A Pediatric Case of Severe Atopic Dermatitis on Dupilumab Treatment and Pulmonary Tuberculosis

Atopic dermatitis (AD) is a common disease affecting nearly 20% of the pediatric population in developed countries. The use of biologic therapies, such as dupilumab, has considerably changed the treatment of AD. However, the effects of biologic drugs on the immune system may raise doubts and concerns, particularly in special populations, like those with active or latent infections [1]. Here, we present the case of a patient with AD who was found to be infected with Mycobacterium tuberculosis during treatment with dupilumab. Our patient is a 12-year-old boy who has suffered from severe AD since age 1 year and has been on dupilumab treatment for the past 2 years. Prior to this, he had been treated with topical steroids, topical tacrolimus, systemic steroids, and ciclosporin. Before starting dupilumab, his EASI score ranged between 30 and 35, he experienced severe itching, and the disease had a significant impact on his quality of life. Additionally, he was hospitalized twice for impetiginization of AD lesions, which was treated with systemic benzylpenicillin. At the time of this report, he was receiving dupilumab 200 mg twice a month. He was screened, as his mother was diagnosed with smear negative pleuro-pulmonary tuberculosis (TB), resulting in a positive interferon-gamma release assay and tuberculin skin test. Therefore, a chest radiograph and CT scan were performed, showing pulmonary lymphadenopathy and a reticular pattern with tree-in-bud sign. He was treated with isoniazid, rifampicin, pyrazinamide, and ethambutol for 2 months plus an additional 2 months of isoniazid and rifampicin, in accordance with the 4-month short-treatment protocol indicated in this uncomplicated form [2]. In agreement with pediatric infectious diseases specialists managing the patient, we decided to continue the therapy with dupilumab 200 mg twice a month. Follow-up evaluations were conducted monthly over a period of 6 months. Throughout this period, the patient did not experience any systemic or cutaneous adverse effects, and the TB therapy was carried out successfully. A chest radiograph performed at the end of treatment was normal. Dupilumab, an antibody targeting the interleukin-4 receptor alpha (IL-4Rα), is approved for the treatment of AD in the pediatric population aged months and older. Biologics targeting the IL-13/IL- 4Rα axis are apparently not able to compromise the integrity of tubercular granulomas, making bacterial reactivation very unlikely [3]. Consequently, TB screening is not required prior to the initiation of dupilumab therapy. A recent expert consensus stated that JAK-inhibitors and traditional systemic drugs, such as methotrexate and cyclosporine, should be avoided in patients with untreated TB infection, while biologics approved for AD, such as dupilumab, should represent a preferred option [1]. Moreover, two cases of bullous pemphigoid and one case of pemphigus vulgaris in which off-label dupilumab treatment was started and carried on without any complication during TB disease further support the notion that dupilumab is a safe option in this particular group of patients [4, 5]. In conclusion, dupilumab seems to be a viable alternative in AD patients with TB. However, additional studies are needed to further confirm its safety in this population. The authors declare no conflicts of interest. The patients in this manuscript have given written informed consent to publication of their case details. The data that support the findings of this study are available from the corresponding author upon reasonable request.