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Medicina Clinica Apr 2019
Topics: Humans; Job Syndrome; Male; Mutation; Photography; STAT3 Transcription Factor; Young Adult
PubMed: 30220469
DOI: 10.1016/j.medcli.2018.06.005 -
Journal of Clinical Immunology Jul 2021The hyper-IgE syndromes (HIES) are a heterogeneous group of inborn errors of immunity sharing manifestations including increased infection susceptibility, eczema, and... (Review)
Review
The hyper-IgE syndromes (HIES) are a heterogeneous group of inborn errors of immunity sharing manifestations including increased infection susceptibility, eczema, and raised serum IgE. Since the prototypical HIES description 55 years ago, areas of significant progress have included description of key disease-causing genes and differentiation into clinically distinct entities. The first two patients reported had what is now understood to be HIES from dominant-negative mutations in signal transduction and activator of transcription 3 (STAT3-HIES), conferring a broad immune defect across both innate and acquired arms, as well as defects in skeletal, connective tissue, and vascular function, causing a clinical phenotype including eczema, staphylococcal and fungal skin and pulmonary infection, scoliosis and minimal trauma fractures, and vascular tortuosity and aneurysm. Due to the constitutionally expressed nature of STAT3, initial reports at treatment with allogeneic stem cell transplantation were not positive and treatment has hinged on aggressive antimicrobial prophylaxis and treatment to prevent the development of end-organ disease such as pneumatocele. Research into the pathophysiology of STAT3-HIES has driven understanding of the interface of several signaling pathways, including the JAK-STAT pathways, interleukins 6 and 17, and the role of Th17 lymphocytes, and has been expanded by identification of phenocopies such as mutations in IL6ST and ZNF341. In this review we summarize the published literature on STAT3-HIES, present the diverse clinical manifestations of this syndrome with current management strategies, and update on the uncertain role of stem cell transplantation for this disease. We outline key unanswered questions for further study.
Topics: Hematopoietic Stem Cell Transplantation; Humans; Job Syndrome; Quality of Life; STAT3 Transcription Factor
PubMed: 33932191
DOI: 10.1007/s10875-021-01051-1 -
Immunology and Cell Biology Apr 2019Hyper IgE syndromes comprise a group of rare primary immunodeficiency disorders characterized by a triad of atopic dermatitis, recurrent skin and lung infections along... (Review)
Review
Hyper IgE syndromes comprise a group of rare primary immunodeficiency disorders characterized by a triad of atopic dermatitis, recurrent skin and lung infections along with elevated IgE levels. Job syndrome or autosomal dominant hyper IgE syndrome because of heterozygous loss-of-function mutations with dominant negative effect in signal transducer and activator of transcription-3 is the prototype of these disorders. However, several other genetically characterized immunodeficiency disorders have been identified over the past decade and joined the umbrella of hyper IgE syndromes including autosomal recessive mutations in the DOCK8, ZNF431 and PGM3 genes and heterozygous mutations with dominant negative effect in the CARD11 gene. Moreover, a number of phenotypically distinct immunodeficiency disorders can mimic hyper IgE syndromes, adding to the diagnostic challenge. Herein, we will concisely review these disorders, their molecular bases, highlighting key distinguishing clinical and laboratory findings and therapeutic options.
Topics: Genes, Dominant; Humans; Job Syndrome; Mutation; Phenotype; STAT3 Transcription Factor; Transcription, Genetic
PubMed: 30264496
DOI: 10.1111/imcb.12209 -
The Laryngoscope Aug 1980Job's syndrome is characterized by the clinical features of fair skin, red hair, recurrent cold staphylococcal skin abscesses with concurrent other bacterial infections...
Job's syndrome is characterized by the clinical features of fair skin, red hair, recurrent cold staphylococcal skin abscesses with concurrent other bacterial infections and skin lesions. This case report chronicles a classic presentation of Job's syndrome. A brief review of the otolaryngological presentations of immune deficiencies is presented. Other than its relationship to the manifestations of other immunological defects, Job's syndrome is of interest to the otolaryngologist because of the head and neck infections represented in its clinical expression. Familiarity with phenotypic and laboratory manifestations of such diseases will enable earlier recognition and treatment of this syndrome.
Topics: Abscess; Adult; Female; Humans; Job Syndrome; Phagocyte Bactericidal Dysfunction; Zygoma
PubMed: 7401839
DOI: No ID Found -
Clinical Pediatrics May 2020
Topics: Child; Diagnosis, Differential; Humans; India; Job Syndrome; Male
PubMed: 32019325
DOI: 10.1177/0009922820903517 -
JPMA. the Journal of the Pakistan... Dec 2000
Topics: Fatal Outcome; Humans; Infant; Job Syndrome; Male; Pakistan
PubMed: 11191445
DOI: No ID Found -
Clinical Immunology (Orlando, Fla.) Apr 2022Hyper IgE syndromes (HIESs) are a group of rare inborn errors of immunity with a triad of eczema, increase susceptibility to sinopulmonary and skin infections with high... (Review)
Review
Hyper IgE syndromes (HIESs) are a group of rare inborn errors of immunity with a triad of eczema, increase susceptibility to sinopulmonary and skin infections with high level of IgE serum. Although most of HIESs are sporadic, hereditary types of these disorders have been studied well. There are several distinct immunodeficiency disorders which are phenotypically similar to HIES, and thus make the diagnosis of HIES challenging. In fact, the diagnosis of HIES is typically based on the clinical suspicion and immunological assessments. There is yet no specific curative treatment for most of HIESs at present, and the treatments are mostly standing on early diagnosis and preventive therapies. For instance, the genetic diagnosis is an important module, while, due to DOCK8 mutations, the hematopoietic stem cell transplantation is necessary for patients with autosomal recessive form of HIESs. Herein, we overview HIESs, highlight their peculiar clinical and laboratory features, and finally suggest a practical forthright diagnostic chart for clinical purposes.
Topics: Eczema; Guanine Nucleotide Exchange Factors; Hematopoietic Stem Cell Transplantation; Humans; Immunologic Deficiency Syndromes; Job Syndrome; Mutation; STAT3 Transcription Factor
PubMed: 35351598
DOI: 10.1016/j.clim.2022.108988 -
Annals of the New York Academy of... Feb 2012Autosomal dominant hyper-IgE syndrome (AD-HIES) or Job's syndrome is a primary immunodeficiency with a wide array of clinical features caused by dominant negative... (Review)
Review
Autosomal dominant hyper-IgE syndrome (AD-HIES) or Job's syndrome is a primary immunodeficiency with a wide array of clinical features caused by dominant negative mutations in STAT3. In recent years, not only the clinical phenotype of the disease has been expanded with recognition of features such as arterial aneurysms, but also our understanding of the pathogenesis of the disease has greatly improved.
Topics: Aneurysm; Animals; Humans; Job Syndrome; Mutation; STAT3 Transcription Factor
PubMed: 22268731
DOI: 10.1111/j.1749-6632.2011.06387.x -
Oral Diseases Jan 2009Autosomal dominant hyper IgE (HIES or Job's) syndrome is a rare primary immune deficiency characterized by eczema, recurrent skin and lung infections, extremely elevated... (Review)
Review
Autosomal dominant hyper IgE (HIES or Job's) syndrome is a rare primary immune deficiency characterized by eczema, recurrent skin and lung infections, extremely elevated serum IgE, and a variety of connective tissue and skeletal abnormalities. Individuals with HIES share a characteristic facial appearance and many oral manifestations including retained primary dentition, a high arched palate, variations of the oral mucosa and gingiva, and recurrent oral candidiasis. Mutations in STAT3 account for the majority, if not all, of the cases of autosomal dominant HIES, but the pathogenesis of the many varied features remains poorly understood. In this review, we discuss the clinical phenotype of HIES including immunologic and non-immunologic features, the genetics of HIES, and treatment.
Topics: Candidiasis, Oral; Facies; Gingival Diseases; Humans; Job Syndrome; Mouth Diseases; Mouth Mucosa; Mutation; Palate; Phenotype; Recurrence; STAT3 Transcription Factor; Tooth Diseases; Tooth, Deciduous
PubMed: 19036057
DOI: 10.1111/j.1601-0825.2008.01463.x -
Spine Jun 2006A case report of the hyperimmunoglobulin E syndrome (Job syndrome) presenting in the context of late postoperative infection after corrective surgery for scoliosis. (Review)
Review
STUDY DESIGN
A case report of the hyperimmunoglobulin E syndrome (Job syndrome) presenting in the context of late postoperative infection after corrective surgery for scoliosis.
OBJECTIVE
To describe the clinical presentation and treatment of a patient with Job syndrome, and its implications for spine surgeons.
SUMMARY OF BACKGROUND DATA
Job syndrome classically presents with a triad of increased serum immunoglobulin E, multiple abscesses, and pneumonia with pneumatocele formation. In recent years nonimmunologic manifestations have been described, including scoliosis, joint hypermobility, eosinophilia, and atopy.
METHODS
A 15-year-old female presented with local swelling and fever 2 years after anterior lumbar discectomy and fusion with spinal instrumentation involving T11-L3 levels. Computerized tomography revealed paravertebral, psoas, and pulmonary abscesses. The implants were removed and antibiotic therapy instituted. Further investigation revealed features of the hyperimmunoglobulin E syndrome (Job syndrome).
RESULTS
The patient's symptoms resolved, as did markers of inflammation.
CONCLUSIONS
Job syndrome is a primary immunodeficiency often associated with scoliosis. Given the implications for surgical outcome in immunodeficient patients, the diagnosis should be considered and, blood tests instituted in patients with scoliosis with any of the associated history and physical findings of Job syndrome.
Topics: Adolescent; Anti-Bacterial Agents; Device Removal; Female; Humans; Infections; Internal Fixators; Job Syndrome; Postoperative Complications; Scoliosis; Spinal Fusion; Tomography, X-Ray Computed
PubMed: 16778678
DOI: 10.1097/01.brs.0000222025.14483.6d