Omenn Syndrome Treatment & Management

  • Author: Robert A Schwartz, MD, MPH; Chief Editor: Harumi Jyonouchi, MD   more...
 
Updated: May 9, 2011
 

Medical Care

Conventional care for any patient with severe combined immunodeficiency (SCID) includes isolation to prevent infection and also meticulous skin and mucosal hygienic care while the patient is awaiting stem cell reconstitution. Signs of sepsis and pulmonary infections may be subtle; thus, fever alone requires a detailed search for infectious agents. Empirical broad-spectrum antibiotics are administered parenterally while cultures and body fluid analyses are in progress. Consider prophylactic treatment with nystatin to prevent mucocutaneous candidiasis. In individual cases, prophylaxis with antiviral agents (eg, acyclovir) or antibiotics may be appropriate. Parenteral nutrition is customarily provided as therapy for diarrhea and failure to thrive.

Bone marrow or other stem cell reconstitution is first-line conventional therapy for most forms of SCID, including Omenn syndrome, although the mortality rate is higher when compared to other types of SCID. Workup includes major histocompatibility complex (MHC) typing to identify a fully matched sibling, or, in the case of consanguinity, possibly a parent. Reconstitution by using a matched unrelated donor or haploidentical parent has also been successful, although more complications and higher mortality have been reported. Preparatory immunosuppression of malfunctioning activated T cells has decreased the incidence of graft failure in Omenn syndrome. Nutritional support and T-cell suppression prior to BMT may reduce the risk of complications. Pretransplantional evaluation routinely includes testing of the recipient and the donor for infectious agents, such as cytomegalovirus (CMV), HIV, and hepatitis viruses.

Specific therapy for dermatitis and eosinophilia in Omenn syndrome is immunosuppression with cyclosporine. Interferon gamma has been administered in an attempt to down-regulate interleukin 4 (IL-4) and interleukin 5 (IL-5) production by the oligoclonal Th2 cells. Interferon gamma may independently modulate the inflammatory reaction by enhancing phagocytic functions.

Ancillary therapy includes intravenous immunoglobulin (IVIG) replacement. Live viral vaccines should not be administered.

In the future, the identification of the recombinase mutations as the cause of Omenn syndrome should enable gene transfer therapy. At this time, successful gene therapy is available only for the X-linked T-B+ form of SCID, in which mutations in the common γ chain are necessary for function of the cell surface receptors of interleukin 2 (IL-2), IL-4, interleukin 7 (IL-7), interleukin 9 (IL-9), and interleukin 15 (IL-15).

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Surgical Care

Surgical intervention is not routinely considered.

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Consultations

Promptly initiate workup for stem cell reconstitution with the bone marrow transplant (BMT) team. In the meantime, consult a gastroenterologist and a nutritionist for important support.

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Diet

A patient with chronic diarrhea and a failure to thrive requires consultation with a gastroenterologist and nutritionist to adequately provide calories, nutrients, and vitamins. Parenteral or enteral nutrition supplementation is usually necessary.

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Activity

Infants with any form of SCID should be isolated to decrease the risk of common viral and bacterial infections. Patients should avoid crowds in locations such as stores, doctors' offices, and hospitals, and they and their caregivers should engage in customary hygiene practices such as strict hand washing.

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Contributor Information and Disclosures
Author

Robert A Schwartz, MD, MPH  Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, University of Medicine and Dentistry of New Jersey-New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi

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 and American Federation for Medical Research

Disclosure: Nothing to disclose.

Specialty Editor Board

Terry W Chin, MD, PhD  Associate Director, Pediatric Allergy/Immunology/Pulmonology, Miller Children's Hospital, Long Beach Memorial Medical Center; Associate Professor, Department of Pediatrics, University of California, Irvine, School of Medicine

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 Thoracic Society, California Thoracic Society, Clinical Immunology Society, and Western Society for Pediatric Research

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Pharmacy Editor, eMedicine

Disclosure: Nothing to disclose.

David J Valacer, MD  Consulting Staff, Hoffman La Roche Pharmaceuticals

David J Valacer, MD 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 Thoracic Society, and New York Academy of Sciences

Disclosure: Nothing to disclose.

David Pallares, MD  Clinical Assistant Professor, Department of Pediatrics, Division of Allergy and Immunology, University of Louisville

David Pallares, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology

Disclosure: Nothing to disclose.

Chief Editor

Harumi Jyonouchi, MD  Associate Professor, Division of Pulmonary Allergy/Immunology and Infectious Diseases, Department of Pediatrics, UMDNJ-New Jersey Medical School

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 Mucosal Immunology, and Society for Pediatric Research

Disclosure: Nothing to disclose.

References

  1. 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. Apr 2010;120(4):1337-44. [Medline]. [Full Text].

  2. Jaouad IC, Ouldim K, Ali Ou Alla S, Kriouile Y, Villa A, Sefiani A. Omenn syndrome with mutation in RAG1 gene. Indian J Pediatr. Sep 2008;75(9):944-6. [Medline].

  3. Villa A, Notarangelo LD, Roifman CM. Omenn syndrome: Inflammation in leaky severe combined immunodeficiency. J Allergy Clin Immunol. Dec 2008;122(6):1082-6. [Medline].

  4. 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. Sep 15 2008;181(6):4124-30. [Medline].

  5. 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. Feb 2010;31(2):197-207. [Medline].

  6. Mancebo E, Recio MJ, Martinez-Busto E, et al. Possible role of Artemis c.512C>G polymorphic variant in Omenn syndrome. DNA Repair (Amst). Jan 2 2011;10(1):3-4. [Medline].

  7. Marrella V, Poliani PL, Casati A, et al. A hypomorphic R229Q Rag2 mouse mutant recapitulates human Omenn syndrome. J Clin Invest. May 2007;117(5):1260-9. [Medline].

  8. 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. May 2007;117(5):1270-81. [Medline].

  9. 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. Oct 25 2008;[Medline].

  10. Schonberger S, Ott H, Gudowius S, et al. Saving the red baby: Successful allogeneic cord blood transplantation in Omenn syndrome. Clin Immunol. Dec 7 2008;[Medline].

  11. Garcia-Lloret M, McGhee S, Chatila TA. Immunoglobulin replacement therapy in children. Immunol Allergy Clin North Am. Nov 2008;28(4):833-49. [Medline].

  12. Siegel J. The product: All intravenous immunoglobulins are not equivalent. Pharmacotherapy. Nov 2005;25(11 Pt 2):78S-84S. [Medline].

  13. Shah S. Pharmacy considerations for the use of IGIV therapy. Am J Health Syst Pharm. Aug 15 2005;62(16 Suppl 3):S5-11. [Medline].

  14. Hooper JA. Intravenous immunoglobulins: evolution of commercial IVIG preparations. Immunol Allergy Clin North Am. Nov 2008;28(4):765-78, viii. [Medline].

  15. 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. Mar 17 2011;117(11):3243-6. [Medline].

  16. Aleman K, Noordzij JG, de Groot R, et al. Reviewing Omenn syndrome. Eur J Pediatr. Dec 2001;160(12):718-25. [Medline].

  17. 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. Jan 1 1999;93(1):242-50. [Medline].

  18. Brugnoni D, Airo P, Facchetti F, et al. In vitro cell death of activated lymphocytes in Omenn's syndrome. Eur J Immunol. Nov 1997;27(11):2765-73. [Medline].

  19. Chan A, Scalchunes C, Boyle M, Puck JM. Early vs. delayed diagnosis of severe combined immunodeficiency: a family perspective survey. Clin Immunol. Jan 2011;138(1):3-8. [Medline]. [Full Text].

  20. 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. Feb 1996;26(2):329-34. [Medline].

  21. Lacy CF, Armstrong LL, Goldman MP, Lance LL (Editors). Drug Information Handbook 2008-2009. 16th edition. Cleveland, Ohio: Lexi-Comp, Inc; 2008.

  22. Ege M, Ma Y, Manfras B, et al. Omenn syndrome due to ARTEMIS mutations. Blood. Jun 1 2005;105(11):4179-86. [Medline]. [Full Text].

  23. Gennery AR, Hodges E, Williams AP, et al. Omenn's syndrome occurring in patients without mutations in recombination activating genes. Clin Immunol. Sep 2005;116(3):246-56. [Medline].

  24. Giliani S, Bonfim C, de Saint Basile G, et al. Omenn syndrome in an infant with IL7RA gene mutation. J Pediatr. Feb 2006;148(2):272-4. [Medline].

  25. Gomez L, Le Deist F, Blanche S, et al. Treatment of Omenn syndrome by bone marrow transplantation. J Pediatr. Jul 1995;127(1):76-81. [Medline].

  26. Gruber TA, Shah AJ, Hernandez M, et al. Clinical and genetic heterogeneity in Omenn syndrome and severe combined immune deficiency. Pediatr Transplant. Sep 15 2008;[Medline].

  27. Grunebaum E, Bates A, Roifman CM. Omenn syndrome is associated with mutations in DNA ligase IV. J Allergy Clin Immunol. Dec 2008;122(6):1219-20. [Medline].

  28. Mazzolari E, Moshous D, Forino C, et al. Hematopoietic stem cell transplantation in Omenn syndrome: a single-center experience. Bone Marrow Transplant. Jul 2005;36(2):107-14. [Medline].

  29. Omenn GS. Familial reticuloendotheliosis with eosinophilia. N Engl J Med. Aug 19 1965;273:427-32. [Medline].

  30. 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. Jul 15 1998;102(2):312-21. [Medline]. [Full Text].

  31. Santagata S, Villa A, Sobacchi C, et al. The genetic and biochemical basis of Omenn syndrome. Immunol Rev. Dec 2000;178:64-74. [Medline].

  32. Schwartz SA. Intravenous immunoglobulin treatment of immunodeficiency disorders. Pediatr Clin North Am. Dec 2000;47(6):1355-69. [Medline].

  33. Signorini S, Imberti L, Pirovano S, et al. Intrathymic restriction and peripheral expansion of the T-cell repertoire in Omenn syndrome. Blood. Nov 15 1999;94(10):3468-78. [Medline]. [Full Text].

  34. 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].

  35. 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. Nov 2005;75(5):441-4. [Medline].

  36. Villa A, Santagata S, Bozzi F, et al. Partial V(D)J recombination activity leads to Omenn syndrome. Cell. May 29 1998;93(5):885-96. [Medline].

 
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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.
Table. Immune Globulin, Intravenous[12, 13, 11, 14]
Brand(Manufacturer)Manufacturing ProcesspHAdditives (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 ConcentrationsIgA Content (mcg/mL)
Carimune NF



(CSL Behring)



Kistler-Nitschmann fractionation; pH 4 incubation, nanofiltration6.4-6.86% solution: 10% sucrose, < 20 mg NaCl/g proteinLyophilized powder 3%, 6%, 9%, 12%Trace
Flebogamma



(Grifols USA)



Cohn-Oncley fractionation, PEG precipitation, ion-exchange chromatography, pasteurization5.1-6Sucrose free, contains 5% D-sorbitolLiquid 5%< 50
Gammagard Liquid 10%



(Baxter Bioscience)



Cohn-Oncley cold ethanol fractionation, cation and anion exchange chromatography, solvent detergent treated, nanofiltration, low pH incubation 4.6-5.10.25M glycineReady-for-use Liquid 10%37
Gamunex



(Talecris Biotherapeutics)



Cohn-Oncley fractionation, caprylate-chromatography purification, cloth and depth filtration, low pH incubation4-4.5Contains no sugar, contains glycineLiquid 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 4.8-5.1Contains sorbitol (40 mg/mL); do not administer if fructose intolerantReady-for-use solution 5%< 10
Iveegam EN



(Baxter Bioscience)



Cohn-Oncley fraction II/III; ultrafiltration; pasteurization6.4-7.25% solution: 5% glucose, 0.3% NaClLyophilized 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 6.4-7.25% solution: 0.3% albumin, 2.25% glycine, 2% glucoseLyophilized 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 pasteurization5.1-610% maltoseLiquid 5%200
Panglobulin



(Swiss Red Cross for the American Red Cross)



Kistler-Nitschmann fractionation; pH 4, trace pepsin, nanofiltration6.6Per gram of IgG: 1.67 g sucrose, < 20 mg NaClLyophilized 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 filtration4.6-5L-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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