Abdominal Pain and Weight Loss After Adalimumab Therapy

Abstract

Question: A 70-year-old Spanish woman with a history of rheumatoid arthritis has been treated for 1 year with adalimumab 40 mg subcutaneously every 2 weeks, prednisone 10 mg orally daily, and methotrexate 10 mg orally every week. She was admitted owing to abdominal pain and severe weight loss of 2-month duration. Physical examination was remarkable for a temperature of 37.2°C and distended abdomen with marked mesogastric tenderness to palpation. Laboratory tests showed mild anemia (11.4 g/dL) and elevated sedimentation rate (120 mm), in addition to an elevation of serum CA 125 (584.40 IU/mL; normal range, 0–35). Contrast-enhanced computed tomography showed smooth and uniform thickening of peritoneum (Figures A and B, arrowheads) and ascitic fluid in the pelvic recesses. Screening test results for tuberculosis (TB) screening before adalimumab therapy (chest radiograph and tuberculin skin test [TST] with booster) were negative and the patient denied previous history or known exposure to TB. Repeat chest radiograph and TST, as well as interferon-gamma release assay, were negative for TB. What is the most likely diagnosis? Look on page 189 for the answer and see the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. Laparoscopy showed whitish miliary nodules on the peritoneum and small bowel (Figures C and D). Histopathologic examination revealed noncaseating epithelioid granulomas (Figure E; stain: H&E; original magnification, ×200), and mycobacteria were not identified by acid-fast bacillus staining. Although bacteriologic culture, auramine stain, and detection of DNA with polymerase chain reaction were negative for TB, empirical anti-TB treatment was started. Mycobacterium tuberculosis grew on culture 5 weeks later. Adalimumab was discontinued and anti-TB therapy was completed for 9 months. The risk of TB increases 5-fold after the use of anti–tumor necrosis factor (TNF)-α, especially in 3 groups1British Thoracic Society Standards of Care CommitteeBTS recommendations for assessing risk and for managing M. tuberculosis infection and disease in patients due to start anti-TNF-alpha treatment.Thorax. 2005; 60: 800-805Crossref PubMed Scopus (402) Google Scholar: (1) Patients with occupational exposure, such as healthcare workers, (2) patients native from Sub-Saharan Africa and Asia, where TB is endemic,2Mankia S. Peters J.E. Kang S. et al.Tuberculosis and anti-TNF treatment: experience of a central London Hospital.Clin Rheumatol. 2011; 30: 399-401Crossref PubMed Scopus (17) Google Scholar and (3) patients born in countries with high prevalence of latent TB infection (LTBI), principally Spain and Portugal.3Gomez-Reino J.J. Carmona L. Valverde V.R. et al.Treatment of rheumatoid arthritis with tumor necrosis factor inhibitors may predispose to significant increase in tuberculosis risk: a multicenter active-surveillance report.Arthritis Rheum. 2003; 48: 2122Crossref PubMed Scopus (913) Google Scholar Additionally, the lack of utility of chest radiograph and TST to identify LTBI is demonstrated by growing cases of adalimumab-induced TB (most of them native from Spain or Asia) in immunosuppressed rheumatic patients after negative TB screening. As such, emerging recommendations balance the need for systematic TB chemoprophylaxis in high-risk, immunosuppressed patients on anti–TNF-α therapy.1British Thoracic Society Standards of Care CommitteeBTS recommendations for assessing risk and for managing M. tuberculosis infection and disease in patients due to start anti-TNF-alpha treatment.Thorax. 2005; 60: 800-805Crossref PubMed Scopus (402) Google Scholar Although this strategy seems rational in Asian or African immigrants <35 years old in their 4 first years after entry,1British Thoracic Society Standards of Care CommitteeBTS recommendations for assessing risk and for managing M. tuberculosis infection and disease in patients due to start anti-TNF-alpha treatment.Thorax. 2005; 60: 800-805Crossref PubMed Scopus (402) Google Scholar it remains to be proven cost effective for other groups. Furthermore, concomitant intake of azathioprine or methotrexate can increase the risk of hepatotoxicity. As indications for adalimumab use grow in inflammatory bowel disease, a careful epidemiologic and clinical history, beside TB screening at the very outset of the disease (inmmunosuppressant-naive state), combining TST and interferon-gamma release assay, are required to enhance the diagnosis of LTBI. Likewise, inactive inflammatory bowel disease on anti–TNF-α and either fever of unknown origin or atypical symptoms should lead to a diagnostic workup for TB. Negative results do not preclude TB, owing to its paucibacillary expression, and histopathology should be sought quickly. Of note, early concurrent anti-TB treatment should be started under TB suspicion until microbiological confirmation. The authors thank Dr Lucia Ferrando-Lamana, Department of Anatomic Pathology, Hospital San Pedro de Alcantara, Caceres, Spain, for providing the histopathology image and Dr Javier P. Gisbert, for his useful comments on this manuscript.