Omenn Syndrome Workup

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

Laboratory Studies

In patients with Omenn syndrome, the peripheral WBC count may be normal or elevated with a predominance of lymphocytes. Eosinophilia is invariably present.

Flow cytometry should include the customary T, B, and natural killer cell (NKC) markers with additional T-cell markers including CD25, CD30, human leukocyte antigen (HLA)–DR, CD95, and CD69. CD25 is expressed in Treg cells as well as in the effector T cells while CD30 is expressed in activated T and B cells. CD45RO and CD45RA are used to identify cells responding to antigen stimulation and naïve T cells.

See the Differential Diagnosis section of the eMedicine article Severe Combined Immunodeficiency for a table of the lymphocyte profiles characteristic for various T-cell disorders.

The results show the presence of an oligoclonal set of activated antigen-stimulated Th2 cells.

B cells are absent, and NKC are present. T cells may have normal distribution of CD4 and CD8 or a predominance of CD8.

Immunoglobulin levels show absent immunoglobulin A (IgA) and immunoglobulin M (IgM), elevated IgE levels, and immunoglobulin G (IgG) that is maternal in origin. IgG antibodies against T-dependent antigens, such as tetanus, are nonprotective. Specific IgM antibodies, such as isohemagglutinins, are absent.

Lymphocyte mitogen responses to phytohemagglutinin (PHA), concanavalin A (conA), and pokeweed mitogen (PWM) are absent or profoundly decreased. In contrast, response to anti-CD3, superantigens, and phorbol myristate acetate (PMA)/ionomycin may be detectable. Addition of interleukin 2 (IL-2) can enhance the latter responses.

Cultures and the histologic examination of tissues and body fluids for infectious agents are mandatory for appropriate management of the infections.

When a T-cell disorder is suspected, the Immune Deficiency Foundation has a consultative service for physicians. Laboratories in New York City and at the University of Washington in Seattle and at the Children's Hospital in Boston are funded by the Jeffrey Modell Foundation. They provide molecular analysis or assistance in contacting other research facilities.

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Imaging Studies

The thymus is absent on chest radiographs of most forms of severe combined immunodeficiency (SCID), including Omenn syndrome.

In the initial workup or if fever develops, look for pulmonary infiltrates due to viral infections and interstitial pneumonitis caused by P carinii.

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Other Tests

Perform mutational analysis for RAG-1 and RAG-2 to permit genetic counseling and prenatal diagnosis in subsequent pregnancies. Other mutation analysis may be indicated depending on clinical features.

Serum interleukin 4 (IL-4) and interleukin 5 (IL-5) levels are typically increased. In vitro cells produce decreased levels of IL-2 and interferon-gamma (IFN-γ) compared with the elevated IL-4 and IL-5 production by Th2 cells. These findings are consistent with decreased T helper 1 (Th1) cell activity.

Molecular analysis of HLA alleles by means of the polymerase chain reaction (PCR) or restriction fragment length polymorphism (RFLP) may be needed to detect engraftment of maternal T cells or graft versus host disease (GVHD) from transfusion-associated cells.

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Procedures

Skin biopsy may be considered, although an experienced immunologist may be able to make the diagnosis without this data in the appropriate clinical setting. The presence of maternally engrafted cells is more sensitively assessed with DNA techniques and peripheral blood lymphocytes, as indicated above.

Lymph node biopsy is unlikely to contribute additional information; fluorocytometric analysis of peripheral blood lymphocytes and lymphocyte mitogen assays provide more detailed diagnostic data.

Bronchoscopy is frequently necessary to identify P carinii, viral, and fungal etiologies of pulmonary infection.

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Histologic Findings

Skin biopsy findings reveal psoriasiform hyperplasia of the epidermis with parakeratosis, cellular dyskeratosis, and necrosis.

The partial T-cell defects result in infiltration of the skin, with activated autoreactive T cells expressing CD30 and CD45RO. Eosinophils and histiocytes also populate the skin.

Reactive lymph nodes show infiltrating eosinophils and histiocytic cells but lack germinal centers and cortical T lymphocytes.

The gut lacks lymphocytes in Peyer patches and in the lamina propria.

Rudimentary thymic tissue shows poorly formed and decreased Hassall corpuscles with few lymphocytes.

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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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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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