Fever of unknown origin in children: the experience of one center in Turkey.

Knowledge about the etiology of fever of unknown origin (FUO) has been changed under the influence of new advances in diagnostic techniques in both adulthood and childhood. Seventy-seven patients with the diagnosis of FUO were evaluated retrospectively. Forty-six (60%) of the patients were male and 31 (40%) were female, with ages ranging from 4 months to 16 years (mean: 4.5 years). Physical findings were absolutely normal in 33 (42.9%) patients, and the most common findings were hepatosplenomegaly (15.5%) and lymphadenopathy (15.5%). The etiologies were determined in 69 patients with FUO. The most common diagnoses were infectious diseases (50.7%), malignancy (14.4%), collagen vascular disorders (7.2%), and miscellaneous conditions (27.5%). With the development of diagnostic tools, the etiologies in a considerable number of patients with FUO were diagnosed. A detailed history and physical examination are required for accurate diagnosis, and if indicated, invasive procedures should be instituted.

Comparison of sulbactam-cefoperazone with carbapenems as empirical monotherapy for febrile neutropenic children with lymphoma and solid tumors.

Febrile neutropenia (FEN) is a leading complication of intensive chemotherapy. With this prospective randomized study, the authors aimed to compare the effectiveness of sulbactam-cefoperazone (SC) versus carbapenems, as empirical monotherapy in febrile neutropenic children with lymphoma and solid tumors. Febrile neutropenic children (age ≤16 years) hospitalized at the authors' center for lymphomas or solid tumors between March 2007 and June 2009 were included in the study. Patients randomly received SC or carbapenem. Patients were reevaluated at 72 hours and in case of persistent fever, an aminoglycoside and/or a glycopeptide was added to the antibiotic treatment. When a resistant pathogen was isolated, the antibiotic therapy was modified. Treatment responses was defined as success without modification, overall success, or failure. Two hundred and eight episodes were documented in 128 patients (F/M: 56/72), with a median age of 7 years (0.5-17.4 years). Absolute neutrophil count and duration of neutropenia in patients treated with SC and carbapenems were 133/mm(3) (0-500) and 113/mm(3) (0-500), and 4 days (1-21) and 5 days (2-20), respectively. In the SC and carbapenem groups, 82 (78.8%) and 84 episodes (80.7%) improved with treatment, whereas 21 (20.2%) and 19 (18.3%) episodes required treatment modification respectively. One patient from each treatment group died according to febrile neutropenia. The overall success rates were 99% in both groups (P = .94). Empiric SC therapy was found to be as effective as carbapenem monotherapy in pediatric febrile neutropenic patients with lymphoma and solid tumors.

Infectious mononucleosis in Turkish children.

The aim of this study was to analyze the demographic, clinical and laboratory characteristics and prognoses of children diagnosed with infectious mononucleosis (IM). The demographic features, referral complaints, clinical and laboratory findings, follow-up, and prognoses of 44 patients diagnosed with IM between January 2000 and June 2006 at the Infectious Diseases Department of Hacettepe University Ihsan Dogramaci Children's Hospital were analyzed retrospectively. The children suspected of IM based on clinical findings and whose diagnoses were proven by serological tests were enrolled in the study. In addition, the patients were divided into four groups -namely, age 0-4, age 5-8, age 9-12 and age 13-16, and the differences among groups were investigated in terms of their clinical and laboratory findings. The patients were aged between 3 months and 16 years. The median age was 4, and 56.8% of patients were below age 5. The male/female ratio was 1.6. No statistically significant variation was observed in the seasonal distribution of patients (p = 0.131). The most common referral complaints were swollen cervical lymph nodes or swollen neck (68.1%), followed by fever (43.1%) and sore throat (25%). Lymphadenopathy (79.5%), tonsillopharyngitis (72.7%), splenomegaly (34%), and hepatomegaly (25%) were the most common physical examination findings. Leukocyte count was normal in 68.3% of the cases. Leukocytosis was detected in 29.5% of the patients, and leukopenia in 2.2%. Lymphocytosis was detected in 44.7% of patients. Downey cell was detected in the peripheral blood smear of 23.6% of patients, and thrombocytopenia in 11.3%. Elevated alanine aminotransferase and aspartate aminotransferase levels were detected in 61.9% and 90.4% of patients who were investigated for these parameters, respectively. The clinical, hematological and biochemical findings of patients did not vary significantly among age groups (p > 0.05). Only one complication (hemophagocytic syndrome) was observed in one patient.

Risks and outcome of fungal infection in neutropenic children with hematologic diseases.

In this retrospective study, we report the results of antifungal treatments (AFTs) in febrile neutropenic episodes in patients with acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML) and aplastic anemia (AA) in our center. From January 2004 to December 2005, a total of 52 patients and 221 febrile neutropenic episodes were evaluated. AFT was started in 96 (43%) of the 221 episodes. Amphotericin B and fluconazole were used in 44 (46%) and 52 (54%) febrile neutropenic episodes, respectively. Microbiologically or histopathologically evident fungal infections were detected in 35 of 96 febrile neutropenic episodes. The mortality rate due to fungal infection was higher in patients with AA (7/8 patients) and AML (7/12 patients) than in ALL patients (1/32). Mortality for the whole group was 28%. When the mortality rate was compared between the two treatment groups (amphotericin B vs fluconazole), mortality was significantly higher in patients receiving amphotericin B [n = 14 (93%) and n = 1 (7%), respectively].

Chronic recurrent multifocal osteomyelitis as the first presentation of acute lymphoblastic leukemia in a 2-year-old boy.

SUMMARY: We present herein a 2-year-old boy who suffered from chronic recurrent multifocal osteomyelitis for 6 months and was later diagnosed as acute lymphoblastic leukemia. In view of the rarity of bilateral symmetric and multifocal lesions in osteomyelitis in children, we suggest that leukemia should be investigated with bone marrow aspiration in such patients, even if complete blood count parameters are normal, and there is no hepatosplenomegaly.

Comparison of nasopharyngeal culture, polymerase chain reaction (PCR) and serological test for diagnosis of pertussis.

This prospective study, which was designed to compare nasopharyngeal culture, polymerase chain reaction (PCR) and serology in the diagnosis of pertussis, covered 35 children aged between 0 and 16 who were admitted to Hacettepe University Ihsan Dogramaci Children's Hospital between 1 March 2005 and 31 August 2006 with coughing for 7 days or longer, paroxysmal cough of any duration, or cough with inspiratory whoop and/or vomiting (or apnea) after coughs. The demographic data and vaccination history of the patients were recorded. During the initial examination, samples were taken from the posterior nasopharynx for Bordetella pertussis (B. pertussis) culture and PCR analysis. In order to determine antibody positivity and antibody levels against B. pertussis antigens, serum samples were taken during the initial examination (acute phase) and two weeks later (convalescent phase). In the first serum sample, immunoglobulin M (IgM) was determined against pertussis toxin. In the first and second samples, IgA and IgG antibodies were evaluated against pertussis toxin and filamentous hemagglutinin. Culture yielded negative results in all of the patients. PCR was positive in two cases (5.7%). In the PCR-positive patients, IgM, IgA and IgG type anti-pertussis antibodies were found to be positive in the first serum samples, and IgA and IgG antibodies were found to be positive in the second serum samples. Therefore, it was considered that serology could be as sensitive as PCR when type IgM, IgA and IgG antibodies were found to be positive against a minimum of two antigens of B. pertussis. In conclusion, both PCR and serologic tests--if evaluating all types of antibodies to a minimum of two antigens of B. pertussis obtained in both acute and convalescent sera--could be more sensitive than culture in the diagnosis of pertussis.

Is the axilla the right site for temperature measurement in children by chemical thermometer?

Although each method has its own advantages and disadvantages compared with the conservative mercury-in-glass thermometers, there are conflicting opinions about the optimal anatomic site for measuring body temperature as well about the variations in measurements with different methods. In this study, we aimed to assess the accuracy and reliability of measurements obtained from the axilla with the chemical thermometer (Tempa DOT TM) compared with the classic mercury-in-glass instruments. Sixty randomly selected pediatric patients who were admitted to our hospital were enrolled. Simultaneous temperature axillary measurements (n: 1300) were performed with the chemical thermometer and mercury-in-glass instruments. The mean results of the axillary mercury-in-glass thermometers and axillary chemical thermometer were 36.8 +/- 0.6 and 37.2 +/- 0.7, respectively. The Bland-Altman plot of differences suggests that 95% of the chemical thermometer (Tempa.DOT TM) readings were within limits of agreement (+0.37 and -1.24 degrees C) when mercury-in-glass thermometer is considered as the standard. Our results showed that limits of agreement were wide (+0.37 and -1.24 degrees C) between readings of axillary mercury-in-glass thermometers and chemical thermometers. Since approximately 20% of febrile patients with mercury-in-glass temperature were misdiagnosed as afebrile with measurements via chemical thermometer, we suggest that the axilla is not a suitable anatomic site for screening of fever with Tempa.DOT. Further studies involving larger study groups with similar age should be done to more definitely assess its screening value in pediatrics.

Pediatric pleural effusions: etiological evaluation in 492 patients over 29 years.

Pediatric pleural effusions present a changing profile over time, both in terms of etiological subgroups and causative microorganisms in parapneumonic effusions. This retrospective study aimed to review pediatric pleural effusions in a large cohort over a 29-year period, with special emphasis on the etiological subgroups and microbiological causes of parapneumonic effusions. The medical records of 492 pediatric patients were reviewed for a comparison of subgroups of pleural effusions and microbiological causes of parapneumonic effusions between three decades. Parapneumonic effusions (381 patients) made up 77.4% of the group. Tuberculous pleurisy decreased, but malignant effusions doubled in number over time. A causative microorganism was identified in 34.6% overall, with Staphylococcus aureus and Streptococcus pneumoniae being the two most common. Relative frequency of S. aureus decreased, whereas pneumococci and Haemophilus influenzae were more frequent in recent years.

Animal carcass and eyelid anthrax: a case report.

Anthrax is a worldwide zoonosis of herbivores, which is caused by the spore-forming bacteria Bacillus anthracis, and humans become infected when they are exposed to infected animals and their tissues or the organism directly. In this report, we present a 13-year-old boy who developed eyelid anthrax after contact with a sheep carcass during his summer holiday that resulted in eyelid anthrax and cicatricial ectropion.

Transient depletion of innate immunity in varicella infections in otherwise healthy children.

OBJECTIVE: Varicella is a common childhood infection and has a number of complications in the unvaccinated population. Perforin, found in natural killer cells, is important for the killing of virally infected cells. For this reason, the aim of this study was to determine natural killer cell count and activity, perforin expression, and Fas and soluble Fas ligand (sFas-L) levels in immunocompetent children with varicella infection and define any possible relations between the levels and varicella complications. METHODS: Forty children were analyzed at diagnosis and on the 15th day of varicella infection. There was a significant difference in hemoglobin levels and leukocyte and platelet counts between days 0 and 15. RESULTS: Thirteen (32%) patients were found to be lymphopenic. Natural killer cell count and activity were significantly higher on day 15 when compared to values at diagnosis. The Fas-mediated apoptotic pathway was found to be active in acute varicella infection because Fas and sFas-L levels at diagnosis were higher than values on day 15. CONCLUSION: These findings suggest that the Fas and Fas-L apoptotic pathway is active during the acute phase of the viral infection and that it becomes inactive by day 15, paralleling the hematologic recovery.

Comparing body temperature measurements by mothers and physicians using mercury-in-glass, digital mercury and infrared tympanic membrane thermometers in healthy newborn babies.

While planning medical care, health care workers must consider the body temperature changes as measured by the mothers on most occasions. We evaluated the reliability of three different temperature measurement methods when they were used by the mothers by comparing with the measurements taken by the pediatrician. In this prospective study, body temperatures of 50 healthy newborns during their 2nd day of life were measured by mothers and one physician with mercury-in-glass (MG), digital mercury (DM) and infrared tympanic membrane thermometers (ITMT). Measurements by the mothers and the physician were correlated for the three different methods. The effects of the educational level of the mothers and the presence of children at home on the reliability and the number of differences > or = 0.5 degrees C were also evaluated for each of the methods. In comparing the measurements by the mothers and the pediatrician, correlation coefficient was 0.12 in MG thermometer readings, 0.23 in DM thermometer readings and 0.78 in ITMT readings, meaning that tympanic measurements by the mothers and the pediatricians were more correlated (p < 0.0001). The means and ranges of absolute differences of MG, DM, and tympanic thermometer measurements were 0.43 +/- 0.42, 0-1.7; 0.36 +/- 0.45, 0-2.2; and 0.13 +/- 0.12, 0-0.7 degrees C, respectively. The number of measurements with an absolute difference > or = 0.5 degrees C was 17 in MG readings, 11 in DM readings, and 1 in ITMT readings, The educational level of the mothers and the presence of children at home had no effect on the correlations. The intraclass coefficient for the three sets of measurements by the pediatricians was 0.91. Body temperature measurements in newborn babies as taken by their mothers were more correlated with the readings by the pediatricians when the ITMT was used. Tympanic thermometers seem to be useful for the mothers of any educational level and are independent of having experience with a previous child. The ease of use and short calibration time for reading are also advantageous for these thermometers.

Relapsing Herpes simplex virus encephalitis despite high-dose acyclovir therapy: a case report.

Central nervous system infection of Herpes simplex virus (HSV) is the most common etiologic agent of the non-epidemic fatal form of encephalitis. Relapse of HSV encephalitis is rare in childhood. In this report, we present our experience in a 36-month-old child with relapse of HSV encephalitis after 14-day acyclovir therapy. A 36-month-old boy who was presented with deterioration in speech and motor functions and fluctuation of consciousness was treated with acyclovir for 14 days for HSV encephalitis. He was discharged since his cerebrospinal fluid findings returned to normal range and clinical improvement was seen. Ten days later, he was readmitted to our clinic with acute fever, focal convulsions and choreoathetoid movements, and altered consciousness. Acyclovir was started immediately, but he died on the 17th day because of respiratory failure. Relapses due to HSV encephalitis are rare and limited to a small number of case reports in the literature. Persistence of HSV, detection of high viral load or detection of HSV by polymerase chain reaction, prior corticosteroid therapy, low total dosage of acyclovir (especially for children under 2 years of age) and short duration of therapy were suspected risk factors. Even absence of pleocytosis and normal cerebrospinal fluid biochemistry in our patient after treatment did not indicate eradication of HSV. In our opinion, treatment duration of HSV encephalitis, especially in small children, must be at least 21 days. Clinical and experimental studies are required since only case reports on this topic exist.

Preseptal and orbital cellulitis: 15-year experience with sulbactam ampicillin treatment.

The infection of the orbita and ocular tissues can result in severe local and systemic complications. We aimed to determine the predisposing factors for preseptal and orbital cellulitis, the clinical and routine laboratory differences between orbital and preseptal cellulitis, and the change in the spectrum of the pathogens and the antibiotics used in the last 10 years. One hundred thirty-nine patients, hospitalized in Hacettepe University Faculty of Medicine Children's Hospital between 1 January 1990 and 31 December 2003 with diagnosis ofperiorbital or orbital cellulitis, were reviewed retrospectively. Ten of the patients (7%) had orbital and 129 (93%) had preseptal cellulitis. The male/female ratio was 1.7:1. The average age (mean+/-standard deviation) was 5.7+/-4 years. The seasonal distribution was most marked in spring and fall periods. When compared with preseptal cellulitis, the mean blood cell count, erythrocyte sedimentation rate and C-reactive protein levels were significantly higher in patients with orbital cellulitis. Staphylococcus aureus was isolated in 13 (41.9% of total microbiologically confirmed cases), coagulase-negative staphylococcus in 8 (25.8%), and H. influenza type b in 2 patients (6%). Thirty out of 77 clinical sample cultures (39%) were positive. In clinical studies, etiological agents of orbital and preseptal cellulitis could be identified in only 20-30% of cases, so in clinical practice treatment is usually empiric. We observed that sulbactam-ampicillin was a safe and effective choice of treatment in orbital and preseptal cellulitis in our cases.

Cytomegalovirus hepatitis and ganciclovir treatment in immunocompetent children.

Ganciclovir treatment in children with cytomegalovirus (CMV) infection is still controversial and only indicated in selected cases. The aim of thi study was to evaluate clinical and demographic features of CMV hepatitis in immunocompetent children and to determine the effect of ganciclovir treatment in these patients retrospectively. The study was carried out in a group o 29 children with CMV hepatitis. All the patients were investigated for signs of infection, inborn errors of metabolism, genetic diseases, extrahepatic biliary atresia and other causes of hepatitis. Two patients with congenital CMV infection and two patients with biliary atresia were excluded from the study group. The patients included in the study were divided into two groups: non-cholestatic hepatitis (n=16) as Group I and cholestatic hepatitis (n=9) as Group II. Four (25%) patients in the non-cholestatic group and four (44.4 in the cholestatic group were treated with ganciclovir for a median of 21 days. The mean age was 9.6+/- 10.9 months (median age 6 months) in Group I, while cholestatic hepatitis patients in Group II were significantly younger, with a mean age of 2.7+/-0.9 months (p<0.01). The most prominent symptoms at admission were diarrhea and vomiting (25%) in Group I. In Group I, all cases (100%) and in Group II, three of four cases (75%) treated with ganciclovir had recovery from acute CMV hepatitis. In the non-cholestatic group, no relapses were observed while one patient in the cholestatic group relapsed and progressed into chronic liver disease. Patients who received supportive treatment showed a marked decrease in GGT, ALT, AST and bilirubin levels spontaneously and no relapses of hepatitis were observed in at least one year of follow-up. Although ganciclovir therapy is not indicated particularly in immunocompetent cases, since most were self-limited infections, in case of progressive and persistent hepatitis, such as in our cases, ganciclovir was a treatment option; no side effect due to ganciclovir therapy was observed in our cases. Although ganciclovir seems to be effective in progressive CMV hepatitis, multicenter randomized studies in a large study group are necessar to determine the efficacy and indications for ganciclovir treatment.

A prospective study of etiology of childhood acute bacterial meningitis, Turkey.

Determination of the etiology of bacterial meningitis and estimating cost of disease are important in guiding vaccination policies. To determine the incidence and etiology of meningitis in Turkey, cerebrospinal fluid (CSF) samples were obtained prospectively from children (1 month-17 years of age) with a clinical diagnosis of acute bacterial meningitis. Multiplex PCR was used to detect DNA evidence of Streptococcus pneumoniae, Haemophilus influenzae type b (Hib), and Neisseria meningitidis. In total, 408 CSF samples were collected, and bacterial etiology was determined in 243 cases; N. meningitidis was detected in 56.5%, S. pneumoniae in 22.5%, and Hib in 20.5% of the PCR-positive samples. Among N. meningitidis-positive CSF samples, 42.7%, 31.1%, 2.2%, and 0.7% belonged to serogroups W-135, B, Y, and A, respectively. This study highlights the emergence of serogroup W-135 disease in Turkey and concludes that vaccines to prevent meningococcal disease in this region must provide reliable protection against this serogroup.

Intravenous immunoglobulin in the treatment of severe methotrexate-induced acral erythema.

Chemotherapy-induced acral erythema is an uncommon and dramatic reaction to high-dose chemotherapy. It is characterized by painful erythema of both palms and soles with symmetrically well-defined borders, which may progress to bullae formation and desquamation. The bullous variant of this reaction has been reported with methotrexate and more frequently cytosine arabinoside. Rapid differential diagnosis and discrimination from more serious conditions such as graft versus host disease or toxic epidermal necrolysis is essential. In this case report, we present a 13-year-old boy who developed severe and prolonged chemotherapy-induced acral erythema after high-dose methotrexate treatment and successfully responded to intravenous immunoglobulin.

Long-term effects of dexamethasone on hearing ability in children with pneumococcal meningitis.

Controlled trials concerning adjuvant dexamethasone therapy in bacterial meningitis do not point unequivocally to a beneficial effect on hearing ability. We investigated the remote adverse outcomes of pneumococcal meningitis and, if any, beneficial effects of adjuvant dexamethasone therapy on hearing ability. Fifty-five subjects who experienced pneumococcal meningitis between 1987-97 were divided into two groups as 25 subjects who did not receive dexamethasone (Group 1) and the remaining 30 subjects who did (Group 2). All subjects underwent pure tone thresholds estimation. There were a total of 11 subjects (20%) with sensorineural hearing impairment (SNHI): 6 in the first group (24%) and 5 in the second group (16%). Although there was no statistically significant difference in the SNHI ratio between the groups, all the subjects who used adjuvant dexamethasone therapy suffered only minimal-borderline SNHI, whereas 2 patients in Group 1 had moderate-serious SNHI. Even though adjuvant dexamethasone therapy had no statistically significant impact on hearing ability after long-term follow-up, its use may be a good choice in terms of preventing serious SNHI.

Community-acquired pneumonia and parapneumonic effusions in developing countries.

Ninety-eight patients with diagnosis of community-acquired pneumonia and parapneumonic effusion were retrospectively evaluated in order to determine the demographic properties of the patients, etiologic microorganism and the resistance patterns. Ages of study groups were between 2 to 16 years (mean 6.5 +/- 3.5 years) and 56 of 98 patients (56%) were male. There were four groups: Pneumonia (Group 1, n: 57), pleural effusion-medical treatment (Group 2, n: 18), pleural effusion-tube thoracostomy (Group 3, n: 19), and pleural effusion-operative treatment (Group 4, n: 4). Pre-admission antibiotic use was up to 84% in study groups. Evaluation of seasonal dispersion revealed that 86.7% of patients were admitted to hospital in the October-May period. Blood cultures were positive in 4 of 98 patients (4%). Nine of 27 (33.3%) pleural effusion cultures were positive and 4 of them revealed Streptococcus pneumoniae. Intermediate penicillin resistance was found in 1/4 of S. pneumoniae isolates (25%). Our study illustrates the problems in the diagnosis and management of pediatric respiratory tract infections in developing countries. Chest X-ray together with erythrocyte sedimentation rate (ESR) was also shown to be important in classifying lower respiratory tract infections. Increase in the usage of specific viral serologic studies will probably lower the percentage of antibiotic usage and lower the costs of cultures.

Foamy histiocytes in a patient with visceral leishmaniasis after treatment with liposomal amphotericin B.

A seven-year-old patient was admitted to our hospital with the complaints of fever, malaise, and abdominal distention. In the bone marrow aspiration smears, leishmania amastigotes were observed. The patient was diagnosed as having visceral leishmaniasis (VL) and treated with liposomal amphotericin B (L-AMB). The authors report their observation of foamy histiocytes seen in the bone marrow aspiration smears of the patient with VL after L-AMB treatment. This effect of L-AMB needs to be recognized, since L-AMB may represent a further condition in addition to the other diseases that are associated with foamy histiocytes in the bone marrow.

Linezolid-induced reversible bicytopenia in a 4-year-old boy with methicillin-resistant Staphylococcus aureus bacteremia.

The authors report on a 4-year-old child with the diagnosis of tetralogy of Fallot (TOF) and infective endocarditis. Methicillin-resistant Staphylococcus aureus (MRSA) was isolated from the blood culture of the patient. While receiving imipenem, amikacin, and linezolid therapies, the boy's general condition improved, acute phase reactants decreased, and his blood culture became negative for MRSA. On his follow-up echocardiography, the vegetation had also disappeared. However, he developed progressive bicytopenia following linezolid therapy for 5 weeks. During linezolid therapy, his hemoglobin level decreased from 12.1 to 5.3 g/dL and his platelet count from 242 x 10(9) to 14 x 10(9)/L. His white blood cell count (WBC) did not decrease during linezolid therapy. Six days following termination of linezolid therapy, his hemoglobin had increased to 8.2 g/dL and platelet count to 192 x 10(9)/L. Thus, it should be kept in mind that linezolid may induce cytopenias in children. If these side effects of linezolid are known, unnecessary laboratory investigations may be prevented and cessation of the drug may be sufficient for reversal of the cytopenias.