Omenn Syndrome Workup

Updated: Mar 01, 2017
  • Author: Robert A Schwartz, MD, MPH; Chief Editor: Harumi Jyonouchi, MD  more...
  • Print
Workup

Laboratory Studies

Since the prognosis depends on a presymptomatic diagnosis and early treatment before complications occur, a simplified, practical and economic newborn screening method would be highly desirable and has been suggested. [16]

 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 Medscape Reference article Pediatric 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.

Next:

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.

Previous
Next:

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.

Previous
Next:

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.

Previous
Next:

Histologic Findings

Skin biopsy findings reveal psoriasiform hyperplasia of the epidermis with parakeratosis, cellular dyskeratosis, and necrosis. The skin may show an infiltration of CD4+ (helper) T cells typically, but has been described with CD8+ (cytotoxic) T cells instead. [17]

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.

Previous