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• W2039232896 abstract "Mycobacterium chelonae is a rapidly growing mycobacterium belonging to Runyon group IV. Formerly known as M. chelonae subspecies chelonae, this pathogen is found widely in soil throughout the United States and causes skin and soft tissue infections in immunocompromised adults or in association with trauma.1 person-to-person transmission is uncommon. The most likely source of infection in humans is the environment.2 We report a case of disseminated infection caused by M. chelonae in an immunocompetent child that was probably responsible for more than 3 years of fever of unknown origin before recognition and was cured with prolonged clarithromycin therapy. Case report. An 18-month-old white male from northeastern Pennsylvania with no significant past medical history had spontaneous onset of episodes of recurrent fever of 39-40°C every 6 to 8 weeks, lasting for 7 to 10 days, with intermittent constipation, cough and complaints of earache and sore throat. Antibiotic therapies did not affect the courses of fever, and he was completely well and thriving between episodes. Abnormal laboratory test results were limited to erythrocyte sedimentation rate ranging between 17 and 34 mm/h and a slightly elevated serum IgG of 1450 mg/dl (IgA 54 mg/dl and IgM 161 mg/dl). He had not had serious or unusual numbers of infections, used corticosteroids or had any injuries. He received his immunizations on time including his measles-mumps-rubella immunization at 15 months of age. There was no family history of infectious diseases, childhood deaths, immunodeficiency or autoimmune disease. The family lived in a suburban community and used spring water. They had a healthy dog and cat and had not traveled. At 2 years of age he began to complain of leg and joint pain during febrile episodes, in addition to other symptoms, and activity had decreased. Several throat cultures were negative for group A Streptococcus. Physical examination was unremarkable except for enlarged tonsils. He was evaluated by a pediatric infectious disease consultant and the following tests were normal: complete blood count and peripheral blood smear; urinalysis; urine and stool cultures; viral throat cultures (positive for enterovirus on one occasion); serum hepatic enzymes; antinuclear antibody; streptozyme; antibodies to cytomegalovirus, Epstein-Barr virus and human immunodeficiency virus; B and T lymphocyte count; and CD4:CD8 ratio. Absolute neutrophil count was >6000 cells/mm3 on multiple samplings. Imaging studies including technetium bone scans on two occasions, sinus and chest radiographs, barium upper gastrointestinal series with small bowel follow-through and computed tomography of the abdomen and pelvis were normal. Ibuprofen was given during febrile episodes and erythromycin was given for prophylaxis of recurrent ear and throat infections without clear benefit. Episodes of fever continued. Height and weight remained at or above the 25th percentile. At 5½ years of age the boy was reevaluated for continued episodic fever. His mother reported that he had developed crops of 3 to 5 small, red, painful lesions on his hands and feet intermittently for the previously 18 months, not always related to fever. Initially lasting for 2 to 3 days (and disppearing without drainage, but with desquamation), they now lasted longer. Biopsy of a lesion revealed acid-fast organisms on two occasions and a rapidly growing Mycobacterium, M. chelonae, was isolated on both biopsies and confirmed at the Pennsylvania State Laboratory, at the National Jewish Center in Denver, CO, and at the University of Texas Health Sciences Center, Tyler, TX (Richard J. Wallace, Jr., M.D.). Testing revealed susceptibility to clarithromycin (MIC 0.125 μg/ml), aminoglycosides (MICs 2-16 μg/ml) and azithromycin (MIC 1 μg/ml); and resistance to cefoxitin and rifampin. Erythromycin MIC was 8 μg/ml. A Mantoux purified protein derivative was negative and Candida (1:100) was positive. Repeat blood count, screening metabolic tests and echocardiogram were normal. The patient was referred to St. Christopher's Hospital for Children where the diagnosis of chronic disseminated M. chelonae infection was reaffirmed. Clarithromycin 18.75 mg/kg/day was administered for 6 months. Recurrent fevers and lesions on his hands and feet disappeared with only two recurrences during the first 2 weeks of clarithromycin therapy. Fever and skin lesions recurred at the age of 6 years and 6 months after discontinuing clarithromycin therapy for 7 months. Physical examination was unremarkable except for lesions on his hands and feet and enlarged tonsils. M. chelonae was isolated from a skin lesion biopsy with antimicrobial susceptibility similar to that of the original isolate. Clarithromycin suspension 28 mg/kg/day was begun, and tonsillectomy was performed 4 months later. Histologic examination, special stains and culture of tonsillar tissue were negative for mycobacteria. Clarithromycin was discontinued after 6 months of therapy. He subsequently had two episodes of fever and skin lesions 6 months later; acid-fast stain and culture of biopsy were negative and the course was self-limited. He is now 10 years old and had not received therapy for 3 years and is well, with no recurrences or other health problems. An IgD at 10 years of age was 15 mg/dl (normal, 0 to 30 mg/dl). Discussion. The Runyon group IV, rapidly growing mycobacteria of clinical significance include M. chelonae, Mycobacterium fortuitum and Mycobacterium abscessus. They are distinguished from other mycobacteria by the growth of nonpigmented colonies within 3 to 7 days on selective media and from each other by growth characteristics, biochemical tests and gas-liquid chromatography of metabolic products. Organisms are ubiquitous in the environment and have been recovered from fresh and salt water, hospital dust and soil2 and can occasionally be part of normal flora of the respiratory and gastrointestinal tract.3M. fortuitum and M. chelonae are most significant clinically, causing predominantly skin and soft tissue infection in immunocompetent adults4, 5 and children6 after trauma, particularly penetrating trauma with soil contamination. Disseminated infection caused by M. chelonae is uncommon in adults, occurring in patients with serious underlying disease or immunocompromised state such as after renal transplantation, chronic dialysis or use of immunosuppressive agents for autoimmune disease. In a recent review 92% of patients with disseminated disease were being treated with corticosteroids.1 Infections caused by Mycobacterium fortuitum-chelonae complex related to indwelling catheters are reported increasingly, especially in patients with cancer,7, 8 in whom neutropenia is probably a significant predisposition.9 Experimentally M. chelonae adheres extremely well to silicone catheters.10 Disseminated M. chelonae infection is rare in children with cases reported in a prematurely born neonate,3 in a 3-year-old child with trisomy 2111 and in several children with cancer and vascular catheters.7, 9, 11, 12 Disseminated infection as defined by Ingram et al.11 includes any of the following clinical variants: (1) multiple cutaneous abscesses; (2) visceral infection with or without cutaneous manifestation; (3) bloodstream infection (blood or bone marrow) with evidence of deep infection. Fever and rash have been the clinical features reported most consistently in patients with disseminated infection.11 Fatality is uncommon when there is no immune defect, but chronic infection is typical and can cause significant morbidity requiring prolonged therapy. The diagnosis usually is made by stain and culture of biopsies of skin lesions. Blood or bone marrow cultures are often positive. Our patient is unique in that he had disseminated infection manifested for 5 years as recurrent episodes of fever and embolic lesions confined to hands and feet and had no identifiable underlying disease, predisposing trauma or corticosteroid use. Although a subtle neutrophil deficiency cannot be excluded, absence of other clinical manifestations or other infections makes this unlikely. Possible chronic infection in tonsils is speculated. Localized cutaneous M. chelonae infection can often be treated successfully with excision alone. Patients with disseminated infection are more difficult to manage because a focus of infection usually cannot be found, organisms are resistant to most antimycobacterial agents and long term therapy is required to prevent relapse. Current treatment practices are derived largely from case reports.13 Clarithromycin has most exquisite activity against M. chelonae, is well-absorbed from the gastrointestinal tract, penetrates into tissues and cells including macrophages and neutrophils14 and has been successful as monotherapy in cases of disseminated infection.12, 13 Two or three drug therapy (including clarithromycin) should be considered for treatment in immunosuppressed patients initially to limit emergence of resistance.15 Ciprofloxacin and amikacin frequently are active but susceptibility testing should be performed to guide therapy. The E test has promising application for susceptibility testing of rapidly growing mycobacteria.16 Adherence to clarithromycin therapy in our patient improved when the more palatable suspension became available; inadequate therapy resulting from poor compliance may have been the cause of his relapse. Recurrent crops of skin lesions have been observed in adults during therapy. Those skin lesions are acid-fast stain-negative and culture-negative after the first 6 weeks of therapy (as seen in our patient) and may reflect immune phenomena. Whether our patient is a medical curiosity or represents an unrecognized entity of some frequency remains to be clarified. Acknowledgment. We thank Richard J. Wallace, Jr., M.D., at the University of Texas Health science Center, Tyler, TX, for performing susceptibility testing. Michael E. Ryan, D.O.; Kelly Ferrigno, M.D.; Tomas O'Boyle, M.D.; Sarah S. Long, M.D. Department of Pediatric Subspecialties Geisinger Clinic Danville, PA (MER, KF, TO) Department of Pediatrics Temple University School of Medicine Section of Infectious Diseases St. Christopher's Hospital for Children Philadelphia, PA (SSL)" @default.
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• W2039232896 title "PERIODIC FEVER AND SKIN LESIONS CAUSED BY DISSEMINATED MYCOBACTERIUM CHELONAE INFECTION IN AN IMMUNOCOMPETENT CHILD" @default.
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