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.

Keywords: Common variable immunodeficiency; Granulomatous-lymphocytic interstitial lung disease; Sarcoidosis.

Fig. 1

MRI brain imaging. MRI Brain showing high signal in the right cerebellar hemisphere. a Coronal FLAIR, arrow with a corresponding abnormal focal area of enhancement shown on the b Axial post-gadolinium images. Repeat MRI Brain after 3 months (while the patient was on treatment) shows almost complete resolution of these findings c Coronal FLAIR d Axial post-gadolinium

Fig. 2

Timeline. Relevant medical history and clinical course

Fig. 3

CT and PET imaging. a CT Thorax showing a right lower lobe pulmonary nodule (arrow, June 2016), b PET-CT showing the same right lower lobe pulmonary nodule (arrow) and splenomegaly (broken arrow). c New left lower lobe pulmonary nodule (broken arrow) and resolving right lower lobe nodule (arrow, July 2016). d New left lower lobe nodule (arrow, April 2018) e New right lower lobe nodule (arrow, Sept 2019) f) New lower lobe nodules (arrows, Sept 2019)

Fig. 4

Pulmonary and cerebellar histology. Histopathological characteristics supporting a diagnosis of GLILD: a the core biopsy of pulmonary parenchyma showing a reticular pattern of fibrosis and interstitial lymphocytic infiltration (H & E, × 100 magnification); b at higher magnification, the lymphocytes can be seen to form aggregates giving a nodular appearance. On CD3 immunostaining these lymphocytes proved to be of predominantly T-cell lineage (H & E, × 400); c the cerebellar biopsy from the same patient 10 years previously showing lymphocytic infiltration (red dot) with a similar pattern to that seen in the lung biopsy (H & E, × 100)