AUTHOR AND EDITOR INFORMATION

Section 1 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

INTRODUCTION

Section 2 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Background

Omenn syndrome (MIM 603554) is an autosomal recessive form of severe combined immunodeficiency (SCID) characterized by erythroderma, desquamation, alopecia, chronic diarrhea, failure to thrive, lymphadenopathy, and hepatosplenomegaly. Patients develop fungal, bacterial, and viral infections typical of SCID. Lymphocytosis results from the expansion of an oligoclonal population of activated and antigen-stimulated T helper 2 (T_H2) cells that produce elevated levels of interleukin 4 (IL-4) and interleukin 5 (IL-5). The latter cytokines mediate eosinophilia and elevated immunoglobulin E (IgE) levels.

Pathophysiology

Hypomorphic mutations in recombinase genes RAG-1 and RAG-2 cause Omenn syndrome. RAG-1 and RAG-2 mutations impair, but do not eliminate, variable diversity joining (VDJ) recombination, which is required for the development of mature T cells and B cells.

The inability to productively rearrange VDJ regions in T-cell and B-cell receptors leads to abnormal T-cells and absent B-cells. The mutations in RAG-1 and RAG-2 in Omenn syndrome differ from those in SCID that is T cell negative (T^-), B cell negative (B^-), and natural killer cell positive (NKC⁺) SCID. In these conditions, the mutations affect the active core of the recombinase genes and typically negate the production of the recombinase protein.

In Omenn syndrome, the mutated RAG-1 and RAG-2 proteins remain normally distributed in the nucleus of cells. An oligoclonal T_H2 population is expanded, possibly as a result of increased exposure to inadequately cleared antigens. These autoreactive T cells have a highly restricted receptor repertoire, as well as increased apoptosis due to overexpression of CD95 and underexpression of antiapoptotic factors, such as bcl-2.

The predominance of few T-cell receptor clonotypes detectable in the thymus and the differing distribution of clonotypes found in different tissues suggests that the oligoclonality of the T-cell repertoire is due to both intrathymic restriction as well as peripheral expansion. The autoimmune manifestations of the disease may be related to decreased thymic expression of tissue-specific antigens.

Germinal centers are absent in the lymph nodes, which is consistent with the inability to produce functional antibodies. Hassall corpuscles are poorly formed, and lymphocytes are deficient in the thymus. Paracortical lymphocytes are absent in the spleen.

RAG-deficient mice have been developed. Their defects are restricted to the T^-B^- immunologic abnormalities observed in humans. Other murine models with defective VDJ recombination have growth retardation in addition to immune deficiency.

Frequency

United States

The frequency of Omenn syndrome is difficult to ascertain. The prevalence of all forms of SCID is estimated to be 1 case per 50,000 population.

International

Omenn syndrome has been reported in patients from throughout the world, mainly North America and Europe.

Mortality/Morbidity

Omenn syndrome is fatal if untreated.

• Patients have life-threatening viral, bacterial, fungal, and Pneumocystis carinii infections that are observed in other types of SCID. Patients commonly have Staphylococcus aureus sepsis, which is related to the generalized dermatitis. Live viral infections, including those due to attenuated oral poliovirus, may cause death. In addition, chronic diarrhea and resulting inanition may be responsible for death.
• Bone marrow transplantation (BMT) is usually successful, but life-threatening acute or chronic graft-versus-host disease (GVHD) may be a complication. This can occur in any stem cell reconstitution procedure.

Race

Patients have been identified in the United States, Canada, Europe, and India.

Sex

The incidences are equal among male and female infants; this observation is consistent with the autosomal recessive etiology of Omenn syndrome.

Age

Infants present within weeks of birth and usually by age 3 months, as do those with other types of SCID. The characteristic dermatitis, chronic diarrhea, and failure to thrive often precede the onset of infections. Published reports of patients describe presentation by the time the patient is aged 6 months.

CLINICAL

Section 3 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

History

• In the first weeks after birth, infants present with erythrodermia and diarrhea. The severity of the dermatitis is associated with episodes of S aureus sepsis; diarrhea predisposes patients to gram-negative enteric bacterial sepsis.
• As in other forms of SCID, life-threatening infections with common viral, bacterial, and fungal pathogens occur next.
• Chronic diarrhea and infection lead to failure to thrive, which is also characteristic of any other type of SCID.
• Lymphadenopathy and hepatosplenomegaly soon develop; however, these are unusual in other types of SCID unless maternal engraftment or transfusion-associated GVHD occurs.
• P carinii pneumonia and poliomyelitis due to the attenuated oral poliovirus are classic infections in Omenn syndrome and in other types of SCID.

Physical

• Patients present in the first weeks of life with a unique generalized dermatitis that may be mistaken for eczema. However, the dermatitis has a pachydermatis appearance that progresses to desquamation. Protein loss via the skin and gut may result in generalized edema.
• Lymphadenopathy distinguishes Omenn syndrome from most other SCID variants.
• Hepatosplenomegaly is also usually present.
• Failure to thrive associated with chronic diarrhea and dermatitis should always raise the suspicion of SCID.
• Alopecia is another frequent finding.

Causes

• When mutations in the recombinase genes RAG-1 and RAG-2 have been sought, homozygous and heterozygous mutations have been found. In contrast to T^-B^-NKC⁺ SCID in which RAG-1 and RAG-2 mutations affect the active core of the gene, homozygous mutations affecting the active core have not been observed in Omenn syndrome. Approximately half of the mutations are missense mutations, and the remainder are nonsense, deletional, frameshift, duplication, and splice mutations. RAG-1 and RAG-2 genes have been mapped to chromosome band 11p13.
• Although most cases of Omenn syndrome are due to mutations in the RAG genes, recent reports describe Omenn syndrome in the absence of RAG mutations. Mutations in ARTEMIS and ILRA7 have been described, thus defining Omenn syndrome as a genetically heterogeneous condition in which patients with similar phenotypes may have unidentified genetic defects.

DIFFERENTIALS

Section 4 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Other Problems to be Considered

The major reason for a missed or delayed diagnosis of Omenn syndrome is the eczematoid appearance of the dermatitis when the infections have not yet appeared. The eczema associated with diarrhea raises the possibility of a food allergy. Nevertheless, Omenn syndrome is usually accompanied by a failure to thrive not expected with common atopic dermatitis and by hypereosinophilia. Furthermore, the dermatitis has the unique appearance of pachydermia, which progresses to desquamation.

The clinical presentation also may suggest the possibility of other forms of SCID complicated by maternal T-cell engraftment or transfusion-related GVHD. Patients with these conditions are typically more lymphopenic than those with other diseases.

Hyperimmunoglobulin E (HIE) syndrome in infants may need to be considered because these infants have eczema and infections with Candida species and S aureus. However, patients with Omenn syndrome are likely to have invasive infections, such as staphylococcal sepsis, whereas patients with HIE syndrome have infections limited to the lung, skin, and mucosal surfaces.

WORKUP

Section 5 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Lab Studies

• The peripheral WBC 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-activation markers of CD25, human leukocyte antigen (HLA)–DR, CD95, and CD69. CD30 is used to identify T_H2 cells, and CD45RO and CD45RA are used to identify cells responding to antigen stimulation and naïve 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 T_H2 cells.
  • B cells are absent, and NKC are present. T cells may show 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 (www.primaryimmune.org) 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 (www.jmfworld.com). They provide molecular analysis or assistance in contacting other research facilities.

Imaging Studies

• The thymus is absent on chest radiographs of most forms of 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.

Other Tests

• Perform mutational analysis for RAG-1 and RAG-2 to permit genetic counseling and prenatal diagnosis in subsequent pregnancies.
• Serum IL-4 and IL-5 levels are typically increased. In vitro cells produce decreased levels of IL-2 and interferon-gamma (IFN-g) compared with the elevated IL-4 and IL-5 production by T_H2 cells. These findings are consistent with decreased T helper 1 (T_H1) 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 GVHD from transfusion-associated cells.

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.

Histologic Findings

Skin biopsy will show psoriasiform hyperplasia of the epidermis with parakeratosis, cellular dyskeratosis, and necrosis. The T-cell defects result in infiltration of the skin, with activated T cells expressing the T_H2 marker CD30. CD45RO represents antigen-stimulated T cells. Eosinophils and histiocytes also populate the skin. Reactive lymph nodes show infiltrating eosinophils and histiocytic cells, but they 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.

TREATMENT

Section 6 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Medical Care

Conventional care for any patient with SCID includes his or her 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 supression 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 IL-4 and IL-5 production by the oligoclonal T_H2 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 g chain are necessary for function of the cell surface receptors of IL-2, IL-4, interleukin 7 (IL-7), interleukin 9 (IL-9), and interleukin 15 (IL-15).

Surgical Care

Surgical intervention is not routinely considered.

Consultations

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

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.

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.

MEDICATION

Section 7 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Overview

Specific therapy for dermatitis and lymphadenitis involves immunosuppression with cyclosporine and the down-regulation of IL-4 and IL-5 with interferon gamma. Broad-spectrum antibiotics are needed to treat invasive infections, especially those due to the common S aureus and gram-negative enteric bacteria. Prophylactic antibiotics and antifungal agents are often appropriate. Ancillary treatment with IVIG replacement further decreases the risk of infection. Nutritional supplementation is mandatory to decrease the risk of infection and increase the likelihood of successful stem cell reconstitution.

Replacement therapy with IVIG in patients with primary immune deficiencies

The overall consensus among clinical immunologists is that an IVIG dose of 400-600 mg/kg/mo or a dose that maintains trough serum IgG levels greater than 500 mg/dL is desirable. Patients with meningoencephalitis (X-linked agammaglobulinemia) require higher doses (1 g/kg) and perhaps intrathecal therapy. The measurement of preinfusion, ie, trough serum IgG levels every 3 months until a steady state is achieved and then every 6 months if the patient is stable may be helpful in adjusting the dose of IVIG to achieve adequate serum levels. For persons in whom the catabolism of infused IgG is high, more frequent (eg, q2-3wk) infusions of smaller doses may maintain the serum level in the reference range. The rate of elimination of IgG may be higher during a period of active infection; measuring serum IgG levels and adjusting to higher doses or shorter intervals may be required.

For replacement therapy for patients with primary immune deficiency, all brands of IVIG are probably equivalent, although differences in viral inactivation processes (eg, solvent detergent versus pasteurization and liquid versus lyophilized) do exist. The choice of brands may depend on the hospital or home care formulary and on local availability and cost. The dose, manufacturer, and lot number should be recorded for each infusion to review for adverse events or other consequences. Recording of all adverse effects that occur during the infusion is crucial.

Periodic liver and renal function testing, approximately 3-4 times yearly, is also recommended. The FDA advises that, in patients at risk for renal failure, the recommended doses should not be exceeded and that infusion rates and concentrations should be the practical minimum levels. Examples of patients at risk for renal failure include those older than 65 years; those who use nephrotoxic drugs; and those with preexisting renal insufficiency, diabetes mellitus, volume depletion, sepsis, or paraproteinemia.

The initial treatment should be administered under the close supervision of experienced personnel. The risk of adverse reactions in the initial treatments is high, especially in patients with infections and in those in whom immune complexes form. In patients with active infection, infusion rates may need to be slower, and the dose halved (ie, 200-300 mg/kg). The remaining half should be given the next day to achieve a full dose. Treatment should not be discontinued. After normal serum IgG levels are achieved, adverse reactions are uncommon unless patients have active infections.

With the new generation of IVIG products, adverse effects are reduced. Adverse effects include tachycardia, chest tightness, back pain, arthralgia, myalgia, hypertension or hypotension, headache, pruritus, rash, and low-grade fever. More serious reactions are dyspnea, nausea, vomiting, circulatory collapse, and loss of consciousness. Patients with more profound immunodeficiency and patients with active infections have more severe reactions.

The anticomplementary activity of IgG aggregates in the IVIG and the formation of immune complexes are thought to be related to the adverse reactions. The formation of oligomeric or polymeric IgG complexes that interact with fragment crystallizable (Fc) receptors and that trigger the release of inflammatory mediators is another cause. Most adverse reactions are rate related. Slowing the infusion rate or discontinuing therapy until symptoms subside may diminish the reaction. Pretreatment with ibuprofen (5-10 mg/kg q6-8h), acetaminophen (15 mg/kg/dose), diphenhydramine (1 mg/kg/dose), and/or hydrocortisone (6 mg/kg/dose; maximum, 100 mg) 1 hour before the infusion may prevent adverse reactions. In some patients with a history of severe adverse effects, therapy with analgesics and antihistamines may be repeated.

Acute renal failure is a rare but significant complication of IVIG treatment. Reports suggest that IVIG products with sucrose as a stabilizer may be associated with a greater risk for this renal complication. Acute tubular necrosis, vacuolar degeneration, and osmotic nephrosis are suggestive of osmotic injury to the proximal renal tubules. The infusion rate for sucrose-containing IVIG should not exceed 3 mg/kg/min based on the amount of sucrose. Risk factors for this adverse reaction include preexisting renal insufficiency, diabetes mellitus, dehydration, age older than 65 years, sepsis, paraproteinemia, and concomitant use of nephrotoxic agents. For patients at increased risk, monitoring the blood urea nitrogen and creatinine levels before starting the treatment and prior to each infusion is necessary. If the patient's renal function deteriorates, the treatment should be discontinued.

IgE antibodies to IgA have been reported to cause severe transfusion reactions in patients with IgA deficiency. A few cases of true anaphylaxis have been reported in patients with selective IgA deficiency and common variable immunodeficiency who developed IgE antibodies to IgA after treatment with immunoglobulin. However, in actual experience this is rare. In addition, this is not a problem in patients with X-linked agammaglobulinemia (Bruton disease) or in those with SCID. Caution should be exercised in patients with IgA deficiency ( <7 mg/dL) who need IVIG because of IgG-subclass deficiencies. IVIG preparations with low concentrations of contaminating IgA are advised (see the Table below).

Immune Globulin, Intravenous

*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).

Contents of table are adapted from the following sources:

1. Manufacturers' literature.
2. Siegel J. The Product: All intravenous immunoglobulins are not equivalent. Pharmacotherapy. 2005; 25(11 Pt 2):78S-84S.
3. Shah S. Pharmacy consideration for the use of IGIV therapy. Am J Health-Syst Pharm. 2005; 62(Suppl 3):S5-11.

Drug Category: Immunosuppressive agents

Specific therapy for dermatitis and lymphadenitis involves immunosuppression with cyclosporine and the down-regulation of IL-4 and IL-5 with INF-g.

Drug Category: Interferons

These agents are naturally occurring cytokines that possess a variety of biologic functions, including immunosuppressive action. They are produced by cells in response to viruses, double-stranded ribonucleic acid (RNA), antigens, or mitogens, and they are classified in relation to biochemical properties and the cell of origin. These agents are commercially produced by means of recombinant DNA technology. Interferon gamma has been administered subcutaneously on a daily basis to interrupt processes mediated by IL-4 and IL-5 and to enhance a functional inflammatory response to infection.

FOLLOW-UP

Section 8 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Further Inpatient Care

• Coordinating medical management between immunologists, infectious disease specialists, pulmonologists, and gastroenterologists can be challenging. 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.

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.

In/Out Patient Meds

• See Medication

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.

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.

Complications

• Graft failure with BMT and posttransplantional 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 recently 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 graft versus host disease.

Prognosis

• Patients with Omenn syndrome have fully recovered after BMT, with or without pretransplantation immunosuppression. As with any BMT procedure, a risk of GVHD exists, even with a fully 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 IL-4 and 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 and 1999 found the mortality rate of 28 patients who received BMT to be 47%. The cause of death was frequently respiratory failure and sepsis. More recently, an 18.2% mortality rate in a series of hematopoietic stem cell transplantations in 11 patients with Omenn syndrome was reported.

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, and some states have local chapters. The Jeffrey Modell Foundation at 43 W 47th St, New York, NY 10036 also provides support and patient education.

MISCELLANEOUS

Section 9 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Medical/Legal Pitfalls

• Any autosomal recessive mutation causing SCID places siblings of the patient at a 1:4 risk of SCID. Offer mutational analysis and discuss the possibility of prenatal diagnosis with the family.
• Misdiagnosing atopic dermatitis and food allergy in infants with Omenn syndrome is a risk.
• Do not give live vaccines nor nonirradiated blood products to patients with SCID or who are suspected of a SCID, until the diagnosis has been definitely ruled out.

Special Concerns

• Isolation procedures at home and in the hospital are essential to decrease exposure to common infectious agents.

ACKNOWLEDGMENTS

Section 10 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

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

MULTIMEDIA

Section 11 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

Media file 1:  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.
	View Full Size Image
Media type:  Photo

Media file 2:  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.
	View Full Size Image
Media type:  Photo

REFERENCES

Section 12 of 12

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• Multimedia
• References

• Aleman K, Noordzij JG, de Groot R, et al. Reviewing Omenn syndrome. Eur J Pediatr. Dec 2001;160(12):718-25. [Medline].
• Brooks EG, Filipovich AH, Padgett JW, et al. 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].
• 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].
• 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].
• 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].
• 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].
• 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].
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• Lacy CF, Armstrong LL, Goldman MP, Lance LL, eds. Drug Information Handbook. Cleveland, Ohio: Lexi-Comp, Inc; 2000-2001..
• 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].
• Omenn GS. Familial reticuloendotheliosis with eosinophilia. N Engl J Med. 1965;273:427-432.
• 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].
• Santagata S, Villa A, Sobacchi C, et al. The genetic and biochemical basis of Omenn syndrome. Immunol Rev. Dec 2000;178:64-74. [Medline].
• Schwartz SA. Intravenous immunoglobulin treatment of immunodeficiency disorders. Pediatr Clin North Am. Dec 2000;47(6):1355-69. [Medline].
• 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].
• 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.
• 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].
• 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].

Article Last Updated: Aug 10, 2006