Patients receiving TNF-α antagonists therapy remain at a selectively increased risk for more severe primary varicella infections compared with the general population, with the estimated incidence rate of hospitalization due to chickenpox of 26 cases per 100,000 (95% CI 10–69) compared with the expected rate of 1.9 (95% CI 1.8–2.0) in the general population [
7]. Contradictory results have been published reporting the association between TNF-α therapy and herpes zoster.
Several large population-based studies have been conducted, with those performed in the United States not finding an increased risk with TNF-α inhibitors, contrary to those in Europe generally showing an increased risk [
4,
8,
9]. There were multiple reports of severe and disseminated herpes zoster and primary varicella associated with TNF-α therapy (infliximab and adalimumab) [
1,
10‐
15]. In contrast, recurrent varicella infections during TNF-α therapy were rarely reported, with only one case featuring few clinical symptoms (no dissemination and resolution of skin lesions without antiviral treatment) in the course of etanercept administration [
16]. VZV causes two clinically distinct diseases - primary infection resulting in varicella and herpes zoster resulting from the reactivation of latent VZV that gained access to sensory ganglia during varicella [
17]. It is traditionally considered that VZV infection provides lifelong immunity but recurrent infection (also referred to as reinfection or second varicella infection) with VZV occur more commonly than previously thought [
18,
19]. In an active surveillance initiative in California, the percentage of patients diagnosed with varicella who reported previous varicella infections ranged from 4.5 to 13.3% [
18]. VZV recurrent infection can occur even in immunocompetent patients, and our patient was predisposed to infection by his rheumatologic disease and immunosuppressive therapy. Patients with a history of underlying malignancy, steroid use or immunosuppressive therapy, HIV infection, or solid organ transplantation are susceptible for disseminated varicella due to impaired cellular immunity. Clinical manifestations in the immunosuppressed host can include atypical and severe manifestations such as development of crops of vesicles over weeks, large and haemorrhagic skin lesions, pneumonia, or widespread disease with disseminated intravascular coagulation [
17,
20]. The antiviral therapy is recommended for immunocompromised hosts who present with varicella because they are at risk for developing disseminated varicella, as our patient has been, and can also experience more frequent severe morbidity and higher mortality rates compared with immunocompetent hosts [
20,
21]. Early clinical recognition of VZV infection in high risk patients, such are all immunocompromised patients, as well as laboratory detection and confirmation of VZV require early aggressive antiviral treatment leading to favourable clinical outcome [
7,
17,
20].
Due to the use of biological agents, particularly TNF-α inhibitors, as a well-established therapy for some autoimmune diseases, new potential adverse events can be expected in the future and we wanted to point out one of them. To the best of our knowledge, this is the first case of confirmed recurrent varicella with disseminated disease and pneumonia in a patient receiving adalimumab since this drug has been approved for use in 2002 in the United States and 2003 in the European Union [
22,
23].