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Job Syndrome

Job syndrome, also known as hyper-immunoglobulin E (IgE) syndrome, is a type of primary immune deficiency that presents with recurrent bacterial infections, various skin lesions, distinct facial changes, and a range of other laboratory and clinical abnormalities. Both autosomal dominant and autosomal recessive forms have been described in the literature. The diagnosis rests on identifying elevated serum IgE levels and eosinophilia in addition to findings observed during the physical examination.


Presentation

Job syndrome, initially named after the biblical character Job because of its description that resembles patients suffering from this condition, is more commonly referred to as hyper-immunoglobulin E syndrome, a form of primary immunodeficiency that affects multiple systems [1] [2] [3] [4]. Two forms have been described so far:

  • Autosomal dominant - Mutations in the signal transducer and activator of transcription 3 (STAT3) gene, which seems to affect the activity of interleukins 6 and 22 (IL-6 and IL-22, respectively), causing changes in Th17 cell function [5], is the primary cause of this syndrome [1] [2] [5]. As a result of these immunological deficits, recurrent bacterial infections of the skin and the lungs are one of the main clinical manifestations [1]. Staphylococcus aureus is the causative agent of furuncles (or boils), which are the hallmark of Job syndrome, whereas a neonatal onset of pustules and eczema (primarily affecting the face and scalp) is an equally important cutaneous sign [1] [4]. Mucocutaneous infections by candida albicans, in the form of oral thrush, onychomycosis, or vaginal infections, are also reported in a significant number of cases [1] [2]. Conversely, streptococcus pneumoniae and haemophilus influenza are main pathogens implicated in the development of recurrent pyogenic pneumonia (presenting with a cough and sputum production), another key feature of Job syndrome [1]. In addition to infections, skeletal changes (scoliosis, osteopenia, increased rate of pelvic and rib bone fractures, as well as degenerative joint disease), dental abnormalities (retention of primary teeth is common) and facial asymmetry with deep-set eyes and a prominent nose comprise the symptomatology of Job syndrome [1] [2] [6].
  • Autosomal recessive - The absence of skeletal and connective tissue symptoms, but with severe cutaneous involvement (particularly eczema) is the main distinguishing feature of autosomal recessive Job syndrome [5]. In addition to the mentioned pathogens responsible for lung infections seen in autosomal dominant forms, pseudomonas aeruginosa, proteus mirabilis, but also cryptococcus, pneumocystis jirovecii, adenovirus, and respiratory syncytial virus are important causative agents of pneumonia that may lead to life-threatening complications and sepsis [1] [5].
Recurrent Infection
  • These data suggest the need for a double-blind, placebo-controlled trial of interferon gamma in a larger group of patients with the syndrome of hyperimmunoglobulinemia E and recurrent infections.[ncbi.nlm.nih.gov]
  • Grimbacher, B ; view all (2008) Diagnostic criteria for the hyper IgE recurrent infection syndrome/Job's syndrome/STAT3 deficiency. In: CLINICAL AND EXPERIMENTAL IMMUNOLOGY. (pp. 154 - 155).[discovery.ucl.ac.uk]
  • Primary immunodeficiency syndrome characterized by recurrent infections and hyperimmunoglobulinemia E. Most cases are sporadic.[profiles.umassmed.edu]
  • AD-HIES autosomal dominant HIES autosomal dominant hyper-IgE recurrent infection syndrome autosomal dominant hyperimmunoglobulin E recurrent infection syndrome autosomal dominant Job syndrome Buckley syndrome Job-Buckley syndrome Job syndrome Job's Syndrome[ghr.nlm.nih.gov]
  • A detailed patient history should be obtained first, during which patients (or parents of affected children) should be inquired about the appearance of recurrent infections and skin lesions.[symptoma.com]
Gangrene
  • This is a rare case of Fournier gangrene associated with hyper IgE syndrome (Job syndrome). When a patient without diabetes mellitus has repeated infections and atopic-like dermatitis, Job syndrome should be considered.[ncbi.nlm.nih.gov]
  • Fournier gangrene associated with hyper IgE syndrome (Job syndrome). Int J Urol . 2008 Apr. 15(4):372-3. [Medline] . Kumanovics A, Perkins SL, Gilbert H, Cessna MH, Augustine NH, Hill HR.[emedicine.com]
  • Fournier gangrene associated with hyper IgE syndrome (Job syndrome). Int J Urol. 2008 Apr. 15(4):372-3. [Medline]. Kumanovics A, Perkins SL, Gilbert H, Cessna MH, Augustine NH, Hill HR.[emedicine.medscape.com]
Hyperextensible Joints
  • 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.[doi.org]
Furunculosis
  • Buckley syndrome - recurrent furunculosis, recurrent pneumonias, and pruritic dermatitis. Patients have a markedly elevated serum IgE.[medical-dictionary.thefreedictionary.com]
  • 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]
  • Impetigo, furunculosis, paronychia, cellulitis and characteristic "cold abscesses" are the staphylococcal infections seen. Pulmonary bacterial pneumonia, abscesses and empyema resulting in pneumatoceles are most frequent.[ijpd.in]
  • Skin infections also occur frequently - furunculosis and cellulitis may be observed early on in infancy.[ojrd.biomedcentral.com]
Facial Skin Lesion
  • At the age of almost 6 yr, he developed herpes gingivostomatitis and facial skin lesions, and, at the age of 10 yr, he was admitted with aseptic herpes meningitis and disseminated cutaneous herpetic lesions (HSV PCR: positive).[doi.org]
Neonate-Onset
  • Staphylococcus aureus is the causative agent of furuncles (or boils), which are the hallmark of Job syndrome, whereas a neonatal onset of pustules and eczema (primarily affecting the face and scalp) is an equally important cutaneous sign.[symptoma.com]

Workup

The diagnosis of Job syndrome rests on the ability of the physician to recognize the signs and symptoms followed by identification of key laboratory criteria. A detailed patient history should be obtained first, during which patients (or parents of affected children) should be inquired about the appearance of recurrent infections and skin lesions. Furthermore, the autosomal dominant pattern of inheritance suggests that the disease must be present in one of the parents, thus a positive family history might be a crucial piece of information. After a thorough physical examination, laboratory studies are the next step in the workup. A complete blood count (CBC) revealing an elevated eosinophil count and abnormally high serum immunoglobulin E (IgE) levels (exceeding > 2,000 IU/mL) are the two cardinal laboratory criteria for the diagnosis of Job syndrome [1] [2] [5]. IgE levels are elevated from birth, but may gradually reduce by adulthood, and isolated studies report that up to 20% of patients had normal IgE levels despite confirmed mutations [1] [2]. For this reason, a scoring system was designed in order to aid physicians in determining the probability of Job syndrome as the underlying cause, including all of the mentioned findings [4]. A definite diagnosis can be achieved by performing genetic testing that will confirm STAT3 mutations in the case of autosomal dominant Job syndrome, but mutations responsible for autosomal recessive forms are yet to be elucidated.

Treatment

  • 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]
  • OBJECTIVE: To describe the clinical presentation and treatment of a patient with Job syndrome, and its implications for spine surgeons.[ncbi.nlm.nih.gov]
  • Skin lesions improved and prophylactic treatment with trimethoprim‐sulfamethoxazole was recommended.[elsevier.pt]
  • What is the treatment for Job syndrome ? There is no known cure for Job syndrome . Antibiotics are used to control bacterial infections, often requiring a longer course of treatment than is usually necessary.[dermnetnz.org]
  • What is the treatment for Job syndrome ? There is no known cure for Job syndrome. Antibiotics are used to control bacterial infections, often requiring a longer course of treatment than is usually necessary.[dermnetnz.org]

Prognosis

  • Prognosis Few data are available on the prognosis of patients with Job syndrome (HIE syndrome, or hyper-IgE syndrome).[emedicine.com]
  • Other investigations include X-ray of the sinuses, X-ray of the bones, computed tomography scan of the chest and cultures of infected site. [4] Prognosis in these patients is difficult to predict due to lack of correlation between serum levels of IgE,[ijpd.in]
  • Prognosis Although HIES is associated with significant morbidity and mortality, adequate care, close monitoring, and patient compliance improve the prognosis and can lead to survival of 50 years of age or over.[orpha.net]

Etiology

  • Indian Journal of Ophthalmology. 2010; 58(3): 254-255 [Pubmed] 5 Etiology and management of hyperimmunoglobulinemia e syndrome Gonzalez-Granado, L.I. Indian Journal of Ophthalmology. 2010; 58(3): 254 [Pubmed][ijo.in]
  • Through these studies we hope to better characterize the clinical presentation of HIES and to be able to identify further genetic etiologies, as well as understand the pathogenesis of HIES. We seek to enroll 200 patients and 300 relatives.[clinicalstudies.info.nih.gov]
  • Etiology In 70% of patients, the phenotype is associated with heterozygous mutations of the signal transducer and activator of transcription 3 gene ( STAT3 ; 17q21.31).[orpha.net]
  • 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]

Epidemiology

  • Summary Epidemiology Annual incidence is estimated at around 1/1,000,000. The syndrome affects males and females equally.[orpha.net]
  • STAT3 mosaicism may produce a milder phenotype. [25] Epidemiology Frequency Job syndrome (HIE syndrome, or hyper-IgE syndrome) is a rare disorder; about 250 cases have been published.[emedicine.com]
  • STAT3 mosaicism may produce a milder phenotype. [26] Epidemiology Frequency Job syndrome (HIE syndrome, or hyper-IgE syndrome) is a rare disorder; about 250 cases have been published.[emedicine.medscape.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.[doi.org]
Sex distribution
Age distribution

Pathophysiology

  • Pathophysiology The pathophysiology of Job syndrome (HIE syndrome, or hyper-IgE syndrome) is not completely understood. [6] Patients consistently have a poor, delayed hypersensitivity response to antigens.[emedicine.com]
  • Pathophysiology The pathophysiology of Job syndrome (HIE syndrome, or hyper-IgE syndrome) is not completely understood. [7] Patients consistently have a poor, delayed hypersensitivity response to antigens.[emedicine.medscape.com]
  • Alejandro Restrepo for his care of these patients and his insights into pathophysiological mechanisms that result in the renal injury pattern observed. No external financial support for this manuscript.[link.springer.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

  • […] the disorder should practice good hygiene to prevent contracting recurrent infections and illnesses.[herbalremedies.com]
  • This can include: Antibiotics to treat infections Cream medicine for skin rash Checking pulmonary (lung) function with spirometry and imaging Some patients may need to take medicine every day to prevent infection Some patients may need to get an IV medicine[cincinnatichildrens.org]
  • They’re high in sulfur and can help to both prevent and cure abscesses. *Add kelp to your diet. *Try applying honey to any affected area. Honey destroys bacteria and viruses.[blog.imwithoutstress.com]
  • Primary teeth are retained for a longer time which in turn prevents eruption of the permanent teeth.[pediatriconcall.com]

References

Article

  1. Freeman AF, Holland SM. The Hyper IgE Syndromes. Immunol Allergy Clin North Am. 2008;28(2):277-viii.
  2. Grimbacher B, Holland SM, Gallin JI, et al. Hyper-IgE syndrome with recurrent infections-an autosomal dominant multisystem disorder. N Engl J Med. 1999;340:692–702.
  3. Holland SM, DeLeo FR, Elloumi HZ, et al. STAT3 mutations in the Hyper-IgE syndrome. N Engl J Med. 2007;18:1608–1619.
  4. Grimbacher B, Schaffer AA, Holland SM, et al. Genetic linkage of hyper-IgE syndrome to chromosome 4. Am J Hum Genet. 1999;65:735–744.
  5. Szczawinska-Poplonyk A, Kycler Z, Pietrucha B, Heropolitanska-Pliszka E, Breborowicz A, Gerreth K. The hyperimmunoglobulin E syndrome - clinical manifestation diversity in primary immune deficiency. Orphanet J Rare Dis. 2011;6:76.
  6. O'Connell AC, Puck JM, Grimbacher B, et al. Delayed eruption of permanent teeth in hyperimmunoglobulinemia E recurrent infection syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2000;89:177–185.

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Last updated: 2017-08-09 17:34