Al-Herz W, Nanda A. Skin manifestations in primary immunodeficient children. Pediatr Dermatol. 2011 Sep-Oct. 28(5):494-501. [QxMD MEDLINE Link].
Couëdel C, Roman C, Jones A, Vezzoni P, Villa A, Cortes P. Analysis of mutations from SCID and Omenn syndrome patients reveals the central role of the Rag2 PHD domain in regulating V(D)J recombination. J Clin Invest. 2010 Apr. 120(4):1337-44. [QxMD MEDLINE Link]. [Full Text].
Wang YQ, Cui YX, Feng J. [Clinical phenotype and gene diagnostic analysis of Omenn syndrome]. Zhonghua Er Ke Za Zhi. 2013 Jan. 51(1):64-8. [QxMD MEDLINE Link].
Cutts L, Bakshi A, Walsh M, Parslew R, Eustace K. Diagnosing Omenn syndrome. Pediatr Dermatol. 2021 Mar. 38 (2):541-543. [QxMD MEDLINE Link].
Marrella V, Maina V, Villa A. Omenn syndrome does not live by V(D)J recombination alone. Curr Opin Allergy Clin Immunol. 2011 Dec. 11(6):525-31. [QxMD MEDLINE Link].
Bai X, Liu J, Zhang Z, Liu C, Zhang Y, Tang W, et al. Clinical, immunologic, and genetic characteristics of RAG mutations in 15 Chinese patients with SCID and Omenn syndrome. Immunol Res. 2015 Oct 17. [QxMD MEDLINE Link].
Jaouad IC, Ouldim K, Ali Ou Alla S, Kriouile Y, Villa A, Sefiani A. Omenn syndrome with mutation in RAG1 gene. Indian J Pediatr. 2008 Sep. 75(9):944-6. [QxMD MEDLINE Link].
Villa A, Notarangelo LD, Roifman CM. Omenn syndrome: Inflammation in leaky severe combined immunodeficiency. J Allergy Clin Immunol. 2008 Dec. 122(6):1082-6. [QxMD MEDLINE Link].
Wong SY, Lu CP, Roth DB. A RAG1 mutation found in Omenn syndrome causes coding flank hypersensitivity: a novel mechanism for antigen receptor repertoire restriction. J Immunol. 2008 Sep 15. 181(6):4124-30. [QxMD MEDLINE Link].
Liao CY, Yu HW, Cheng CN, Chen JS, Lin CW, Chen PC, et al. A novel pathogenic mutation on Interleukin-7 receptor leading to severe combined immunodeficiency identified with newborn screening and whole exome sequencing. J Microbiol Immunol Infect. 2018 Mar 2. [QxMD MEDLINE Link].
Pannicke U, Hönig M, Schulze I, Rohr J, Heinz GA, Braun S, et al. The most frequent DCLRE1C (ARTEMIS) mutations are based on homologous recombination events. Hum Mutat. 2010 Feb. 31(2):197-207. [QxMD MEDLINE Link].
Mancebo E, Recio MJ, Martinez-Busto E, et al. Possible role of Artemis c.512C>G polymorphic variant in Omenn syndrome. DNA Repair (Amst). 2011 Jan 2. 10(1):3-4. [QxMD MEDLINE Link].
Rigoni R, Fontana E, Dobbs K, et al. Cutaneous barrier leakage and gut inflammation drive skin disease in Omenn syndrome. J Allergy Clin Immunol. 2020 Apr 18. [QxMD MEDLINE Link].
Marrella V, Poliani PL, Casati A, et al. A hypomorphic R229Q Rag2 mouse mutant recapitulates human Omenn syndrome. J Clin Invest. 2007 May. 117(5):1260-9. [QxMD MEDLINE Link].
Khiong K, Murakami M, Kitabayashi C, et al. Homeostatically proliferating CD4 T cells are involved in the pathogenesis of an Omenn syndrome murine model. J Clin Invest. 2007 May. 117(5):1270-81. [QxMD MEDLINE Link].
Henderson LA, Frugoni F, Hopkins G, Al-Herz W, Weinacht K, Comeau AM, et al. First reported case of Omenn syndrome in a patient with reticular dysgenesis. J Allergy Clin Immunol. 2013 Apr. 131(4):1227-30, 1230.e1-3. [QxMD MEDLINE Link].
Nanda A, Al-Herz W, Al-Sabah H, Al-Ajmi H. Noninfectious cutaneous granulomas in primary immunodeficiency disorders: report from a national registry. Am J Dermatopathol. 2014 Oct. 36(10):832-7. [QxMD MEDLINE Link].
Harp J, Coggshall K, Ruben BS, Ramírez-Valle F, He SY, Berger TG. Cutaneous granulomas in the setting of primary immunodeficiency: a report of four cases and review of the literature. Int J Dermatol. 2015 Jun. 54 (6):617-25. [QxMD MEDLINE Link].
Tagliaferri L, Kunz JB, Happich M, Esposito S, Bruckner T, Hübschmann D, et al. Newborn screening for severe combined immunodeficiency using a novel and simplified method to measure T-cell excision circles (TREC). Clin Immunol. 2017 Feb. 175:51-55. [QxMD MEDLINE Link].
Tallar M, Routes J. Omenn Syndrome Identified by Newborn Screening. Clin Perinatol. 2020 Mar. 47 (1):77-86. [QxMD MEDLINE Link].
Zafar R, Ver Heul A, Beigelman A, Bednarski JJ, Bayliss SJ, Dehner LP, et al. Omenn Syndrome Presenting with Striking Erythroderma and Extreme Lymphocytosis in a Newborn. Pediatr Dermatol. 2017 Jan. 34 (1):e37-e39. [QxMD MEDLINE Link].
Capo V, Castiello MC, Fontana E, Penna S, Bosticardo M, Draghici E, et al. Efficacy of lentivirus-mediated gene therapy in an Omenn syndrome recombination-activating gene 2 mouse model is not hindered by inflammation and immune dysregulation. J Allergy Clin Immunol. 2017 Dec 11. [QxMD MEDLINE Link].
Wat M, Olicker A, Meyerson H, Nedorost S, Paller AS, Cooper K. Topical Hypochlorite and Skin Acidification Improves Erythroderma of Omenn Syndrome. Pediatrics. 2018 Apr. 141 (Suppl 5):S408-S411. [QxMD MEDLINE Link].
Caglayan Sozmen S, Isik S, Arikan Ayyildiz Z, Yildiz K, Cakır Y, Ozer E, et al. Cyclosporin treatment improves skin findings in omenn syndrome. Pediatr Dermatol. 2015 Mar-Apr. 32 (2):e54-7. [QxMD MEDLINE Link].
Gozdzik J, Czogala W, Skoczen S, et al. Rapid full engraftment and successful immune reconstitution after allogeneic hematopoietic stem cell transplantation with reduced intensity conditioning in Omenn syndrome. Pediatr Transplant. 2008 Oct 25. [QxMD MEDLINE Link].
Schonberger S, Ott H, Gudowius S, et al. Saving the red baby: Successful allogeneic cord blood transplantation in Omenn syndrome. Clin Immunol. 2008 Dec 7. [QxMD MEDLINE Link].
Garcia-Lloret M, McGhee S, Chatila TA. Immunoglobulin replacement therapy in children. Immunol Allergy Clin North Am. 2008 Nov. 28(4):833-49. [QxMD MEDLINE Link]. [Full Text].
Siegel J. The product: All intravenous immunoglobulins are not equivalent. Pharmacotherapy. 2005 Nov. 25(11 Pt 2):78S-84S. [QxMD MEDLINE Link].
Shah S. Pharmacy considerations for the use of IGIV therapy. Am J Health Syst Pharm. 2005 Aug 15. 62(16 Suppl 3):S5-11. [QxMD MEDLINE Link].
Hooper JA. Intravenous immunoglobulins: evolution of commercial IVIG preparations. Immunol Allergy Clin North Am. 2008 Nov. 28(4):765-78, viii. [QxMD MEDLINE Link].
Pai SY, Logan BR, Griffith LM, Buckley RH, Parrott RE, Dvorak CC, et al. Transplantation outcomes for severe combined immunodeficiency, 2000-2009. N Engl J Med. 2014 Jul 31. 371(5):434-46. [QxMD MEDLINE Link]. [Full Text].
Grasso AG, Del Bufalo F, Boccieri E, Russo AF, Carta R, Algeri M, et al. Use of ruxolitinib to control graft-versus-host-like disease in Omenn syndrome and successfully bridging to HSCT. J Allergy Clin Immunol Pract. 2021 Feb 23. [QxMD MEDLINE Link].
Brown L, Xu-Bayford J, Allwood Z, et al. Neonatal diagnosis of severe combined immunodeficiency leads to significantly improved survival outcome: the case for newborn screening. Blood. 2011 Mar 17. 117(11):3243-6. [QxMD MEDLINE Link].
Van der Ploeg CPB, Blom M, Bredius RGM, van der Burg M, Schielen PCJI, Verkerk PH, et al. Cost-effectiveness of newborn screening for severe combined immunodeficiency. Eur J Pediatr. 2019 Feb 25. [QxMD MEDLINE Link].
Aleman K, Noordzij JG, de Groot R, et al. Reviewing Omenn syndrome. Eur J Pediatr. 2001 Dec. 160(12):718-25. [QxMD MEDLINE Link].
Brooks EG, Filipovich AH, Padgett JW, Mamlock R, Goldblum RM. T-cell receptor analysis in Omenn's syndrome: evidence for defects in gene rearrangement and assembly. Blood. 1999 Jan 1. 93(1):242-50. [QxMD MEDLINE Link].
Brugnoni D, Airo P, Facchetti F, et al. In vitro cell death of activated lymphocytes in Omenn's syndrome. Eur J Immunol. 1997 Nov. 27(11):2765-73. [QxMD MEDLINE Link].
Chan A, Scalchunes C, Boyle M, Puck JM. Early vs. delayed diagnosis of severe combined immunodeficiency: a family perspective survey. Clin Immunol. 2011 Jan. 138(1):3-8. [QxMD MEDLINE Link]. [Full Text].
Chilosi M, Facchetti F, Notarangelo LD, et al. CD30 cell expression and abnormal soluble CD30 serum accumulation in Omenn's syndrome: evidence for a T helper 2-mediated condition. Eur J Immunol. 1996 Feb. 26(2):329-34. [QxMD MEDLINE Link].
Lacy CF, Armstrong LL, Goldman MP, Lance LL (Editors). Drug Information Handbook 2008-2009. 16th edition. Cleveland, Ohio: Lexi-Comp, Inc; 2008.
Ege M, Ma Y, Manfras B, et al. Omenn syndrome due to ARTEMIS mutations. Blood. 2005 Jun 1. 105(11):4179-86. [QxMD MEDLINE Link]. [Full Text].
Gennery AR, Hodges E, Williams AP, et al. Omenn's syndrome occurring in patients without mutations in recombination activating genes. Clin Immunol. 2005 Sep. 116(3):246-56. [QxMD MEDLINE Link].
Giliani S, Bonfim C, de Saint Basile G, et al. Omenn syndrome in an infant with IL7RA gene mutation. J Pediatr. 2006 Feb. 148(2):272-4. [QxMD MEDLINE Link].
Gomez L, Le Deist F, Blanche S, et al. Treatment of Omenn syndrome by bone marrow transplantation. J Pediatr. 1995 Jul. 127(1):76-81. [QxMD MEDLINE Link].
Gruber TA, Shah AJ, Hernandez M, et al. Clinical and genetic heterogeneity in Omenn syndrome and severe combined immune deficiency. Pediatr Transplant. 2008 Sep 15. [QxMD MEDLINE Link].
Grunebaum E, Bates A, Roifman CM. Omenn syndrome is associated with mutations in DNA ligase IV. J Allergy Clin Immunol. 2008 Dec. 122(6):1219-20. [QxMD MEDLINE Link].
Mazzolari E, Moshous D, Forino C, et al. Hematopoietic stem cell transplantation in Omenn syndrome: a single-center experience. Bone Marrow Transplant. 2005 Jul. 36(2):107-14. [QxMD MEDLINE Link].
Omenn GS. Familial reticuloendotheliosis with eosinophilia. N Engl J Med. 1965 Aug 19. 273:427-32. [QxMD MEDLINE Link].
Rieux-Laucat F, Bahadoran P, Brousse N, et al. Highly restricted human T cell repertoire in peripheral blood and tissue-infiltrating lymphocytes in Omenn's syndrome. J Clin Invest. 1998 Jul 15. 102(2):312-21. [QxMD MEDLINE Link]. [Full Text].
Santagata S, Villa A, Sobacchi C, et al. The genetic and biochemical basis of Omenn syndrome. Immunol Rev. 2000 Dec. 178:64-74. [QxMD MEDLINE Link].
Schwartz SA. Intravenous immunoglobulin treatment of immunodeficiency disorders. Pediatr Clin North Am. 2000 Dec. 47(6):1355-69. [QxMD MEDLINE Link].
Signorini S, Imberti L, Pirovano S, et al. Intrathymic restriction and peripheral expansion of the T-cell repertoire in Omenn syndrome. Blood. 1999 Nov 15. 94(10):3468-78. [QxMD MEDLINE Link]. [Full Text].
Thampakkul S, Ballow M. Replacement intravenous immune serum globulin therapy in patients with antibody immune deficiency. Immunol Allergy Clin North Am. 2001. 21(1):165. [Full Text].
Tomizawa D, Aoki Y, Nagasawa M, et al. Novel adopted immunotherapy for mixed chimerism after unrelated cord blood transplantation in Omenn syndrome. Eur J Haematol. 2005 Nov. 75(5):441-4. [QxMD MEDLINE Link].
Villa A, Santagata S, Bozzi F, et al. Partial V(D)J recombination activity leads to Omenn syndrome. Cell. 1998 May 29. 93(5):885-96. [QxMD MEDLINE Link].
Sanghvi SY, Schwartz RA. Leiner's disease (erythroderma desquamativum): A review and approach to therapy. Dermatol Ther. 2021 Jan. 34 (1):e14510. [QxMD MEDLINE Link].

Media Gallery

A unique dermatitis characterizes Omenn syndrome. The dermatitis initially resembles eczema, but with a pachydermia, as observed here. The lesions progress to desquamation. Failure to thrive is evident. This infant weighed 6 pounds at age 6 months; his weight had not changed since birth.
Common viral infections are fatal in severe combined immunodeficiency (SCID). This female infant died before bone marrow stem cell engraftment could occur, when varicella became resistant to acyclovir. The nasal bridge reveals superinfection with Klebsiella pneumoniae. Lymphedema, a characteristic of Omenn syndrome, is also shown.

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Table. Immune Globulin, Intravenous^[28, 29, 27, 30]

Table. Immune Globulin, Intravenous ^{[28, 29, 27, 30]}

Brand(Manufacturer)	Manufacturing Process	pH	Additives (IVIG products containing sucrose are more often associated with renal dysfunction, acute renal failure, and osmotic nephrosis, particularly with preexisting risk factors [eg, history of renal insufficiency, diabetes mellitus, age >65 y, dehydration, sepsis, paraproteinemia, nephrotoxic drugs].)	Parenteral Form and Final Concentrations	IgA Content (mcg/mL)
Carimune NF (CSL Behring)	Kistler-Nitschmann fractionation; pH 4 incubation, nanofiltration	6.4-6.8	6% solution: 10% sucrose, < 20 mg NaCl/g protein	Lyophilized powder 3%, 6%, 9%, 12%	Trace
Flebogamma (Grifols USA)	Cohn-Oncley fractionation, PEG precipitation, ion-exchange chromatography, pasteurization	5.1-6	Sucrose free, contains 5% D-sorbitol	Liquid 5%	< 50
Gammagard Liquid 10% (Baxter Bioscience)	Cohn-Oncley cold ethanol fractionation, cation and anion exchange chromatography, solvent detergent treated, nanofiltration, low pH incubation	4.6-5.1	0.25M glycine	Ready-for-use Liquid 10%	37
Gamunex (Talecris Biotherapeutics)	Cohn-Oncley fractionation, caprylate-chromatography purification, cloth and depth filtration, low pH incubation	4-4.5	Contains no sugar, contains glycine	Liquid 10%	46
Gammaplex (Bio Products)	Solvent/detergent treatment targeted to enveloped viruses; virus filtration using Pall Ultipor to remove small viruses including nonenveloped viruses; low pH incubation	4.8-5.1	Contains sorbitol (40 mg/mL); do not administer if fructose intolerant	Ready-for-use solution 5%	< 10
Iveegam EN (Baxter Bioscience)	Cohn-Oncley fraction II/III; ultrafiltration; pasteurization	6.4-7.2	5% solution: 5% glucose, 0.3% NaCl	Lyophilized powder 5%	< 10
Polygam S/D Gammagard S/D (Baxter Bioscience for the American Red Cross)	Cohn-Oncley cold ethanol fractionation, followed by ultracentrafiltration and ion exchange chromatography; solvent detergent treated	6.4-7.2	5% solution: 0.3% albumin, 2.25% glycine, 2% glucose	Lyophilized powder 5%, 10%	< 1.6 (5% solution)
Octagam (Octapharma USA) 9/24/10: Withdrawn from market because of unexplained reports of thromboembolic events	Cohn-Oncley fraction II/III; ultrafiltration; low pH incubation; S/D treatment pasteurization	5.1-6	10% maltose	Liquid 5%	200
Panglobulin (Swiss Red Cross for the American Red Cross)	Kistler-Nitschmann fractionation; pH 4, trace pepsin, nanofiltration	6.6	Per gram of IgG: 1.67 g sucrose, < 20 mg NaCl	Lyophilized powder 3%, 6%, 9%, 12%	720
Privigen Liquid 10% (CSL Behring)	Cold ethanol fractionation, octanoic acid fractionation, and anion exchange chromatography; pH 4 incubation and depth filtration	4.6-5	L-proline (approximately 250 mmol/L) as stabilizer; trace sodium; does not contain carbohydrate stabilizers (eg, sucrose, maltose)	Ready-for use liquid 10%	< 25

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Author

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Professor of Pediatrics, Professor of Medicine, Rutgers New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, New York Academy of Medicine, Royal College of Physicians of Edinburgh, Sigma Xi, The Scientific Research Honor Society

Disclosure: Nothing to disclose.

Coauthor(s)

Robert Y Lin, MD Professor, Department of Medicine, New York Medical College; Chief, Allergy and Immunology, and Director of Utilization Review, Department Medicine, New York Downtown Hospital

Robert Y Lin, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, New York Allergy & Asthma Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

David J Valacer, MD, MS Chief Medical Officer, Regor Therapeutics Group

David J Valacer, MD, MS is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association for the Advancement of Science, American College of Allergy, Asthma and Immunology, American Thoracic Society, Asthma and Allergy Foundation of America, New York Academy of Sciences, New York Allergy & Asthma Society

Disclosure: Nothing to disclose.

Chief Editor

Harumi Jyonouchi, MD Faculty, Division of Allergy/Immunology and Infectious Diseases, Department of Pediatrics, Saint Peter's University Hospital

Harumi Jyonouchi, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association of Immunologists, American Medical Association, Clinical Immunology Society, New York Academy of Sciences, Society for Experimental Biology and Medicine, Society for Pediatric Research, Society for Mucosal Immunology

Disclosure: Nothing to disclose.

Additional Contributors

Terry W Chin, MD, PhD Associate Clinical Professor, Department of Pediatrics, University of California, Irvine, School of Medicine; Associate Director, Cystic Fibrosis Center, Attending Staff Physician, Department of Pediatric Pulmonology, Allergy, and Immunology, Memorial Miller Children's Hospital

Terry W Chin, MD, PhD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Association of Immunologists, American College of Allergy, Asthma and Immunology, American College of Chest Physicians, American Federation for Clinical Research, American Thoracic Society, California Society of Allergy, Asthma and Immunology, California Thoracic Society, Clinical Immunology Society, Los Angeles Pediatric Society, Western Society for Pediatric Research

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author Ann O'Neill Shigeoka, MD to the development and writing of this article.

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