Immunoglobulin E Syndrome Research Articles

Obstructive uropathy in STAT 3 hyper immunoglobulin E syndrome: A 5year old Middle Eastern boy.

Autosomal dominant hyper immunoglobulin E (IgE) syndrome is a rare inborn error of immunity that affects approximately one in a million individuals worldwide. It presents with various symptoms owing to multisystem involvement (immunological and non-immunological). Recurrent infections (mainly in the skin and lungs) are common presentations. A 5-year-old Middle Eastern boy presented with symptoms suggestive of obstructive uropathy secondary to multiple large pelviabdominal abscesses and acute kidney injury with hyperkalemia that necessitated admission to the intensive care unit. Upon further investigation, the patient's genetic test (whole exome sequencing) demonstrated a heterozygous missense variant in the STAT3 gene. The patient completely recovered and did not require further admission after initiating prophylactic antibiotics. Although deep-seated infections are uncommon in STAT3 hyper IgE syndrome, skin and lung infections are most commonly observed. Multiple deep collections can occur and require prompt intervention and aggressive treatment.

Viral infections and inborn errors of immunity.

The purpose of this focused review is to discuss unusual presentations of viral infections in the context of specific inborn errors of immunity. We will discuss hyper immunoglobulin E (IgE) syndromes, epidermodysplasia verruciformis, and X-linked agammaglobulinemia as examples of inborn errors of immunity associated with specific presentations of viral infection and disease. Advances in both genetic and viral diagnostics have broadened our understanding of viral pathogenesis in the setting of immune dysfunction and the variable phenotype of inborn errors of immunity. Dedicator of cytokinesis 8 (DOCK8) deficiency is now recognized as an inborn error of immunity within the hyper IgE syndrome phenotype and is associated with unusually aggressive cutaneous disease caused by herpes simplex and other viruses. Studies of patients with epidermodysplasia verruciformis have proven that rarely detected human papillomavirus subtypes may cause malignancy in the absence of adequate host defenses. Finally, patients with X-linked agammaglobulinemia may remain at risk for severe and chronic viral infections, even as immune globulin supplementation reduces the risk of bacterial infection. Susceptibility to viral infections in patients with inborn errors of immunity is conferred by specific, molecular defects. Recurrent, severe, or otherwise unusual presentations of viral disease should prompt investigation for an underlying genetic defect.

Very high immunoglobulin E levels in children: when from pediatrician to immunologist?

Total serum immunoglobulin E (IgE) is increased in many situations such as allergic diseases, primary immunodeficiencies (PID), parasitosis, infections and malignancies. When IgE levels are >1000 kU/L PIDs are suspected by pediatricians. We tried to define some clinical and laboratory parameters to distinguish PID from the others. We evaluated 158 children between 1.7-17 years (mean: 6.6±3.4) for allergic diseases, PID, parasitosis and others. Total IgE, specific IgE, immunoglobulin levels and skin prick tests were performed to all patients. Parasite investigations, viral serological tests and detailed immunologic tests were analyzed in only patients who had suspected complaints. Hyper IgE syndrome (HIES) scoring sheet was filled out for all patients. Among all patients, 114 were diagnosed as bronchial asthma, allergic rhino-conjunctivitis or atopic dermatitis. PID diagnosis was established in totally 32 patients. Immunological evaluations were normal in 126 patients. Eleven patients were accepted as parasitosis. Median HIES score was 18 (5-44 points). Pediatricians may use HIES scoring sheet when they suspect a patient with PID. If the patient has very low points, they may follow the patient. If there are about 18-20 points, they should get an opinion from an immunologist for detailed immunologic tests.

Hyper IgE syndrome with autoimmune hemolytic anemia in Saudi Arabia

Background: Hyper IgE syndrome (HIES) is a rare primary immunodeficiency disorder characterized by elevated serum immunoglobulin E (IgE) levels. Autosomal dominant and autosomal recessive forms of HIES have been reported. Autosomal recessive HIES typically includes a history of asthma, atopic dermatitis, food allergy, and recurrent viral infection. HIES diagnosis requires genetic study, which is time-consuming and not always feasible. Case Presentation: We report the case of an 8-year-old female. The patient recently presented to our emergency department with pallor and syncope. Upon examination, the hemoglobin level was 4.9 g/dl. Direct antiglobulin test showed a positive result. The patient had an admitting diagnosis of autoimmune hemolytic anemia, a rare complication of autosomal recessive HIES. The patient is a known case of asthma, herpetiformis dermatitis, nut allergy, and allergic rhinitis. HIES was the first possible diagnosis, which was further confirmed by clinical presentation and a high serum IgE count. The patient was referred to a tertiary care center for genetic counseling and further follow-up. Conclusion: HIES is a rare immune deficiency disorder that can be inherited in either an autosomal dominant or recessive pattern. Although these two types show similar clinical presentations, certain features remain distinct, providing a valuable insight into the final diagnosis even without the gene study results. To the best of our knowledge, no study has evaluated HIES in general, and no case report has evaluated autosomal recessive HIES in Saudi Arabia. This case study will guide the medical community in the early-stage diagnosis and management of HIES.

Very high IgE levels in children: when from pediatrician to immunologist?

Total serum immunoglobulin E (IgE) is increased in many situations such as allergic diseases, primary immunodeficiencies (PID), parasitosis, infections and malignancies. When IgE levels >1000 kU/L are suspected PID by pediatricians. We tried to define some clinical and laboratory parameters to distinguish PID from the others. We evaluated 158 children between 1.7 - 17 years (Mean: 6.6 ±3.4) for allergic diseases, PID, parasitosis and others. Total IgE, specific IgE, immunoglobulin levels and skin prick tests were performed to all patients. Parasite investigations, viral serological tests and detailed immunologic tests were analyzed in only patients who had suspected complaints. Hyper IgE syndrome (HIES) scoring sheet was filled out for all patients. Among all patients, 114 were diagnosed as bronchial asthma, allergic rhino-conjunctivitis or atopic dermatitis. PID diagnosis was established in totally 32 patients. Immunological evaluations were normal in 126 patients. Eleven patients were accepted as parasitosis. Median HIES score was 18 (5-44 points). Pediatricians may use HIES scoring sheet when they suspect a patient with PID. If the patient has very low points, they may follow the patient. If there are about 18-20 points, they should get an opinion from an immunologist for detailed immunologic tests.

Pediatric anaphylaxis and hyper IgE syndrome.

Patients with autosomal-dominant (AD) hyper immunoglobulin E (IgE) syndrome (HIES) or Job syndrome develop frequent dermatologic and pulmonary infections. As patients have an extreme elevation of IgE levels, this database analysis study sought to study the association between AD HIES, Job syndrome, and anaphylaxis. HIES is a heterogeneous group of immune disorders characterized by extremely elevated levels of serum IgE. Although the molecular defects and clinical phenotypes found in association with Job syndrome are well characterized, the association with severe allergic reactions and anaphylaxis is a subject of ongoing investigation.

Liver abscess in a boy with hyper IgE syndrome

Hyper immunoglobulin-E syndrome is a rare primary immunodeficiency disease, characterized by the classical triad of recurrent staphylococcal skin abscesses, pneumonia with pneumatocele formation, and elevated levels of serum IgE, usually over 2000 IU/mL. Chronic granulomatous disease, hyper IgE, and complement deficiencies are immunopathologies known to be associated with liver abscesses. We present a 2 ½-year-old boy with liver abscess and associated hyper IgE.

Hyper IgE syndrome (hies; job syndrome): A case report

AbstractThe hyper-immunoglobulin E syndrome (HIES) is a rare primary immunodeficiency disorder characterized by high serum levels of immunoglobulin E (IgE), recurrent cutaneous and pulmonary infections, chronic dermatitis and a variety of connective tissue and skeletal abnormalities. These patients share characteristic facial appearance and many oral manifestations. We report a case of hyper IgE syndrome (HIES) also known as “Job syndrome“.

Novel DOCK8 Mutation

Background: Hyper IgE syndrome (HIES) is a primary immunodeficiency with sporadic, autosomal dominant (STAT3 mutation) and autosomal recessive (DOCK8 and TYK2 mutations) inheritance patterns. HIES secondary to DOCK8 mutation is characterized by extensive cutaneous viral and staphylococcal infections, recurrent sinopulmonary infections, severe allergic diseases, increased susceptibility to malignancy with lymphopenia, eosinophilia, and elevated immunoglobulin E (IgE). Methods: This case report highlights the clinical presentation and immune investigations of a male patient with a novel DOCK8 mutation. Results: Our patient presented with cutaneous viral infections including severe molluscum contagiosum and herpes simplex virus plus skin abscesses and acute otitis media. In addition to infections, he developed intermittent diarrhea, eczematous lesions, abnormal fingernails, oral ulcers, and Bell's palsy. Immune evaluation revealed lymphopenia, in particular low CD8 cells, low mitogen stimulation response, and poor specific antibody production requiring immunoglobulin replacement. Genetic sequencing confirmed a novel mutation in DOCK8. Conclusion: Patients with significant cutaneous viral and bacterial infections, recurrent sinopulmonary infections, severe allergic diseases, and lymphopenia with associated elevated IgE should be investigated for DOCK8 mutation. This case report highlights a novel mutation in the DOCK8 exon 45 aa1970, c.5908 G>C change alanine to proline homozygous change A1970 to P1970 Statement of novelty: This case reports on a novel mutation in DOCK8

Brain Abscess and Keratoacanthoma Suggestive of Hyper IgE Syndrome.

Hyper immunoglobulin-E (IgE) syndrome is an autosomal immune deficiency disease. It is characterized by an increase in IgE and eosinophil count with both T-cell and B-cell malfunction. Here, we report an 8-year-old boy whose disease started with an unusual skin manifestation. When 6 months old he developed generalized red, nontender nodules and pathologic report of the skin lesion was unremarkable (inflammatory). Then he developed a painless, cold abscess. At the age of 4 years, he developed a seronegative polyarticular arthritis. Another skin biopsy was taken which was in favor of Keratoacanthoma. Laboratory workup for immune deficiency showed high eosinophil count and high level of immunoglobulin-E, due to some diagnostic criteria (NIH sores: 41 in 9-year-olds), he was suggestive of hyper IgE syndrome. At the age of 8, the patient developed an abscess in the left inguinal region. While in hospital, the patient developed generalized tonic colonic convulsion and fever. Brain computed tomography scan revealed an abscess in the right frontal lobe. Subsequently magnetic resonance imaging (MRI) of the brain indicated expansion of the existing abscess to contralateral frontal lobe (left side). After evacuating the abscesses and administrating intravenous antibiotic, the patient's condition improved dramatically and fever stopped.

A Case of Hyper Immunoglobulin-E Syndrome Associated with Scrotal Tongue and Intraoral Hyperpigmentation.

A Case of Hyper Immunoglobulin-E Syndrome Associated with Scrotal Tongue and Intraoral Hyperpigmentation.

Elevated serum immunoglobulin E (IgE): When to suspect hyper-IgE syndrome—A 10-year pediatric tertiary care center experience

Elevated serum immunoglobulin E(IgE) can be caused by allergies, infections and immune conditions including hyper IgE syndrome (HIES). HIES is a rare primary immunodeficiency disease most commonly characterized by a triad of findings, including increased serum IgE levels, recurrent skin abscesses, and pneumonias leading to pneumatocele formation. The objective of this study was to characterize the clinical profile of patients presenting with increased IgE levels (>or=2000 IU/mL) focusing specifically on HIES. A database search identified 70 patients in the pediatric age range (<or=18 yrs.) between January 1997 and December 2006 who had an IgE level of >or=2000 IU/mL. Charts were abstracted for clinical diagnosis, comorbidities, and laboratory parameters. Data were analyzed using the students t-test, Wilcoxon signed rank test, and univariate/multivariate regression models. Clinical diagnosis in 70 patients with elevated IgE levels were: atopic diseases (n = 54; 77%), parasitic diseases (n = 1; 1.5%), malignancy (n = 2; 3%), and HIES (n = 6; 8%), among other causes. There was a statistically significant association between IgE levels and the severity of eczema (p = 0.009). Ninety percent of the subjects with IgE level >or=2000 IU/mL did not have HIES. There was no correlation between IgE levels and the diagnosis of HIES (p = 0.5). A variety of clinical situations result in an elevated IgE level, with atopy being the most common cause. In the absence of typical clinical features, elevated serum IgE levels are not predictive of HIES.