eMedicine Specialties > Dermatology > Allergy & Immunology
Job Syndrome: Treatment & Medication
Updated: Jul 17, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
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.
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
May decrease effects of warfarin and contraceptives when administered concurrently; bacteriostatic action of tetracycline derivatives may decrease effects
Documented hypersensitivity
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.
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
Decreases effects of contraceptives and tetracycline; concomitant disulfiram and probenecid may decrease levels; large IV doses may increase effect of anticoagulants
Documented hypersensitivity
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.
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
Probenecid and disulfiram increase levels; allopurinol decreases effects and has additive effects on ampicillin rash; may decrease effects of oral contraceptives
Documented hypersensitivity
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.
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
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
Documented hypersensitivity
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.
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
Probenecid prolongs effect; coadministration with aminoglycosides may increase renal toxicity; may yield false-positive results with urine-dip test for glucose
Documented hypersensitivity
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.
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
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
Documented hypersensitivity; megaloblastic anemia due to folate deficiency
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.
Adult
2.5-5 mg/kg/d PO in divided doses
Pediatric
Administer as in adults
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
Documented hypersensitivity; uncontrolled hypertension or malignancies; do not administer concomitantly with PUVA or UVB radiation in psoriasis (may increase risk of cancer)
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.
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
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
Documented hypersensitivity
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.
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
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
Documented hypersensitivity; fungal meningitis
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
More on Job Syndrome |
| Overview: Job Syndrome |
| Differential Diagnoses & Workup: Job Syndrome |
 Treatment & Medication: Job Syndrome |
| Follow-up: Job Syndrome |
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References
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Further Reading
Keywords
Job syndrome, hyperimmunoglobulin E syndrome, hyper IgE syndrome, hyper-IgE syndrome, HIE syndrome, Job's syndrome, IgE, immunoglobulin E
