treated with methotrexate

“…Although the mechanisms of action of MTX in RA are unknown, the drug may have immunomodulatory effects (31). The immu-nomodulatory effects could in turn cause an increased risk of infection in patients with RA (26)(27)(28)(29). This is an especially important concern in the postoperative setting after total hip or knee replacement.…”