Omenn Syndrome Follow-up

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

Further Inpatient Care

Coordinating medical management of Omenn syndrome between immunologists, infectious disease specialists, pulmonologists, and gastroenterologists can be challenging. Bone marrow transplantation (BMT) is best coordinated between the immunologist and the BMT team.

The necessity for excellent laboratory and radiology support mandates hospitalization of the patient in a tertiary children's medical facility.

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Further Outpatient Care

As noted above, patient isolation to prevent the transmission of infection is compulsory.

Usually, contacts are restricted to immediate family members and friends whose risks for infection can be monitored.

Carefully orchestrate visits to doctors' offices and hospitals to prevent exposing the patient to infectious agents.

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Inpatient & Outpatient Medications

See Medication.

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Transfer

The great complexity of medical problems for any primary immunodeficiency disease requires that an immunologist treat the patient.

The subtle signs of infection, the need to offer stem cell transplantation, and the early deaths in Omenn syndrome indicate that frequent monitoring by a clinical immunologist is essential.

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Deterrence/Prevention

In families in whom the exact mutations have been established, prenatal diagnosis is possible by means of chorionic villus sampling or amniocentesis with DNA methods.

Fetal blood sampling for fluorocytometric testing and mitogen response assessments can aid in the diagnosis when DNA analysis is not available.

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Complications

Graft failure with BMT and posttransplantational graft versus host disease (GVHD) are well recognized, although the incidences of both have decreased because of improved BMT preparatory regimens and techniques.

Donor lymphocyte infusion with donor cord blood–derived activated CD4+ T cells has been reported to be an effective method to overcome the risk of graft rejection in stem cell transplant with residual cell-mediated immunity without compounding GVHD.

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Prognosis

Patients with Omenn syndrome have fully recovered after BMT, with or without pretransplantation immunosuppression. As with any BMT procedure, a risk of GVHD is recognized, even with a fully major histocompatibility complex (MHC)-matched donor.

Patients who do not receive BMT have not survived with the supportive management involving prophylactic antibiotics and parenteral nutrition alone. Interferon gamma has been administered in an effort to down-regulate interleukin 4 (IL-4) and interleukin 5 (IL-5) production. Cyclosporine therapy does improve the dermatitis and diarrhea while the workup for BMT is in progress.

A review of 68 patients with Omenn syndrome treated between 1965-1999 found the mortality rate of 28 patients who received BMT to be 47%. The main cause of death was respiratory failure and sepsis. More recently, an 18.2% mortality rate was reported in a series of hematopoietic stem cell transplantations (HSCT) in 11 patients with Omenn syndrome.

Diagnosis at birth may protect from infection and improve transplantation outcome. Neonatal screening for this disorder is desirable.[15]

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Patient Education

Inform families about the risks of infection so that appropriate steps to avoid exposure to infection can be instituted. They should be aware that live viral vaccines are contraindicated.

In obtaining adequate informed consent for stem cell reconstitution, the physician must review the high rate of GVHD, the risk of the failure to engraft, and the high risk for life-threatening infection during the preparative immunosuppressive regimen. Although successful complete immune reconstitution with BMT is reported with the use of fully matched related and unrelated donors or haploidentical parents, a failure to engraft may occur in patients with Omenn syndrome, or they may have posttransplantational GVHD.

The Immune Deficiency Foundation is an important resource for the education and support of patients and families with any primary immunodeficiency disease. Its current address is 25 W Chesapeake Ave, Suite 206, Towson, MD 21204; some states have local chapters. The Jeffrey Modell Foundation at 43 W 47th St, New York, NY 10036 also provides support and patient education.

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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

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

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  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].

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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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