Case Report
Immune reconstitution inflammatory syndrome after cessation of the tumor necrosis factor α blocker adalimumab in cryptococcal pneumonia

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Abstract

Tumor necrosis factor α antagonists have proven efficacious for a variety of autoimmune-mediated diseases. However, recent data have highlighted the risk of invasive fungal infections with their use. These agents are typically discontinued when infectious complications occur during therapy; however, the immune reconstitution inflammatory syndrome (IRIS) may be seen after drug cessation. We describe the 1st case of IRIS secondary to cryptococcal pneumonia after cessation of adalimumab.

Introduction

Tumor necrosis factor antagonists (adalimumab, etanercept, and infliximab) have been used successfully for a variety of rheumatologic and dermatologic conditions, including rheumatoid arthritis (RA), psoriasis, ankylosing spondylitis, and inflammatory bowel disease. Although these new agents have dramatically improved the outcomes of many debilitating conditions, an increase in bacterial, mycobacterial, and fungal infections have been observed with their use (Wallis et al., 2004).

A recent Food and Drug Administration (FDA) advisory has notified health care professionals that histoplasmosis and other invasive fungal infections are not consistently recognized in patients taking tumor necrosis factor α (TNF-α) blockers, and the resultant delay in appropriate treatment has resulted in patient death (US FDA advisory, 2008). When infection does occur, cessation of immunosuppressive medications is often advocated. However, a paradoxical response with worsening symptoms may be observed after withdrawal of immunosuppressive medications similar to the immune reconstitution inflammatory syndrome (IRIS) reported after initiation of highly active antiretroviral therapy in the presence of concurrent opportunistic infection (Singh et al., 2005). This inflammatory syndrome is typically self-limited if the underlying infection is effectively treated; yet, a failure to recognize this condition can result in an exacerbation of the inflammatory manifestations of infection and the erroneous interpretation of drug failure, and may result in long-term sequela or fatal outcomes (Singh and Perfect, 2007a). We present the 1st case of IRIS associated with invasive fungal infection after cessation of a TNF-α blocker and discuss the differing pharmacokinetics of the anti-TNF agents and the immunologic mechanism of IRIS.

Section snippets

Case report

A 56 year-old Hispanic female, with RA diagnosed 1 year before admission, presented with fever, dyspnea, a nonproductive cough, and a frontal headache of 3 weeks' duration. She had previously received multiple medications for her RA; however, because of severe impairment in her ability to perform the activities of daily living, she was placed on oral methotrexate 15 mg weekly and adalimumab 40 mg sc every other week with the last dose administered 2 weeks before hospitalization. She had a

Discussion

IRIS has been well described in AIDS patients receiving antiretroviral therapy. This paradoxical worsening of clinical symptoms after immunologic recovery has been associated with multiple opportunistic infections, including infections from/caused by cytomegalovirus, JC virus, hepatitis B and C, varicella–zoster virus, Pneumocystis jirovecii, and Histoplasma capsulatum, and it has been frequently observed with concurrent cryptococcal or mycobacterial infections in this population (Hirsch et

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