PMID- 36860874 OWN - NLM STAT- MEDLINE DCOM- 20230303 LR - 20230307 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 14 DP - 2023 TI - Case Report: Nontuberculous mycobacterial infections in children with complete DiGeorge anomaly. PG - 1078976 LID - 10.3389/fimmu.2023.1078976 [doi] LID - 1078976 AB - Children with complete DiGeorge anomaly (cDGA) have congenital athymia, resulting in severe T cell immunodeficiency and susceptibility to a broad range of infections. We report the clinical course, immunologic phenotypes, treatment, and outcomes of three cases of disseminated nontuberculous mycobacterial infections (NTM) in patients with cDGA who underwent cultured thymus tissue implantation (CTTI). Two patients were diagnosed with Mycobacterium avium complex (MAC) and one patient with Mycobacterium kansasii. All three patients required protracted therapy with multiple antimycobacterial agents. One patient, who was treated with steroids due to concern for immune reconstitution inflammatory syndrome (IRIS), died due to MAC infection. Two patients have completed therapy and are alive and well. T cell counts and cultured thymus tissue biopsies demonstrated good thymic function and thymopoiesis despite NTM infection. Based on our experience with these three patients, we recommend that providers strongly consider macrolide prophylaxis upon diagnosis of cDGA. We obtain mycobacterial blood cultures when cDGA patients have fevers without a localizing source. In cDGA patients with disseminated NTM, treatment should consist of at least two antimycobacterial medications and be provided in close consultation with an infectious diseases subspecialist. Therapy should be continued until T cell reconstitution is achieved. CI - Copyright (c) 2023 Hicks, Agada, Yates, Kelly, Tam, Ferdman, Dibernardo, Madden, Moody and Markert. FAU - Hicks, Elizabeth Daly AU - Hicks ED AD - Division of Pediatric Allergy, Immunology, and Pulmonology, Department of Pediatrics, Duke University Medical Center, Durham, NC, United States. FAU - Agada, Noah O AU - Agada NO AD - Division of Pediatric Allergy, Immunology, and Pulmonology, Department of Pediatrics, Duke University Medical Center, Durham, NC, United States. FAU - Yates, Tyler R AU - Yates TR AD - Division of Pediatric Allergy, Immunology, and Pulmonology, Department of Pediatrics, Duke University Medical Center, Durham, NC, United States. FAU - Kelly, Matthew S AU - Kelly MS AD - Division of Infectious Diseases, Department of Pediatrics, Duke University Medical Center, Durham, NC, United States. FAU - Tam, Jonathan S AU - Tam JS AD - Division of Clinical Immunology and Allergy, Children's Hospital Los Angeles, Los Angeles, CA, United States. FAU - Ferdman, Ronald M AU - Ferdman RM AD - Division of Clinical Immunology and Allergy, Children's Hospital Los Angeles, Los Angeles, CA, United States. FAU - Dibernardo, Louis R AU - Dibernardo LR AD - Department of Pathology, Duke University Medical Center, Durham, NC, United States. FAU - Madden, John F AU - Madden JF AD - Department of Pathology, Duke University Medical Center, Durham, NC, United States. FAU - Moody, M Anthony AU - Moody MA AD - Division of Pediatric Allergy, Immunology, and Pulmonology, Department of Pediatrics, Duke University Medical Center, Durham, NC, United States. AD - Division of Infectious Diseases, Department of Pediatrics, Duke University Medical Center, Durham, NC, United States. AD - Department of Immunology, Duke University Medical Center, Durham, NC, United States. FAU - Markert, Mary Louise AU - Markert ML AD - Division of Pediatric Allergy, Immunology, and Pulmonology, Department of Pediatrics, Duke University Medical Center, Durham, NC, United States. AD - Department of Immunology, Duke University Medical Center, Durham, NC, United States. LA - eng GR - T32 AI007062/AI/NIAID NIH HHS/United States PT - Case Reports PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20230213 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Anti-Bacterial Agents) SB - IM MH - Humans MH - *DiGeorge Syndrome/complications MH - Thymus Gland MH - Anti-Bacterial Agents MH - Biopsy MH - Mycobacterium avium Complex MH - *Mycobacterium avium-intracellulare Infection PMC - PMC9969526 OTO - NOTNLM OT - DiGeorge anomaly OT - Mycobacterium avium complex OT - Mycobacterium kansasii OT - athymia OT - complete DiGeorge syndrome OT - nontuberculous mycobacteria OT - primary immunodeficiency OT - thymus transplantation COIS- Cultured thymus tissue (CTT) is an investigational product implanted into patients under an Investigational New Drug (IND) application with the US Food and Drug Administration. MMa was the "sponsor" of the investigations. MMa developed the technology for CTT. Duke University has licensed the technology to Enzyvant Therapeutics GmbH. MMa and Duke University have received royalties from Enzyvant. Portions of MMa's and her research team's salaries are being paid by funding from Enzyvant. If the technology is commercially successful in the future, MMa and Duke University may benefit financially. The salary and other items needed to create CTT are paid at cost by insurance. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2023/03/03 06:00 MHDA- 2023/03/04 06:00 PMCR- 2023/01/01 CRDT- 2023/03/02 02:14 PHST- 2022/10/24 00:00 [received] PHST- 2023/01/25 00:00 [accepted] PHST- 2023/03/02 02:14 [entrez] PHST- 2023/03/03 06:00 [pubmed] PHST- 2023/03/04 06:00 [medline] PHST- 2023/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2023.1078976 [doi] PST - epublish SO - Front Immunol. 2023 Feb 13;14:1078976. doi: 10.3389/fimmu.2023.1078976. eCollection 2023.