Recognition, diagnosis, and treatment of histoplasmosis complicating tumor necrosis factor blocker therapy.

Life-threatening histoplasmosis is one of the most common opportunistic infections in patients receiving tumor necrosis factor (TNF) blockers. Delays in considering the diagnosis may lead to increased morbidity and mortality. Most affected patients present with pneumonitis, usually accompanied by additional signs of progressive dissemination, or with signs of progressive dissemination alone. The diagnosis often can be promptly established using antigen detection or direct examination of bronchoalveolar lavage specimens. If histoplasmosis is diagnosed promptly, antifungal therapy is highly effective. After a favorable clinical response, the safety of both discontinuation of antifungal therapy and the resumption of TNF blocker remains undetermined. The management of the immune reconstitution inflammatory syndrome that may follow discontinuation of TNF blockers also requires investigation. Prescribers should become aware of the recognition, diagnosis, and treatment of histoplasmosis and educate recipients about decreasing their risk of exposure and both recognizing and reporting signs of early infection.

False-negative Histoplasma antigen in acute pulmonary histoplasmosis: the value of urinary concentration by ultrafiltration and heat denaturation of serum proteins in detection of Histoplasma antigen.

We report an infant with localized pulmonary histoplasmosis in whom Histoplasma antibody assays, quantitative Histoplasma urine and serum antigen concentrations, and histopathologic findings of a mediastinal mass were nondiagnostic. A provisional diagnosis of histoplasmosis was established by using laboratory methods that increase the sensitivity of the antigen assay using ultrafiltration of urine and ethylenediaminetetraacetic acid/heat denaturation of serum proteins.

Ileocecal histoplasmosis simulating Crohn disease in a patient with hyperimmunoglobulin E syndrome.

We describe a 14-year-old girl with hyperimmunoglobulin E (Job) syndrome who presented with fatigue, abdominal pain, fever, and weight loss. Endoscopic examination of the terminal ileum revealed ulceration, edema, and erythema. Histopathologic findings of the terminal ileum demonstrated intracellular yeast forms compatible with Histoplasma capsulatum. The patient was treated with oral itraconazole and had a rapid and complete response.

Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America.

Evidence-based guidelines for the management of patients with histoplasmosis were prepared by an Expert Panel of the Infectious Diseases Society of America. These updated guidelines replace the previous treatment guidelines published in 2000 (Clin Infect Dis 2000; 30:688-95). The guidelines are intended for use by health care providers who care for patients who either have these infections or may be at risk for them. Since 2000, several new antifungal agents have become available, and clinical trials and case series have increased our understanding of the management of histoplasmosis. Advances in immunosuppressive treatment for inflammatory disorders have created new questions about the approach to prevention and treatment of histoplasmosis. New information, based on publications from the period 1999-2006, are incorporated into this guideline document. In addition, the panel added recommendations for management of histoplasmosis in children for those aspects that differ from aspects in adults.

Capnocytophaga canimorsus meningitis in a newborn: an avoidable infection.

Capnocytophaga canimorsus causes dog-bite wound induced sepsis in adults, but infection may follow mucous membrane exposure. Systemic infection in children is extremely rare. A neonate with frequent exposure to a family dog and no cutaneous infection developed C. canimorsus meningitis. Suspicion of this pathogen requires laboratory consultation. Parental counseling can limit the risk of pet acquired infections.

Oral erythromycin prophylaxis vs watchful waiting in caring for newborns exposed to Chlamydia trachomatis.

BACKGROUND: Chlamydia trachomatis exposure at birth may cause conjunctivitis or pneumonia. Until recently, a course of oral erythromycin prophylaxis was recommended for C trachomatis-exposed neonates. However, recognition of an association between erythromycin and pyloric stenosis prompted a change to a watchful waiting recommendation under which only infants who develop symptomatic C trachomatis infection are treated with oral erythromycin. OBJECTIVE: To compare erythromycin prophylaxis with watchful waiting for a hypothetical cohort of 100 000 neonates exposed to C trachomatis. METHODS: In a decision tree, potential outcomes were C trachomatis conjunctivitis, C trachomatis pneumonia (which could require inpatient or outpatient therapy), no clinical disease, and pyloric stenosis. Published data were reviewed to derive probability point estimates and ranges. Estimated charges served as outcome measures. RESULTS: Watchful waiting is less expensive than erythromycin prophylaxis ($15.1 million vs $28.3 million); prophylaxis prevents 5986 cases of C trachomatis pneumonia, including 1197 hospital admissions, but causes 3284 pyloric stenosis cases. (For every 30 infants given oral erythromycin prophylaxis, one additional case of pyloric stenosis would be expected to occur, and approximately 1.8 cases of C trachomatis pneumonia would be prevented.) In sensitivity analyses, if more than 3.4% of exposed neonates are hospitalized for C trachomatis pneumonia, prophylaxis becomes favored. CONCLUSIONS: This study supports the watchful waiting recommendation for asymptomatic C trachomatis-exposed neonates. However, there are wide plausible ranges for pyloric stenosis risk after erythromycin administration and for the incidence of C trachomatis pneumonia severe enough to require hospitalization; under some combinations of these rates, prophylaxis could be favored.

Disseminated histoplasmosis of infancy in one of the twins.

This report describes clinical manifestations of histoplasmosis in 6-month-old dizygotic twins, one of whom developed disseminated histoplasmosis of infancy while his sibling remained well, but developed serologic evidence of histoplasmosis. The report also documents histoplasma antigen concentrations in serum and urine before, during and after completing antifungal therapy.

Assessment of the validity of reported antibiotic allergic reactions in pediatric patients.

STUDY OBJECTIVE: To determine whether a reported antibiotic allergy was likely to have been immunologically mediated. DESIGN: Questionnaire-based study. SETTING: Tertiary care, freestanding children's hospital. PATIENTS: One hundred patients aged 1 month-18 years for whom guardians reported an allergy to an antibiotic at the time of hospital admission between October 2009 and March 2010. INTERVENTION: guardians of the patients were interviewed by using a standardized allergy assessment questionnaire. MEASUREMENTS AND MAIN RESULTS: Based on answers to the questionnaire, the reported allergic reactions were categorized to determine if they were true allergies or adverse reactions. Among the 100 patients, reported allergies were categorized as immunologically mediated reactions in 58%, non-immunologically mediated adverse drug reactions in 27%, no reaction in 3%, and unknown in 12%. Reactions to penicillins, cephalosporins, or sulfonamides were reported most frequently and were attributed to immunologically mediated reactions in 68% (26/38), 74% (17/23), and 67% (10/15) of instances, respectively. CONCLUSION: Use of the allergy assessment questionnaire determined that 58% of the 100 reported antibiotic allergies fulfilled criteria for an immuno-logically mediated reaction. These findings underscore the utility of an allergy assessment questionnaire, versus a simple drug history, in improving the accuracy of reported antibiotic reactions.

The role of pelvic magnetic resonance in evaluating nonhip sources of infection in children with acute nontraumatic hip pain.

We retrospectively identified all children with acute hip pain who underwent pelvic magnetic resonance (MR). Children with septic hip or history of trauma were excluded; the remaining children with signs of infection (fever, >38 degrees C; leukocytosis, >12 x 10(9)/L; or elevated erythrocyte sedimentation rate [ESR], >30 mm/h) comprised the study group. Thirty-three children (9 girls; age, 0.8-15.8 years) were identified. On MR examination, 18 (55%) of 33 children had hip joint effusion, whereas 19 (58%) of 33 children had other abnormalities, including pyomyositis (n=15), osteomyelitis (n=12), and sacroiliitis (n=3). Staphylococcus aureus was cultured from 13 (68%) of these 19 children. Compared with MR, sensitivity for bone and soft tissue abnormalities was 30% for pelvic radiography (n=26) and 71% for bone scintigraphy (n=8). Elevated ESR (>30 mm/h) was the clinical finding that best predicted pelvic osteomyelitis or pyomyositis. Pelvic MR should be performed to rule out pelvic osteomyelitis or pyomyositis in children with acute hip pain, ESR of more than 30 mm/h, and no evidence of septic hip.

Acute pyomyositis of the pelvis: the spectrum of clinical presentations and MR findings.

BACKGROUND: Acute pelvic pyomyositis is uncommon in non-tropical areas. OBJECTIVE: To summarize the clinical and MR findings in children with acute pelvic pyomyositis. MATERIALS AND METHODS: We retrospectively identified 20 children (mean age 9.4 years) who were evaluated by MR and diagnosed with acute pelvis pyomyositis during the time period between January 2002 and June 2005. We reviewed clinical, laboratory, and imaging findings. RESULTS: Fifteen of the 20 children had secondary pyomyositis associated with osteomyelitis (n=13), septic hip (n=4) or sacroiliitis (n=4); all were previously healthy except for one child with leukemia. Seven of the children with secondary pyomyositis underwent bone scintigraphy; three (43%) did not show pelvic abnormalities. Staphylococcus aureus was cultured in 13 of the 15 (87%) children. Five of the 20 children had primary pyomyositis. Three had underlying disease and two others were engaged in vigorous physical activity. Bone scintigraphies (n=2) were negative. Cultures were positive for S. aureus in three of the five (60%) children. CONCLUSION: Septic hip should be the first diagnostic consideration in children with fever and acute hip pain. Pyomyositis should be considered if arthrocentesis is negative or there is clinical suspicion of infection outside the hip joint. MR is the preferred imaging modality for evaluating foci of pyomyositis, muscle abscesses, and additional foci of infection within the pelvis.

Esophageal diverticulum: a complication of histoplasmosis in children.

We report three boys, ages 8 to 14 years, who experienced dysphagia or chest pain while eating. In each patient, contrast esophagrams or esophagogastroduodenoscopy (EGD) demonstrated mid-esophageal traction diverticula, and serologic findings were compatible with acute or recent histoplasmosis. Diverticula appear to result from esophageal traction induced by inflammatory changes in adjacent infected lymph nodes. Antifungal and anti-inflammatory therapies were individualized in each case; all patients recovered fully.

Cervical abscess and mediastinal adenopathy: an unusual presentation of childhood histoplasmosis.

Histoplasmosis is the most common endemic respiratory mycosis in the United States. We report the clinical and imaging findings in a case of a child with the rare presentation of a neck abscess and mediastinal lymphadenopathy secondary to acute, non-disseminated histoplasmosis. Imaging findings often mimic other granulomatous infections such as tuberculosis or neoplastic processes such as lymphoma. Histoplasmosis should be considered in the differential diagnosis of a child who presents with enlarged mediastinal and cervical lymphadenopathy.

Histoplasmosis after treatment with anti-tumor necrosis factor-alpha therapy.

Anti-tumor necrosis factor-alpha (TNF-alpha) antibodies are frequently used to treat inflammatory diseases. However, these drugs also have immunosuppressive effects. We report on three patients who developed disseminated histoplasmosis on therapy with TNF-alpha inhibitors. In vitro assays were used to characterize the role of these agents in host defense against Histoplasma capsulatum. Intracellular proliferation of H. capsulatum was measured in alveolar macrophages and peripheral monocytes of normal volunteers in the presence and absence of the TNF-alpha antibody, infliximab. Both infliximab and control antibody enhanced fungal growth in monocytes and alveolar macrophages, suggesting this was a nonspecific antibody response. Despite similar intracellular fungal loads in the presence of both antibodies, lymphocyte proliferation in response to blood monocytes and alveolar macrophages infected with H. capsulatum was inhibited by the addition of physiologic doses of infliximab, whereas control antibody had no effect. The production of H. capsulatum-induced interferon-gamma and TNF-alpha was assessed in 5-day cultures containing lymphocytes and alveolar macrophages or monocytes. Interferon-gamma secretion was significantly reduced in the presence of infliximab. In summary, patients receiving anti-TNF-alpha therapy are at risk for developing disseminated histoplasmosis. This may be due to a defect in the TH1 arm of cellular immunity.