Lung disease in STAT3 hyper-IgE syndrome requires intense therapy

BACKGROUND: Pulmonary complications are responsible for high morbidity and mortality rates in patients with the rare immunodeficiency disorder STAT3 hyper-IgE syndrome (STAT3-HIES). The aim of this study was to expand knowledge about lung disease in STAT3-HIES. METHODS: The course of pulmonary disease, radiological and histopathological interrelations, therapeutic management, and the outcome of 14 STAT3-HIES patients were assessed. RESULTS: The patients' quality of life was compromised most by pulmonary disease. All 14 patients showed first signs of lung disease at a median onset of 1.5 years of age. Lung function revealed a mixed obstructive-restrictive impairment with reduced FEV1 and FVC in 75% of the patients. The severity of lung function impairment was associated with Aspergillus fumigatus infection and prior lung surgery. Severe lung tissue damage, with reduced numbers of ATP-binding cassette sub-family A member 3 (ABCA3) positive type II pneumocytes, was observed in the histological assessment of two deceased patients. Imaging studies of all patients above 6 years of age showed severe airway and parenchyma destruction. Lung surgeries frequently led to complications, including fistula formation. Long-term antifungal and antibacterial treatment proved to be beneficial, as were inhalation therapy, chest physiotherapy, and exercise. Regular immunoglobulin replacement therapy tended to stabilize lung function. CONCLUSIONS: Due to its severity, pulmonary disease in STAT3-HIES patients requires strict monitoring and intensive therapy.

• Kroner, C.
• Neumann, J.
• Ley-Zaporozhan, J.
• Hagl, B.
• Meixner, I.
• Spielberger, B. D.
• Duckers, G.
• Belohradsky, B. H.
• Niehues, T.
• Borte, M.
• Rosenecker, J.
• Kappler, M.
• Nahrig, S.
• Reu, S.
• Griese, M.
• Renner, E. D.