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Managing Inflammatory Manifestations in Patients with Chronic Granulomatous Disease

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Abstract

Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by lack of phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, which results in inflammatory dysregulation and increased susceptibility to infections. Patients with CGD may develop severe obstructive disorders of the digestive tract as a result of their dysregulated inflammatory response. Despite a growing focus on inflammatory manifestations in CGD, the literature data on obstructive complications are far less extensive than those on infectious complications. Diagnosis and management of patients with concomitant predispositions to infections and hyperinflammation are particularly challenging. Although the inflammatory and granulomatous manifestations of CGD usually respond rapidly to steroid treatment, second-line therapies (immunosuppressants and biologics) may be required in refractory cases. Indeed, immunosuppressants (such as anti-tumor necrosis factor agents, thalidomide, and anakinra) have shown some efficacy, but the value of this approach is controversial, given the questionable risk-to-benefit ratio and the small numbers of patients treated to date. Significant progress in allogeneic hematopoietic stem cell transplantation (the only curative treatment for CGD) has been made through better supportive care and implementation of improved, reduced-intensity conditioning regimens. Gene therapy may eventually be an option for patients lacking a suitable donor; clinical trials with new, safer vectors are ongoing at a few centers.

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References

  1. Winkelstein JA, Marino MC, Johnston RB Jr, Boyle J, Curnutte J, Gallin JI, et al. Chronic granulomatous disease: report on a national registry of 368 patients. Medicine (Baltimore). 2000;79(3):155–69.

    Article  CAS  PubMed  Google Scholar 

  2. Liese J, Kloos S, Jendrossek V, Petropoulou T, Wintergerst U, Notheis G, et al. Long-term follow-up and outcome of 39 patients with chronic granulomatous disease. J Pediatr. 2000;137(5):687–93.

    Article  CAS  PubMed  Google Scholar 

  3. Magnani A, Brosselin P, Beaute J, de Vergnes N, Mouy R, Debre M, et al. Inflammatory manifestations in a single-center cohort of patients with chronic granulomatous disease. J Allergy Clin Immunol. 2014;134(3):655–62 e8.

  4. Seger RA. Modern management of chronic granulomatous disease. Br J Haematol. 2008;140(3):255–66.

    Article  CAS  PubMed  Google Scholar 

  5. Alvarez-Downing MM, Kamal N, Inchauste SM, Khangura SK, Malech HL, Holland SM, et al. The role of surgery in the management of patients with refractory chronic granulomatous disease colitis. Dis Colon Rectum. 2013;56(5):609–14.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Battersby AC, Cale AM, Goldblatt D, Gennery AR. Clinical manifestations of disease in X-linked carriers of chronic granulomatous disease. J Clin Immunol. 2013;33(8):1276–84.

    Article  CAS  PubMed  Google Scholar 

  7. Cale CM, Morton L, Goldblatt D. Cutaneous and other lupus-like symptoms in carriers of X-linked chronic granulomatous disease: incidence and autoimmune serology. Clin Exp Immunol. 2007;148(1):79–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Kuhns DB, Alvord WG, Heller T, Feld JJ, Pike KM, Marciano BE, et al. Residual NADPH oxidase and survival in chronic granulomatous disease. N Engl J Med. 2010;363(27):2600–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Schappi MG, Klein NJ, Lindley KJ, Rampling D, Smith VV, Goldblatt D, et al. The nature of colitis in chronic granulomatous disease. J Pediatr Gastroenterol Nutr. 2003;36(5):623–31.

    Article  PubMed  Google Scholar 

  10. Schappi MG, Jaquet V, Belli DC, Krause KH. Hyperinflammation in chronic granulomatous disease and anti-inflammatory role of the phagocyte NADPH oxidase. Semin Immunopathol. 2008;30(3):255–71.

    Article  PubMed  Google Scholar 

  11. Segal BH, Leto TL, Gallin JI, Malech HL, Holland SM. Genetic, biochemical, and clinical features of chronic granulomatous disease. Medicine (Baltimore). 2000;79(3):170–200.

    Article  CAS  PubMed  Google Scholar 

  12. Geiszt M, Kapus A, Nemet K, Farkas L, Ligeti E. Regulation of capacitative Ca2+ influx in human neutrophil granulocytes: alterations in chronic granulomatous disease. J Biol Chem. 1997;272(42):26471–8.

    Article  CAS  PubMed  Google Scholar 

  13. Roxo-Junior P, Simao HM. Chronic granulomatous disease: why an inflammatory disease? Braz J Med Biol Res. 2014;47(11):924–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Hartl D, Lehmann N, Hoffmann F, Jansson A, Hector A, Notheis G, et al. Dysregulation of innate immune receptors on neutrophils in chronic granulomatous disease. J Allergy Clin Immunol. 2008;121(2):375–82 e9.

  15. de Luca A, Smeekens SP, Casagrande A, Iannitti R, Conway KL, Gresnigt MS, et al. IL-1 receptor blockade restores autophagy and reduces inflammation in chronic granulomatous disease in mice and in humans. Proc Natl Acad Sci. 2014;111(9):3526–31.

    Article  PubMed  PubMed Central  Google Scholar 

  16. van de Veerdonk FL, Dinarello CA. Deficient autophagy unravels the ROS paradox in chronic granulomatous disease. Autophagy. 2014;10(6):1141–2.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Meissner F, Seger RA, Moshous D, Fischer A, Reichenbach J, Zychlinsky A. Inflammasome activation in NADPH oxidase defective mononuclear phagocytes from patients with chronic granulomatous disease. Blood. 2010;116(9):1570–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. van de Veerdonk FL, Smeekens SP, Joosten LA, Kullberg BJ, Dinarello CA, van der Meer JW, et al. Reactive oxygen species-independent activation of the IL-1beta inflammasome in cells from patients with chronic granulomatous disease. Proc Natl Acad Sci. 2010;107(7):3030–3.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Foster CB, Lehrnbecher T, Mol F, Steinberg SM, Venzon DJ, Walsh TJ, et al. Host defense molecule polymorphisms influence the risk for immune-mediated complications in chronic granulomatous disease. J Clin Invest. 1998;102(12):2146–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Bridges RA, Berendes H, Good RA. A fatal granulomatous disease of childhood; the clinical, pathological, and laboratory features of a new syndrome. AMA J Dis Child. 1959;97(4):387–408.

    Article  CAS  PubMed  Google Scholar 

  21. Aguilar C, Malphettes M, Donadieu J, Chandesris O, Coignard-Biehler H, Catherinot E, et al. Prevention of infections during primary immunodeficiency. Clin Infect Dis. 2014;59(10):1462–70.

    Article  PubMed  Google Scholar 

  22. Jones LB, McGrogan P, Flood TJ, Gennery AR, Morton L, Thrasher A, et al. Special article: chronic granulomatous disease in the United Kingdom and Ireland: a comprehensive national patient-based registry. Clin Exp Immunol. 2008;152(2):211–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. The International Chronic Granulomatous Disease Cooperative Study Group. A controlled trial of interferon gamma to prevent infection in chronic granulomatous disease. N Engl J Med. 1991;324(8):509–16.

    Article  Google Scholar 

  24. Gallin JI, Zarember K. Lessons about the pathogenesis and management of aspergillosis from studies in chronic granulomatous disease. Trans Am Clin Climatol Assoc. 2007;118:175–85.

    PubMed  PubMed Central  Google Scholar 

  25. van den Berg JM, van Koppen E, Ahlin A, Belohradsky BH, Bernatowska E, Corbeel L, et al. Chronic granulomatous disease: the European experience. PLoS One. 2009;4(4):e5234.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Mouy R, Seger R, Bourquin JP, Veber F, Blanche S, Griscelli C, et al. Interferon gamma for chronic granulomatous disease. N Engl J Med. 1991;325(21):1516–7.

    Article  CAS  PubMed  Google Scholar 

  27. Gungor T, Teira P, Slatter M, Stussi G, Stepensky P, Moshous D, et al. Reduced-intensity conditioning and HLA-matched haemopoietic stem-cell transplantation in patients with chronic granulomatous disease: a prospective multicentre study. Lancet. 2014;383(9915):436–48.

    Article  CAS  PubMed  Google Scholar 

  28. Grez M, Reichenbach J, Schwable J, Seger R, Dinauer MC, Thrasher AJ. Gene therapy of chronic granulomatous disease: the engraftment dilemma. Mol Ther. 2011;19(1):28–35.

    Article  CAS  PubMed  Google Scholar 

  29. Kang EM, Marciano BE, DeRavin S, Zarember KA, Holland SM, Malech HL. Chronic granulomatous disease: overview and hematopoietic stem cell transplantation. J Allergy Clin Immunol. 2011;127(6):1319–26 (quiz 1327–8).

  30. Malech HL, Maples PB, Whiting-Theobald N, Linton GF, Sekhsaria S, Vowells SJ, et al. Prolonged production of NADPH oxidase-corrected granulocytes after gene therapy of chronic granulomatous disease. Proc Natl Acad Sci. 1997;94(22):12133–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Ott MG, Schmidt M, Schwarzwaelder K, Stein S, Siler U, Koehl U, et al. Correction of X-linked chronic granulomatous disease by gene therapy, augmented by insertional activation of MDS1-EVI1, PRDM16 or SETBP1. Nat Med. 2006;12(4):401–9.

    Article  CAS  PubMed  Google Scholar 

  32. Stein S, Siler U, Ott MG, Seger R, Grez M. Gene therapy for chronic granulomatous disease. Curr Opin Mol Ther. 2006;8(5):415–22.

    CAS  PubMed  Google Scholar 

  33. Marciano BE, Rosenzweig SD, Kleiner DE, Anderson VL, Darnell DN, Anaya-O’Brien S, et al. Gastrointestinal involvement in chronic granulomatous disease. Pediatrics. 2004;114(2):462–8.

    Article  PubMed  Google Scholar 

  34. Huang A, Abbasakoor F, Vaizey CJ. Gastrointestinal manifestations of chronic granulomatous disease. Colorectal Dis. 2006;8(8):637–44.

    Article  CAS  PubMed  Google Scholar 

  35. Schappi MG, Smith VV, Goldblatt D, Lindley KJ, Milla PJ. Colitis in chronic granulomatous disease. Arch Dis Child. 2001;84(2):147–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Barton LL, Moussa SL, Villar RG, Hulett RL. Gastrointestinal complications of chronic granulomatous disease: case report and literature review. Clin Pediatr (Phila). 1998;37(4):231–6.

    Article  CAS  PubMed  Google Scholar 

  37. Alimchandani M, Lai JP, Aung PP, Khangura S, Kamal N, Gallin JI, et al. Gastrointestinal histopathology in chronic granulomatous disease: a study of 87 patients. Am J Surg Pathol. 2013;37(9):1365–72.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Levine S, Smith VV, Malone M, Sebire NJ. Histopathological features of chronic granulomatous disease (CGD) in childhood. Histopathology. 2005;47(5):508–16.

    Article  CAS  PubMed  Google Scholar 

  39. Liu S, Russo PA, Baldassano RN, Sullivan KE. CD68 expression is markedly different in Crohn’s disease and the colitis associated with chronic granulomatous disease. Inflamm Bowel Dis. 2009;15(8):1213–7.

    Article  PubMed  Google Scholar 

  40. Marks DJ, Miyagi K, Rahman FZ, Novelli M, Bloom SL, Segal AW. Inflammatory bowel disease in CGD reproduces the clinicopathological features of Crohn’s disease. Am J Gastroenterol. 2009;104(1):117–24.

    Article  CAS  PubMed  Google Scholar 

  41. Leiding JW, Freeman AF, Marciano BE, Anderson VL, Uzel G, Malech HL, et al. Corticosteroid therapy for liver abscess in chronic granulomatous disease. Clin Infect Dis. 2012;54(5):694–700.

    Article  CAS  PubMed  Google Scholar 

  42. Laskey HL, Gopal L, Gallin JI, Holland SM, Heller T. Twenty-year follow-up of esophageal involvement in chronic granulomatous disease. Am J Gastroenterol. 2009;104(9):2368–70.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Varma VA, Sessions JT, Kahn LB, Lipper S. Chronic granulomatous disease of childhood presenting as gastric outlet obstruction. Am J Surg Pathol. 1982;6(7):673–6.

    Article  CAS  PubMed  Google Scholar 

  44. Mahdaviani SA, Mohajerani SA, Rezaei N, Casanova JL, Mansouri SD, Velayati AA. Pulmonary manifestations of chronic granulomatous disease. Expert Rev Clin Immunol. 2013;9(2):153–60.

    Article  CAS  PubMed  Google Scholar 

  45. Salvator H, Mahlaoui N, Catherinot E, Rivaud E, Pilmis B, Borie R, et al. Pulmonary manifestations in adult patients with chronic granulomatous disease. Eur Respir J. 2015;45(6):1613–23.

    Article  PubMed  Google Scholar 

  46. Siddiqui S, Anderson VL, Hilligoss DM, Abinun M, Kuijpers TW, Masur H, et al. Fulminant mulch pneumonitis: an emergency presentation of chronic granulomatous disease. Clin Infect Dis. 2007;45(6):673–81.

    Article  CAS  PubMed  Google Scholar 

  47. Walther MM, Malech H, Berman A, Choyke P, Venzon DJ, Linehan WM, et al. The urological manifestations of chronic granulomatous disease. J Urol. 1992;147(5):1314–8.

    CAS  PubMed  Google Scholar 

  48. Barese CN, Podesta M, Litvak E, Villa M, Rivas EM. Recurrent eosinophilic cystitis in a child with chronic granulomatous disease. J Pediatr Hematol Oncol. 2004;26(3):209–12.

    Article  PubMed  Google Scholar 

  49. Rosenzweig SD. Inflammatory manifestations in chronic granulomatous disease (CGD). J Clin Immunol. 2008;28(Suppl 1):S67–72.

    Article  PubMed  Google Scholar 

  50. Al-Muhsen S, Al-Hemidan A, Al-Shehri A, Al-Harbi A, Al-Ghonaium A, Al-Saud B, et al. Ocular manifestations in chronic granulomatous disease in Saudi Arabia. J AAPOS. 2009;13(4):396–9.

    Article  PubMed  Google Scholar 

  51. Goldblatt D, Butcher J, Thrasher AJ, Russell-Eggitt I. Chorioretinal lesions in patients and carriers of chronic granulomatous disease. J Pediatr. 1999;134(6):780–3.

    Article  CAS  PubMed  Google Scholar 

  52. Kim SJ, Kim JG, Yu YS. Chorioretinal lesions in patients with chronic granulomatous disease. Retina. 2003;23(3):360–5.

    Article  PubMed  Google Scholar 

  53. Palestine AG, Meyers SM, Fauci AS, Gallin JI. Ocular findings in patients with neutrophil dysfunction. Am J Ophthalmol. 1983;95(5):598–604.

    Article  CAS  PubMed  Google Scholar 

  54. Valluri S, Chu FC, Smith ME. Ocular pathologic findings of chronic granulomatous disease of childhood. Am J Ophthalmol. 1995;120(1):120–3.

    Article  CAS  PubMed  Google Scholar 

  55. Wang Y, Marciano BE, Shen D, Bishop RJ, Park S, Holland SM, et al. Molecular identification of bacterial DNA in the chorioretinal scars of chronic granulomatous disease. J Clin Immunol. 2013;33(5):917–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. De Ravin SS, Naumann N, Cowen EW, Friend J, Hilligoss D, Marquesen M, et al. Chronic granulomatous disease as a risk factor for autoimmune disease. J Allergy Clin Immunol. 2008;122(6):1097–103.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Sillevis Smitt JH, Weening RS, Krieg SR, Bos JD. Discoid lupus erythematosus-like lesions in carriers of X-linked chronic granulomatous disease. Br J Dermatol. 1990;122(5):643–50.

    Article  CAS  PubMed  Google Scholar 

  58. Chowdhury MM, Anstey A, Matthews CN. The dermatosis of chronic granulomatous disease. Clin Exp Dermatol. 2000;25(3):190–4.

    Article  CAS  PubMed  Google Scholar 

  59. Sillevis Smitt JH, Bos JD, Weening RS, Krieg SR. Discoid lupus erythematosus-like skin changes in patients with autosomal recessive chronic granulomatous disease. Arch Dermatol. 1990;126(12):1656–8.

    Article  CAS  PubMed  Google Scholar 

  60. Maltzman JS, Koretzky GA. Azathioprine: old drug, new actions. J Clin Invest. 2003;111(8):1122–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Kirschner BS. Safety of azathioprine and 6-mercaptopurine in pediatric patients with inflammatory bowel disease. Gastroenterology. 1998;115(4):813–21.

    Article  CAS  PubMed  Google Scholar 

  62. Mantzaris GJ, Christidou A, Sfakianakis M, Roussos A, Koilakou S, Petraki K, et al. Azathioprine is superior to budesonide in achieving and maintaining mucosal healing and histologic remission in steroid-dependent Crohn’s disease. Inflamm Bowel Dis. 2009;15(3):375–82.

    Article  PubMed  Google Scholar 

  63. Zanditenas D, Hagege H, Rosa I, Cattan P, Ratel-Saby S, Lons T, et al. Inflammatory colitis and chronic granulomatous disease, a steroid-dependent case report [in French]. Gastroenterol Clin Biol. 2004;28(4):398–401.

    Article  PubMed  Google Scholar 

  64. Seger RA. Chronic granulomatous disease: recent advances in pathophysiology and treatment. Neth J Med. 2010;68(11):334–40.

    CAS  PubMed  Google Scholar 

  65. Zic JA, Horowitz DH, Arzubiaga C, King LE Jr. Treatment of cutaneous sarcoidosis with chloroquine: review of the literature. Arch Dermatol. 1991;127(7):1034–40.

    Article  CAS  PubMed  Google Scholar 

  66. Lee SJ, Silverman E, Bargman JM. The role of antimalarial agents in the treatment of SLE and lupus nephritis. Nat Rev Nephrol. 2011;7(12):718–29.

    Article  CAS  PubMed  Google Scholar 

  67. Henriet SS, Jans J, Simonetti E, Kwon-Chung KJ, Rijs AJ, Hermans PW, et al. Chloroquine modulates the fungal immune response in phagocytic cells from patients with chronic granulomatous disease. J Infect Dis. 2013;207(12):1932–9.

    Article  CAS  PubMed  Google Scholar 

  68. Arlet JB, Aouba A, Suarez F, Blanche S, Valeyre D, Fischer A, et al. Efficiency of hydroxychloroquine in the treatment of granulomatous complications in chronic granulomatous disease. Eur J Gastroenterol Hepatol. 2008;20(2):142–4.

    Article  CAS  PubMed  Google Scholar 

  69. Rosh JR, Tang HB, Mayer L, Groisman G, Abraham SK, Prince A. Treatment of intractable gastrointestinal manifestations of chronic granulomatous disease with cyclosporine. J Pediatr. 1995;126(1):143–5.

    Article  CAS  PubMed  Google Scholar 

  70. Keating GM, Perry CM. Infliximab: an updated review of its use in Crohn’s disease and rheumatoid arthritis. BioDrugs. 2002;16(2):111–48.

    Article  CAS  PubMed  Google Scholar 

  71. Hamilton CD. Infectious complications of treatment with biologic agents. Curr Opin Rheumatol. 2004;16(4):393–8.

    Article  PubMed  Google Scholar 

  72. Toussirot E, Streit G, Wendling D. Infectious complications with anti-TNFalpha therapy in rheumatic diseases: a review. Recent Pat Inflamm Allergy Drug Discov. 2007;1(1):39–47.

    Article  CAS  PubMed  Google Scholar 

  73. Uzel G, Orange JS, Poliak N, Marciano BE, Heller T, Holland SM. Complications of tumor necrosis factor-alpha blockade in chronic granulomatous disease-related colitis. Clin Infect Dis. 2010;51(12):1429–34.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Freudenberg F, Wintergerst U, Roesen-Wolff A, Albert MH, Prell C, Strahm B, et al. Therapeutic strategy in p47-phox deficient chronic granulomatous disease presenting as inflammatory bowel disease. J Allergy Clin Immunol. 2010;125(4):943–6 e1.

  75. 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):820–7.

    Article  CAS  PubMed  Google Scholar 

  76. Deffert C, Olleros ML, Huiping Y, Herrmann FR, Zekry D, Garcia I, et al. TNF-alpha blockade in chronic granulomatous disease-induced hyperinflammation: patient analysis and murine model. J Allergy Clin Immunol. 2011;128(3):675–7.

    Article  CAS  PubMed  Google Scholar 

  77. Alkan C, Kavak P, Somel M, Gokcumen O, Ugurlu S, Saygi C, et al. Whole genome sequencing of Turkish genomes reveals functional private alleles and impact of genetic interactions with Europe, Asia and Africa. BMC Genom. 2014;15:963.

    Article  Google Scholar 

  78. Dinarello CA. Keep up the heat on IL-1. Blood. 2012;120(13):2538–9.

    Article  CAS  PubMed  Google Scholar 

  79. Hahn KJ, Ho N, Yockey L, Kreuzberg S, Daub J, Rump A, et al. Treatment with anakinra, a recombinant IL-1 receptor antagonist, unlikely to induce lasting remission in patients with CGD colitis. Am J Gastroenterol. 2015;110(6):938–9.

    Article  CAS  PubMed  Google Scholar 

  80. Eski M, Sahin I, Sengezer M, Serdar M, Ifran A. Thalidomide decreases the plasma levels of IL-1 and TNF following burn injury: is it a new drug for modulation of systemic inflammatory response. Burns. 2008;34(1):104–8.

    Article  PubMed  Google Scholar 

  81. Keller M, Sollberger G, Beer HD. Thalidomide inhibits activation of caspase-1. J Immunol. 2009;183(9):5593–9.

    Article  CAS  PubMed  Google Scholar 

  82. Meierhofer C, Wiedermann CJ. New insights into the pharmacological and toxicological effects of thalidomide. Curr Opin Drug Discov Devel. 2003;6(1):92–9.

    CAS  PubMed  Google Scholar 

  83. Noel N, Mahlaoui N, Blanche S, Suarez F, Coignard-Biehler H, Durieu I, et al. Efficacy and safety of thalidomide in patients with inflammatory manifestations of chronic granulomatous disease: a retrospective case series. J Allergy Clin Immunol. 2013.

  84. Sokol H, Suarez F, Meatchi T, Malamut G, Pocidalo MA, Blanche S, et al. Thalidomide as a treatment for refractory CGD colitis. Am J Gastroenterol. 2009;104(4):1069.

    Article  PubMed  Google Scholar 

  85. Kyriakou C, Thomson K, D’Sa S, Flory A, Hanslip J, Goldstone AH, et al. Low-dose thalidomide in combination with oral weekly cyclophosphamide and pulsed dexamethasone is a well tolerated and effective regimen in patients with relapsed and refractory multiple myeloma. Br J Haematol. 2005;129(6):763–70.

    Article  CAS  PubMed  Google Scholar 

  86. Kawai T, Watanabe N, Yokoyama M, Arai K, Oana S, Harayama S, et al. Thalidomide attenuates excessive inflammation without interrupting lipopolysaccharide-driven inflammatory cytokine production in chronic granulomatous disease. Clin Immunol. 2013;147(2):122–8.

    Article  CAS  PubMed  Google Scholar 

  87. Palumbo A, Facon T, Sonneveld P, Blade J, Offidani M, Gay F, et al. Thalidomide for treatment of multiple myeloma: 10 years later. Blood. 2008;111(8):3968–77.

    Article  CAS  PubMed  Google Scholar 

  88. Fidanboylu M, Griffiths LA, Flatters SJ. Global inhibition of reactive oxygen species (ROS) inhibits paclitaxel-induced painful peripheral neuropathy. PLoS One. 2011;6(9):e25212.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Eckert JW, Abramson SL, Starke J, Brandt ML. The surgical implications of chronic granulomatous disease. Am J Surg. 1995;169(3):320–3.

    Article  CAS  PubMed  Google Scholar 

  90. Gennery AR, Slatter MA, Grandin L, Taupin P, Cant AJ, Veys P, et al. Transplantation of hematopoietic stem cells and long-term survival for primary immunodeficiencies in Europe: entering a new century, do we do better? J Allergy Clin Immunol. 2010.126(3):602–10 e1–11.

  91. Gungor T, Halter J, Klink A, Junge S, Stumpe KD, Seger R, et al. Successful low toxicity hematopoietic stem cell transplantation for high-risk adult chronic granulomatous disease patients. Transplantation. 2005;79(11):1596–606.

    Article  PubMed  Google Scholar 

  92. Kang HJ, Bartholomae CC, Paruzynski A, Arens A, Kim S, Yu SS, et al. Retroviral gene therapy for X-linked chronic granulomatous disease: results from phase I/II trial. Mol Ther. 2011;19(11):2092–101.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Dropulic B. Lentiviral vectors: their molecular design, safety, and use in laboratory and preclinical research. Hum Gene Ther. 2011;22(6):649–57.

    Article  CAS  PubMed  Google Scholar 

  94. Galy A, Roncarolo MG, Thrasher AJ. Development of lentiviral gene therapy for Wiskott Aldrich syndrome. Expert Opin Biol Ther. 2008;8(2):181–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Cattoglio C, Pellin D, Rizzi E, Maruggi G, Corti G, Miselli F, et al. High-definition mapping of retroviral integration sites identifies active regulatory elements in human multipotent hematopoietic progenitors. Blood. 2010;116(25):5507–17.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors thank the pediatric and adult clinical teams at Necker Children’s Hospital (Paris, France), Saint-Antoine Hospital (Paris, France), and Foch Hospital (Suresnes, France). They also thank the patients and families who participated in the cohort studies.

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Authors and Affiliations

  1. Biotherapy Department, Necker-Enfants Malades University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France

    Alessandra Magnani

  2. Paris Descartes University, Sorbonne Paris Cité, Imagine Institute, Paris, France

    Alessandra Magnani & Nizar Mahlaoui

  3. French National Reference Center for Primary Immune Deficiencies (CEREDIH), Necker-Enfants Malades University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France

    Nizar Mahlaoui

  4. INSERM UMR 1163, Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Paris, France

    Nizar Mahlaoui

  5. Pediatric Immunohematology and Rheumatology Unit, Necker-Enfants Malades University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France

    Nizar Mahlaoui

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  1. Alessandra Magnani
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Correspondence to Alessandra Magnani or Nizar Mahlaoui.

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Alessandra Magnani and Nizar Mahlaoui declare no conflicts of interest.

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Magnani, A., Mahlaoui, N. Managing Inflammatory Manifestations in Patients with Chronic Granulomatous Disease. Pediatr Drugs 18, 335–345 (2016). https://doi.org/10.1007/s40272-016-0182-4

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