Lung disease in STAT3 hyper-IgE syndrome requires intense therapy

Allergy. 2019 Sep;74(9):1691-1702. doi: 10.1111/all.13753. Epub 2019 Apr 4.

Abstract

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.

Keywords: ABCA3; STAT3 hyper-IgE syndrome; bronchiectasis; lung disease; pneumatocele; primary immunodeficiency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anti-Infective Agents / therapeutic use
  • Biopsy
  • Child
  • Combined Modality Therapy
  • Disease Management
  • Disease Susceptibility*
  • Female
  • Humans
  • Immunohistochemistry
  • Job Syndrome / complications*
  • Job Syndrome / genetics
  • Job Syndrome / metabolism*
  • Job Syndrome / mortality
  • Lung Diseases / diagnosis
  • Lung Diseases / etiology*
  • Lung Diseases / therapy*
  • Male
  • Middle Aged
  • Prognosis
  • Radiography, Thoracic
  • Respiratory Function Tests
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism*
  • Symptom Assessment
  • Tomography, X-Ray Computed
  • Treatment Outcome
  • Young Adult

Substances

  • Anti-Infective Agents
  • STAT3 Transcription Factor
  • STAT3 protein, human