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Autosomal Dominant Hyper-IgE Syndrome

Job syndrome


Presentation

  • An eczematous dermatitis was almost always present before the age of 18 months (95% of patients) and was mainly confined to the face, scalp, chest, and buttocks.[ncbi.nlm.nih.gov]
  • Aims: This study aims to evaluate variable presentations and associations of job syndrome. Methods: Analysis of ten cases, presented at our department between October 2015 and September 2016, with suspected HIES was done retrospectively.[ijpd.in]
  • Abstract: We present three cases of Hyper IgE syndrome who presented with recurrent episodes of lower respiratory tract infection, skin lesions and facial dysmorphism. Evaluation revealed high levels of serum IgE.[edoj.org.eg]
Recurrent Infection
  • Syndromes[accessedResource: MSH:D007589][accessDate: 05-04-2011], Primary immunodeficiency syndrome characterized by recurrent infections and hyperimmunoglobulinemia E.[ebi.ac.uk]
  • PURPOSE: Autosomal dominant hyper-IgE syndrome (AD-HIES) due to heterozygous STAT3 mutation is a primary immunodeficiency characterized by eczema, elevated serum IgE, recurrent infections, and connective tissue and skeletal findings.[ncbi.nlm.nih.gov]
  • recurrent infection syndrome is caused by mutation in the STAT3 gene (MIM.102582) (Job-Beckley syndrome).[humpath.com]
  • Non-specific agents like levamisole and ascorbic acid may reduce recurrent infections.[ijdvl.com]
Failure to Thrive
  • Other features of Netherton syndrome include environmental and food allergies, enteropathy, and failure to thrive.[invitae.com]
  • Similar to graft vs host disease, generalized exudative erythroderma with desquamation, lymphadenopathy and hepatosplenomegaly are seen along with severe respiratory tract infections, intractable diarrhea and failure to thrive (FTT).[medcraveonline.com]
  • Frequently an enteropathy is present with failure to thrive. Omenn syndrome also presents in the newborn period with rash and typically elevated serum IgE.[ncbi.nlm.nih.gov]
Osteoporosis
  • Osteopenia or osteoporosis was found in 79% of children and adults. Only radial BMD correlated with the qualitative occurrence of fractures but it did not correlate with the numbers of fractures.[ncbi.nlm.nih.gov]
  • Osteopenia or osteoporosis was found in 79 % of children and adults. Only radial BMD correlated with the qualitative occurrence of fractures but it did not correlate with the numbers of fractures.[link.springer.com]
  • Skeletal manifestations include scoliosis, minimal trauma fractures due to osteoporosis, and hyperextensibility of the joints. Failure of exfoliation of primary teeth.[radiopaedia.org]
  • Skeletal abnormalities include abnormal side-to-side curvature of the spine (scoliosis), abnormally increased flexibility of certain joints (joint hyperextensibility), progressive thinning and loss of protein of the bones (osteoporosis), and repeated[rarediseases.org]
Hyperextensible Joints
  • Nonimmunologic manifestations of HIES include a characteristic face, pathologic dentition, scoliosis, bone alterations, hyperextensible joints, and vascular abnormalities.[ncbi.nlm.nih.gov]
  • Common findings among patients were recurrent fractures (in 57 percent of patients), hyperextensible joints (in 68 percent), and scoliosis (in 76 percent of patients 16 years of age or older).[scienceopen.com]
  • Eczema, mucocutaneous candidiasis, retention of the primary teeth, coarse facial features, osteopenia, hyperextensible joints and increased risk of malignancy are also common.[medcraveonline.com]
  • Hyperextensible joints, including fingers, wrists, shoulders, hips, and knees, were found in 68 percent of the patients, and three patients (Patients 7, 11, and 29) had genu valgum.[nejm.org]
Eczema
  • Skin Affected by Hyper IgE Syndrome A newborn rash or eczema is frequently the first manifestation of AD-HIES. Pustular and eczema-like rashes usually begin within the first month of life, first affecting the face and scalp.[primaryimmune.org]
  • In this condition, high serum IgE level causes multiple recurrent conditions, including, skin eruption, eczema, infections in lungs, eosinophilia 1,2.[syndromespedia.com]
  • The constellation of elevated IgE and low IgM with severe allergies or eczema should raise the possibility of DOCK8 deficiency.[oncologynurseadvisor.com]
  • Symptoms of Job's syndrome include eczema, recurrent abscesses, pneumonia and recurrent candida infections. Eczema usually occurs in the creases behind the ears, the back, buttocks and scalp.[pediatriconcall.com]
  • PURPOSE: Autosomal dominant hyper-IgE syndrome (AD-HIES) due to heterozygous STAT3 mutation is a primary immunodeficiency characterized by eczema, elevated serum IgE, recurrent infections, and connective tissue and skeletal findings.[ncbi.nlm.nih.gov]
Furunculosis
  • ExonArray CGH Ordering Preferred Specimen: 2-5 mL Blood - Lavender Top Tube Alternative Specimen: Oral Rinse (30-40 mL) Buccal Swabs Billing CPT Codes: 81405x1, 81479x1 ICD Codes: 513 Abscess of lung and mediastinum 680 Carbuncle and furuncle Includes: boil furunculosis[genedx.com]
  • The skin and soft tissue infections present as cellulitis, furunculosis, paronychia, suppurative adenitis and deep soft tissue 'cold' abscesses. Severe pulmonary infections caused by either S. aureus or H. influenzae are common.[edoj.org.eg]
  • The skin and soft tissue infections may present in the form of cellulitis, furunculosis, paronychia, suppurative adenitis and \\\'cold\\\' abscesses. 1 IgE level in HIES is usually higher than 2000 IU/ml however, it does not correlate with disease severity[jpma.org.pk]
  • The other types of bacterial skin infections observed included impetigo, pustulosis, and pyodermatitis in 45% of patients (n 27), folliculitis and/or furunculosis in 35% (n 21), paronychia in 23% (n 14), lymph node abscesses in 20% (n 12), and cellulitis[journals.lww.com]
  • Skin infections also occur frequently - furunculosis and cellulitis may be observed early on in infancy.[ojrd.biomedcentral.com]
Dry Skin
  • Symptoms include fatigue, constipation, weight gain, depression, dry skin, and sensitivity to cold. Taking a daily oral synthetic thyroid hormone pill restores normal body functions. Myasthenia gravis.[webmd.com]
  • skin and itchy/irritated skin.[allmedx.com]

Workup

  • The differential diagnosis of extremely elevated IgE levels is also discussed to help assist the clinician in the workup of a patient with elevated IgE levels.[medcraveonline.com]
Pulmonary Pneumatocele
  • Symptoms and Signs Hyper-IgE syndrome typically causes recurrent staphylococcal abscesses of the skin, lungs, joints, and viscera; sinopulmonary infections; pulmonary pneumatoceles; and a severe pruritic eosinophilic dermatitis.[msdmanuals.com]
Anergy
  • There is cutaneous anergy to skin prick tests and a reduced or absent in vitro lymphocyte response to mitogens.[medcraveonline.com]

Treatment

  • Thus, most AD-HIES STAT3 mutations are destabilizing; agents that modulate chaperone protein function improve STAT3 stability and activity in T cells and may provide a specific treatment.[ncbi.nlm.nih.gov]
  • Treatment includes reducing immune system activity, usually with prednisone or another corticosteroid.[webmd.com]
  • Treatment There is no known cure for this condition. The goal of treatment is to prevent and treat infections with long-term use of antibiotics and antifungal medication. Sometimes, surgery is needed to drain abscesses, especially in the lungs.[cpi.org.au]
  • What is the treatment of Hyper IgE syndrome? Depending on the underlying condition causing the HIES, the treatment could differ. For some of these patients, skin care and prompt treatment of infections are essential.[pediatriconcall.com]

Prognosis

  • What should you tell the patient and the family about prognosis? STAT3 mutations occur spontaneously at certain spots in the gene. However, once they have occurred, they are transmitted in an autosomal dominant fashion.[oncologynurseadvisor.com]
  • Variant of hyper-IgE syndrome: the differentiation from atopic dermatitis is important because of treatment and prognosis. Dermatologica 1991 ;182: 7 - 11 Citing Articles (385) Letters Article Figures/Media[nejm.org]
  • Overall, the prognosis of STAT3 deficiency may be considered good, provided that multiple prophylactic measures, including IgG infusions, are implemented. Supplemental digital content is available in the text.[journals.lww.com]
  • PubMed Central PubMed Google Scholar Hochreutener H, Wüthrich B, Huwyler T, Schopfer K, Seger R, Baerlocher K: Variant of hyper-IgE syndrome: the differentiation from atopic dermatitis is important because of treatment and prognosis.[ojrd.biomedcentral.com]

Etiology

  • There are two types of HIES 2 : autosomal dominant ( STAT3 deficiency ) more common caused by a mutation in STAT3 gene autosomal recessive etiology unknown This article is concerned with the more common autosomal dominant HIES.[radiopaedia.org]
  • Ongoing controversies regarding etiology, diagnosis, treatment Much still needs to be learned about the etiology of this disease and the reason for the appearance of its different clinical features.[clinicaladvisor.com]
  • Etiology germline mutations of STAT3 (MIM.102582) in hyper-IgE syndrome (MIM.147060) (autosomal dominant hyper-IgE recurrent infection syndrome / Job-Buckley syndrome) Clinical synopsis coarse facies asymmetric face prominent forehead mild prognathism[humpath.com]
  • The etiology & pathophysiology of Job syndrome are not completely understood. The mechanisms responsible for increased IgE production are unknown.[edoj.org.eg]
  • This results in decreased chemotaxis and acute phase response that is responsible for recurrent infections. 3 The etiology of AR-HIES is under debate.[jpma.org.pk]

Epidemiology

  • Association Between Psoriasis and Sexual and Erectile Dysfunction in Epidemiologic Stud... Preview JAMA Dermatology; Molina-Leyva A, Salvador-Rodriguez L et. al. Oct 12th, 2018 - Sexual health is a major aspect of life.[allmedx.com]
  • School-screening for scoliosis: a prospective epidemiological study in northwestern and central Greece. J Bone Joint Surg Am 1997 ;79: 1498 - 1503 57. Dreskin SC, Kaliner MA, Gallin JI.[nejm.org]
Sex distribution
Age distribution

Pathophysiology

  • These approaches allow for a better understanding of complex phenotypes associated with somatic mosaicisms, and present the possibility to analyze the role of B lymphocytes in the pathophysiology of this disease.[ncbi.nlm.nih.gov]
  • The pathophysiologic mechanism of hyperimmunoglobulin E syndrome immunodeficiency has recently been linked to a disorder in the T helper 17 pathway and disruption of the interleukin -23/interleukin-17 axis.[pediatrics.aappublications.org]
  • The etiology & pathophysiology of Job syndrome are not completely understood. The mechanisms responsible for increased IgE production are unknown.[edoj.org.eg]
  • Pathophysiology STAT3 is a major signal transduction molecule that mediates signals from a variety of immune and somatic pathways, including IL-6, IL-10, IL-11, IL-23, leukemia inhibitory factor and oncostatin M.[oncologynurseadvisor.com]
  • Pathophysiology [ edit ] Abnormal neutrophil chemotaxis due to decreased production of interferon gamma by T lymphocytes is thought to cause the disease. [4] Both autosomal dominant and recessive inheritance have been described: [5] [6] Autosomal dominant[en.wikipedia.org]

Prevention

  • Treatment with bisphosphonates increased BMD but its role in fracture prevention remains undefined.[ncbi.nlm.nih.gov]
  • Antibiotics, usually trimethoprim /sulfamethoxazole, are given continuously to prevent staphylococcal infections. The rash is treated with moisturizing creams, antihistamines, and, if infection is likely, antibiotics.[merckmanuals.com]
  • Treatment is centred on preventing and treating infections using antibiotic, antifungal and antiviral medicines. Good skin care and hygiene to prevent infection is essential.[piduk.org]
  • Treatment may include prophylactic antibiotics to prevent respiratory and skin infections, extraction of the primary teeth for healthy dentition, prompt and aggressive treatment of infections, and appropriate skin care.[columbiadoctors.org]

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