Case Presentation: A 51-year-old man with history of psoriasis presented to the emergency department for abdominal discomfort and distention for 2 weeks, associated with fever, weight loss, night sweats, non-productive cough, and shortness of breath. He previously lived in Mexico and was treated in the past for latent tuberculosis (TB) with 6 months of isoniazid. He received adalimumab for psoriasis for a year, but one month prior to presentation his dermatologist discontinued the treatment after noting a positive QuantiFERON test and new right upper lobe opacities on chest X-ray. He last visited Mexico two years prior, had no known TB exposures, and worked in a factory with multiple coworkers who were previously in prison.Exam revealed normal vital signs, bibasilar crackles on lung auscultation, and abdominal distention with dullness to percussion at the flanks. He had no scleral icterus, spider angiomas, or other signs of liver disease. Labs showed normal white blood count of 5.8 K/mcL, and liver function tests were remarkable only for low albumin 2.8 g/dL. CT abdomen/pelvis showed diffuse ascites with mesenteric edema and inflammation, no masses, and a normal liver. CT chest revealed bilateral upper lobe centrilobular micronodules and ill-defined consolidative opacities with enlarged mediastinal lymph nodes and trace bilateral pleural effusions.The patient was admitted for pneumonia and new onset ascites concerning for tuberculosis. He was placed in airborne isolation. Paracentesis yielded 4.5 L clear, yellow fluid with lymphocyte predominance, low serum-ascites albumin gradient (SAAG) < 1.1, and no malignant cells. Ascitic fluid studies showed elevated adenosine deaminase (ADA) 46 U/L and negative TB PCR and acid fast bacilli (AFB) stain and culture. Three sputum AFB stains were negative, as were blood cultures and fungal serologies for Histoplasma, Cryptococcus, and Coccidioides. After infectious disease consultation, the patient was started on therapy with rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE) with pyridoxine given high concern for post-primary TB despite negative AFB and TB PCR.
Discussion: This case illustrates the risk of TB reactivation associated with tumor necrosis factor (TNF) alpha inhibitors. TNF plays a role in the pathogenesis of psoriasis and in the immune defense against TB. Guidelines recommend screening all patients considered for biologics with TB skin test or interferon gamma release assay (IGRA).1,2This patient was appropriately screened and referred to outpatient infectious disease clinic prior to starting adalimumab. He completed six months of isoniazid, however the optimal duration is nine months.3 Not all patients need to be rescreened, and there is no optimal approach to interpreting repeat IGRA results after TB treatment.4 In this case, repeat QuantiFERON and chest Xray were performed simply because the patient saw a new provider, but led to abnormal findings and discontinuation of adalimumab.The timeline is interesting since the patient became symptomatic after stopping adalimumab. There have been other cases showing paradoxical worsening of TB following discontinuation of anti-TNF drugs, which may be related to immune reconstitution.5,6
Conclusions: Patients on TNF-alpha inhibitors are at high risk for reactivation of TB, and vigilance is required to ensure this diagnosis is not missed. Microbiologic confirmation of TB can be challenging, and at times empiric therapy is warranted to prevent worsening disseminated infection.