hyper ige syndrome

Hyper-immunoglobulin E syndrome (HIES),also known asJob's syndrome, is a rare primary immunodeficiency disorder characterized by a classic triad: elevated immunoglobulin E (IgE) levels, recurrent pneumonia with pneumatocele formation, and recurrent cold skin abscesses.

Case:

A 5-year-old girl was referred to the pediatric dentistrydepartment for tooth decay and multiple dental abscesses. Her medical history revealed elevated serum IgE levels, and she was receiving treatment with warfarin due to a history of jugular vein thrombosis. Clinical examination showed numerous skin abscesses alongside multiple eczemas.Angular cheilitis, de-papillation of the tongue, deep furrows on the tongue, numerous intraoral ulcerated lesions, poor oral hygiene, and gingivitis were seen in the intraoral examination.Due to the systemic conditions and thechild's non-cooperation, treatment under general anesthesia was planned.

Dentists play an essential role in the early diagnosis of HIES and in monitoring their oral health conditions. Timely extraction of over-retained primary teeth can reduce the necessity for complex treatments, thereby facilitating the management of patients with Job's syndrome.

The prevalence of primary immunodeficiency (PID) is rather high in Iran compared to the world average, mainly due to the high rate of consanguineous marriage. Despite that, little genetic information is available about primary immunodeficiencies in Iran. Autosomal recessive hyper IgE syndrome (AR-HIES) is a severe type of immunodeficiency, mainly caused by mutations in the dedicator of cytokinesis 8 (DOCK8). Rapid and precise diagnoses of patients suffering from AR-HIES can help to manage the patients and reach properly the treatment decision. However, in regions with low financial resources and limited expertise, deep phenotyping is uncommon. Therefore, an exome-first approach is helpful to make a genetic-based diagnosis. In the present study, whole-exome sequencing (WES) was applied to detect causative mutations in three unrelated primary immunodeficient patients with poor clinical information. One of the cases was a deceased patient with suspected hyper IgE syndrome (HIES) whose parents were subjected to WES. As a result, three novel pathogenic variants were detected in the DOCK8 gene, including two splicing sites (c.4241+1G>T and c.4886+1G>T) and one-stop-gain (c.4201G>T, p.Glu1401Ter) variants. Sanger sequencing confirmed the mutations’ segregation in corresponding families. Further immunological investigations confirmed that HIES in the studied probands. The presence of frontal bossing and broad nose in one of the studied cases, in addition to the typical clinical presentation of DOCK8-AR-HIES, is notable. This work suggests that an exome-first approach can be a valuable alternative strategy for precise diagnosis of primary immunodeficiency patients.

Patients with Hyper-IgE syndrome suffer from fungal and bacterial infections, especially Candida albicans and Staphylococcus aureus. Due to the important role of T helper17 (Th17) lymphocytes in defense against fungal infections, the percentage of Th17 lymphocytes was studied in the patients with autosomal recessive hyper-IgE syndrome (AR-HIES).
In this case-control study, six patients with AR-HIES (with DOCK-8 mutation) and seven healthy age and sex-matched controls were included. Peripheral blood mononuclear cells were isolated from their venous blood and the percentage of Th17 lymphocytes were determined by flow cytometry.
There was no statistical difference between the percentage of Th17 lymphocytes (p=0.15) in the case and control groups. Also in comparison to the control subjects, the numbers of eosinophils were dramatically increased (p=0.000). Also, there was a significant negative correlation between serum IgE levels and Th17 lymphocytes’ percentage (r=-0.927, p=0.006) and a significant positive correlation between eosinophils number and Th17 lymphocytes’ percentage (r=0.557, p=0.01). Serum IgE levels showed a significant positive correlation with the numbers of eosinophils in the patients’ peripheral blood with AR-HIES (r=0.961, p=0.003).
The numbers of Th17 in the patients with AR-HIES may not show statistical differences between the cases and controls. The numbers of eosinophils significantly increased in the patients AR-HIES compare to the controls.

Hyper IgE Syndrome (HIES) is a rare primary immunodeficiency disease. Most of HIES cases are sporadic. HIES type AD is caused by mutation in signal transducer and activator of transcription-3 (STAT-3). A number of mosaicism HIES has been reported that is associated with intermediate phenotype. Autosomal recessive HIES (AR-HIES) is due to mutation in Dock-8 or cytokine sis 8 and TYK2 or tyrosine kinase 2. The common manifestations are atopic eczema, staphylococcal dermatitis, cellulitis and folliculitis (cold dermal abscesses that are not warm, painful and without redness), recurrent pneumonia and pulmonary abscesses, osteopenia and recurrent bone fracture. The diagnosis of standard HIES is based on clinical suspicion. There is no specific treatment for HIES. The treatment should be based on the prevention of developing infections. Prophylactic antibiotics such as cotrimoxazole and IVIG are administered. Hematopoietic stem cell transplantation was done for all types of HIES, but there is a little information and experience about the long term results of this therapy.

Hyper IgE syndrome (HIES) is a rare primary immune deficiency, described as Job`s syndrome characterized by increased serum levels of IgE, eczema, recurrent cutaneous and pulmonary infections. In this paper, we presented a case of Hyper IgE syndrome. A 16-year-old Iranian boy presented with a one year history of skin lesions in knees and elbows was diagnosed of psoriasis disease. He had a history of recurrent infections including otitis media, pneumonia, diarrea and skin infection. Laboratory results showed increased level of total IgE and normal in other immunoglobulin. Histologic finding showed hyperkeratosis, parakeratosis of acanthotic epidermis with regular elongation of rete ridges diagnose psoriasis disorder. In conclusion, this is the first case of hyper IgE patient with psoriasis disorder. We addressed the important laboratory findings and actual theories explaining possible association between hyper IgE immunoglobulinemia and psoriasis disorder.