Pulmonary Hypertension in Patients with Common Variable Immunodeficiency

J Clin Immunol. 2021 Oct;41(7):1549-1562. doi: 10.1007/s10875-021-01064-w. Epub 2021 Jun 10.

Abstract

Purpose: Common variable immunodeficiency (CVID) is known to cause infectious, inflammatory, and autoimmune manifestations. Pulmonary hypertension (PH) is an unusual complication of CVID with largely unknown characteristics and mechanisms.

Methods: We report the clinical, functional, hemodynamics, radiologic and histologic characteristics, and outcomes of CVID-associated PH patients from the French PH Network.

Results: Ten patients were identified. The median (range) age at CVID diagnosis was 36.5 (4-49) years and the median delay between CVID and PH diagnosis was 12 (0-30) years. CVID-associated PH affected predominantly women (female-to-male ratio 9:1). Most patients were New York Heart Association functional class III with a severe hemodynamic profile and frequent portal hypertension (n = 6). Pulmonary function tests were almost normal in 70% of patients and showed a mild restrictive syndrome in 30% of patients while the diffusing capacity for carbon monoxide was decreased in all but one patient. High-resolution computed tomography found enlarged mediastinal nodes, mild interstitial infiltration with reticulations and nodules. Two patients had a CIVD-interstitial lung disease, and one presented with bronchiectasis. Pathologic assessment of lymph nodes performed in 5 patients revealed the presence of granulomas (n = 5) and follicular lymphoid hyperplasia (n = 3). At last follow-up (median 24.5 months), 9 patients were alive, and one patient died of Hodgkin disease.

Conclusion: PH is a possible complication of CVID whose pathophysiological mechanisms, while still unclear, would be due to the inflammatory nature of CVID. CVID-associated PH presents as precapillary PH with multiple possible causes, acting in concert in some patients: a portal hypertension, a pulmonary vascular remodeling, sometimes a pulmonary parenchymal involvement and occasionally an extrinsic compression by mediastinal lymphadenopathies, which would be consistent with its classification in group 5 of the current PH classification.

Keywords: Common variable immunodeficiency; Granulomatous lymphocytic granulomas; Interstitial lung disease; Pulmonary hypertension.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Child, Preschool
  • Common Variable Immunodeficiency / complications*
  • Common Variable Immunodeficiency / diagnostic imaging
  • Common Variable Immunodeficiency / pathology
  • Common Variable Immunodeficiency / therapy
  • Female
  • France
  • Humans
  • Hypertension, Pulmonary / diagnostic imaging
  • Hypertension, Pulmonary / etiology*
  • Hypertension, Pulmonary / pathology
  • Hypertension, Pulmonary / therapy
  • Lymph Nodes / pathology
  • Male
  • Middle Aged
  • Positron-Emission Tomography
  • Thorax / diagnostic imaging
  • Tomography, X-Ray Computed
  • Young Adult