Eight to 22 % of common variable immunodeficiency (CVID) patients exhibit granulomas of the lungs, spleen, liver, and/or skin. Granulomas can be the most medically significant day-to-day problem for CVID patients. Currently, there are limited options for treatment of granulomas associated with CVID.
We treated five patients with CVID who exhibited significant clinical symptoms secondary to granulomas with infliximab. The patients were selected and treated based solely on clinical need and were not otherwise controlled or blinded to the therapy. After obtaining baseline studies (labs, spirometry, radiology) and excluding infection, they were treated with infliximab 5 mg/kg at week 0, 2, 6 and every 4 weeks thereafter.
Post treatment improvements were seen in all 5 patients with significant clinical responses observed for both visceral and cutaneous granulomata. Four of the five patients were maintained on infliximab for 5 to 18 months (mean 9.4 months) without adverse reaction or increased susceptibility to infection. One patient completed 6 months of therapy with improvement of respiratory parameters but discontinued infliximab due to joint stiffness and rash that she attributed to the medication.
In our series, infliximab (5 mg/kg monthly) was an effective treatment for cutaneous and visceral granulomas in patients with CVID.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
Conley ME, Notarangelo LD, Etzioni A. Diagnostic criteria for primary immunodeficiencies. Representing PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies). Clin Immunol. 1999;93(3):190–7.
Morimoto Y, Routes JM. Granulomatous disease in common variable immunodeficiency. Curr Allergy Asthma Rep. 2005;5(5):370–5.
Cunningham-Rundles C. How I, treat common variable immune deficiency. Blood. 2010;116(1):7–15.
Ardeniz O, Cunningham-Rundles C. Granulomatous disease in common variable immunodeficiency. Clin Immunol. 2009;133(2):198–207.
Mullighan CG, Fanning GC, Chapel HM, Welsh KI. TNF and lymphotoxin-alpha polymorphisms associated with common variable immunodeficiency: role in the pathogenesis of granulomatous disease. J Immunol. 1997;159(12):6236–41.
Boursiquot JN, Gerard L, Malphettes M, Fieschi C, Galicier L, Boutboul D, et al. 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.
Mechanic LJ, Dikman S, Cunningham-Rundles C. Granulomatous disease in common variable immunodeficiency. Ann Intern Med. 1997;127(8 Pt 1):613–7.
Kanathur N, Byrd Jr RP, Fields CL, Roy TM. Noncaseating granulomatous disease in common variable immunodeficiency. South Med J. 2000;93(6):631–3.
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.
Roach DR, Bean AG, Demangel C, France MP, Briscoe H, Britton WJ. TNF regulates chemokine induction essential for cell recruitment, granuloma formation, and clearance of mycobacterial infection. J Immunol. 2002;168(9):4620–7.
Aukrust P, Lien E, Kristoffersen AK, Muller F, Haug CJ, Espevik T, et al. Persistent activation of the tumor necrosis factor system in a subgroup of patients with common variable immunodeficiency–possible immunologic and clinical consequences. Blood. 1996;87(2):674–81.
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):878–82.
Malbran A, Juri MC, Fernandez Romero DS. Common variable immunodeficiency and granulomatosis treated with infliximab. Clin Immunol. 2010;134(3):359–60.
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):415–21.
Resnick ES, Moshier EL, Godbold JH, Cunningham-Rundles C. Morbidity and mortality in common variable immune deficiency over 4 decades. Blood. 2012;119(7):1650–7.
Chase NM, Verbsky JW, Hintermeyer MK, Waukau JK, Tomita-Mitchell A, Casper JT, 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):30–9.
Hatab AZ, Ballas ZK. Caseating granulomatous disease in common variable immunodeficiency treated with infliximab. J Allergy Clin Immunol. 2005;116(5):1161–2.
Smith KJ, Skelton H. Common variable immunodeficiency treated with a recombinant human IgG, tumour necrosis factor-alpha receptor fusion protein. Br J Dermatol. 2001;144(3):597–600.
Douni E, Akassoglou K, Alexopoulou L, Georgopoulos S, Haralambous S, Hill S, et al. Transgenic and knockout analyses of the role of TNF in immune regulation and disease pathogenesis. J Inflamm. 1995–1996;47(1–2):27–38.
Myatt N, Coghill G, Morrison K, Jones D, Cree IA. Detection of tumour necrosis factor alpha in sarcoidosis and tuberculosis granulomas using in situ hybridisation. J Clin Pathol. 1994;47(5):423–6.
Joseph AL, Boros DL. Tumor necrosis factor plays a role in Schistosoma mansoni egg-induced granulomatous inflammation. J Immunol. 1993;151(10):5461–71.
Aukrust P, Muller F, Froland SS. Elevated serum levels of interleukin-4 and interleukin-6 in patients with common variable immunodeficiency (CVI) are associated with chronic immune activation and low numbers of CD4+ lymphocytes. Clin Immunol Immunopathol. 1994;70(3):217–24.
North ME, Spickett GP, Webster AD, Farrant J. Raised serum levels of CD8, CD25 and beta 2-microglobulin in common variable immunodeficiency. Clin Exp Immunol. 1991;86(2):252–5.
Girardin E, Roux-Lombard P, Grau GE, Suter P, Gallati H, Dayer JM. Imbalance between tumour necrosis factor-alpha and soluble TNF receptor concentrations in severe meningococcaemia. The J5 study group. Immunology. 1992;76(1):20–3.
Flammiger A, Fiedler W, Bacher U, Bokemeyer C, Schneider M, Binder M. Critical imbalance of TNF-alpha and soluble TNF receptor 1 in a patient with macrophage activation syndrome: potential implications for diagnostics and treatment. Acta Haematol. 2012;128(2):69–72.
Heaney ML, Golde DW. Soluble receptors in human disease. J Leukoc Biol. 1998;64(2):135–46.
Scallon B, Cai A, Solowski N, Rosenberg A, Song XY, Shealy D, et al. Binding and functional comparisons of two types of tumor necrosis factor antagonists. J Pharmacol Exp Ther. 2002;301(2):418–26.
Ehlers S. Tumor necrosis factor and its blockade in granulomatous infections: differential modes of action of infliximab and etanercept? Clin Infect Dis. 2005;41 Suppl 3:S199–203.
Fallahi-Sichani M, Flynn JL, Linderman JJ, Kirschner DE. Differential risk of ctuberculosis reactivation among anti-TNF therapies is due to drug bindingckinetics and permeability. J Immunol. 2012;188(7):3169–78.
Mitoma H, Horiuchi T, Tsukamoto H, Tamimoto Y, Kimoto Y, Uchino A, et al. Mechanisms for cytotoxic effects of anti-tumor necrosis factor agents on transmembrane tumor necrosis factor alpha-expressing cells: comparison among infliximab, etanercept, and adalimumab. Arthritis Rheum. 2008;58(5):1248–57.
Salzer U, Chapel HM, Webster AD, Pan-Hammarstrom Q, Schmitt-Graeff A, Schlesier M, et al. Mutations in TNFRSF13B encoding TACI are associated with common variable immunodeficiency in humans. Nat Genet. 2005;37(8):820–8.
Castigli E, Wilson SA, Garibyan L, Rachid R, Bonilla F, Schneider L, et al. TACI is mutant in common variable immunodeficiency and IgA deficiency. Nat Genet. 2005;37(8):829–34.
Salzer U, Bacchelli C, Buckridge S, Pan-Hammarstrom Q, Jennings S, Lougaris V, 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):1967–76.
About this article
Cite this article
Franxman, T.J., Howe, L.E. & Baker, J.R. Infliximab for Treatment of Granulomatous Disease in Patients with Common Variable Immunodeficiency. J Clin Immunol 34, 820–827 (2014). https://doi.org/10.1007/s10875-014-0079-3
- common variable immunodeficiency (CVID)