Infliximab-induced nonspecific interstitial pneumonia.
ABSTRACT Infliximab has well-established complications including injection site and allergic reactions, cytopenias, induction of autoimmune and demyelinating diseases and malignancy, especially lymphoma. Pulmonary complications are well documented and include serious respiratory infections from tuberculosis, fungal and opportunistic pathogens. This has prompted a Food and Drug Administration black-box warning recommending close surveillance for these diseases. Nonspecific interstitial pneumonitis (NSIP) secondary to tumor necrosis factor-alpha inhibitor (TNF-alpha) therapy is less well described. Rarely, TNF-alpha inhibitor therapy has been reported to cause NSIP when used in conjunction with other immunosuppressive agents. Literature search revealed 12 independent patients with presumed infliximab-induced NSIP in 8 separate publications; all patients were on concomitant steroid sparing immunosuppressive agents, complicating cause and effect. The authors report a case in which infliximab is surmised to cause NSIP in the absence of other steroid sparing immunosuppressants in a young female with ulcerative colitis. Of importance, the patient was taking no additional steroid sparing immunomodulating agents. The diagnosis was based on clinical presentation and radiologic and histopathological data. Cessation of infliximab and high-dose steroid therapy resulted in complete resolution of the patient's presenting signs and symptoms.
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ABSTRACT: Interstitial lung disease (ILD) is a relevant extra-articular manifestation of rheumatoid arthritis (RA) that may occur either in early stages or as a complication of long-standing disease. RA related ILD (RA-ILD) significantly influences the quoad vitam prognosis of these patients. Several histopathological patterns of RA-ILD have been described: usual interstitial pneumonia (UIP) is the most frequent one, followed by nonspecific interstitial pneumonia (NSIP); other patterns are less commonly observed. Several factors have been associated with an increased risk of developing RA-ILD. The genetic background plays a fundamental but not sufficient role; smoking is an independent predictor of ILD, and a correlation with the presence of rheumatoid factor and anti-cyclic citrullinated peptide antibodies has also been reported. Moreover, both exnovo occurrence and progression of ILD have been related to drug therapies that are commonly prescribed in RA, such as methotrexate, leflunomide, anti-TNF alpha agents, and rituximab. A greater understanding of the disease process is necessary in order to improve the therapeutic approach to ILD and RA itself and to reduce the burden of this severe extra-articular manifestation.BioMed research international. 01/2013; 2013:759760.
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ABSTRACT: To review published cases of induced or exacerbated interstitial lung disease (ILD) in rheumatoid arthritis (RA) associated with non-biologic disease-modifying antirheumatic drugs (nbDMARDs) and biologics and to discuss clinical implications in daily practice. We performed a systematic literature review from 1975 to July 2013 using Medline, Embase, Cochrane, and abstracts from the ACR 2010-2012 and EULAR 2010-2013 annual meetings. Case reports and series that suggest a causative role of nbDMARDs (methotrexate [MTX], leflunomide [LEF], gold, azathioprine [AZA], sulfasalazine [SSZ], and hydroxychloroquine [HCQ]) and biologic agents (TNF inhibitors [TNFi], rituximab [RTX], tocilizumab [TCZ], abatacept [ABA], and anakinra) in causing ILD or worsening a pre-existing ILD in RA patients were included. Results from observational and postmarketing studies as well as reviews on this topic were excluded from the qualitative analysis but still considered to discuss the implication of such drugs in generating or worsening ILD in RA patients. Comparisons were made between MTX-induced ILD in RA and the cases reported with other agents, in terms of clinical presentation, radiological features, and therapeutic management and outcomes. The literature search identified 32 articles for MTX, 12 for LEF (resulting in 34 case reports), 3 for gold, 1 for AZA, 4 for SSZ, 27 for TNFi (resulting in 31 case reports), 3 for RTX, 5 for TCZ (resulting in 8 case reports), and 1 for ABA. No case was found for HCQ or anakinra. Common points are noted between LEF- and TNFi-related ILD in RA: ILD is a rare severe adverse event, mostly occurs within the first 20 weeks after initiation of therapy, causes dyspnea mostly in older patients, and can be fatal. Although no definitive causative relationship can be drawn from case reports and observational studies, these data argue for a pulmonary follow-up in RA patients with pre-existing ILD, while receiving biologic therapy or nbDMARDs. As previously described for MTX, growing evidence highlights that LEF, TNFi, RTX, and TCZ may induce pneumonitis or worsen RA-related pre-existing ILD. Nonetheless, identifying a causal relationship between RA therapy and ILD-induced toxicity clearly appears difficult, partly because it is a rare condition.Seminars in arthritis and rheumatism 10/2013; · 4.72 Impact Factor
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ABSTRACT: Pulmonary involvement in Crohn's disease (CD) may precede the development of intestinal inflammation, but in most cases occurs during the course of treatment, either as an extra-intestinal manifestation, due to secondary infections, or as a side effect of the therapy itself. This case highlights the differential diagnosis and work up for multiple pulmonary nodules that developed in a patient with CD who had been in remission on Infliximab therapy. Even though infectious causes, such as Mycobacteria and Fungi, account for majority of these cases, the possibility of non-infectious conditions such as autoimmune disorders should also be considered.The Clinical Respiratory Journal 05/2014; · 2.20 Impact Factor