Interstitial lung disease in patients with common variable immunodeficiency disorders: several different pathologies?

Patel, Smita Y.; Anzilotti, Consuelo; Lucas, Mary; Moore, N. W.; Chapel, Helen

doi:10.1111/cei.13343

Cited by 30 publications

(46 citation statements)

References 38 publications

(88 reference statements)

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“…Furthermore, there is no current histological or molecular evidence for chronic bacterial, EBV or CMV viral infections as triggers for inflammation (16,(28)(29)(30), though granulomas in other PIDs, such as those with DNA repair defects, show evidence of vaccine derived rubella virus (31). Other related complications, including splenomegaly, autoimmune cytopaenias, persistent lymphadenopathy and lymphoproliferation, but not necessarily granulomata, occur more frequently in patients with CVID-related ILD, supporting at least a role for intrinsic immune dysregulation driving these varied features (6,9,16,21,27,32,33).…”

Section: Interstitial Lung Disease In Common Variable Immune Deficienmentioning

confidence: 99%

“…Lymphoid interstitial pneumonitis was first reported in patients with antibody deficiency in 1973 (46). Since then, various histopathological entities have been reported within lung biopsies of CVID ILD patients, from those caused by polyclonal lymphocytic inflammation to well-formed granulomata, organizing pneumonia, or pulmonary fibrosis, often with mixed pathology within individual patient biopsies (7,9,16,27,33,35,44). "Granulomatous-lymphocytic interstitial lung disease" (GLILD), first proposed in 2004, is often used as an overarching term to describe CVID ILD with lymphocytic infiltrates and/or granulomata (9,45).…”

Section: Nomenclaturementioning

confidence: 99%

“…However, the accuracy of this term has been called into question. Since not all patients have pulmonary granulomata, it does not fully capture the heterogeneity of the histopathology and similar histological patterns fulfilling a GLILD diagnosis are found in non-CVID PIDs (33,47).…”

Section: Nomenclaturementioning

confidence: 99%

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Histology of Interstitial Lung Disease in Common Variable Immune Deficiency

et al. 2020

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Interstitial lung disease (ILD) is an important non-infectious complication in several primary immune deficiencies. In common variable immune deficiency (CVID) it is associated with complex clinical phenotypes and adverse outcomes. The histology of ILD in CVID is heterogeneous and mixed patterns are frequently observed within a single biopsy, including non-necrotising granulomatous inflammation, lymphoid interstitial pneumonitis, lymphoid hyperplasia, follicular bronchiolitis, organizing pneumonia, and interstitial fibrosis; ILD has to be differentiated from lymphoma. The term granulomatous-lymphocytic interstitial lung disease (GLILD), coined to describe the histopathological findings within the lungs of patients with CVID with or without multisystem granulomata, is somewhat controversial as pulmonary granulomata are not always present on histology and the nature of infiltrating lymphocytes is variable. In this mini review we summarize the literature on the histology of CVID-related ILD and discuss some of the factors that may contribute to the inter- and intra- patient variability in the histological patterns reported. Finally, we highlight areas for future development. In particular, there is a need for standardization of histological assessments and reporting, together with a better understanding of the immunopathogenesis of CVID-related ILD to resolve the apparent heterogeneity of ILD in this setting and guide the selection of rational targeted therapies in different patients.

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Section: Interstitial Lung Disease In Common Variable Immune Deficienmentioning

confidence: 99%

Section: Nomenclaturementioning

confidence: 99%

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Histology of Interstitial Lung Disease in Common Variable Immune Deficiency

et al. 2020

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“…pneumonia, and larger, often bronchocentric nodules, often in the context of background bronchiectasis (figure 1) [12,13]. No pathogen has been identified and the mechanism is likely immune dysregulation.…”

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confidence: 99%

Interstitial lung disease in primary immunodeficiency: towards a brighter future

Hurst

Warnatz

2020

Eur Respir J

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]. Lung disease is a frequent clinical manifestation in people living with primary immunodeficiency diseases, the most prevalent of which are common variable immunodeficiency disorders (CVID). CVID is primarily characterised by antibody deficiency, but recent definitions and diagnostic criteria recognise a much more complex pattern of immunological defects [1]. CVID can be classified into two major clinical phenotypes. One group experiences infection as the only major clinical manifestation, whilst the other present a variety of lymphoproliferative, inflammatory and/or autoimmune complications. The most frequent consequences in the lung of CVID are acute infections, and secondary airway complications of infection, such as bronchiectasis. However, up to 15% of patients with CVID develop an interstitial lung disease [2, 3]. Infections and bronchiectasis are primarily driven by antibody deficiency, but CVID associated interstitial lung disease (CVID-ILD) is best considered part of a systemic immune dysregulatory process [4] such that people with CVID-ILD often have splenomegaly, lymphadenopathy and autoimmune cytopenias [5-7]. With an EU population of 747 million, we estimate there are up to 30 000 people living with CVID in Europe, and thus 4500 with CVID-ILD. Whilst people with "infection only" CVID can now expect a near normal life expectancy [8], those with systemic immune dysregulation including CVID-ILD often have a much more complicated course. CVID-ILD increases morbidity and mortality in CVID [9], although the outcome is now recognised to be more variable than originally reported [10]. The terminology in use for ILD in CVID is complex and there is no consensus. The term granulomatous-lymphocytic interstitial lung disease (GLILD) is in common use but there need not be granuloma. We previously proposed the following working definition of GLILD: "GLILD is a distinct clinico-radio-pathological ILD occurring in patients with CVID, associated with a lymphocytic infiltrate and/or granuloma in the lung, and in whom other conditions have been considered and where possible excluded" [11]. Lung pathology and its radiological correlate in CVID-ILD/GLILD are heterogeneous including frequent ground-glass opacities due to lymphocytic interstitial pneumonitis, organising

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“…In contrast, the lack of granuloma in patient clusters 1, 4, and 5 might indicate that the cause of granulomata is quite different from that of other disease-related complications. 8 This elegant methodology is the first to correlate in vitro assays with clinical phenotypes. This article becomes an invaluable tool if it can provide tools to identify patients at high risk of complications when they present.…”

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confidence: 99%