Pictorial ReviewRespiratory disease in common variable immunodeficiency and other primary immunodeficiency disorders
Introduction
The primary immunodeficiency disorders (PIDs) are a broad spectrum of genetically determined diseases which result in impaired immunity and increased susceptibility to infection. Since Ogden Bruton first described X-linked agammaglobulinaemia (XLA) in 1952, over 100 additional genetically determined PIDs have been described.1
Humoral immunodeficiencies, i.e., those characterized by defective B cells and antibody production, are most common, accounting for about 70% of all primary immunodeficiencies.2, 3 Respiratory disease is a significant cause of morbidity and mortality amongst affected patients. The thoracic complications of the PIDs include: respiratory tract infections, airways disease, interstitial lung disease (ILD), and malignancy.
An understanding of the PIDs, their functional consequences, and histopathological sequelae enables greater understanding of the spectrum of radiological abnormalities encountered and, in turn, permits a more focused differential diagnosis to be offered. Computed tomography (CT) plays an important role in the multidisciplinary approach to these conditions, in detecting, characterizing, and quantifying the extent of lung damage, and in directing and monitoring treatment.
The aim of this review is to provide the classification and clinical manifestations of the PIDs, describe the thoracic complications and the associated imaging findings, and discuss the role of radiology in diagnosis and surveillance.
Section snippets
Classification and clinical manifestations of the PIDs
PID classification is summarized in Fig 1, and the various clinical manifestations are summarized in Table 1. Common variable immunodeficiency (CVID) is the most commonly encountered PID in our centre (Papworth and Addenbrooke's Hospitals). It is an immunologically heterogeneous group of disorders characterized primarily by a generalized failure of antibody production. T-cell-mediated immunity is often intact; however, T-cell abnormalities have been found in up to 60% of individuals.4 CVID has
Recurrent respiratory tract infections
Recurrent pneumonia is one of the most frequent clinical manifestations of primary humoral immunodeficiency. The most common respiratory pathogens are encapsulated pyogenic bacteria, such as Haemophilus influenzae, Streptococcus pneumoniae, and Staphylococcus.6 Bordetella pertussis is also an important cause of respiratory illness in children with CVID.7 Recurrent infection with encapsulated bacteria is the direct result of failure to produce antigen-specific IgG antibodies.
Although there are
Malignancy in primary humoral immunodeficiency
Patients with CVID frequently develop lymphoproliferative disorders. The relative risk of developing malignant lymphoma is increased by more than 300-fold.37, 38, 39 The high incidence of lymphoma, and other cancers, particularly gastric carcinoma, probably indicates that some patients with CVID have clinically important defects in cell-mediated immunity. Thymoma may occur in association with combined B- and T-cell immunodeficiency. This rare entity is known as Good syndrome.40
Non-Hodgkin’s
Patient management pathways
At our institution (Papworth and Addenbrooke's Hospitals) at presentation all patients undergo a clinical assessment; pulmonary function tests (PFTs) and chest radiography. Abnormal respiratory symptoms, signs, or investigations lead to review in a joint respiratory and immunology clinic. Those with significant symptoms or significantly abnormal investigations undergo a CT examination.
All patients are reviewed at least 6 monthly in clinic with repeat chest radiography and PFTs. CT examination
Conclusion
Imaging plays an important role in the initial detection of both infection and airways disease in patients with PID. Early detection of these entities is vital if physical and pharmacological therapies are to be instituted in order to slow the progression of disease. There should be a low threshold for performing an HRCT in clinically suspected bronchiectasis, even when the chest radiograph is normal.
HRCT can effectively differentiate infection and bronchiectasis from ILD in patients with
Acknowledgements
The authors acknowledge the histopathologists for their input at both Addenbrooke’s and Papworth Hospitals.
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