Case of a 38-year-old man with NEMO deficiency syndrome complicated by marginal zone lymphoma

Abstract

Here, we present a unique case of a 38-year-old man with history of Nuclear Factor-Kappa B Essential Modulator (NEMO) deficiency syndrome, whose course was complicated by marginal zone lymphoma. At 7 years of age, he was found to have MAI infection and throughout his life, developed further complications of MAI including osteomyelitis, intracranial lesions, adrenal abscesses, and cavitary pulmonary disease. Genetic testing revealed 1207 C-to-T mutation in NEMO, leading to R-for-C substitution at position 417 in the zinc finger domain. He has had a long history of recurrent viral and bacterial sinopulmonary infections since infancy continuing into adulthood, with over thirty lifetime episodes of serious pneumonia requiring hospitalizations, which has led to bronchiectasis.At 36 years of age, he presented to the hospital for five months of progressively worsening dyspnea and wheezing, hypoxemic respiratory failure, and a 15-pound weight loss. CT imaging demonstrated increased consolidation and nodularity, and sputum culture revealed methicillinsusceptible Staphylococcus aureus and Corynebacterium pneumonia treated with vancomycin. He was incidentally found to have a new 7.5 cm left periaortic lymph node conglomerate on CT abdomen/pelvis. Lymph node biopsy showed B-cell lymphoma with plasmacytic differentiation and with increased large cells, most concerning for marginal zone lymphoma. He received eight doses of rituximab as well as radiation therapy, with subsequent improvement on imaging. Following this diagnosis, lung biopsy was obtained, demonstrating nodular fibrosis in a primarily airwaycentered distribution with patchy, focal organizing pneumonia, most consistent with fibrosing chronic organizing pneumonia, treated with high dose prednisone. However, his course had since been complicated by increasingly frequent hospitalizations for acute on chronic hypoxemic respiratory failure corresponding with superimposed respiratory infectious as well as exacerbations of his organizing pneumonia.Hematopoietic stem cell transplantation was strongly considered as this would be a definitive treatment for his NEMO syndrome, as he has multiple severe complications of his NEMO deficiency syndrome. Unfortunately, after multidisciplinary discussions, he was ultimately considered to not be a candidate given his very poor pulmonary status. The patient was started on rituximab for his organizing pneumonia and continued on antibiotic prophylaxis with immunoglobulin replacement.