trimethoprim--sulfamethoxazole-drug-combination and Job-Syndrome

Hyperimmunoglobulin E syndrome (HIES) is a rare immunodeficiency associated with elevated serum IgE levels, eczematous skin, recurrent cutaneous infections, and distinctive musculoskeletal features. We report two cases seen at our institution and review the current literature. Patient 1 was an 18-month-old African American boy with recurrent staphylococcal cold abscesses, pneumonia, and bacteremia. He had severely eczematous skin, ultimately complicated by eczema herpeticum. After treatment of systemic infections with culture-directed antibiotics, a brief course of cyclosporine, 5 mg/kg, improved the dermatitis and allowed transition to long-term therapy with oral trimethoprim-sulfamethoxazole. Patient 2 was a 15-year-old Caucasian boy with long-standing HIES. He has been maintained on a regimen of interferon gamma injections given 3 times weekly and monthly intravenous immunoglobulin since the age of 3 years, prophylactic antibiotics, and low-dose fluconazole. He has occasional episodes of cold abscesses and sinusitis, but has had excellent control since institution of this regimen and has not experienced any adverse effects.

Topics: Adolescent; Anti-Bacterial Agents; Anti-Infective Agents; Antifungal Agents; Fluconazole; Humans; Immunoglobulins, Intravenous; Infant; Job Syndrome; Kaposi Varicelliform Eruption; Male; Prognosis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Hyper-IgE syndrome (HIE) and chronic granulomatous disease (CGD) are congenital immunodeficiency diseases with increased susceptibility to bacterial and fungal infections. Both carry significant morbidity and mortality rates because of invasive infections by Aspergillus species. We encountered 2 patients, one with HIE and one with CGD, in whom detection of sensitization to Aspergillus species preceded the diagnosis of immunodeficiency. With high-dose systemic corticosteroids for allergic bronchopulmonary aspergillosis (ABPA), an inflammatory disorder caused by sensitization to Aspergillus species, pulmonary abscesses developed in the patient with HIE, and the patient with CGD succumbed to an overwhelming Aspergillus species-induced pneumonia.. We sought to assess the prevalence of sensitization to Aspergillus fumigatus and the presence of diagnostic criteria for ABPA in patients with CGD and HIE.. We measured A fumigatus-specific serum IgE, IgG, and precipitating antibodies as indicators for A fumigatus sensitization in the sera of 18 patients with neutrophil disorders (7 with HIE and 11 with CGD). Hospital records were reviewed for the presence of other diagnostic criteria for ABPA (asthma, elevated total serum IgE concentration, and radiographic abnormalities).. Twelve (67%) of 18 patients were sensitized to A fumigatus, as evidenced by precipitating A fumigatus-specific antibodies. Six (33%) of 18 patients had serologic evidence of ABPA. Five of those 6 patients had radiologic abnormalities consistent with a diagnosis of ABPA. One patient with HIE also had asthma, thus fulfilling minimal essential criteria for concurrent ABPA.. Patients with HIE syndrome and CGD have a high incidence of sensitization to Aspergillus species. A clinical picture indistinguishable from ABPA may coexist or emerge in patients with CGD or HIE and create a major management dilemma because systemic corticosteroids may accelerate tissue damage and invasive fungal infections. It is important to distinguish individuals with congenital neutrophil disorders from uncomplicated classic ABPA.

Topics: Adult; Antibiotic Prophylaxis; Aspergillosis; Aspergillus fumigatus; Female; Granulomatous Disease, Chronic; Humans; Immunity, Innate; Immunization; Job Syndrome; Male; Trimethoprim, Sulfamethoxazole Drug Combination

A male patient with hyperimmunoglobulin E syndrome is described. Recurrent lymphadenitis and cutaneous staphylococcal abscesses were resistant to various antibiotics, and chemotaxis and hydrogen peroxide production of polymorphonuclear leukocytes were impaired. Following trimethoprim-sulfamethoxazole therapy, he was free from the above infections, and impaired polymorphonuclear leukocyte functions recovered and serum IgE decreased to approximately one-fifth of its initial level. Subsequent irregular medications, however, resulted in impairment of polymorphonuclear leukocyte functions and an increased serum IgE concentration, which recovered after regular resumption of trimethoprim-sulfamethoxazole treatment. From these results, the beneficial effects of trimethoprim-sulfamethoxazole in hyperimmunoglobulin E syndrome are clinically apparent, but in vitro studies failed to demonstrate the positive effect of trimethoprim-sulfamethoxazole on polymorphonuclear leukocytes and their mechanism still remains to be elucidated.

Topics: Adolescent; Humans; Immunoglobulin E; Job Syndrome; Male; Neutrophils; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination