Orbital Abscess in an Infant With STAT3 Hyper-IgE Syndrome.

NOVEL HETEROZYGOUS SINGLE NUCLEOTIDE POLYMORPHISM IN STAT-3 GENE IN PATIENT WITH SUSPECTED HYPER IGE SYNDROME

A CASE OF AUTOSOMAL-DOMINANT HYPER-IGE SYNDROME MASQUERADING AS CYSTIC FIBROSIS

NK Cell Deficiency in Job's Syndrome Patients

Rationale:Hyper-IgE syndrome (HIES) is a rare primary immunodeficiency presenting as two forms including autosomal dominant HIES (AD-HIES) and autosomal recessive HIES (AR-HIES), which are mainly caused by mutations in STAT3 and DOCK8, respectively. To date, only about 500 cases have been reported worldwide including 37 cases in China. The spectrum and prevalence of mutations and molecular pathogenesis in HIES remain poorly understood.Patient concerns:Here we reported two Chinese children presenting clinical manifestations of HIES.Diagnosis:Based on medical history, clinical manifestations, and laboratory findings, a diagnosis of HIES was made for both children. Targeted next-generation sequencing (NGS) identified a novel heterozygous deletion of 15 bp (c.1960_1974del, p.G654_D658del or alternatively c.1966_1980del, and p.G656_D660del), and a recurrent missense mutation (c.1144C>T, p.R382W) in STAT3 in the two patients, respectively.Interventions:The two patients have been given the successful treatment of skin infections with cefaclor.Outcomes:Both patients have been under follow-up for more than 6 months, with no signs of recurrent infections.Lessons:Our results extend the spectrum of STAT3 mutations associated with ADHIES and highlight the value of targeted NGS in confirming diagnosis of genetic disorders.

Genetic Linkage of Hyper-IgE Syndrome to Chromosome 4

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.

OC1 Clinical and molecular features of twenty children with hyper-IgE syndrome caused by stat3 gene mutation in mainland china

Infantile Orbital Cellulitis

1. Samantha Meaney, MD* 2. Ana Swafford, MD† 3. Jacob J. Rosenberg, MD†‡ 1. *American University of the Caribbean, Cupecoy, St. Maarten. 2. †Nassau University Medical Center, East Meadow, NY. 3. ‡SUNY at Stony Brook, West Hempstead, NY. An 18-year-old woman presents to the emergency department with 2 days of right eye swelling. The patient was in her usual state of good health until 2 days ago, when she noted swelling around her right eye. She presents to the emergency department today because the swelling has increased during the past 24 hours and she now has eye pain. There is no history of fever, trauma, recent bug bites, allergic rhinitis, or recent upper respiratory tract infection symptoms. In the emergency department the patient is afebrile, yet her right eyelids are swollen and mildly erythematous. She has pain with upward and lateral gaze and some mild limitation of superior and lateral right eye movement. There is no nasal congestion; the rest of her physical examination findings are normal. Several laboratory examinations are performed. A complete blood cell count reveals the following: hemoglobin, 14.7 g/dL (147 g/L); hematocrit, 42.9% (0.43); leukocytes, 4,400/μL (4.4 × 109/L) (35% neutrophils, 44% lymphocytes, 13% monocytes, and 8% eosinophils); and platelets, 238 ×103/μL (238 × 109/L). Serum electrolytes, glucose, blood urea nitrogen, creatinine, and liver enzyme levels are normal. The C-reactive protein level is 3.0 mg/L (28.6 nmol/L), and the erythrocyte sedimentation rate is 1 mm/h. Computed tomography (CT) of her orbits and sinuses is performed ( Figure 1 ). Figure 1. Sinus computed tomogram showing a right-sided septal mass that extends into the inferior rectus muscle and is suggestive of an abscess. There is no evidence of sinus disease. The patient is admitted to the pediatric department and administered intravenous ceftriaxone and vancomycin for presumed right orbital abscess with …

To report the occurrence of recurrent multiple giant chalazia in the hyperimmunoglobulin E syndrome (hyper-IgE syndrome or Job syndrome). Two patients with hyperimmunoglobulinemia E (>500 IU/ml) had ophthalmologic examination and surgical treatment for chalazia of the eyelids. The hyper-IgE syndrome is a rare immunodeficiency and multisystem disorder characterized by recurrent skin and pulmonary abscesses, connective tissue abnormalities, and elevated levels of serum IgE. In two patients with the hyper-IgE syndrome, multiple giant chalazia were seen in upper and lower eyelids. Despite surgical incision new giant chalazia arose. Recurrent multiple giant chalazia may occur as an ophthalmic feature of the hyper-IgE syndrome. (Eur J Ophthalmol 2004; 14: 258-60).

Life-threatening cervicofacial infection in a child with hyperimmunoglobulin-E syndrome

The hyper-immunoglobulin E syndrome (HIES) is a primary immunodeficiency disease originally described as Job syndrome. The fundamental causative variant of the HIES is an autosomal dominant mutation in the signal transducer and activator of transcription 3 (STAT3) gene. It is characterized by recurrent staphylococcal cold skin abscess, sinopulmonary infection, eczema, head and face anomalies, frequent bone fractures, eosinophilia and extremely high serum IgE levels (IgE ≥ 2000 IU/mL). However, multiple other genetic defects are also known as HIES-like disorders. Apart from infectious manifestations, STAT3, DOCK8 and TYK2 gene mutations are associated with various malignancies. The most common malignancies reported in these patients are lymphomas, including Hodgkin's and non-Hodgkin's lymphomas (NHL) of B and T cells. This systematic review aimed to investigate the prevalence of malignancies in HIES and the factors associated with malignancy in these patients. In this survey, all articles published until April 1st, 2023, in Scopus, PubMed and Web of Science databases based on three groups of keywords related to HIES syndrome and malignancy were reviewed by three different researchers. Finally, 26 articles were evaluated from which 24 papers were meta-analyzed. In the current study, the demographic information of 1133 patients with HIES, which was mentioned in 24 articles enrolled in the project, was collected, and the information related to patients who had malignancy was analyzed and meta-analyzed. A total of 96 patients out of 1133 studied patients had at least one type of malignancy, the overall prevalence of malignancies reported in the articles was 6.5% (95% confidence interval 4.1-9%), and the total prevalence of malignancy in patients with NHL type and patients with squamous cell carcinoma (SCC) was 2.9% (95% confidence interval 1.7-4.4%) and 2.2% (95% confidence interval 0.3-4.1%), respectively. The results of this study indicated that in 6.5% of cases, HIES was complicated with malignancy, and considering the higher rate of these malignancies in women as well as in DOCK8 mutation sufferers, it is necessary for physicians to be aware of this association and includes malignancy screening in follow-up and periodic examinations of these patients. Indeed, more studies in this field will help to clarify the precise figures and predisposing factors of the relationship between HIES and malignancy.

Hyperimmunoglobulin E Syndrome (HIES) Treated with Thalidomide Plus Dexamethasone with Encouraging Results

Defects along the T H17 differentiation pathway underlie genetically distinct forms of the hyper IgE syndrome

Abstract&#x0D; Introduction : Hyperimmunoglobulinemia E syndrome (HIES) is a rare primary immunodeficiency disorder that manifests as elevated level of serum immunoglobulin E (IgE) higher than 1.000 IU/mL and multisystem disorder characterized by recurrent skin and pulmonary abscesses caused by autosomal dominant or recessive disorder with gene mutation. We present a case of multiple giant chalazion ina patient with HIES.&#x0D; Case Illustration : A 15-year-old boy was referred to Ophthalmology Department with multiple giant lumps on the left eyelid for the last 2 weeks. He had a history of recurrent multiple lumps on the left lower eyelid in the last 1 year. He was diagnosed with HIES since 8 years ago. He had normal visual acuity of both eyes. Multiple giant chalazion were observed on the left upper and lower eyelid. The patient also presented with scalp and neck infection. Laboratory studies showed elevated total serum IgE level of 53,032 IU/mL and eosinophilia.&#x0D; Discussion : Ocular manifestations in HIES patients are not common. Some cases reported chalazia, keratoconus, and blepharitis. Surgical incision drainage was performed in our patient. Medications and surgical intervention had produced only transient improvement. The patient was treated conservatively. Riskof chalazia recurrence remains unknown as reported cases presented with diverse clinical presentation and follow-up serum IgE evaluation is not routinely performed.&#x0D; Conclusion : Recurrent multiple giant chalazia may occur as an ophthalmic feature of HIES. HIES should be considered and investigated in patients presenting with recurrent giant chalazia.