Malignancies and Cryptococcal Infection in a Patient with Ataxia-Telangiectasia

Ataxia-telangiectasia (A-T) is an inborn error of immunity caused by mutations in the A-T-mutated (ATM) gene, involved in coordinating cellular signaling pathways in response to DNA double-stranded breaks and oxidative stress. This results in immunodeficiency, neurodegeneration, and increased risk of malignancies. The most prevalent types of malignancy in A-T patients are leukemia and lymphoma, but multiple primary hematologic malignancies are uncommon. While A-T results in combined immunodeficiency with frequent bacterial sinopulmonary infections, opportunistic infections are very rare, and cryptococcal infections have not been reported. We present the case of a 5-year-old girl diagnosed with T cell acute lymphoblastic leukemia at the age of 2. She was referred to immunology due to severe lymphopenia and infections complicating her chemotherapy course and was diagnosed with A-T. After 1 year of remission, she presented with back pain, and a bone marrow biopsy confirmed a new CD20+CD19+ mature large B cell lymphoma. She received chemotherapy per ANHL1131 Group C1 with rituximab and successfully achieved remission. She was maintained on immunoglobulin replacement therapy and PJP prophylaxis. She remained significantly T and B cell lymphopenic (Table 1) and developed respiratory insufficiency with persistent rhinovirus/enterovirus requiring O2 supplementation. Eight months after completion of her B cell chemotherapy, she returned to the hospital for acute worsening respiratory status. Despite antibiotics, her respiratory status worsened, prompting further workup with an expanded differential including interstitial lung disease, bronchiectasis, and opportunistic infections. A bronchoalveolar lavage was performed, with fungal cultures growing Cryptococcus (Figure 1). Serum cryptococcal antigen (CrAg) resulted positive; however, lumbar puncture reported a normal opening pressure with negative cerebrospinal fluid CrAg. Fluconazole was not effective, so she was treated with amphotericin B and flucytosine for two weeks, followed by fluconazole maintenance therapy. Table 1. Lymphocyte characterization Component Reference range in cells per cubic millimeter Total T Cells (CD3 Avg) 758 1,400 – 3,700 Total Suppressor Cells (CD8) 316 490 – 1,300 Total Helper Cells (CD4) 236 700 – 2,200 Helper-Suppressor Ratio 0.75 Total B Cells (CD19) 186 390 – 1,400 Total NK Cells (CD16/CD56) 852 130 – 720 Figure 1. Microscopic and macroscopic images of Cryptococcus on fungal culture from bronchoalveolar lavage. We report a case of a 5-year-old girl with A-T diagnosed after almost a complete course of chemotherapy with numerous imaging studies, possibly contributing to a second malignancy. In addition, we report the first case of cryptococcal pneumonia in a patient with A-T. For patients with A-T and a history of malignancy, opportunistic infections such as cryptococcus should be considered.