Critical Care Medicine-Infections and Immunologic Disease>>>>>Immunological Diseases
Question 5#

A 68-year-old woman, who immigrated to the United States from Peru 7 years ago, with a history of rheumatoid arthritis (RA), maintained on adalimumab, presents to the emergency department with fever, arthralgias, dyspnea, and a productive cough. Physical examination is notable for distended abdomen with splenomegaly and ascites. Chest x-ray shows bilateral micronodular opacities, seen on subsequent chest CT scan with mediastinal lymphadenopathy and lymph node calcifications. Despite empiric antibiotic and antifungal coverage, her clinical condition worsened and was transferred to the ICU where intubation and mechanical ventilation instituted. Diagnostic bronchoscopy and paracentesis are performed. Rapid tuberculosis (TB) testing shows positivity in both the sputum and ascitic fluid samples, and both develop positive mycobacterial cultures at day 14.

Which of the following statements is true of her disseminated TB?

A. Completion of 9 months of chemoprophylaxis eliminates the risk of reactivation of TB among purified protein derivative (PPD)–positive patients started on adalimumab
B. Immunosuppression may result in a false-negative PPD test, but QuantiFERON-TB Gold assay is unaffected
C. Adalimumab’s mechanism of action is by competitively binding to the IL-6 receptor
D. The risk of TB is 4X higher in patients on anti-tumor necrosis factor α (anti-TNFα) therapies

Correct Answer is D


Correct Answer: D

RA affects 5 in 1000 individuals worldwide, with 2 to 3× as many women as men affected and peak incidence in the sixth decade of life. Treatment of RA has evolved over the last 2 decades with the advent of biologic therapies targeted at stopping or substantially slowing the joint destruction seen in RA. Modern therapy for RA includes disease-modifying antirheumatic drugs (DMARDs), which refer to medications that reduce the signs and symptoms of RA, improve physical function, and inhibit progression of joint destruction. Methotrexate, together with steroid therapy, is the firstline DMARD. Biological agents are second-line therapy. 

Biologic agents for RA include the TNFα-inhibitors (etanercept, infliximab, adalimumab, golimumab, certolizumab), IL-6 receptor antibodies (tocilizumab, sarilumab), the anti-CD20 antibody rituximab, and the anti-CD80/86 antibody abatacept. The TNFα antibodies place patients at increased risk for infection, reactivation of TB, drug-induced lupus, exacerbation of demyelinating diseases, nonmelanoma skin cancer, psoriaform skin changes, and injection or infusion site reactions. The risk for reactivation of TB is present for all biologic DMARDs except rituximab and perhaps abatacept. Thus, patients must be screened for latent TB before initiation of therapy and treated if positive. Despite this, false negatives are possible for both PPD and QuantiFERON-Gold tests; in addition, patients may develop new TB infection during therapy. The DMARDs targeted at the janus kinase (JAK) pathway, tofacitinib and baricitinib, increase risk for herpes zoster reactivation, not the anti-TNFα medications.

In patients maintained on anti-TNFα therapy, there is a fourfold increased risk of active TB infection, and in those who develop TB, extrapulmonary and disseminated TB are increased even when compared with other immunocompromised populations such as human immunodeficiency virus (HIV)–infected patients. 


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