Medication Summary
Patients with severe HIES require prophylactic antibiotics to cover S aureus and an antifungal to cover C albicans. Pneumonia and deep-seeded abscesses caused by S aureus are treated intravenously with nafcillin if the isolate is methicillin-sensitive and with vancomycin if it is methicillin-resistant. Lung abscesses superinfected with Aspergillus species require intravenous amphotericin B for several months. Gram-negative bacteria, including P aeruginosa, require an aminoglycoside and a third-generation cephalosporin or another synergistic antibiotic.
Any deep-seeded abscess must be adequately debrided and drained surgically.
Eczematous dermatitis is treated with a topical corticosteroid, a moisturizing cream, and an antihistamine to decrease pruritus.
Respiratory care may require a beta2-agonist and an inhaled corticosteroid with careful monitoring of pulmonary function tests and clinical response.
HIES patients who were found to have profound functional Ab deficiency may be benefited from exogenous immunoglobulins given monthly basis. However, in most patients with AD HIES, Ab deficiency or decreased memory B cell numbers are not associated with infection history. [21]
Antibiotics
Class Summary
Antibiotics are first line therapy for S aureus. Response can often be achieved using oral dicloxacillin when the organism is methicillin-sensitive S aureus (MSSA). For more deep-seated infections, intravenous therapy with nafcillin or oxacillin is necessary. MRSA infections are usually managed with intravenous vancomycin because these organisms are often hospital acquired. Community-acquired methicillin-resistant S aureus (MRSA) infections at more superficial, cutaneous sites may be susceptible to oral fluoroquinolones, clindamycin, or trimethoprim-sulfamethoxazole. Vancomycin resistance (ie, glycopeptide intermediate S aureus resistance [GISA]) is managed with antibiotics such as quinupristin-dalfopristin (Synercid), linezolid, or fluoroquinolones. For severe staphylococcal infections, a combination of a beta-lactam antibiotic and an aminoglycoside may be the initial treatment.
Additional antistaphylococcal therapy may include topical mupirocin to the nares to eradicate colonization.
Dicloxacillin
Well-absorbed but poor aftertaste. Follow by 1 tsp chocolate syrup to increase palatability. Binds to ≥ 1 penicillin-binding protein, which, in turn, inhibits synthesis of bacterial cell walls.
Nafcillin
Use for invasive infections including abscesses. Vancomycin preferred for CNS infection because does not penetrate well into CSF.
Vancomycin (Vancocin, Vancoled)
Use for MRSA infection and penicillin allergy. Monitoring of peak and trough levels is controversial; steady state is achieved at peak 60 min after the third through fifth consecutive dose. Achieving above MIC for infecting organism is critical; consultation with infectious disease specialist may be appropriate, particularly with advent of GISA.
Linezolid (Zyvox)
May be considered for therapy for MRSA, GISA, vancomycin-resistant enterococci, and penicillin-resistant pneumococci but does not cover gram-negative bacteria.
Has good PO absorption. Available as PO susp at 100 mg/5 mL.
Quinupristin/Dalfopristin (Synercid)
Active against MRSA, MSSA, penicillin-sensitive or resistant S pneumoniae, and vancomycin-resistant Enterococcus faecium. Administered IV only. Inhibits CYP3A4.
Mupirocin (Bactroban)
Topical antibiotic used to eliminate S aureus colonization, particularly of the nares.
Topical corticosteroids
Class Summary
Multiple preparations of topical corticosteroids of varying potencies are available. The eczematous dermatitis of hyperimmunoglobulinemia E syndrome typically requires high-potency ointments used in conjunction with an emollient bid. Dermatitis may subside for no apparent reason; interestingly, it may improve during acute infection.
Adverse effects that must be discussed with the patient and family include damage to the skin, especially of the face and intertriginous areas, and the potential for systemic absorption leading to growth impairment, adrenal suppression, and the other common complications of systemic steroids. Occlusive dressings increase systemic absorption from the skin.
Triamcinolone topical (Aristocort)
Categorized in group III potency with betamethasone dipropionate lotion 0.05%. Treats inflammatory dermatosis that is responsive to steroids. Decreases inflammation by suppressing the migration of polymorphonuclear leukocytes and reversing capillary permeability.
Betamethasone dipropionate ointment 0.05% (Alphatrex, Diprolene, Maxivate)
Categorized as group II, more potent than group III topical steroids. For inflammatory dermatoses responsive to steroids. Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing capillary permeability.
Topical calcineurin inhibitors
Class Summary
These agents modify immune processes that promote inflammation.
Tacrolimus, topical 0.03%, 0.1% (Protopic)
Reduces itching and inflammation by suppressing the release of cytokines from T cells. Also inhibits transcription for genes that encode IL-3, IL-4, IL-5, GM-CSF, and TNF-alpha, all of which are involved in the early stages of T-cell activation. Additionally, may inhibit release of preformed mediators from skin mast cells and basophils, and may down-regulate expression of FCeRI on Langerhans cells. Indicated for eczema and atopic dermatitis only after other treatment options have failed.
Pimecrolimus (Elidel cream)
Indicated for eczema and atopic dermatitis. Indicated only after other treatment options have failed. First nonsteroid cream approved in the United States for mild-to-moderate atopic dermatitis. Derived from ascomycin, a natural substance produced by fungus Streptomyces hygroscopicus var ascomyceticus. Selectively inhibits production and release of inflammatory cytokines from activated T cells by binding to cytosolic immunophilin receptor macrophilin-12. Resulting complex inhibits phosphatase calcineurin, thus blocking T-cell activation and cytokine release.
Cutaneous atrophy was not observed in clinical trials, a potential advantage over topical corticosteroids.
Second-line antistaphylococcal antibiotics
Class Summary
In specific cases in which the patient has hypersensitivity to penicillin and a limited cutaneous infection with S aureus or if the patient has a more minor infection such as otitis media, trimethoprim-sulfamethoxazole or cephalexin can be considered for management. MSSA infection may be sensitive to cephalexin. Certain community-acquired MRSA infections may be sensitive to trimethoprim-sulfamethoxazole.
Trimethoprim-sulfamethoxazole (Bactrim, Septra, Cotrim)
Second line because it achieves significant intracellular levels.
Inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid.
Cephalexin (Keflex, Biocef, Keftab)
Can be used in penicillin-allergic patients, but its tissue penetration is less reliable than TMP-SMZ.
First-generation cephalosporin arrests bacterial growth by inhibiting bacterial cell wall synthesis.
Antifungal agents
Class Summary
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)
DOC to prevent or treat candidal infections.
Fungistatic activity.
Synthetic oral antifungal (broad-spectrum bistriazole) that selectively inhibits fungal CYP450 and sterol C-14 alpha-demethylation, which prevents conversion of lanosterol to ergosterol, thereby disrupting cellular membranes.
Amphotericin B (Amphocin, Fungizone)
First-line therapy for Aspergillus, Candida resistant to fluconazole, and other invasive fungi.
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Chest radiograph of a patient with autosomal dominant (AD) hyperimmunoglobulin E syndrome (HIES) and a lung abscess following multiple staphylococcal pneumonias. Aspergillus fumigatus was isolated from the abscess.
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Father and daughter with autosomal dominant (AD) hyperimmunoglobulin E syndrome (HIES). Note the father's distinctive facies with prominent forehead, deep-set eyes, broad nasal bridge, and wide interalar distance.
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Mother and son with autosomal dominant (AD) hyperimmunoglobulin E syndrome (HIES). Note the mother's distinctive facies. She had a history of multiple deep-seated abscesses that took months to heal after incision and drainage.
