A case report published in BMC Infectious Diseases details recurrent disseminated varicella infection with accompanying pneumonitis in an adult male patient who had been receiving a combination of adalimumab and methotrexate for 2 to 3 years for the treatment of ankylosing spondylitis (AS).

Tumor necrosis factor-α (TNF-α) inhibitors, such as adalimumab, have been approved for treatment of autoimmune diseases since 2002 in the United States and have had great success in mitigating the inflammatory response in affected patients, including patients with AS. However, they are not without adverse effects and carry an increased risk for active tuberculosis and other serious microbial infections. 

A 34-year-old man with a history of AS presented to the hospital complaining of fever, cough, malaise, and widespread vesicular rash and was admitted for diagnostic workup and treatment. He was on a regimen of subcutaneous adalimumab 40 mg every 2 weeks with methotrexate 10 mg once per week for the previous 2 to 3 years. His son had developed chickenpox 14 days prior to the onset of his illness. Before initiating TNF-α antagonist therapy with adalimumab, the patient reported a history of chickenpox at age 5 and had a positive varicella zoster virus (VZV) immunoglobulin G titer in 2014 by enzyme immunoassay (EIA).

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On physical exam, a papulovesicular rash was noted throughout his body and a chest radiograph revealed bilateral diffuse nodular infiltrates. He was admitted for further workup and treatment, with the suspicion of varicella infection prompting initiation of empirical intravenous (IV) acyclovir therapy. Laboratory results confirmed this diagnosis via EIA serologically and polymerase chain reaction that demonstrated VZV DNA in vesicular fluid. A definitive diagnosis of recurrent varicella with pneumonia was established and the patient was placed on IV acyclovir 750 mg every 8 hours for 7 days, followed by oral acyclovir 800 mg 5 times per day for 3 days. After treatment, the rash and pulmonary infiltrates resolved completely.

Investigators believed this to be the first reported occurrence of recurrent disseminated varicella with pneumonitis in an individual taking adalimumab (or any TNF-α inhibitor) since its approval. They warned that immunocompromised individuals are at increased risk for similar developments as a consequence of impaired cellular immunity. Clinicians should be aware of these issues and expect to see additional adverse effects in the future as the use of TNF-α blockers and similar therapies becomes more widespread.

“Early clinical recognition of VZV infection in high risk patients, such as [are] all immunocompromised patients, as well as laboratory detection and confirmation of VZV require early aggressive antiviral treatment leading to favourable clinical outcome,” noted the authors.

Reference

Skuhala T, Atelj A, Prepolec J, Al-Mufleh M, Stanimirović A, Vukelić D. A case report of severe recurrent varicella in an ankylosing spondylitis patient treated with adalimumab – a new side effect after 15 years of usage. BMC Infect Dis. 2019;19(1):1-4.