TY - JOUR
T1 - STAT5b gain-of-function disease in a child with mycobacterial osteomyelitis of the skull
T2 - rare presentation of an emerging disease entity
AU - Kobets, Andrew J.
AU - Ahmad, Samuel
AU - Boyke, Andre
AU - Oriko, David
AU - Holland, Ryan
AU - Eisenberg, Rachel
AU - Alavi, Seyed Ahmad Naseri
AU - Abbott, Rick
N1 - Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2023/8
Y1 - 2023/8
N2 - Purpose: STAT proteins play a key role in several cellular functions related to cell development, differentiation, proliferation, and survival. Persistent STAT activation due to somatic STAT5bN642H gain-of-function mutation is a rare mechanism of STAT dysregulation that results in hypereosinophilia, frequent infections, leukemias, and pulmonary diseases. Herein, we describe a case of a child with a rare early onset STAT5b gain-of-function disease treated with targeted JAK inhibition who developed a cranial Mycobacterium avium osteomyelitis. Methods: A 3-year-old male with a known STAT5b gain-of-function mutation presented with a 10-day history of a firm, immobile, non-painful cranial mycobacterium mass with dural infiltration located anterior to the coronal suture. Stepwise management finalized with complete resection of the lesion with calvarial reconstruction. A case-based literature review was performed evaluating all patients with this mutation who developed cranial disease. Results: The patient was symptom and lesion-free at 1 year since surgical resection and initiation of triple mycobacterial pharmacotherapy. Our literature review demonstrated the rarity of this disease, as well as other presentations of this disease in other patients. Conclusion: Patients with STAT5b gain-of-function mutations have attenuated Th1 responses and are treated with medications, such as JAK inhibitors, which further inhibit other STAT proteins that regulate immunity against rare infectious entities, such as mycobacterium. Our case highlights the importance of considering these rare infections in patients on JAK inhibitors and with STAT protein mutations. Possessing a clear mechanistic understanding of this genetic mutation, its downstream effect, and the consequences of treatment may enhance a physician’s diagnostic and clinical management of similar patients in the future.
AB - Purpose: STAT proteins play a key role in several cellular functions related to cell development, differentiation, proliferation, and survival. Persistent STAT activation due to somatic STAT5bN642H gain-of-function mutation is a rare mechanism of STAT dysregulation that results in hypereosinophilia, frequent infections, leukemias, and pulmonary diseases. Herein, we describe a case of a child with a rare early onset STAT5b gain-of-function disease treated with targeted JAK inhibition who developed a cranial Mycobacterium avium osteomyelitis. Methods: A 3-year-old male with a known STAT5b gain-of-function mutation presented with a 10-day history of a firm, immobile, non-painful cranial mycobacterium mass with dural infiltration located anterior to the coronal suture. Stepwise management finalized with complete resection of the lesion with calvarial reconstruction. A case-based literature review was performed evaluating all patients with this mutation who developed cranial disease. Results: The patient was symptom and lesion-free at 1 year since surgical resection and initiation of triple mycobacterial pharmacotherapy. Our literature review demonstrated the rarity of this disease, as well as other presentations of this disease in other patients. Conclusion: Patients with STAT5b gain-of-function mutations have attenuated Th1 responses and are treated with medications, such as JAK inhibitors, which further inhibit other STAT proteins that regulate immunity against rare infectious entities, such as mycobacterium. Our case highlights the importance of considering these rare infections in patients on JAK inhibitors and with STAT protein mutations. Possessing a clear mechanistic understanding of this genetic mutation, its downstream effect, and the consequences of treatment may enhance a physician’s diagnostic and clinical management of similar patients in the future.
KW - Hypereosinophilia
KW - Mycobacterium avium
KW - Ruxolitinib
KW - STAT5b gain-of-function
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U2 - 10.1007/s00381-023-05997-y
DO - 10.1007/s00381-023-05997-y
M3 - Review article
C2 - 37243811
AN - SCOPUS:85160276765
SN - 0256-7040
VL - 39
SP - 2071
EP - 2077
JO - Child's Nervous System
JF - Child's Nervous System
IS - 8
ER -