br Hyperimmunoglobulin E syndrome HIES Job s Syndrome is a

Hyperimmunoglobulin E syndrome (HIES, Job\'s Syndrome) is a rare primary immunodeficiency disease characterized by a clinical triad of recurrent staphylococcal abscesses, pneumonia, and pneumatoceles, with a tendency for recurrent pyogenic infections and elevation of serum immunoglobulin E (IgE) levels. A 12-year-old girl presented with flexural eczema and intense pruritus. The symptoms started when she was 2 months old. She also suffered from mental motor retardation and frequent upper respiratory tract infections. Physical examination revealed coarse facial structure, deep-set eyes, a prominent forehead, prognathism, thick lower lip and auricles, a wide nose, increased interalar distance, and postural abnormality. She had eczema plaques on both sides of her neck, bilateral antecubital fossa, and popliteal fossa (). Pruritic papules were seen on the dorsum of the hands, extensor side of ankles, and lumbar region. She had a pronounced high IgE level (3800 IU/mL) and positive reactions to house dust mites, dog dander, and banana in a prick test. Based on the clinical and laboratory findings, HIES was diagnosed and the HIES score was 28. Treatment with omalizumab was considered as an option, given the resistant nature of the disease in this patient who had even previously received interferon treatment without benefit. A treatment schedule of 300 mg/mo omalizumab injections gave no benefit, and after the fifth dose, the schedule was changed to 300 mg every other week, which provided relief of the pruritus and skin lesions. After the second injection of 300 mg omalizumab every other week, the Scoring Atopic Dermatitis scores decreased from 42 to 22, and total IgE values decreased to 1376 IU/mL (). Autosomal cyclobenzaprine hydrochloride and sporadic cases of HIES are caused by mutations in the signal transducer and activator of transcription-3 gene () on chromosome 17q21, whereas a null mutation in tyrosine kinase 2 () is responsible for autosomal recessive cases. regulates cytokines responsible for Th cell differentiation and is important in the inflammatory response to bacterial and fungal infections. In addition, plays a role in innate and adaptive immune systems. Al Khatib et al reported that both mutation-positive and mutation-negative HIES exhibited a profound deficit in Th differentiation. Considering this fact, dysfunction of Th cells is the common pathology in autosomal dominant, autosomal recessive, and sporadic forms of HIES. Imbalance between Th and Th cells is caused by increased IgE values. High IgE values suppress Th cells, which produce interferon-γ, IL-12, and activate suppressor Th cells. Intravenous Ig, cyclosporine-A, plasmapheresis, and interferon-γ are reported to be successful in individual cases. Omalizumab acts by lowering free IgE concentration in the blood and interstitial spaces and down regulates high affinity IgE receptors (FcƐRI) on basophils, mast cells, and dendritic cells. Omalizumab has been successfully used for the treatment of various atopic diseases related to elevated IgE levels. We found three cases of patients with HIES in literature whose skin lesions improved with omalizumab treatment. The first case was a 26-year-old woman with asthma and hepatitis C infection. One month after treatment with subcutaneous omalizumab 450 mg/2 wk, her asthma and skin lesions remarkably improved. She remained in remission for 6 months after cessation of treatment. In the second case, one month of treatment with subcutaneous omalizumab 300 mg/2 wk provided marked improvement of her skin lesions. The third case received three injections of monthly subcutaneous omalizumab 375 mg/2 wk and no active eczematous skin lesions and pruritus were found after 3 months. The mechanism of action of omalizumab in HIES could be related to its binding ability of free IgE in blood and down regulation of FcƐRI on basophils, mast cells, and dendritic cells. Omalizumab also down regulates CD23 (FcƐRII) on B cells and down regulates B lymphoblasts and memory B cells that express IgE, which may cause a reduction in IgE-secreting plasma cells. Consequently, these phenomena lead to the inhibition of allergens to activate basophils and mast cells, which in turn prevent the release of inflammatory mediators and cytokines.