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Hematology & immune disorders

Primary immunodeficiency disorders

Omenn syndrome

Author: Shamayel Mohammed, M.D.

Last author update: 1 December 2015

Last staff update: 14 June 2022

Copyright: 2003-2024, PathologyOutlines.com, Inc.

PubMed Search: Omenn syndrome [title] lymph nodes

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Table of Contents

Cite this page: Mohammed, S. Omenn syndrome . PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/lymphnodesomennssyndrome.html. Accessed December 2nd, 2024.

Definition / general

Rare, autosomal recessive form of severe combined immunodeficiency (SCID) of infancy
Recurrent infections, early diffuse erythrodermia, failure to thrive, protracted diarrhea, hepatosplenomegaly, elevated serum IgE and eosinophilia, lymphadenopathy, oligoclonal T cell expansions
Often recombinase activating gene mutations (Clin Immunol 2005;116:246)

Pathophysiology

Most common genetic alteration is the partial loss of function for recombinase activating genes RAG (RAG1 and RAG2)
The RAG genes are essential for gene recombination in the T cell receptor and B cell receptor
This mutation leads to the Inability to productively rearrange VDJ regions in T cell and B cell receptors, which leads to abnormal T cell proliferation and absent B cells
As a result, the immune system has difficulty recognizing specific pathogens
An impaired V(D)J recombination process leads to the generation of a few T cells expanding in the periphery, infiltrating target organs such as skin and gut, resulting in the erythroderma and colitis typical of this syndrome
The disease is characteristically associated with an oligoclonal expansion of Th2 population

Clinical features

Recurrent infections
Early diffuse erythrodermia, failure to thrive, protracted diarrhea, hepatosplenomegaly
Elevated serum IgE and eosinophilia, lymphadenopathy, oligoclonal T cell expansions
Suppurative lymphadenitis and disseminated sometimes fatal tuberculosis as a reaction to the immunization for Bacille Calmette-Guerin (BCG)
Lymphoproliferative disorders associated with Primary Immune Disorders (PID) such as SCID

Diagnosis

WBC count may be normal or elevated with a predominance of lymphocytes
Eosinophilia is invariably present
Molecular studies show presence of an oligoclonal set of activated antigen stimulated Th2 cells
B cells are absent, and NK cells are present
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

Case reports

Infant with Omenn syndrome and reticular dysgenesis (J Allergy Clin Immunol 2013;131:1227)

Treatment

Isolation to prevent infection
Prophylactic treatment with nystatin, antiviral agents (e.g. acyclovir) or antibiotics may be considered
Immunosuppression with cyclosporine (Arch Dis Child 2002;87:231)
Bone marrow or other stem cell reconstitution is first line conventional therapy
Diagnosis at birth may lead to protection from infection and improve transplantation outcome (Blood 2011;117:3243)

Clinical images

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Pre- and post-treatment

Alopecia and erythroderma

Microscopic (histologic) description

Total effacement of nodal architecture with no distinct cortex and no follicles
Also B cell depletion and accumulation of interdigitating reticulum cells (Am J Surg Pathol 1995;19:1082)
Hassall corpuscles are poorly formed, and lymphocytes are deficient in the thymus
Paracortical lymphocytes are absent in the spleen
The spleen, skin and mucosa associated lymphoid tissues contain only a few scattered CD3+ T lymphocytes, and B cells are totally absent (Blood 1999;94:3468)
Non caseating granulomatous inflammation with BCG / Bacille Calmette-Guerin lymphadenitis (Am J Clin Pathol 2000;113:703)
Lymphoproliferative disease associated with primary immune disorders:
- EBV is involved in most cases
- Morphology includes reactive lymphoid hyperplasia, polymorphous infiltrate with immunoblast proliferation and overt lymphoma
  - Diffuse Large B-cell Lymphoma (DLBCL) is the most common type of lymphoma
  - May present as Fatal Infectious Mononucleosis (FIM)