Download PDF
Semin Respir Crit Care Med 2014; 35(03): 330-335
DOI: 10.1055/s-0034-1376862
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Sarcoidosis and Common Variable Immunodeficiency: Similarities and Differences

James W. Verbsky
1   Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin
2   Children's Research Institute, Medical College of Wisconsin, Milwaukee, Wisconsin
3   Medical College of Wisconsin, Milwaukee, Wisconsin
,
John M. Routes
1   Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin
2   Children's Research Institute, Medical College of Wisconsin, Milwaukee, Wisconsin
3   Medical College of Wisconsin, Milwaukee, Wisconsin
› Author Affiliations
Further Information

Publication History

Publication Date:
09 July 2014 (online)

    Permissions and Reprints

Abstract

Common variable immunodeficiency (CVID) is a primary immunodeficiency that is characterized by hypogammaglobulinemia and poor/absent specific antibody production. Granulomatous and lymphocytic interstitial lung disease (GLILD) is an increasingly recognized complication of CVID, occurring in 10 to 20% of patients. GLILD is characterized by non-necrotizing granuloma, lymphocytic interstitial pneumonitis and follicular bronchiolitis-histological patterns that are typically present in the same biopsy. GLILD is a multisystem disease and is frequently accompanied by diffuse adenopathy, splenomegaly, and extrapulmonary granulomatous disease most commonly in the lymph nodes, spleen, liver, and gastrointestinal tract. The presence of noncaseating granuloma in the lung along with some of the extrapulmonary features of GLILD may lead to an incorrect diagnosis of sarcoidosis. However, GLILD differs from sarcoidosis in several important ways including mode of presentation, extrapulmonary manifestations, radiographic abnormalities on high-resolution computed tomography scan of the chest, and laboratory features (serum immunoglobulins, bronchoalveolar lavage, and histopathology). The misdiagnosis of sarcoidosis in a patient with CVID and GLILD can lead to inappropriate treatment and increase the morbidity and mortality of the disorder.

Keywords

common variable immunodeficiency - sarcoidosis - granulomatous and interstitial lung disease - immunodeficiency
 

  • References

  • 1 Bonilla FA, Bernstein IL, Khan DA , et al; American Academy of Allergy, Asthma and Immunology; American College of Allergy, Asthma and Immunology; Joint Council of Allergy, Asthma and Immunology. Practice parameter for the diagnosis and management of primary immunodeficiency. Ann Allergy Asthma Immunol 2005; 94 (5) (Suppl. 01) S1-S63
    CrossrefPubMedGoogle Scholar
  • 2 Yong PF, Thaventhiran JE, Grimbacher B. “A rose is a rose is a rose,” but CVID is Not CVID common variable immune deficiency (CVID), what do we know in 2011?. Adv Immunol 2011; 111: 47-107
    PubMedGoogle Scholar
  • 3 Salzer U, Bacchelli C, Buckridge S , et al. Relevance of biallelic versus monoallelic TNFRSF13B mutations in distinguishing disease-causing from risk-increasing TNFRSF13B variants in antibody deficiency syndromes. Blood 2009; 113 (9) 1967-1976
    CrossrefPubMedGoogle Scholar
  • 4 Cunningham-Rundles C, Bodian C. Common variable immunodeficiency: clinical and immunological features of 248 patients. Clin Immunol 1999; 92 (1) 34-48
    CrossrefPubMedGoogle Scholar
  • 5 Resnick ES, Moshier EL, Godbold JH, Cunningham-Rundles C. Morbidity and mortality in common variable immune deficiency over 4 decades. Blood 2012; 119 (7) 1650-1657
    CrossrefPubMedGoogle Scholar
  • 6 Busse PJ, Razvi S, Cunningham-Rundles C. Efficacy of intravenous immunoglobulin in the prevention of pneumonia in patients with common variable immunodeficiency. J Allergy Clin Immunol 2002; 109 (6) 1001-1004
    CrossrefPubMedGoogle Scholar
  • 7 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
    CrossrefPubMedGoogle Scholar
  • 8 Prasse A, Kayser G, Warnatz K. Common variable immunodeficiency-associated granulomatous and interstitial lung disease. Curr Opin Pulm Med 2013; 19 (5) 503-509
    CrossrefPubMedGoogle Scholar
  • 9 Wheat WH, Cool CD, Morimoto Y , et al. Possible role of human herpesvirus 8 in the lymphoproliferative disorders in common variable immunodeficiency. J Exp Med 2005; 202 (4) 479-484
    CrossrefPubMedGoogle Scholar
  • 10 Rybicki BA, Major M, Popovich Jr J, Maliarik MJ, Iannuzzi MC. Racial differences in sarcoidosis incidence: a 5-year study in a health maintenance organization. Am J Epidemiol 1997; 145 (3) 234-241
    CrossrefPubMedGoogle Scholar
  • 11 Bouvry D, Mouthon L, Brillet PY , et al; Groupe Sarcoïdose Francophone. Granulomatosis-associated common variable immunodeficiency disorder: a case-control study versus sarcoidosis. Eur Respir J 2013; 41 (1) 115-122
    CrossrefPubMedGoogle Scholar
  • 12 Oksenhendler E, Gérard L, Fieschi C , et al; DEFI Study Group. Infections in 252 patients with common variable immunodeficiency. Clin Infect Dis 2008; 46 (10) 1547-1554
    CrossrefPubMedGoogle Scholar
  • 13 Chapel H, Lucas M, Lee M , et al. Common variable immunodeficiency disorders: division into distinct clinical phenotypes. Blood 2008; 112 (2) 277-286
    CrossrefPubMedGoogle Scholar
  • 14 Bates CA, Ellison MC, Lynch DA, Cool CD, Brown KK, Routes JM. Granulomatous-lymphocytic lung disease shortens survival in common variable immunodeficiency. J Allergy Clin Immunol 2004; 114 (2) 415-421
    CrossrefPubMedGoogle Scholar
  • 15 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
    CrossrefPubMedGoogle Scholar
  • 16 Torigian DA, LaRosa DF, Levinson AI, Litzky LA, Miller Jr WT. Granulomatous-lymphocytic interstitial lung disease associated with common variable immunodeficiency: CT findings. J Thorac Imaging 2008; 23 (3) 162-169
    CrossrefPubMedGoogle Scholar
  • 17 Fuss IJ, Friend J, Yang Z , et al. Nodular regenerative hyperplasia in common variable immunodeficiency. J Clin Immunol 2013; 33 (4) 748-758
    CrossrefPubMedGoogle Scholar
  • 18 Vatti R, Sharma OP. Course of asymptomatic liver involvement in sarcoidosis: role of therapy in selected cases. Sarcoidosis Vasc Diffuse Lung Dis 1997; 14 (1) 73-76
    PubMedGoogle Scholar
  • 19 Quinti I, Soresina A, Spadaro G , et al; Italian Primary Immunodeficiency Network. Long-term follow-up and outcome of a large cohort of patients with common variable immunodeficiency. J Clin Immunol 2007; 27 (3) 308-316
    CrossrefPubMedGoogle Scholar
  • 20 Hamilos DL, Young RM, Peter JB, Agopian MS, Iklé DN, Barka N. Hypogammaglobulinemia in asthmatic patients. Ann Allergy 1992; 68 (6) 472-481
    PubMedGoogle Scholar
  • 21 Wehr C, Kivioja T, Schmitt C , et al. The EUROclass trial: defining subgroups in common variable immunodeficiency. Blood 2008; 111 (1) 77-85
    CrossrefPubMedGoogle Scholar
  • 22 Fasano MB, Sullivan KE, Sarpong SB , et al. Sarcoidosis and common variable immunodeficiency. Report of 8 cases and review of the literature. Medicine (Baltimore) 1996; 75 (5) 251-261
    CrossrefPubMedGoogle Scholar
  • 23 Tanaka N, Kim JS, Bates CA , et al. Lung diseases in patients with common variable immunodeficiency: chest radiographic, and computed tomographic findings. J Comput Assist Tomogr 2006; 30 (5) 828-838
    CrossrefPubMedGoogle Scholar
  • 24 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
    CrossrefPubMedGoogle Scholar
  • 25 Chase NM, Verbsky JW, Routes JM. Newborn screening for SCID: three years of experience. Ann N Y Acad Sci 2011; 1238: 99-105
    CrossrefPubMedGoogle Scholar
  • 26 Park JE, Beal I, Dilworth JP, Tormey V, Haddock J. The HRCT appearances of granulomatous pulmonary disease in common variable immune deficiency. Eur J Radiol 2005; 54 (3) 359-364
    CrossrefPubMedGoogle Scholar
  • 27 Maglione PJ, Ko HM, Beasley MB, Strauchen JA, Cunningham-Rundles C. Tertiary lymphoid neogenesis is a component of pulmonary lymphoid hyperplasia in patients with common variable immunodeficiency. J Allergy Clin Immunol 2014; 133 (2) 535-542
    CrossrefPubMedGoogle Scholar
  • 28 Hampson FA, Chandra A, Screaton NJ , et al. Respiratory disease in common variable immunodeficiency and other primary immunodeficiency disorders. Clin Radiol 2012; 67 (6) 587-595
    CrossrefPubMedGoogle Scholar
  • 29 Mechanic LJ, Dikman S, Cunningham-Rundles C. Granulomatous disease in common variable immunodeficiency. Ann Intern Med 1997; 127 (8 Pt 1) 613-617
    CrossrefPubMedGoogle Scholar
  • 30 Ardeniz O, Cunningham-Rundles C. Granulomatous disease in common variable immunodeficiency. Clin Immunol 2009; 133 (2) 198-207
    CrossrefPubMedGoogle Scholar
  • 31 Davies CW, Juniper MC, Gray W, Gleeson FV, Chapel HM, Davies RJ. Lymphoid interstitial pneumonitis associated with common variable hypogammaglobulinaemia treated with cyclosporin A. Thorax 2000; 55 (1) 88-90
    CrossrefPubMedGoogle Scholar
  • 32 Gobert D, Bussel JB, Cunningham-Rundles C , et al. Efficacy and safety of rituximab in common variable immunodeficiency-associated immune cytopenias: a retrospective multicentre study on 33 patients. Br J Haematol 2011; 155 (4) 498-508
    CrossrefPubMedGoogle Scholar
  • 33 Hatab AZ, Ballas ZK. Caseating granulomatous disease in common variable immunodeficiency treated with infliximab. J Allergy Clin Immunol 2005; 116 (5) 1161-1162
    CrossrefPubMedGoogle Scholar
  • 34 Lin JH, Liebhaber M, Roberts RL, Dyer Z, Stiehm ER. Etanercept treatment of cutaneous granulomas in common variable immunodeficiency. J Allergy Clin Immunol 2006; 117 (4) 878-882
    CrossrefPubMedGoogle Scholar
  • 35 Thatayatikom A, Thatayatikom S, White AJ. Infliximab treatment for severe granulomatous disease in common variable immunodeficiency: a case report and review of the literature. Ann Allergy Asthma Immunol 2005; 95 (3) 293-300
    CrossrefPubMedGoogle Scholar