trimethoprim--sulfamethoxazole-drug-combination and Arthritis--Rheumatoid

Topics: Acidosis; Aged; Anti-Infective Agents; Anuria; Arthritis, Rheumatoid; Coma; Emergencies; Humans; Hyperkalemia; Hypoglycemia; Kidney Failure, Chronic; Male; Myocardial Ischemia; Pneumocystis Infections; Trimethoprim, Sulfamethoxazole Drug Combination

Accompanying the increased use of biologic and non-biologic antirheumatic agents, patients with RA have been exposed to an increased risk of Pneumocystis jirovecii infection, which causes acute fulminant P. jirovecii pneumonia (PCP). Mortality in this population is higher than in HIV-infected individuals. Several guidelines and recommendations for HIV-infected individuals are available; however, such guidelines for RA patients remain less clear. Between 2006 and 2008 we encountered a clustering event of P. jirovecii infection among RA outpatients. Through our experience with this outbreak and a review of the recent medical literature regarding asymptomatic colonization and its clinical significance, transmission modes of infection and prophylaxis of PCP, we have learned the following lessons: PCP outbreaks among RA patients can occur through person-to-person transmission in outpatient facilities; asymptomatic carriers serve as reservoirs and sources of infection; and short-term prophylaxis for eradication of P. jirovecii is effective in controlling PCP outbreaks among RA outpatients.

Topics: Anti-Infective Agents; Arthritis, Rheumatoid; Contact Tracing; Disease Reservoirs; Humans; Immunologic Deficiency Syndromes; Immunosuppressive Agents; Infectious Disease Transmission, Professional-to-Patient; Kidney Transplantation; Opportunistic Infections; Pneumocystis carinii; Pneumonia, Pneumocystis; Postoperative Complications; Risk Factors; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Patients with rheumatoid arthritis (RA) often have comorbidities that require multiple medications. Several of these medications may alter the efficacy or increase the toxicity of methotrexate (MTX). The purpose of our study was to determine which drugs used in combination with MTX (excluding disease modifying antirheumatic drugs, folic and folinic acid, corticosteroids, and biologic agents) enhance side effects or toxicity of MTX or lower its efficacy.. A systematic literature search was performed with Medline, Embase, Cochrane Register and Database, and abstracts from the 2006/2007 annual congresses of the American College of Rheumatology and the European League Against Rheumatism. A manual search of the citation lists of retrieved publications was performed.. Of the 1172 articles identified, 67 were included: 21 pharmacokinetics studies, 5 observational studies, and 78 case reports. Most medications do not significantly affect the pharmacokinetics profile of MTX. Among the clinical studies, cytopenia and elevation of liver enzymes were the main reported toxicities. The use of trimethoprim-sulfamethoxazole (TMP-SMX) was mentioned as a risk factor for developing cytopenia in one observational study and in 17 case reports. Thirty case reports of cytopenia were attributed to the use of concomitant nonsteroidal antiinflammatory drugs, including acetylsalicylic acid. Two studies described mild abnormalities of liver enzymes with the use of isoniazid, and one study with the use of high-dose ASA.. Based on the published literature, MTX has limited drug interactions, with the exception of TMP-SMX and high-dose ASA, which can exacerbate toxicity of MTX. The clinical significance of these interactions has not been substantiated by extensive clinical observations.

Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Clinical Trials as Topic; Databases, Factual; Drug Interactions; Hematologic Diseases; Humans; Methotrexate; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Rituximab is a B-cell-depleting monoclonal anti-CD20 antibody. It is widely used in haematology and rheumatology. However, usage of rituximab in immunosupressed patient has been associated with various opportunistic infections. The authors reported a case of refractory rheumatoid arthritis treated with rituximab, which later presented with non-resolving pneumonia with pulmonary nodule. Percutaneous computer tomogram guided lung biopsy was arranged to confirm the suspicion of tuberculosis, but did not yield conclusive results. Later, she presented left-chest abscess and underwent incision and drainage. The pus culture and sensitivity confirmed pulmonary nocardiosis with chest wall dissemination. She was treated with 2-week course of trimethoprim sulfamethoxazole and responded. The authors also reviewed published cases of nocardiosis post-rituximab.

Topics: Anti-Bacterial Agents; Antibodies, Monoclonal, Murine-Derived; Antirheumatic Agents; Arthritis, Rheumatoid; Diagnosis, Differential; Female; Humans; Middle Aged; Nocardia Infections; Pneumonia, Bacterial; Rituximab; Trimethoprim, Sulfamethoxazole Drug Combination

To review the literature on the immunomodulatory and anti-inflammatory properties of cotrimoxazole (CTX)-a combination of sulfamethoxazole and trimethoprim, to summarize the use of this medication in the treatment of autoimmune diseases, to stimulate and renew the interest of both physicians and researchers in this possible therapy for rheumatoid arthritis (RA), and to inspire further investigation in this field.. A MEDLINE search of the literature from 1966 until 2000 was performed, and information about the pharmacology of CTX and its use in the therapy of rheumatic diseases was critically reviewed.. RA treatment is associated with numerous problems such as lack of efficacy, frequent side effects, and high cost. Analysis of the relevant literature revealed that experience with CTX in the treatment of RA is limited. However, the results of several nonrandomized and evidently forgotten clinical trials and laboratory investigations suggested that CTX might serve as an effective and inexpensive therapy for RA. Several lines of evidence suggested that CTX has nonspecific anti-inflammatory and immunomodulatory properties. Although nausea and vomiting were common reasons for CTX withdrawal, they were noted in only some studies, and no major organ toxicity was observed.. Because of its therapeutic qualities, low cost, and relative nontoxicity, CTX seems to warrant a role in the treatment of RA.

Topics: Anti-Inflammatory Agents; Antirheumatic Agents; Arthritis, Rheumatoid; Clinical Trials as Topic; Drug Therapy, Combination; Immune System; MEDLINE; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Low-dose weekly pulse MTX therapy is effective for rheumatoid arthritis (RA) and is used for patients with RA who are unresponsive to conventional disease-modifying antirheumatic drugs (DMARDs). We used MTX to a 62-year-old man with RA who had received DMARDs for 5 years. MTX was effective for RA but after 12 weeks MTX therapy started, he complicated pancytopenia and developed Pneumocystis carinii pneumonia. We reviewed all RA patients reported in Japan and in the world from 1965, complicated with Pancytopenia (37 cases) and Pneumocystis carinii pneumonia (13 cases) after MTX therapy. Results were as following; (1) MTX should not be used with TMP-SMX. and risk factors for pancytopenia were (2) age over 60 years old (3) renal hypofunction (4) use of NSAID.

Topics: Age Factors; Anti-Infective Agents; Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Arthritis, Rheumatoid; Contraindications; Humans; Kidney Diseases; Male; Methotrexate; Middle Aged; Pancytopenia; Pneumonia, Pneumocystis; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Use of methotrexate to treat rheumatoid arthritis is associated with pulmonary adverse effects in 3% to 5% of cases. In addition to immunoallergic lung disease, bronchitis and pneumonia due to pyogenic organisms, opportunistic lower respiratory tract infections have been reported, including, to our knowledge, 18 cases of Pneumocystis carinii pneumonia. We report two new cases of P. carinii pneumonia in methotrexate-treated rheumatoid arthritis patients. One case occurred in a 62-year-old woman with a nine-year history of seropositive rheumatoid arthritis treated for the last seven months with methotrexate, 15 mg per week, and prednisone, 10 mg/d. The other patient was a 58-year-old woman who had been diagnosed with rheumatoid arthritis 18 months earlier and had been receiving 15 mg per week of methotrexate for eight months in combination with 12.5 mg of prednisone per day. Both patients had negative tests for the human immunodeficiency virus. Symptoms consisted of fever, cough and dyspnea, with interstitial infiltrates on chest films, hypoxia, and lymphopenia (700 and 600/mm3, respectively). The diagnosis was confirmed by bronchoalveolar lavage. Both patients recovered under treatment with trimethoprim-sulfamethoxazole. An analysis of the 20 cases of P. carinii pneumonia reported to date in methotrexate-treated rheumatoid arthritis patients demonstrated a number of characteristics: the rheumatoid arthritis was of recent onset in some cases (a few months in one patient); lymphopenia was present in two thirds of cases; one-third of patients were not receiving corticosteroid therapy; the dosage and duration of methotrexate therapy varied widely, from 5 to 30 mg per week and two to 48 months; and four patients died.

Topics: Anti-Infective Agents; Antirheumatic Agents; Arthritis, Rheumatoid; Bronchoalveolar Lavage; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Methotrexate; Middle Aged; Pneumonia, Pneumocystis; Prednisone; Trimethoprim, Sulfamethoxazole Drug Combination

The antirheumatoid activity of sulphasalazine and sulphapyridine may result from their antibacterial properties. The second line activity of sulphamethoxazole, in the form of cotrimoxazole (CTZ), has been investigated by treatment of 13 patients with RA for 24 weeks with CTZ (480 mg three times a day). The drug was found to be poorly tolerated, only five of the thirteen patients recruited completing the study. High circulating concentrations of sulphamethoxazole were found, with mean (SD) steady state serum concentrations reaching 54.02 (23.38) micrograms/ml. A significant reduction in serum IgM from 280 to 130 IU/l was observed, but otherwise disease activity remained unchanged or deteriorated throughout the course of the study. In contrast, patients with RA treated with sulphapyridine (1.25 g a day) showed improvement in disease activity. The results argue against an antibacterial mechanism of action for sulphasalazine and sulphapyridine in rheumatoid arthritis, unless this occurs at a site inaccessible to sulphamethoxazole.

Topics: Arthritis, Rheumatoid; Clinical Trials as Topic; Drug Combinations; Humans; Sulfamethoxazole; Sulfapyridine; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

The use of biologic and targeted synthetic (b/ts) DMARDs in the treatment of RA is increasing. Therefore, prevention of b/tsDMARDs-induced infection is important. Here we describe a prophylaxis protocol for preventing pneumocystis pneumonia (PCP) in RA patients treated with b/tsDMARDs.. The study subjects were 3787 RA patients from the FIRST registry. They were divided into cohort 1 (n = 807, requiring prophylaxis against PCP based on physicians' assessment at the point of new treatment with or switch to b/tsDMARDs) and cohort 2 (n = 2980, receiving strategic PCP prophylaxis). The incidence and risk factors for PCP were investigated.. Twenty-six PCP cases were observed throughout the study. After the introduction of strategic PCP prophylaxis, PCP incidence diminished from 0.51/100 person-years (PYs) to 0.21/100 PYs (risk ratio = 0.42). Sulfamethoxazole and trimethoprim in combination (SMX-TMP) showed greater efficacy in the prevention of PCP than pentamidine inhalation (P <0.0001). The prophylaxis rate increased chronologically despite the falls in the average SMX-TMP dose and in the incidence of PCP. Subanalysis of the data for 929 patients from both groups who did not receive prophylaxis showed that old age, high BMI, coexisting lung diseases, low lymphocyte count, and low serum IgG levels increased the risk of PCP development. Development of PCP could be predicted (using an equation based on these variables) in patients not treated with glucocorticoids [area under the curve (AUC) = 0.910)], but less accurately in those on glucocorticoids (AUC = 0.746).. Our study clarified the risk factors for PCP in RA patients on b/tsDMARDs treatment and highlighted and defined the criteria for effective prophylaxis against PCP.

Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Glucocorticoids; Humans; Pneumonia, Pneumocystis; Registries; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

To investigate the clinical features and prognosis of nocardiosis complicated by connective tissue diseases (CTDs).. We examined patients with CTDs who were diagnosed with nocardiosis from October 2004 to 2019. We retrospectively investigated patient characteristics and therapeutic outcomes. We then performed a comparison between survivors and non-survivors.. Fourteen patients were examined. Underlying CTDs were systemic lupus erythematosus (28.6%), vasculitis syndrome (28.6%), rheumatoid arthritis (21.4%), adult Still disease (14.3%) and dermatomyositis (7.1%). Infected organs were lung (85.7%), brain (42.9%), skin/cutaneous lesions (28.6%) and muscle (7.1%). Disseminated infections were seen in nine patients (64.3%). At the onset of nocardiosis, all patients were given prednisolone (23.2 ± 11.9 mg/day). Only two patients (14.3%) were given TMP-SMX for prophylaxis of pneumocystis pneumonia. Relapse occurred in one patient (7.1%) and four patients (28.6%) died from nocardiosis for a cumulative survival rate at 52 weeks of 76.9%. In a comparison of survivors (71.4%) and non-survivors (28.6%), cutaneous lesions were significantly more frequent in the latter (10 vs 75%,. Cutaneous lesions as a result of dissemination might be a risk factor for nocardiosis mortality in patients with CTDs.

Topics: Adult; Anti-Bacterial Agents; Arthritis, Rheumatoid; Female; Humans; Lupus Erythematosus, Systemic; Male; Middle Aged; Nocardia Infections; Prognosis; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination; Vasculitis

A 65-year-old woman with rheumatoid arthritis (RA) visited our hospital because of right facial sensory hypoesthesia. Cerebral toxoplasmosis was suspected on brain magnetic resonance imaging. We discontinued methotrexate for RA and started a sulfamethoxazole/trimethoprim (ST) mixture. Although ST treatment was interrupted because of adverse reactions, her prognosis was favorable. The Toxoplasma 18S rDNA gene was detected by nested-polymerase chain reaction (PCR) from blood and cerebrospinal fluid. Detecting the Toxoplasma 18S rDNA gene by nested-PCR is useful for the diagnosis and safer than a brain biopsy. In addition, the discontinuation of immunosuppressants may be recommended in patients compromised by those immunosuppressants.

Topics: Aged; Arthritis, Rheumatoid; DNA, Ribosomal; Female; Humans; Immunosuppressive Agents; Methotrexate; Polymerase Chain Reaction; Toxoplasma; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination; Withholding Treatment

Topics: Arthritis, Rheumatoid; Glucocorticoids; Humans; Pneumocystis; Pneumonia, Pneumocystis; Rheumatic Diseases; Trimethoprim, Sulfamethoxazole Drug Combination

Immunosuppressant medications (ISPs) increase the occurrence of Pneumocystis jirovecii pneumonia (PCP) in rheumatoid arthritis (RA) patients. The prophylactic administration of trimethoprim/sulfamethoxazole (TMP/SMX) for PCP is effective but has serious adverse effects and so should be selectively used for patients at high risk. The aims of this study were to clarify the risk factors for PCP in RA patients and to establish the indications for administering TMP/SMX.. This retrospective cohort study analyzed data from 2640 patients (2010-2014) diagnosed as having RA who had not received a prophylactic administration of TMP/SMX. The risk factors for PCP were evaluated by comparing the clinical parameters between patients with PCP (PCP group, n = 19) and those without (non-PCP group, n = 2621).. The PCP group was older (70 vs. 64 years), received higher doses of prednisolone (6.2 vs. 2.4 mg/d) and methotrexate (7.7 vs. 5.2 mg/wk), and had a greater number of ISPs (1.3 vs. 0.8) (p < 0.05). We stratified the PCP risk using a scoring system based on odds ratios (ORs) calculated for these parameters (methotrexate ≥6 mg/wk OR = 4.5, 1 point; age ≥65 years, OR = 3.7, 1 point; ≥2 ISPs, OR = 3.7, 1 point; prednisolone ≥5 mg/d, OR = 12.4, 3 points). The incidence of PCP among patients scoring 0 to 2 points was 0.04%; 3 to 4 points, 2.3%; and 5 points or more, 5.8%.. The prophylactic administration of TMP/SMX for PCP is recommended for RA patients who score at least 5 points with our system.

Topics: Aged; Arthritis, Rheumatoid; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Risk Factors; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

We present a case of a 57-year-old woman who contracted

Topics: Anti-Bacterial Agents; Arthritis, Rheumatoid; Diagnosis, Differential; Drug Combinations; Etanercept; Female; Humans; Immunosuppressive Agents; Injections, Subcutaneous; Intensive Care Units; Methotrexate; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Radiography, Thoracic; Respiration, Artificial; Respiratory Insufficiency; Sputum; Steroids; Tomography, X-Ray Computed; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Pulmonary toxoplasmosis is a serious pulmonary condition caused by the protozoan

Topics: Adrenal Cortex Hormones; Antirheumatic Agents; Arthritis, Rheumatoid; Diagnosis, Differential; Drug Therapy, Combination; Female; Humans; Immunocompromised Host; Lung Diseases, Interstitial; Methotrexate; Middle Aged; Tomography, X-Ray Computed; Toxoplasma; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis jirovecii pneumonia (PCP) is potentially fatal infectious complication in patients with rheumatoid arthritis (RA) during immunosuppressive therapy. Hospital survival due to human immunodeficiency virus-unrelated PCP reaches to 60%. The high mortality rate results from difficulties in establishing an early diagnosis, concurrent use of prophylactic drugs, possible bacterial coinfection. We herein report a case of PCP in RA patients who developed the architectural distortions of lung in spite of combined modality therapy.. A 73-year-old Japanese woman with RA was admitted with shortness of breath. Five weeks previously, she had been started on etanercept in addition to methotrexate (MTX). Chest computed tomography (CT) demonstrated diffuse ground glass opacities distributed throughout the bilateral middle to lower lung fields, and serum β-D-glucan was elevated. Bronchoalveolar lavage fluid revealed no P. jirovecii, but the organism was detected by polymerase chain reaction method. Trimethoprim/sulfamethoxazole was administered with methylprednisolone pulse therapy. However, the follow-up chest X-ray and chest CT demonstrated aggravation of the pneumonia with architectural distortions. Additional direct hemoperfusion with polymyxin B-immobilized fibers and intravenous cyclophosphamide therapy were insufficiently effective, and the patient died on day 25.. The architectural distortions of lung should be considered as a cause of death of PCP. For this reason, a high suspicion of this infectious complication must be kept in mind in order to establish an early diagnosis and treatment in patients with RA managed with MTX and biologics.

Topics: Acute Disease; Aged; Anti-Infective Agents; Antirheumatic Agents; Arthritis, Rheumatoid; Disease Progression; Etanercept; Fatal Outcome; Female; Humans; Lung Diseases, Interstitial; Methotrexate; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymyxin B; Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim-sulfamethoxazole (TMP/SMX) treatment for pneumocystis pneumonia (PCP) in patients with autoimmune diseases who developed PCP was conducted in a retrospective study of the following: dosage, frequency of side effects and persistence rate of TMP/SMX and prognosis of patients. Seven patients (two males and five females, mean age: 72 years) were hospitalized between April 1, 2013 and August 31, 2015, and their underlying diseases were rheumatoid arthritis (six patients) and microscopic polyangiitis (one patient). Moderate-dose TMP/SMX (TMP equivalent to TMP/SMX, average: 9.6 mg/kg/day, range: 5.1-12.5 mg/kg/day) was used for PCP treatment. As a result, patients experienced the following side effects: hyponatremia in five patients (71.4%), exanthema in four patients (57.1%), and thrombocytopenia in two patients (28.6%). Elevated creatinine level, increased blood pressure, malaise, and hyperkalemia were experienced by each patient. Six patients (85.7%) discontinued TMP/SMX treatment due to side effects, but once they had recovered, desensitization to TMP/SMX was used to treat them. Eventually, four patients were successfully treated with TMP/SMX (final persistence rate, 57.1%). Their prognoses were good, and no patients died for at least 60 days after admission. Moderate-dose TMP/SMX treatment for PCP in patients with autoimmune diseases who developed PCP may have therapeutic effects equal to high-dose TMP/SMX treatment, and therefore collecting more case studies is expected.

Topics: Aged; Aged, 80 and over; Arthritis, Rheumatoid; Autoimmune Diseases; Female; Humans; Immunocompromised Host; Male; Microscopic Polyangiitis; Middle Aged; Pneumonia, Pneumocystis; Prognosis; Retrospective Studies; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aged; Arthritis, Rheumatoid; Bacteremia; Depressive Disorder; Female; Follow-Up Studies; Humans; Infusions, Intravenous; Magnetic Resonance Imaging; Memory Disorders; Nocardia; Nocardia Infections; Prednisone; Rare Diseases; Risk Assessment; Severity of Illness Index; Tomography, X-Ray Computed; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Pneumocystis pneumonia (PCP) is one of the most prevalent opportunistic infections in patients undergoing immunosuppressive therapy. In this article, we discuss risk factors for PCP development in patients with rheumatoid arthritis (RA) during the course of biologic therapy and describe a prophylactic treatment for PCP with trimethoprim/sulfamethoxazole (TMP/SMX). We also evaluate the effectiveness and safety of the treatment.. We retrospectively analyzed 702 RA patients who received biologic therapy and compared the characteristics of patients with vs. without PCP to identify the risk factors for PCP. Accordingly, we analyzed 214 patients who received the TMP/SMX biologic agents as prophylaxis against PCP at the start of treatment to evaluate their effectiveness and safety.. We identified the following as risk factors for PCP: age at least 65 years (hazard ratio (HR) = 4.37, 95% confidence interval (CI) = 1.04 to 18.2), coexisting pulmonary disease (HR = 8.13, 95% CI = 1.63 to 40.0), and use of glucocorticoids (HR = 11.4, 95% CI = 1.38 to 90.9). We employed a protocol whereby patients with two or three risk factors for PCP would receive prophylactic treatment. In the study with 214 patients, there were no cases of PCP, and the incidence of PCP was reduced to 0.00 per 100 person-years compared with that before the procedure (0.93 per 100 person-years). There were no severe adverse events induced by the TMP/SMX treatment.. RA patients with two or three risk factors for PCP who are receiving biologic therapy can benefit from safe primary prophylaxis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Infective Agents; Antirheumatic Agents; Arthritis, Rheumatoid; Biological Products; Female; Humans; Immunocompromised Host; Male; Middle Aged; Opportunistic Infections; Pneumonia, Pneumocystis; Retrospective Studies; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

A 73-year-old woman with rheumatoid arthritis treated with methotrexate and prednisolone was admitted with dyspnea and ground-glass opacity on chest CT. We diagnosed her with Pneumocystis jirovecii pneumonia (PCP) based on a positive PCR analysis of Pneumocystis jirovecii and the presence of cysts in bronchoalveolar lavage fluid. The PaO2 was 74.7 Torr on room air, and treatment with sulfamethoxazole-trimethoprim only was initiated. The hypoxemia and ground-glass opacity increased on hospital day 3, and the administration of adjunctive steroid therapy resulted in an improvement in the patient's condition. Although patients with PCP with HIV infection and hypoxemia are often treated with adjunctive steroid therapy to prevent adverse immune reactions, the efficacy of additive steroid administration in case of non-HIV PCP has not been established.

Topics: Aged; Anti-Infective Agents; Arthritis, Rheumatoid; Chemotherapy, Adjuvant; Female; Glucocorticoids; Humans; Lung; Methotrexate; Methylprednisolone; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Prednisolone; Radiography; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Arthritis, Rheumatoid; Delayed Diagnosis; Diagnosis, Differential; Humans; Male; Middle Aged; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Whipple Disease

Topics: Anti-Infective Agents; Arthritis, Rheumatoid; Contraindications; Humans; Immunosuppressive Agents; Methotrexate; Pneumocystis carinii; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

While tumor necrosis factor (TNF) inhibitors have dramatically improved the clinical outcomes of rheumatoid arthritis (RA) in recent years, infectious complications are a serious concern. Adalimumab (ADA) is a newly-developed human monoclonal antibody against TNF-alpha. Here we report 2 cases of pneumocystis pneumonia (PCP) which developed in RA patients during ADA therapy. One patient is a 66-year-old woman who had a history of RA for 6 months. The patient was given ADA at 40 mg biweekly for her active arthritis which had been refractory to 6 mg/week of methotrexate (MTX), and 5 mg/day of prednisolone (PSL). One hundred and six days later, she was admitted to our hospital because of fever, cough, and dyspnea. Another patient is a 62-year-old man who had a history of RA for 3 years. Since his arthritis was so active even under the treatment with MTX (8 mg/week) and PSL (15 mg/day), the patient started to be given ADA at 40 mg biweekly. After 28 days, the patient was admitted to the hospital because of dyspnea. Chest roentgenogram and computed tomography revealed interstitial pneumonia in both patients. Beta-D-glucan levels were so high in their serum suggesting the diagnosis of PCP, which was confirmed by the detection of Pneumocystis jirovecii DNA in the sputa by polymerase chain reaction. The patients were immediately treated with sulfamethoxazole/trimethoprim and high-dose prednisolone, which successfully improved pneumonia, and they were discharged from the hospital on the 8(th) and 16(th) day, respectively. PCR and β-D-glucan were useful for the early diagnosis of PCP and lead to the timely induction of adequate treatment and the rescue of these patients.

Topics: Adalimumab; Aged; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Arthritis, Rheumatoid; beta-Glucans; Biomarkers; DNA, Fungal; Early Diagnosis; Female; Humans; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Prednisolone; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Tumor Necrosis Factor-alpha

Tumor necrosis factor-alpha inhibitors are potent anti-rheumatic drugs, but there is evidence that the high level of immunosuppression they provide may also lead to a higher risk of infections. At our institution, 3 patients with inflammatory arthritis treated with tumor necrosis factor-alpha inhibitors developed mycobacterial soft tissue infections after routine hand surgery. All 3 patients required multiple surgical procedures, inpatient hospitalizations, and prolonged antibiotic multidrug therapy to clear the infections.

Topics: Aged; Antibodies, Monoclonal; Antirheumatic Agents; Arthritis, Psoriatic; Arthritis, Rheumatoid; Azithromycin; Etanercept; Female; Hand; Humans; Immunoglobulin G; Infliximab; Male; Methotrexate; Middle Aged; Mycobacterium Infections; Receptors, Tumor Necrosis Factor; Tenosynovitis; Trimethoprim, Sulfamethoxazole Drug Combination; Tumor Necrosis Factor-alpha

To establish proper management of Pneumocystis jiroveci pneumonia (PCP) in rheumatoid arthritis (RA) patients treated with infliximab. PCP has been observed in 0.4% of patients with RA treated with infliximab in Japan.. Data from patients with RA (n = 21) who were diagnosed with PCP during infliximab treatment and from 102 patients with RA who did not develop PCP during infliximab therapy were collected from 14 rheumatology referral centers in Japan. A retrospective review of these patients and a case-control study to compare patients with and without PCP were performed.. The median length of time from the first infliximab infusion to the development of PCP was 8.5 weeks. At the onset of PCP, the median dosages of prednisolone and methotrexate were 7.5 mg/day and 8 mg/week, respectively. Pneumocystis jiroveci was microscopically identified in only 2 patients, although the polymerase chain reaction test for the organism was positive in 20 patients. The patients with PCP had significantly lower serum albumin levels (P < 0.001) and lower serum IgG levels (P < 0.001) than the patients without PCP. Computed tomography of the chest in all patients with PCP revealed ground-glass opacity either with sharp demarcation by interlobular septa or without interlobular septal boundaries. Sixteen of the 21 patients with PCP developed acute respiratory failure, but all survived.. PCP is a serious complication that may occur early in the course of infliximab therapy in patients with RA. For the proper clinical management of this infectious disease, physicians need to be aware of the possibility of PCP developing during infliximab therapy.

Topics: Aged; Anti-Infective Agents; Antibodies, Monoclonal; Antirheumatic Agents; Arthritis, Rheumatoid; Female; Humans; Infliximab; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Tumor Necrosis Factor-alpha

We report that a-63-year-old woman developed Pneumocystis jiroveci pneumonia (PCP) as a complication from treatment with infliximab for rheumatoid arthritis. Although there was neither symptoms of dyspnea nor typical observations on a chest X-ray examination, low levels of oxygen saturation and findings of high-resolution chest computed tomographic scanning suggested a possibility of interstitial pneumonia. A polymerase chain reaction-based detection of Pneumocystis jiroveci in induced sputum allowed an early diagnosis of PCP and subsequent effective treatment.

Topics: Anti-Infective Agents; Antibodies, Monoclonal; Antirheumatic Agents; Arthritis, Rheumatoid; Blood Gas Monitoring, Transcutaneous; Female; Humans; Immunocompromised Host; Infliximab; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination; Tumor Necrosis Factor-alpha

A 64-year-old man was admitted to our hospital complaining of dyspnea and fever. He had been treated with low-dose methotrexate for rheumatoid arthritis. Chest radiography showed diffuse ground-glass attenuation in both lung fields, and hypoxia was detected. Pneumosystis carinii pneumonia was demonstrated on transbronchial lung biopsy, and the serum beta-D glucan level was high. We started treatment with trimethoprim-sulphamethoxazole, but respiratory failure worsened, and drug-induced pancytopenia occurred. Although trimethoprim-sulphamethoxazole was stopped, pancytopenia persisted and the patient required ventilatory support. After we changed the medication from trimethoprim-sulphamethoxazole to pentamidine, respiratory failure improved. It was thought that pneumocystis carinii pneumonia was associated with low-dose methotrexate and that trimethoprim-sulphamethoxazole interacted with methotrexate to induce severe pancytopenia.

Topics: Anti-Infective Agents; Antirheumatic Agents; Arthritis, Rheumatoid; Humans; Male; Methotrexate; Middle Aged; Pancytopenia; Pneumonia, Pneumocystis; Pulse Therapy, Drug; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aged; Anti-Infective Agents; Anti-Inflammatory Agents; Antirheumatic Agents; Arthritis, Rheumatoid; Female; Follow-Up Studies; Humans; Immunocompromised Host; Immunosuppressive Agents; Methotrexate; Pneumonia, Pneumocystis; Prednisolone; Radiography, Thoracic; Time Factors; Tomography, X-Ray Computed; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents, Urinary; Antirheumatic Agents; Arthritis, Rheumatoid; Drug Hypersensitivity; Humans; Male; Methotrexate; Middle Aged; Pancytopenia; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aged; Anti-Infective Agents; Antirheumatic Agents; Arthritis, Rheumatoid; Asbestosis; Bronchoalveolar Lavage Fluid; Fatal Outcome; Humans; Immunocompromised Host; Immunosuppressive Agents; Male; Methotrexate; Opportunistic Infections; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

To determine which risk factors are associated with serious pancytopenia associated with low dose methotrexate (MTX) therapy.. All Ottawa area rheumatologists, hematologists and dermatologists were surveyed to obtain cases of pancytopenia associated with low dose MTX therapy between 1981 and 1991. Pancytopenia was defined as white blood cells < 3.5 x 10(9)/l and platelets < 140 x 10(9)/l and hemoglobin < 100 g/l. A case control method was used to evaluate risk factors.. Fifteen cases of pancytopenia were identified from returned questionnaires (93% response rate) and from reviewing the medical records of 2 major teaching hospitals. All patients were hospitalized, had MTX therapy discontinued and were treated: 12 patients received transfusions, 8 leucovorin therapy, and 4 folic acid. Two patients died, only 1 directly due to MTX therapy. Identified risk factors were (1) elevated BUN or creatinine levels, (2) increasing mean corpuscular volume values, (3) increased age and (4) concomitant trimethoprim-sulfamethoxazole therapy.. Pancytopenia associated with low dose MTX therapy is a life threatening adverse effect often associated with known risk factors. A change in monitoring guidelines and patient education are suggested as means of risk reduction.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Arthritis, Psoriatic; Arthritis, Rheumatoid; Blood Urea Nitrogen; Canada; Creatinine; Dose-Response Relationship, Drug; Female; Folic Acid; Health Surveys; Humans; Leucovorin; Male; Methotrexate; Middle Aged; Pancytopenia; Psoriasis; Risk Factors; Surveys and Questionnaires; Trimethoprim, Sulfamethoxazole Drug Combination

A 74-year-old woman had been treated with methotrexate over 2 years for rheumatoid arthritis. She was admitted to the hospital because of non-healing leg ulcers. After being treated with trimethoprim-sulphamethoxazole for a urinary-tract infection, she developed severe pancytopenia, followed by pneumonia and septic shock. The patient died shortly after. Concomitant treatment with methotrexate and sulphonamides should be strongly discouraged.

Topics: Aged; Arthritis, Rheumatoid; Drug Synergism; Drug Therapy, Combination; Female; Humans; Leg Ulcer; Methotrexate; Pancytopenia; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

Topics: Anti-Infective Agents; Arthritis, Rheumatoid; Drug Combinations; Drug Synergism; Drug Therapy, Combination; Female; Humans; Methotrexate; Middle Aged; Pancytopenia; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

A 61-year-old patient with rheumatoid arthritis receiving treatment with methotrexate developed bone marrow hypoplasia after treatment with trimethoprim-sulfamethoxazole. The bone marrow recovered after stopping methotrexate.

Topics: Arthritis, Rheumatoid; Bone Marrow Diseases; Drug Combinations; Drug Interactions; Female; Humans; Methotrexate; Middle Aged; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

A patient with severe seropositive rheumatoid arthritis and hepatic cirrhosis developed septic arthritis of his knees. Plesiomonas shigelloides was isolated from joint fluid, blood, and also from the gut. The patient's joint symptoms responded to treatment with oral trimethoprim-sulphamethoxazole, but he died of uncontrolled gastrointestinal bleeding five days later.

Topics: Aged; Arthritis, Infectious; Arthritis, Rheumatoid; Bacterial Infections; Drug Combinations; Humans; Knee Joint; Male; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Vibrionaceae