Common variable immunodeficiency with granulomatous-lymphocytic interstitial lung disease and preceding neurological involvement: a case-report

Abstract

Background Common variable immunodeficiency (CVID) is a group of heterogeneous primary immunodeficiencies characterised by a dysregulated and impaired immune response. In addition to an increased susceptibility to infection, it is also associated with noninfectious autoimmune and lymphoproliferative complications. CVID is rarely associated with neurological complications. Pulmonary involvement is more common, and patients can develop an interstitial lung disease known as granulomatous-lymphocytic interstitial lung disease (GLILD). Case presentation A 50-year-old Caucasian female with a history of Evans syndrome (idiopathic thrombocytopaenic purpura and autoimmune haemolytic anaemia) and hypogammaglobulinaemia initially presented to the neurology clinic with marked cerebellar ataxia and headaches. Following extensive investigation (which included brain biopsy), she was diagnosed with neuro-sarcoidosis and her symptoms resolved following treatment with immunosuppressive therapy. Over the following 10 years, she was extensively investigated for recurrent pulmonary infections and abnormal radiological findings, which included pulmonary nodules, infiltrates and splenomegaly. Subsequently, she was referred to an immunology clinic, where immunoglobulin replacement treatment was started for what was ultimately considered to be CVID. Shortly afterwards, evaluation of her clinical, radiological and histological findings at a specialist interstitial lung disease clinic led to a diagnosis of GLILD. Conclusion CVID is a condition which should be suspected in patients with immunodeficiency and recurrent infections. Concomitant autoimmune disorders such as haemolytic anaemia and immune thrombocytopenia may further support the diagnosis. As illustrated in this case, there is a rare association between CVID and inflammatory involvement of the neurological system. Respiratory physicians should also suspect CVID with associated GLILD in patients with apparent pulmonary granulomatous disease and recurrent infections. In addition, this case also highlights the challenge of diagnosing CVID and its associated features, and how the definitive exclusion of other pathologies such as malignancy, mycobacterial infection and lymphoma is required as part of this diagnostic process.

Sarcoidosis: Pitfalls and Challenging Mimickers

“…These patients can present with a clinical picture that mimics sarcoidosis and misdiagnosis can delay the treatment for CVID (IVIG), which in the presence of GLILD portends a poorer prognosis. Steroid therapy can further worsen CVID ( 208 , 210 – 212 ).…”

Common variable immunodeficiency and its inflammatory neurological manifestations: A case report and literature review

“…According to the European Society for Immunode ciencies (ESID), CVID patients are characterized by a family history of antibody de ciency and/or personal history of increased susceptibility to infection as well as autoimmune, granulomatous, or/and lymphoproliferative diseases [6,7]. These clinical features combined with a marked decrease in IgG and IgA (with or without low IgM levels), and evidence B cell differentiation impairment allow the diagnosis of this disorder [1,7]. Being a diagnosis of exclusion, transient and secondary causes of hypogammaglobulinemia, such as drugs (particularly rituximab and anticonvulsants) and profound T-cell de ciency should be rst considered [1,7].…”

“…These clinical features combined with a marked decrease in IgG and IgA (with or without low IgM levels), and evidence B cell differentiation impairment allow the diagnosis of this disorder [1,7]. Being a diagnosis of exclusion, transient and secondary causes of hypogammaglobulinemia, such as drugs (particularly rituximab and anticonvulsants) and profound T-cell de ciency should be rst considered [1,7]. In the present case, considering the clinical, imaging and disease progression, drug-related immunode ciency was unlikely.…”

“…Among the described cases in the literature (Table 1), infections are the main cause of CVID-associated neurological dysfunction, particularly meningitis and encephalitis [4,9]. Autoimmune/in ammatory conditions comprise the second largest category of neurologic complications (1.4% of CVID patients) [4,5], including myelitis [5,[9][10][11][12], brain in ammatory/demyelinating disease [4,5,7,13], unilateral [2,5] and bilateral [14] optic neuritis, cerebral vasculitis [5], and encephalopathy (autoimmune encephalitis [5] and acute encephalomyelitis [15]). Van de Ven et al [16] reported a 4% prevalence of in ammatory CNS disease, higher than previously reported.…”

The Importance of the Transcription Factor Foxp3 in the Development of Primary Immunodeficiencies

“…In the vast majority of cases it is caused by microbes commonly inhabiting the human body which, as a result of weakened immune reactions, cause the so-called opportunistic infections [8]. Apart from the tendency of recurrent infections, immunodeficiency is also accompanied by other health problems such as allergic phenomena [9], autoimmune phenomena [10,11], granulomas [12], tumors [13,14], endocrine disorders [15,16], and various cytopenias (most often thrombocytopenia [17] and neutropenia [18,19]) as well as diseases of the lungs [20] and gastrointestinal tract [21] (e.g., irritable bowel syndrome) [22,23]. Due to the underlying causes of immunodeficiencies, we can divide them into two groups: Primary Immunodeficiencies (PID), which are genetically determined and associated with mutations that are either inherited or appear de novo and Secondary Immunodeficiencies (SID), which are caused by external factors or the presence of comorbid disease [24,25].…”