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

  • Bárbara Martins
    Correspondence
    Corresponding author at: Neurology Department, Centro Hospitalar Universitário de São João, E.P.E., Porto, Portugal; Alameda Prof. Hernâni Monteiro, 4200–319 Porto, Portugal.
    Affiliations
    Neurology Department, Centro Hospitalar Universitário de São João, Porto, Portugal

    Clinical Neuroscience and Mental Health Department, Faculty of Medicine, University of Porto, Porto, Portugal
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  • Joana Miranda
    Affiliations
    Allergy and Clinical Immunology Department, Centro Hospitalar Universitário de São João, Porto, Portugal
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  • Maria João Pinto
    Affiliations
    Neurology Department, Centro Hospitalar Universitário de São João, Porto, Portugal

    Clinical Neuroscience and Mental Health Department, Faculty of Medicine, University of Porto, Porto, Portugal
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  • Andreia Costa
    Affiliations
    Neurology Department, Centro Hospitalar Universitário de São João, Porto, Portugal

    Clinical Neuroscience and Mental Health Department, Faculty of Medicine, University of Porto, Porto, Portugal
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  • André Silva-Pinto
    Affiliations
    Medicine Department, Faculty of Medicine, University of Porto, Porto, Portugal

    Infectious Diseases Department, Centro Hospitalar Universitário de São João, Porto, Portugal
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  • Natália Melo
    Affiliations
    Pneumology Department, Centro Hospitalar Universitário de São João, Porto, Portugal
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  • Filipa Ceia
    Affiliations
    Medicine Department, Faculty of Medicine, University of Porto, Porto, Portugal

    Infectious Diseases Department, Centro Hospitalar Universitário de São João, Porto, Portugal
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  • José Torres Costa
    Affiliations
    Allergy and Clinical Immunology Department, Centro Hospitalar Universitário de São João, Porto, Portugal
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  • Joana Guimarães
    Affiliations
    Neurology Department, Centro Hospitalar Universitário de São João, Porto, Portugal

    Clinical Neuroscience and Mental Health Department, Faculty of Medicine, University of Porto, Porto, Portugal
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      Highlights

      • CVID-associated neurological symptoms are frequently underreported, with studies showing prevalences of up to 50% in these patients.
      • Infections are the main cause of CVID-associated neurological dysfunction, followed by autoimmune/inflammatory conditions.
      • To date, there is no established standard of care for the treatment of patients with CVID, particularly with GLILD, a recently described subtype of interstitial lung disease, or neurological complications.
      • Treatment with steroids seems to be safe and effective in the control of neurological manifestations.

      Abstract

      Background

      Common variable immunodeficiency disorders (CVID) are a group of primary immunodeficiencies characterized by impaired immunoglobulin production and dysregulated immune response. Neurological manifestations have been described in a few patients, and little is known about its clinic and therapeutic approach. Thus, this work aimed to review the literature on it and to help differentiate CVID from its mimics, especially sarcoidosis.

      Methods

      We described a case report and included a literature review of inflammatory neurological involvement in CVID.

      Results

      A 32-year-old female patient with a medical history of recurrent bacterial infections, temporal focal epilepsy and granulomatous lung disease under study, and cervix squamous cell carcinoma, was initially admitted to the emergency department due to intracranial hypertension. After excluding infectious and neoplastic etiologies, the most likely hypothesis was that granulomatous pulmonary, cerebral, and leptomeningeal inflammatory involvement were associated with sarcoidosis. Two years later, a diagnosis of CVID was made, and the patient was secondarily diagnosed with Granulomatous and Lymphocytic Interstitial Lung Disease (GLILD) and related inflammatory brain disease – both complications of CVID. After starting targeted treatment with immunoglobulin replacement and pulse glucocorticoids followed by a chronic taper, the patient became stable. However, three consecutive failures in immunoglobulin intake during the COVID-19 pandemic led to disease recurrence with relapse of neurological manifestations.

      Conclusion

      This case illustrates the complex multiple organ manifestations of CVID. When granulomatous conditions arise in these patients, a rare lung disease arising in the context of CVID, the GLILD disease with multisystem involvement, should be taken into consideration. Early treatment with combined steroids and immunotherapy seems to be effective in controlling CVID's neurological manifestations.

      Keywords

      Abbreviations:

      ACE (Serum angiotensin-converting-enzyme), ADA (Adenosine deaminase test), ANA (Antinuclear antibody), ANCA (Antineutrophil cytoplasmic antibody), Anti-dsDNA (Anti-double strand DNA antibodies), Anti-MOG (Antibodies against myelin-oligodendrocyte-glycoprotein), Anti-AQ4 (Antibodies against aquaporin 4), Ca (Carbohydrate antigen), CDSS (Disease severity score for CVID and CVID-like disorders), CMV (Cytomegalovirus), CVID (Common variable immunodeficiency disorders), EBV (Epstein-Barr virus), ESID (European Society for Immunodeficiencies), GLILD (Granulomatous and Lymphocytic Interstitial Lung Disease), HIV (Human immunodeficiency virus), HSV (Herpes simplex virus), LIP (Lymphocytic interstitial pneumonia), NR (Normal range), PCR (Polymerase chain reaction), PET (Positron Emission Tomography), TPPA (Treponema pallidum particle agglutination), VZV (Varicella-zoster virus)
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