Common variable immunodeficiency presenting as sarcoidosis in a 9-year-old child.

Publisher: Wiley on behalf of the Asia Pacific League of Associations for Rheumatology Country of Publication: England NLM ID: 101474930 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1756-185X (Electronic) Linking ISSN: 17561841 NLM ISO Abbreviation: Int J Rheum Dis Subsets: MEDLINE

Original Publication: [Oxford, UK] : Wiley on behalf of the Asia Pacific League of Associations for Rheumatology

Common Variable Immunodeficiency/*diagnosis ; Granuloma/*diagnosis ; Sarcoidosis/*diagnosis; Child ; Common Variable Immunodeficiency/drug therapy ; Common Variable Immunodeficiency/immunology ; Diagnosis, Differential ; Diagnostic Errors ; Granuloma/drug therapy ; Granuloma/immunology ; Humans ; Immunoglobulins, Intravenous/therapeutic use ; Immunosuppressive Agents/therapeutic use ; Male ; Phenotype ; Predictive Value of Tests ; Sarcoidosis/immunology ; Treatment Outcome

Background: Granulomatous diseases are a heterogeneous group of conditions characterized by an inflammatory infiltrate with a core of macrophages, epithelioid, giant cells and a corona of fibroblasts and lymphocytes. They are associated with a wide range of disorders such as mycobacterial and fungal infections, neoplasms, immunodeficiencies and systemic inflammatory disorders as sarcoidosis.
Case Report: We report the case of a previously healthy 9-year-old male child who presented with persistent cough, diffuse lymphadenopathy, enlargement of liver and spleen and protracted fever. Anemia, lymphopenia and reduced platelet count was reported, with an increase of inflammatory markers. High levels of Angiotensin-converting enzyme and chitotriosidases were noted. A PET-CT scan showed increased uptake of ¹⁸ F-FDG glucose in multiple lymph nodes in thorax and abdomen and in the spleen. Biopsy of inguinal and bronchial nodes showed nodal granulomatous inflammation. The child was diagnosed with sarcoidosis and treated with corticosteroids with only transient efficacy. Further tests reported panhypogammaglobulinaemia and a reduced pool of B-memory lymphocytes. Thus, the diagnosis was revised to common variable immunodeficiency (CVID).
Conclusion: Common variable immunodeficiency is a heterogeneous condition with a highly variable clinical phenotype and a strong association with autoimmune disorders. The presence of noncaseating granuloma and pulmonary lesions, along with extrapulmonary features required a step by step approach to differentiate between CVID and sarcoidosis. This enables early introduction of immunoglobulin replacement therapy and decreases the morbidity and mortality of CVID.
(© 2019 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Rose CD, Neven B, Wouters C. Granulomatous inflammation: the overlap of immune deficiency and inflammation. Best Pract Res Clin Rheumatol. 2014;28(2):191-212. Review. Erratum. In: Best Pract Res Clin Rheumatol. 2014;28(3):533.
Valeyre D, Prasse A, Nunes H, Uzunhan Y, Brillet PY, Müller-Quernheim J. Sarcoidosis. Lancet. 2014;383(9923):1155-1167.
Wessendorf TE, Bonella F, Costabel U. Diagnosis of sarcoidosis. Clin Rev Allergy Immunol. 2015;49(1):54-62.
Spagnolo P. Sarcoidosis: a critical review of history and milestones. Clin Rev Allergy Immunol. 2015;49(1):1-5.
Fauroux B, Clément A. Paediatric sarcoidosis. Paediatr Respir Rev. 2005;6(2):128-133.
Nathan N, Marcelo P, Houdouin V, et al. Lung sarcoidosis in children: update on disease expression and management. Thorax. 2015;70(6):537-542.
Gedalia A, Khan TA, Shetty AK, Dimitriades VR, Espinoza LR. Childhood sarcoidosis: Louisiana experience. Clin Rheumatol. 2016;35(7):1879-1884.
Deverrière G, Flamans-Klein A, Firmin D, Azouzi O, Courville P, Le Roux P. Early onset pediatric sarcoidosis, diagnostic problems. Arch Pediatr. 2012;19(7):707-710.
Sherief LM, Amer OT, Mokhtar WA, Kamal NM, Ibrahim HM. Pediatric sarcoidosis presenting as huge splenomegaly. Pediatr Int. 2017;59(3):366-367.
Heinle R, Chang C. Diagnostic criteria for sarcoidosis. Autoimmun Rev. 2014;13(4-5):383-387.
Valeyre D, Bernaudin JF, Uzunhan Y, et al. Clinical presentation of sarcoidosis and diagnostic work-up. Semin Respir Crit Care Med. 2014;35(3):336-351.
Morbach H, Eichhorn EM, Liese JG, Girschick HJ. Reference values for B cell subpopulations from infancy to adulthood. Clin Exp Immunol. 2010;162(2):271-279.
European Society for Immunodeficiencies [homepage on the Internet], ESID Registry-Working Definitions for Clinical Diagnosis of PID. https://esid.org/Working-Parties/Registry-Working-Party/Diagnosis-criteria. Accessed January 22, 2019.
Ameratunga R, Woon ST, Gillis D, Koopmans W, Steele R. New diagnostic criteria for common variable immune deficiency (CVID), which may assist with decisions to treat with intravenous or subcutaneous immunoglobulin. Clin Exp Immunol. 2013;174(2):203-211.
Artac H, Bozkurt B, Talim B, Reisli I. Sarcoid-like granulomas in common variable immunodeficiency. Rheumatol Int. 2009;30(1):109-112.
Xiao X, Miao Q, Chang C, Gershwin ME, Ma X. Common variable immunodeficiency and autoimmunity-an inconvenient truth. Autoimmun Rev. 2014;13(8):858-864.
Bouvry D, Mouthon L, Brillet PY, et al. Granulomatosis-associated common variable immunodeficiency disorder: a case-control study versus sarcoidosis. Eur Respir J. 2013;41(1):115-122.
Malphettes M, Oksenhendler E, Galicier L, Fieschi C. Granulomatous disease in common variable immunodeficiency. Rev Med Interne. 2008;29(1):28-32.
Boursiquot JN, Gérard L, Malphettes M, et al. DEFI study group. Granulomatous disease in CVID: retrospective analysis of clinical characteristics and treatment efficacy in a cohort of 59 patients. J Clin Immunol. 2013;33(1):84-95.
Verbsky JW, Routes JM. Sarcoidosis and common variable immunodeficiency: similarities and differences. Semin Respir Crit Care Med. 2014;35(3):330-335.
Silva M, Nunes H, Valeyre D, Sverzellati N. Imaging of Sarcoidosis. Clin Rev Allergy Immunol. 2015;49(1):45-53.
Park JH, Levinson AI. Granulomatous-lymphocytic interstitial lung disease (GLILD) in common variable immunodeficiency (CVID). Clin Immunol. 2010;134(2):97-103.
Arnold DF, Wiggins J, Cunningham-Rundles C, Misbah SA, Chapel HM. Granulomatous disease: distinguishing primary antibody disease from sarcoidosis. Clin Immunol. 2008;128(1):18-22.
Kollert F, Venhoff N, Goldacker S, et al. Bronchoalveolar lavage cytology resembles sarcoidosis in a subgroup of granulomatous CVID. Eur Respir J. 2014;43(3):922-924.
Shanks AM, Alluri R, Herriot R, Dempsey O. Misdiagnosis of common variable immune deficiency. BMJ Case Rep. 2014;2014:bcr2013202806.
Azizi G, Abolhassani H, Asgardoon MH, et al. Autoimmunity in common variable immunodeficiency: epidemiology, pathophysiology and management. Expert Rev Clin Immunol. 2017;13(2):101-115.
Chase NM, Verbsky JW, Hintermeyer MK, et al. Use of combination chemotherapy for treatment of granulomatous and lymphocytic interstitial lung disease (GLILD) in patients with common variable immunodeficiency (CVID). J Clin Immunol. 2013;33(1):30-39.
Franxman TJ, Howe LE, Baker JR Jr. Infliximab for treatment of granulomatous disease in patients with common variable immunodeficiency. J Clin Immunol. 2014;34(7):820-827.
Bonilla FA, Barlan I, Chapel H, et al. International Consensus Document (ICON): common variable immunodeficiency disorders. J Allergy Clin Immunol Pract. 2016;4(1):38-59.

Keywords: common variable immunodeficiency; granulomatous diseases; granulomatous-lymphocytic interstitial lung disease; hypogammaglobulinemia; sarcoidosis

0 (Immunoglobulins, Intravenous)
0 (Immunosuppressive Agents)

Date Created: 20191221 Date Completed: 20210111 Latest Revision: 20210111

20221213

10.1111/1756-185X.13775

31858744