eMedicine Specialties > Dermatology > Allergy & Immunology

Job Syndrome

Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Mordechai M Tarlow, MD, Physician, Department of Medicine, Section of Dermatology, Kimball Medical Center

Updated: Jul 17, 2009

Introduction

Background

First described in 1966, the hyperimmunoglobulin E (hyper-IgE or HIE) syndrome is a rare immunodeficiency disorder that has an autosomal dominant inheritance pattern. HIE syndrome has variable expressivity and is associated with multiple abnormalities. The most common findings are recurrent skin abscesses (hence, the name Job syndrome), pneumonia with pneumatocele development, and high serum levels of IgE. Facial, dental, and skeletal features are also associated with this syndrome.

Although most cases are sporadic, multiplex families displaying autosomal dominant and autosomal recessive inheritance have been described.¹ Autosomal recessive patients tend to have severe molluscum contagiosum and other viral infections and may develop severe neurological complications. These patients also lack skeletal or dental involvement and do not develop lung cysts. Some authorities believe 2 separate syndromes exist, not one.

Type 1 HIE syndrome displays abnormalities in multiple systems, including the skeletal, dental, and immune systems, whereas type 2 HIE syndrome shows abnormalities confined to the immune system.² Hypomorphic mutations have been found in the signal transducer and activator of transcription 3 (STAT3) gene in type 1 HIE syndrome and a null mutation in the tyrosine kinase 2 (Tyk2) gene. Cytokine responses in both types of HIE syndrome revealed severe defects leading to impaired T-helper type 17 function. Another study credited deficiency of Th17 cells in HIE syndrome to mutations in STAT3 in a majority of evaluated patients.³

The eMedicine pediatrics article Hyperimmunoglobulinemia E (Job) Syndrome may be of interest.

Pathophysiology

The pathophysiology of Job syndrome (HIE syndrome, or hyper-IgE syndrome) is not completely understood. Patients consistently have a poor, delayed hypersensitivity response to antigens. This delayed response is associated with alterations in T-lymphocyte populations and various interleukin and cytokine abnormalities.⁴ One of the earliest reports on the pathophysiology of Job syndrome described a chemotactic defect in neutrophils.⁵ This defect has since been attributed to defective production of interferon-gamma, a major activator of neutrophils when stimulated by interleukin (IL)–12. The poor production of interferon-gamma in response to IL-12 results in the marked elevation of IgE levels (by means of unopposed IL-4 action).⁶

Other factors in the abnormal immunologic response are described. Patients with HIE syndrome have elevated levels of granulocyte-macrophage colony-stimulating factor, which may also explain the decreased chemotaxis and increased oxygen radical production and tissue damage.⁷ Deficient suppressor T-cell numbers and activity and an imbalance in helper T cell type 1 (TH1) and helper T cell type 2 (TH2) also may play a role in an abnormal response.⁸

Although the cytokine dysregulation seems to play a role in its pathophysiology, the causative gene has not yet been identified.⁹ In one study, no unique polymorphisms or mutations were found in candidate genes from the toll-like receptor pathway.¹⁰ A significantly large number of immunoglobulin-related genes were found to be up-regulated in this syndrome. Perhaps the distinct patterns may facilitate understanding of its pathophysiology and, possibly, its diagnosis.

Frequency

International

Job syndrome is a rare disorder; about 250 cases have been published.

Mortality/Morbidity

• Significant morbidity is associated with Job syndrome.
• The vast majority of patients have severe cutaneous and pulmonary disease, and most patients have multiple bone fractures and scoliosis.
• The mortality rate is elevated because of systemic infections.

Race

The syndrome occurs in people of diverse ethnic backgrounds and does not seem to be more common in any specific population.

Sex

No sex predilection is reported.

Age

HIE syndrome usually commences in infancy, but diagnosis is often delayed until childhood or even adulthood.

Clinical

History

Although the diagnosis of Job syndrome (HIE syndrome, or hyper-IgE syndrome) is usually delayed until the patient reaches childhood or early adulthood, symptoms may begin in infancy.

• Dermatologic features
  • Nearly all patients have a history of moderate-to-severe, pruritic, eczematous skin eruptions in early life. The eruption does not have a seasonal variation and is present, to some degree, at all times.
  • Intermittent episodes of staphylococcal abscesses are common. These abscesses are often referred to as cold abscesses because they do not cause pain, heat, or redness.
  • Chronic mucocutaneous candidiasis and onychomycosis are common and usually caused by Candida species.
• Systemic features
  • Recurrent bronchitis is common, and a history of Staphylococcus aureus or Haemophilus influenzae pneumonia is usually associated with pneumatocele development. These pneumatoceles may become superinfected with Pseudomonas aeruginosa and Aspergillus fumigatus. Also see Pneumonia, Bacterial.
  • Other systemic infections may occur. These may include recurrent bacterial arthritis and a staphylococcal osteomyelitis at fracture sites. Patients also may have a history of otitis externa, chronic otitis media, sinusitis, multiple caries and gingivitis, or cervicofacial infection.¹¹
  • Many patients report retained primary teeth, noneruption of permanent teeth, and double rows of teeth with both primary and permanent intermixed teeth.¹²
  • Multiple bone fractures are common and often due to unrecognized or minor trauma.
  • Scoliosis occurs in most teenaged patients.
  • Peripheral T-cell lymphoma has been described as a rare association with Job syndrome.¹³
  • Coronary artery aneurysms have been described in patients with HIE recurrent infection syndrome.¹⁴
  • Sarmento et al report an association with Dubowitz syndrome, HIE syndrome, and nasal polyposis.¹⁵

Physical

• Dermatologic findings
  • Moderate-to-severe, papular, pruritic eczematous lesions are typical; they may also be pustular and may become impetiginized. The areas of involvement predominately include the flexural areas, the area behind the ears, and the area around the hairline.
  • Cold staphylococcal abscesses that lack the typical signs of infection appear as fluctuant masses. These abscesses may be mistaken for cysts or benign tumors. They vary in size and can occur on any part of the body.
  • Furunculosis and cellulitis may also be present.
  • Chronic mucocutaneous candidiasis and onychomycosis are common.
  • A vesicular eruption similar to herpetic lesions may occur in newborns, with the more typical eczematous component developing over the next several months.
• Systemic findings
  • Fever is rare. Recurrent productive cough is associated with bronchitis. Pneumonia with complicating pneumatocele development and empyema may be present, although these are less common in children who are receiving prophylactic antibiotics.
  • Recurrent bacterial arthritis and staphylococcal osteomyelitis may occur at fracture sites. Culture results in suspected osteomyelitis are often negative, but the findings on diagnostic images are usually consistent with this diagnosis. This osteomyelitis responds well to antibiotic treatment.
  • Frequent bone fractures are a feature of Job syndrome and occur in persons of all ages. The fractures usually occur in the long bones, ribs, and pelvic bones. They are often associated with an absence of pain.
  • Scoliosis is common. Approximately one third of patients have a spinal curvature greater than 20°.
  • Hyperextensible joints are also common.
  • A characteristic coarse facies is associated with Job syndrome.¹⁶ The most striking features are a greater interalar width and a longer outer canthal distance. A prominent brow and supraorbital ridge with the impression of deep-set eyes is observed. These features tend to become more pronounced with age.
  • Oral manifestations include retained primary dentition, a high arched palate, variations of the oral mucosa and gingiva, and recurrent oral candidiasis.¹⁷

Causes

Although the described defects in immune response may explain the recurrent infections and chronic dermatitis associated with Job syndrome (HIE syndrome, or hyper-IgE syndrome), the many other congenital abnormalities are not readily explained. A single-locus autosomal dominant model of inheritance with varying expressivity is described,¹⁸ and the greater severity of cases in younger generations of patients may suggest genetic anticipation. Findings from a multipoint analysis confirm that the proximal 4q region contains the disease locus for Job syndrome.¹⁹

Differential Diagnoses

Atopic Dermatitis
Eosinophilic Pustular Folliculitis
Folliculitis
Gram-Negative Folliculitis
Onychomycosis

Workup

Laboratory Studies

• By definition, hyper-IgE syndrome (HIE syndrome, Job syndrome) is characterized by an elevated serum IgE level.
• Levels vary, but the vast majority of patients have indices greater than 2000 IU/mL, and many patients have levels as high as 50,000 IU/mL. (Normal values of serum IgE tend to be less than 10 IU/mL in an arithmetic distribution or less than 100 IU/mL after logarithmic conversion, although these values may vary among laboratories.)
• Serum IgE values tend to fluctuate to some degree (most often by <50%), and, in some patients, disease activity can significantly decrease over the years.
• A normal IgE level should not exclude Job syndrome in an adult.
• Serum eosinophil counts are more than 2 standard deviations above the normal range of values in more than 90% of patients.
• Elevated eosinophil counts can be found in secretion samples, including those obtained with abscess drainage and sputum samples in cases of bronchitis or pneumonia.
• No correlation is observed between the level of serum IgE and the level of serum eosinophils, and fluctuations in these levels are not associated with infections or flares of the dermatitis.

Imaging Studies

• Pulmonary imaging (eg, x-ray, CT) features typically reveal recurrent alveolar lung infections; pneumatoceles; and, rarely, pneumothorax.
• Radiographs of the teeth indicate the dental development age.

Other Tests

• Neutrophil chemotaxis may be assessed by means of in vitro examination of their ability to move toward a chemoattractant. Such chemoattractants include endotoxin-activated serum, sodium caseinate, and formylmethionine-leucine-phenylalanine (fMet-Leu-Phe).
• Although results with these tests are most often abnormal when compared with control values, chemotactic responsiveness varies, and the magnitude of the defect is less than that in other disorders (eg, Chediak-Higashi syndrome).

Histologic Findings

Histologic examination of vesicopapules may reveal an eosinophil-rich infiltration around the hair follicles, similar to that of eosinophilic pustular folliculitis.

Treatment

Medical Care

No definitive therapy is available for the treatment of hyper-IgE syndrome (HIE syndrome or Job syndrome). The mainstay of treatment is the control of bacterial infections. Early incision and drainage followed by the intravenous administration of antibiotics are used for cutaneous infections. Coverage is usually aimed at Staphylococcus and Haemophilus species.

Job syndrome therapy is usually longer than typical treatment because the disease in these patients responds more slowly than that of patients without Job syndrome. Intravenous antibiotic treatment for 2 weeks is typical. Chronic onychomycosis responds well to oral ketoconazole and fluconazole. Eczematous dermatitis has a varied response to high-dose topical steroids. 

• Chemoprophylaxis in patients with Job syndrome has varied results. Levamisole, an immunopotentiating drug, has been investigated as a therapeutic agent; in one study, it was unhelpful.
  • Long-term trimethoprim-sulfamethoxazole treatment was used in one patient with recurrent pruritic dermatitis, with resolution of symptoms.²⁰
  • Other patients treated with prophylactic antibiotics had both minor and major infections during therapy, often after several months of being infection free.
• Cases in patients with severe hyper-IgE syndrome whose disease was unresponsive to other therapeutic modalities are reported; these cases had a marked clinical response to cyclosporin A. Treatment included low-dose cyclosporin for 6 months or longer. Both cutaneous and pulmonary infections responded to this therapy, and no adverse effects were reported.
  • In one study, oral disodium cromoglycate (2 g/d) prevented the complications of Job syndrome over a 2-year period.²¹
  • Two case studies in patients with Job syndrome have shown a dramatic response in preventing infectious and eczematoid complications; patients were treated for as long as 18 months.
• In one open-labeled study, high-dose intravenous immunoglobulin had no clear clinical benefit in 9 patients with Job syndrome. Another study showed an improvement in severe eczema along with a decrease in serum IgE levels in 2 patients after they were treated with high-dose intravenous gamma globulin.²²

Surgical Care

• Surgical excision and drainage of cutaneous infections are often performed. Drainage is usually followed by intravenous antibiotic therapy.
• Chronic hidradenitis suppurativa occurs in some patients with Job syndrome. Often, these lesions do not respond to antibiotics, and local excision may be required.

Consultations

• An allergist and immunologist may help in establishing the diagnosis of Job syndrome.
• An infectious disease specialist may help in cases with infectious complications.
• An orthopedist should be involved in the care of those with scoliosis and fractures.

Medication

The goals of pharmacotherapy for Job syndrome are to eradicate infections, reduce the morbidity rate, and prevent complications.

Antimicrobials

Therapy must be comprehensive and cover all likely pathogens in the context of the clinical setting.

Nafcillin (Nafcil, Unipen, Nallpen)

Initial therapy for suspected penicillin G-resistant streptococcal or staphylococcal infections. Because of thrombophlebitis, particularly in elderly patients, administer parenterally for only a short term (1-2 d); change to oral route as clinically indicated. Use for treatment of pulmonary and cutaneous infections.

Dosing

Adult

500 mg to 2 g IV/IM q4-6h
Alternatively, 250 mg to 1 g PO q4-6h

Pediatric

0-4 kg (neonates): 10 mg/kg IM bid
4-40 kg: 25 mg/kg IM bid
Alternatively, 100-200 mg/kg/d IV/IM in 4-6 divided doses
PO dose: 50 mg/kg/d divided qid

Interactions

May decrease effects of warfarin and contraceptives when administered concurrently; bacteriostatic action of tetracycline derivatives may decrease effects

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

To optimize therapy, determine causative organisms and susceptibility; use for >10 d to eliminate infection and prevent sequelae (eg, endocarditis, rheumatic fever); obtain cultures after treatment to confirm that infection is eradicated

Oxacillin (Bactocill, Prostaphlin)

Bactericidal antibiotic that inhibits cell wall synthesis. Used in treatment of infections caused by penicillinase-producing staphylococci. May be used to initiate therapy in suspected staphylococcal infection. Use for treatment of pulmonary and cutaneous infections.

Dosing

Adult

500-1000 mg PO q4-6h
150-200 mg/kg/d IV/IM divided q6h

Pediatric

50-100 mg/kg/d PO divided q6h
150-200 mg/kg/d IV/IM divided q6h; not to exceed 12 g/d

Interactions

Decreases effects of contraceptives and tetracycline; concomitant disulfiram and probenecid may decrease levels; large IV doses may increase effect of anticoagulants

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in impaired renal function

Ampicillin (Marcillin, Omnipen, Polycillin, Principen, Totacillin)

Bactericidal activity against susceptible organisms. Use to treat pulmonary and cutaneous infections.

Dosing

Adult

500 mg to 3 g IV q4-6h; not to exceed 12 g/d
500 mg to 1.5 g IM q4-6h

Pediatric

100-400 mg/kg/d IV/IM divided q4-6h

Interactions

Probenecid and disulfiram increase levels; allopurinol decreases effects and has additive effects on ampicillin rash; may decrease effects of oral contraceptives

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adjust dose in renal failure; evaluate rash and differentiate from hypersensitivity reaction

Vancomycin (Lyphocin, Vancocin, Vancoled)

Potent antibiotic directed against gram-positive organisms and active against Enterococcus species. Useful in treatment of septicemia and skin structure infections. Indicated for use in patients who cannot receive penicillins and cephalosporins, those whose disease did not respond to these drugs, and those who have infections with resistant staphylococci. To avoid toxicity, current recommendation is to assay vancomycin trough levels after third dose, with sample drawn 0.5 h prior to next dose. Use creatinine clearance to adjust dose in renal impairment. Use for treatment of pulmonary and cutaneous infections.

Dosing

Adult

500 mg to 2 g/d IV divided tid/qid for 7-10 d

Pediatric

40 mg/kg/d IV divided tid/qid for 7-10 d

Interactions

Erythema, histaminelike flushing, and anaphylactic reactions may occur when administered with anesthetic agents; with concurrent aminoglycosides, risk of nephrotoxicity may increase above that with aminoglycoside monotherapy; coadministration of nondepolarizing muscle relaxants may enhance effects in neuromuscular blockade

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in renal failure, neutropenia; "red man" syndrome is caused by too rapid IV infusion (dose given over a few minutes) but rarely happens when dose given IV over 2 h administration or as PO or IP administration; "red man" syndrome is not an allergic reaction

Cefazolin (Ancef, Kefzol, Zolicef)

First-generation semisynthetic cephalosporin that arrests bacterial cell wall synthesis, inhibiting bacterial growth. Primarily active against skin flora, including S aureus. Typically used alone for skin and skin-structure coverage. IV and IM dosing regimens are similar. Use for treatment of pulmonary and cutaneous infections.

Dosing

Adult

250 mg to 2 g IV/IM q6-12h, depending on severity of infection; not to exceed 12 g/d

Pediatric

25-100 mg/kg/d IV/IM divided q6-8h, depending on severity of infection; not to exceed 6 g/d

Interactions

Probenecid prolongs effect; coadministration with aminoglycosides may increase renal toxicity; may yield false-positive results with urine-dip test for glucose

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adjust dose in severe renal insufficiency (high doses may cause CNS toxicity); superinfections and promotion of nonsusceptible organisms may occur with prolonged or repeated therapy

Sulfamethoxazole and trimethoprim (Bactrim, Bactrim DS)

Inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid. For prevention and/or suppression of inflammatory symptoms of Job syndrome.

Dosing

Adult

160 mg TMP/800 mg SMZ PO q12h for 10-14 d

Pediatric

<2 months: Do not administer
>2 months: 10-20 mg TMP/kg/d PO/IV divided tid/qid for 14 d

Interactions

May increase PT when used with warfarin (perform coagulation tests and adjust dose accordingly); coadministration with dapsone may increase blood levels of both drugs; coadministration of diuretics increases incidence of thrombocytopenia purpura in elderly patients; phenytoin levels may increase with coadministration; may potentiate effects of methotrexate in bone marrow depression; hypoglycemic response to sulfonylureas may increase with coadministration; may increase levels of zidovudine

Contraindications

Documented hypersensitivity; megaloblastic anemia due to folate deficiency

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Discontinue at first appearance of new skin rash or adverse reaction; obtain CBC counts frequently; discontinue therapy if significant hematologic changes occur; goiter, diuresis, and hypoglycemia may occur with sulfonamides; prolonged IV infusions or high doses may cause bone marrow depression (if signs occur, give 5-15 mg/d leucovorin); caution in folate deficiency (eg, patients with long-term alcoholism, elderly patients, those receiving anticonvulsant therapy, those with malabsorption syndrome); hemolysis may occur in G-6-PD deficiency; patients with AIDS may not tolerate or respond to TMP-SMZ; caution in renal or hepatic impairment (perform urinalyses and renal function tests during therapy); give fluids to prevent crystalluria and stone formation

Cyclosporine (Sandimmune, Neoral)

Helpful in a variety of skin disorders. For prevention and/or suppression of inflammatory symptoms of Job syndrome.

Dosing

Adult

2.5-5 mg/kg/d PO in divided doses

Pediatric

Administer as in adults

Interactions

Carbamazepine, phenytoin, isoniazid, rifampin, and phenobarbital may decrease concentrations; azithromycin, itraconazole, nicardipine, ketoconazole, fluconazole, erythromycin, verapamil, grapefruit juice, diltiazem, aminoglycosides, acyclovir, amphotericin B, and clarithromycin may increase toxicity; acute renal failure, rhabdomyolysis, myositis, and myalgia rates increase with concurrent lovastatin

Contraindications

Documented hypersensitivity; uncontrolled hypertension or malignancies; do not administer concomitantly with PUVA or UVB radiation in psoriasis (may increase risk of cancer)

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Evaluate renal and liver functions often by measuring BUN, serum creatinine, serum bilirubin, and liver enzyme levels; may increase risk of infection and lymphoma; use IV only for those who cannot take medication PO

Antifungals

Their mechanism of action may involve an alteration of RNA and DNA metabolism or an intracellular accumulation of peroxide that is toxic to the fungal cell.

Fluconazole (Diflucan)

Fungistatic activity. Synthetic oral antifungal (broad-spectrum bistriazole) that selectively inhibits fungal cytochrome P-450 and sterol C-14 alpha-demethylation, preventing conversion of lanosterol to ergosterol and thereby disrupting cellular membranes. For treatment of fungal infections in Job syndrome, including onychomycosis.

Dosing

Adult

150 mg PO once or 400 mg qd, depending on severity of infection

Pediatric

3-6 mg/kg PO qd for 14-28 d or 6-12 mg/kg qd, depending on severity of infection

Interactions

Hydrochlorothiazides may increase levels; long-term coadministration of rifampin may decrease levels; coadministration may decrease phenytoin clearance; may increase concentrations of theophylline, tolbutamide, glyburide, and glipizide; effects of anticoagulants may increase with coadministration; cyclosporine concentrations may increase when administered concurrently

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Adjust dose in renal insufficiency; monitor closely if rashes develop and discontinue drug if lesions progress; may cause clinical hepatitis, cholestasis, and fulminant hepatic failure (including death) with underlying medical conditions (eg, AIDS, malignancy) or multiple concomitant medications; not recommended for breastfeeding mothers

Ketoconazole (Nizoral)

Fungistatic activity. Imidazole broad-spectrum antifungal agent; inhibits synthesis of ergosterol, causing cellular components to leak and resulting in fungal cell death. For treatment of fungal infections in Job syndrome, including onychomycosis.

Dosing

Adult

200 mg PO qd; increase to 400 mg PO qd, if clinically indicated

Pediatric

<2 years: Not established
>2 years: 3.3-6.6 mg/kg/d PO once

Interactions

Isoniazid may decrease bioavailability; coadministration decreases rifampin or ketoconazole effects; may increase toxicity of anticoagulants, corticosteroids, and cyclosporine (can adjust cyclosporine dosage); may decrease theophylline levels

Contraindications

Documented hypersensitivity; fungal meningitis

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Hepatotoxicity may occur; may reversibly decrease corticosteroid serum levels (adverse effects avoided with dose of 200-400 mg/d); administer antacid, anticholinergics, or H2 blockers at least 2 h after dose

Follow-up

Further Outpatient Care

• Extra vigilance may be required in routine screening of Job syndrome patients for scoliosis.
• If a school-based program exists, healthcare providers should be made aware of the Job syndrome patient's greater-than-typical risk of scoliosis.
• Early detection with proper care can prevent progression of Job syndrome.

Deterrence/Prevention

• Initiate treatment at the first signs of infection to prevent long-term complications.
• Regularly screen Job syndrome patients for scoliosis so that early noninvasive treatment can be used.

Complications

• Fournier gangrene due to infectious multiple atheromas of scrotal skin that progressed to the groin and thigh has been described in a patient with Job syndrome.²³

Prognosis

• Few data are available on the prognosis of patients with Job syndrome.
• Many Job syndrome patients who are undergoing regular monitoring and receiving appropriate treatment will live beyond the age of 50 years.
• Death is often due to infectious complications.

Patient Education

• Educate patients about the importance of recognizing the early signs of infection so that treatment can be initiated as soon as possible.
• Mild local pain should be considered a sign of possible infection, and Job syndrome patients should be taught that the typical inflammatory response does not necessarily occur.

Miscellaneous

Medicolegal Pitfalls

• Physicians should be aware that a normal IgE level does not exclude Job syndrome in an adult.
• If the patient's history is suggestive of this disorder, a complete workup is still in order.
• The threshold for suspected abscesses should be lower in patients with hyper-IgE syndrome because few, if any, signs of inflammation are usually present.

References

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2. Minegishi Y, Karasuyama H. Genetic origins of hyper-IgE syndrome. Curr Allergy Asthma Rep. Sep 2008;8(5):386-91. [Medline].

3. Ma CS, Chew GY, Simpson N, et al. Deficiency of Th17 cells in hyper IgE syndrome due to mutations in STAT3. J Exp Med. Jul 7 2008;205(7):1551-7. [Medline].

4. Stiehm ER. Cytokine dysregulation in the hyperimmunoglobulinemia E syndrome. J Pediatr. Feb 2000;136(2):141-3. [Medline].

5. Paslin D, Norman ME. Atopic dermatitis and impaired neutrophil chemotaxis in Job's syndrome. Arch Dermatol. Jun 1977;113(6):801-5. [Medline].

6. Simon HU, Seger R. Hyper-IgE syndrome associated with an IL-4-producing gamma/delta(+) T-cell clone. J Allergy Clin Immunol. Jan 2007;119(1):246-8. [Medline].

7. Vargas L, Patino PJ, Rodriguez MF, et al. Increase in granulocyte-macrophage-colony-stimulating factor secretion and the respiratory burst with decreased L-selectin expression in hyper-IgE syndrome patients. Ann Allergy Asthma Immunol. Sep 1999;83(3):245-51. [Medline].

8. Shirafuji Y, Matsuura H, Sato A, Kanzaki H, Katayama H, Arata J. Hyperimmunoglobin E syndrome: a sign of TH1/TH2 imbalance?. Eur J Dermatol. Mar 1999;9(2):129-31. [Medline].

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14. Ling JC, Freeman AF, Gharib AM, et al. Coronary artery aneurysms in patients with hyper IgE recurrent infection syndrome. Clin Immunol. Mar 2007;122(3):255-8. [Medline].

15. Sarmento KM Jr, Tomita S, Caliman e Gurgel JD. Association between nasal polyposis, Dubowitz syndrome and hyper-IgE syndrome. Int J Pediatr Otorhinolaryngol. May 2008;72(5):711-4. [Medline].

16. Borges WG, Hensley T, Carey JC, Petrak BA, Hill HR. The face of Job. J Pediatr. Aug 1998;133(2):303-5. [Medline].

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19. Grimbacher B, Schaffer AA, Holland SM, et al. Genetic linkage of hyper-IgE syndrome to chromosome 4. Am J Hum Genet. Sep 1999;65(3):735-44. [Medline].

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21. Kojima K, Inoue Y, Katayama Y, et al. Improvement with disodium cromoglycate of neutrophil phagocytosis and respiratory burst activity in a patient with hyperimmunoglobulin E syndrome. Allergy. Nov 1998;53(11):1101-3. [Medline].

22. Wakim M, Alazard M, Yajima A, Speights D, Saxon A, Stiehm ER. High dose intravenous immunoglobulin in atopic dermatitis and hyper-IgE syndrome. Ann Allergy Asthma Immunol. Aug 1998;81(2):153-8. [Medline].

23. Hori J, Yamaguchi S, Watanabe M, Osanai H, Hori M. Fournier gangrene associated with hyper IgE syndrome (Job syndrome). Int J Urol. Apr 2008;15(4):372-3. [Medline].

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Keywords

Job syndrome, hyperimmunoglobulin E syndrome, hyper IgE syndrome, hyper-IgE syndrome, HIE syndrome, Job's syndrome, IgE, immunoglobulin E

Contributor Information and Disclosures

Author

Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi
Disclosure: Nothing to disclose.

Coauthor(s)

Mordechai M Tarlow, MD, Physician, Department of Medicine, Section of Dermatology, Kimball Medical Center
Mordechai M Tarlow, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for MOHS Surgery, American Society of Cosmetic Dermatology and Aesthetic Surgery, and Sigma Xi
Disclosure: Nothing to disclose.

Medical Editor

Bernice R Krafchik, MBChB, FRCPC, Professor Emeritus, Department of Pediatrics, Section of Dermatology, University of Toronto
Bernice R Krafchik, MBChB, FRCPC is a member of the following medical societies: American Academy of Dermatology, American Dermatological Association, Canadian Medical Association, College of Physicians and Surgeons of Ontario, Royal College of Physicians and Surgeons of Canada, and Society for Pediatric Dermatology
Disclosure: Nothing to disclose.

Pharmacy Editor

David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic
David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Managing Editor

Jeffrey J Miller, MD, Associate Professor of Dermatology, Penn State University College of Medicine; Staff Dermatologist, Penn State Milton S Hershey Medical Center
Jeffrey J Miller, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, Association of Professors of Dermatology, North American Hair Research Society, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

CME Editor

Glen H Crawford, MD, Assistant Clinical Professor, Department of Dermatology, University of Pennsylvania School of Medicine; Chief, Division of Dermatology, The Pennsylvania Hospital
Glen H Crawford, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Phi Beta Kappa, and Society of USAF Flight Surgeons
Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

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