Evaluation of childhood malignancies presenting with musculoskeletal manifestations from two different divisions: a multicenter study.

BACKGROUND: The aim of the study was to evaluate the approaches of pediatric rheumatologists and pediatric hematologists to patients with similar musculoskeletal (MSK) complaints and to highlight the differences that general pediatricians should consider when referring patients to these specialties. METHODS: This is a cross-sectional study involving the patients who applied to pediatric rheumatology centers with MSK complaints and were diagnosed with malignancy, as well as patients who were followed up in pediatric hematology centers with a malignancy diagnosis, and had MSK complaints at the time of admission. RESULTS: A total of 142 patients were enrolled in the study. Of these patients, 83 (58.4%) applied to pediatric rheumatology centers, and 59 (41.6%) applied to pediatric hematology centers. Acute lymphoblastic leukemia (ALL) was the most common diagnosis among the patients who applied to both centers, with 80 cases (56.3%). The median age of diagnosis was 87 (interquartile range, IQR: 48-140) months. The most common preliminary diagnosis in pediatric rheumatology centers was juvenile idiopathic arthritis (JIA), with 37 cases (44.5%). MSK involvement was mainly seen as arthralgia, and bone pain. While arthralgia (92.7%) was the most common complaint in rheumatology centers, bone pain (88.1%) was more common in hematology centers. The most frequently involved joints were the knee (62.9%), ankle (25.9%), hip (25%), and wrist (14%). The most common laboratory abnormalities were high lactate dehydrogenase (LDH), high C-reactive protein (CRP), anemia, and high erythrocyte sedimentation rate (ESR). Thrombocytopenia, neutropenia, and high LDH were statistically significantly more frequent in patients admitted to hematology centers than in patients admitted to rheumatology centers (p < 0.001, p=0.014, p=0.028, respectively). Patients who applied to rheumatology clinics were found to have statistically significantly higher CRP levels (p=0.032). CONCLUSIONS: Malignancies may present with only MSK system complaints in childhood. Therefore, malignancies should be included in the differential diagnosis of patients presenting with MSK complaints.

C-terminal variants in CDC42 drive type I interferon-dependent autoinflammation in NOCARH syndrome reversible by ruxolitinib.

C-terminal variants in CDC42 encoding cell division control protein 42 homolog underlie neonatal-onset cytopenia, autoinflammation, rash, and hemophagocytic lymphohistiocytosis (NOCARH). Pyrin inflammasome hyperactivation has been shown to contribute to disease pathophysiology. However, mortality of NOCARH patients remains high despite inflammasome-focused treatments. Here, we demonstrate in four NOCARH patients from three families that cell-intrinsic activation of type I interferon (IFN) is a previously unrecognized driver of autoinflammation in NOCARH. Our data show that aberrant innate immune activation is caused by sensing of cytosolic nucleic acids released from mitochondria, which exhibit disturbances in integrity and dynamics due to CDC42 dysfunction. In one of our patients, treatment with the Janus kinase inhibitor ruxolitinib led to complete remission, indicating that inhibition of type I IFN signaling may have an important role in the management of autoinflammation in patients with NOCARH.

Clinical usefulness of anti-nuclear antibody in childhood: real-world experience at a tertiary care center : Usefulness of ANA in pediatric autoimmune diseases.

We evaluated the reasons for requesting anti-nuclear antibody (ANA) analysis in clinical practice at a tertiary center and the performance of ANA in pediatric autoimmune diseases. Patients under 18 years of age who underwent ANA testing for various symptoms between 2013 and 2017 were included. We retrieved data from medical records, including demographic and clinical characteristics, diagnoses, ANA results, titers, and staining patterns. The performance assessment tools were calculated according to the ANA titer for autoimmune diseases. Risk factors for autoimmune diseases in ANA-positive patients were evaluated using logistic regression analysis. Changes in ANA titer and seroconversion were evaluated using repeated ANA analyses. A total of 3812 patients underwent ANA. Medical records of 3320 patients were obtained. The rate of ANA positivity was 27.4%. ANA was requested most frequently because of musculoskeletal findings in 1355 patients (40.8%). Juvenile idiopathic arthritis (n = 174, 20.2%) was the most common diagnosis in ANA-positive patients, followed by systemic lupus erythematosus (n = 52, 6%). For autoimmune diseases, a titer of ≥ 1:100, a sensitivity of 40.1%, and a specificity of 77.1% were observed. At a titer ≥ 1:1000, the sensitivity and specificity were 24.1% and 89%, respectively. Homogeneous staining was an additional risk factor for autoimmune diseases in ANA-positive patients by multivariate logistic regression analysis (OR [95% CI]: 4.562 [3.076-6.766], p < 0.001).    Conclusion: Our results revealed that the performance of the ANA test in diagnosing autoimmune diseases in pediatric clinical practice was poor. Therefore, clinical findings should be carefully evaluated before ANA testing is performed. What is Known: • ANA can be detected in systemic autoimmune rheumatic diseases. • The diagnostic role of ANA is controversial, especially in childhood. What is New: • One in four patients who requested the ANA test had an autoimmune disease. • Less than half of patients with an autoimmune disease had ANA positivity.

Gastrointestinal endoscopic findings of autoimmune and autoinflammatory diseases in pediatric rheumatology patients.

OBJECTIVE: Rheumatic diseases in children are chronic and multisystemic diseases. In this study, it was aimed to evaluate gastrointestinal endoscopic findings in children diagnosed as autoimmune or autoinflammatory rheumatic diseases consulted with pediatric gastroenterology for gastrointestinal complaints. METHODS: The patients followed up by the Pediatric Rheumatology Department and consulted to the Pediatric Gastroenterology Department due to gastrointestinal complaints were included in the study. File records of the patients were analyzed retrospectively. RESULTS: A total of 28 patients were included in the study. Twelve of the patients had autoimmune disease (Juvenile idiopathic arthritis [JIA], systemic lupus erythematosus, Sjögren's syndrome, and scleroderma) and the other 16 had autoinflammatory disease (familial Mediterrnean fever, hyper Immunoglobulin D syndrome, undifferantiated systemic autoinflammatory disease, and systemic JIA). Four of the patients with familial Mediterrnean fever also diagnosed as JIA. The mean age of the patients was 11.7±3.5 years. The main gastrointestinal complaints of patients with both autoimmune and autoinflammatory diseases were abdominal pain and diarrhea. Inflammatory bowel disease was found in 33% of those with autoimmune disease and 56% of those with autoinflammatory disease in patients underwent endoscopic evaluation. M694V mutation was present in 62% of the patients with autoinflammatory disease presented with gastrointestinal complaints. CONCLUSION: Both autoimmune and autoinflammatory rheumatic diseases can cause gastrointestinal complaints and should be referred to a pediatric gastroenterologist for early diagnosis.

Neuropsychiatric involvement in juvenile-onset systemic lupus erythematosus: A multicenter study.

INTRODUCTION: Neuropsychiatric (NP) involvement is a restricted area in juvenile-onset systemic lupus erythematosus (jSLE). AIM: To investigate the prevalence, demographic and clinical features, and outcomes of the neurological involvement in the Turkish jSLE population. METHODS: This study was based upon 24 referral centers' SLE cohorts, multicenter and multidisciplinary network in Turkey. Patient data were collected by a case report form which was standardized for NP definitions according to American Collage of Rheumatology (ACR). Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) neuropsychiatric part was used to determine NP damage. Variables were evaluated Ward's hierarchical clustering analyses, univariate, and multivariate logistic regression analyses. RESULTS: A hundred forty-nine of 1107 jSLE patients had NP involvement (13.5%). The most common NPSLE findings were headache (50.3%), seizure (38.3%), and acute confusional state (33.6%). Five clusters were identified with all clinical and laboratory findings. The first two clusters involved neuropathies, demyelinating diseases, aseptic meningitis, and movement disorder. Cluster 3 involved headache, activity markers and other SLE involvements. Idiopathic intracranial hypertension, cerebrovascular disease, cognitive dysfunction, psychiatric disorders and SLE antibodies were in the fourth, and acute confusional state was in the fifth cluster. In multivariate analysis, APA positivity; OR: 2.820, (%95CI: 1.002-7.939), P: 0,050, plasmapheresis; OR: 13.804 (%95CI: 2.785-68.432), P: 0,001, SLEDAI scores; OR: 1.115 (%95CI: (1.049-1.186), P: 0,001 were associated with increased risk for neurologic sequelae. CONCLUSION: We detected the prevalence of juvenile NPSLE manifestations in Turkey. We have identified five clusters that may shed light pathogenesis, treatment and prognosis of NP involvements. We also determined risk factors of neurological sequelae. Our study showed that new definitions NP involvements and sequelae for childhood period are needed.

Evaluation of Baseline Characteristics and Prognostic Factors in Multisystemic Inflammatory Syndrome in Children: Is It Possible to Foresee the Prognosis in the First Step?

Background: Two years after the first cases, critical gaps remain in identifying prognostic factors in multisystem inflammatory syndrome in children (MIS-C). Methods: This retrospective study included 99 patients with MIS-C hospitalized between August 2020 and March 2022 in a pediatric tertiary center. The patients were divided into two groups according to clinical severity (low- and high-risk). Prognostic values of baseline clinical and laboratory characteristics were evaluated with advanced statistical analysis, including machine learning. Results: Sixty-three patients were male, and the median age was 83 (3−205) months. Fifty-nine patients (59.6%) were low-risk cases. Patients aged six years and over tended to be at higher risk. Involvement of aortic or tricuspid valve or >1 valve was more frequent in the high-risk group. Mortality in previously healthy children was 3.2%. Intensive care unit admission and mortality rate in the high-risk group were 37.5% and 7.5%, respectively. At admission, high-risk patients were more likely to have reduced lymphocyte count and total protein level and increased brain natriuretic peptide (BNP), ferritin, D-dimer, and troponin concentrations. The multiple logistic regression model showed that BNP, total protein, and troponin were associated with higher risk. When the laboratory parameters were used together, BNP, total protein, ferritin, and D-dimer provided the highest contribution to the discrimination of the risk groups (100%, 89.6%, 85.6%, and 55.8%, respectively). Conclusions: Our study widely evaluates and points to some clinical and laboratory parameters that, at admission, may indicate a more severe course. Modeling studies with larger sample groups are strongly needed.

Hidden threat in familial Mediterranean fever: subclinical inflammation, oxidative stress and their relationship with vitamin D status.

BACKGROUND: Vitamin D levels have been investigated in children with familial Mediterranean fever (FMF), but the relationship between vitamin D status and inflammation/oxidative stress indicators could not be clearly demonstrated. This study aimed to investigate the relationship between subclinical inflammation/oxidative stress and vitamin D status in children with FMF during an attack-free period. METHODS: In the cross-sectional study, ninety children with FMF in the attack-free period and 30 healthy children were included. Patients were grouped according to their vitamin D status (< 20, 20-29, and 30-100 ng/mL). The groups were compared in terms of pentraxin 3 (PTX-3), total oxidant status (TOS), and total antioxidant status (TAS). Multivariable linear regression analysis was performed to identify factors associated with vitamin D status. RESULTS: PTX-3 levels were significantly higher in patients with vitamin D insufficiency (20-29 ng/mL) than in the group with vitamin D sufficient (30-100 ng/mL). Patients with vitamin D deficiency (< 20 ng/mL) had higher TOS. A strong negative correlation was observed between vitamin D levels and TOS (p = 0.003). Subclinical inflammation (PTX-3 ≥ 0.640) and high TOS levels were negatively associated with vitamin D levels.

Hematological involvement in pediatric systemic lupus erythematosus: A multi-center study.

Introduction: Systemic lupus erythematosus (SLE) may present with features of several systems, including hematological manifestations. In this study, we aimed to evaluate the characteristics of hematological involvement and assess possible associations and correlations in pediatric SLE patients. Method: This is a retrospective multi-center study. The medical records of pediatric SLE patients followed between January 2000 and June 2020 were analyzed. All children fulfilled the criteria of the Systemic Lupus International Collaborating Clinics. Results: The study included 215 children with SLE, 118 of whom had hematological manifestations. Concomitant renal involvement and low C3 levels were significantly more frequent in patients with hematological involvement (p = 0.04, p = 0.008, respectively). Also, anti-cardiolipin, anti-beta-2-glycoprotein I (anti-ß2 GP1), and anti-Sm antibody positivity, and the presence of lupus anticoagulant were more common in the group with hematological findings (p = 0.001 for anti-cardiolipin antibody positivity and p < 0.001 for the positivity of anti-ß2 GP1 antibody, anti-Sm antibody, and lupus anticoagulant). The most common hematologic abnormality was anemia (n = 88, 74.5%), with autoimmune hemolytic anemia constituting the majority (n = 40). Corticosteroids followed by IVIG were the mainstay of treatment. In patients resistant to corticosteroid and IVIG treatments, the most preferred drug was rituximab. Low levels of C3, high SLEDAI score, high incidence of renal involvement, and positive antiphospholipid antibodies were associated with hematological involvement in the univariate analysis. The presence of antiphospholipid antibodies and high SLEDAI score were independently associated with hematological involvement in multivariate analysis (OR: 4.021; 95% CI: 2.041-7.921; p < 0.001 and OR: 1.136; 95% CI: 1.065-1.212; p < 0.001). Conclusion: Hematological abnormalities are frequently encountered in pediatric SLE. Positive antiphospholipid antibodies and high SLEDAI scores were associated with hematological involvement.

Unexpected condition in a rare disease: encephalopathy in early-onset sarcoidosis.

BACKGROUND: Granulomatous autoinflammatory diseases are monogenic syndromes caused by mutations in the region encoding the nucleotide-binding domain of the nucleotide-binding oligomerization domain-containing 2 gene. Blau syndrome and early-onset sarcoidosis are familial and sporadic forms of the same disease and are very rare. Many organ systems may be involved; however, neurologic involvement is infrequent. We reported a case of encephalitis in a 12-year-old girl followed with a diagnosis of early-onset sarcoidosis. CASE: The patient was diagnosed with juvenile idiopathic arthritis at 3 years of age. We considered druginduced sarcoidosis at 6 years of age with granulomatous inflammation of liver and kidney. Small joint involvement and camptodactyly developed during follow-up. M315T mutation was detected in the NOD2 gene supporting the diagnosis of early-onset sarcoidosis. The patient suffered from encephalopathy when she was under methotrexate, infliximab, and systemic steroid treatment at 12 years of age. Cerebrospinal fluid limbic encephalitis antibody panel was negative. CONCLUSION: Encephalopathy is not common in Blau syndrome and early-onset sarcoidosis. The cause of encephalopathy in our patient was interpreted as autoimmune encephalitis.

The influence of carrying MEFV gene variants on juvenile systemic lupus erythematosus.

Juvenile-onset systemic lupus erythematosus (jSLE) patients typically have a more severe disease course than adults with SLE. We aimed to assess the prevalence and disease course of jSLE patients carrying MEFV variants. MEFV variant analyses were performed in 44 jSLE patients and effect of these variants on disease severity and course was analyzed by SLEDAI score and SLICC/ACR index. Ten of the patients (22.7%) had a MEFV variant. The median (min-max) SLEDAI score and SLICC/ACR index were 2(0-13) and 0(0-3), respectively. Median age at disease onset, disease duration, SLICC/ACR indexes, SLEDAI scores, clinical and laboratory findings of the patients were comparable in carriers of variants and non-carriers. Nineteen patients (43.2%) had biopsy-proven lupus nephritis and four of these patients had MEFV variants. There was no significant difference between patients with and without MEFV carriers in terms of lupus nephritis. Even though not significant statistically, renal involvement was milder in MEFV carriers than non-carriers. The presence of MEFV variants does not increase the overall susceptibility to jSLE in our cohort, while larger number of patients is required to display the protective role of MEFV variants in jSLE.

The Possible Relationship Between Familial Mediterranean Fever and Chronic Nonbacterial Osteomyelitis: Coincidence or Coexistence?

BACKGROUND/OBJECTIVES: Chronic nonbacterial osteomyelitis (CNO) is an inflammatory disease characterized by recurrent attacks and remissions due to sterile bone inflammation. The CNO may be accompanied by various inflammatory diseases. The aims of our study were to determine the clinical, laboratory, and radiological characteristics of children with CNO, and to investigate the possible effect of concomitant diseases on the course of CNO. METHODS: Twenty-three patients who were diagnosed with CNO between 2012 and 2019 were analyzed. Demographic characteristics, clinical courses, laboratory and imaging findings, and concomitant diseases were recorded. The characteristics of the CNO patients with and without concomitant diseases were compared. RESULTS: The mean ± SD age of patients at the time of diagnosis and the last follow-up was 10.46 ± 4.1 and 12.47 ± 4.47 years, respectively. The median (range) time interval between disease onset and diagnosis was 5.33 (1-55) months. The mean ± SD duration of disease was 24.71 ± 16.76 months. Twelve patients (52.2%) were male. The most commonly affected areas were femur (74%), tibia/fibula (74%), and pelvis (52.2%). Age at symptom onset, age at diagnosis, mean number of lesions, presence of sacroiliitis, acute phase reactants at the start of disease, clinical and radiological remission rates, and treatment responses were not significantly different between the 13 patients with concomitant diseases and those without. Eight patients (34.8%) had familial Mediterranean fever (FMF), and all of them had exon 10 mutations. Four patients (17.4%) had juvenile spondylarthritis, one had inflammatory bowel disease, and one had psoriatic arthritis as concomitant diseases. Clinical remission was achieved in 19 patients (82.6%) and complete remission in 11 patients (47.8%) at the time of follow-up. CONCLUSIONS: In our cohort, half of the patients with CNO had concomitant diseases, with FMF being the most common. We think that the coexistence of FMF and CNO is not a coincidental one and that both may result due to an abnormality of a common pathogenetic pathway.

The Performances of the ACR 1997, SLICC 2012, and EULAR/ACR 2019 Classification Criteria in Pediatric Systemic Lupus Erythematosus.

OBJECTIVE: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. The American College of Rheumatology (ACR) 1997, Systemic Lupus International Collaborating Clinics (SLICC) 2012, and European League Against Rheumatism (EULAR)/ACR 2019 SLE classification criteria are formed based on data mainly from adult patients. We aimed to test the performances of the SLE classification criteria among pediatric patients with SLE. METHODS: Pediatric patients with SLE (n = 262; 80.9% female) were included from 3 different centers in Turkey. As controls, 174 children (60.9% female) with other diseases who had ANA (antinuclear antibody) test results were included. The gold standard for SLE diagnosis was expert opinion. RESULTS: The sensitivities of the ACR 1997, SLICC 2012, and EULAR/ACR 2019 criteria were 68.7%, 95.4%, and 91.6%, respectively. The specificities of the ACR 1997, SLICC 2012, and EULAR/ACR 2019 criteria were 94.8%, 89.7%, and 88.5%, respectively. Eighteen patients with SLE met the SLICC 2012 but not the EULAR/ACR 2019 criteria. Among these, hematologic involvement was prominent (n = 13; 72.2%). Eight patients with SLE fulfilled the EULAR/ACR 2019 but not the SLICC 2012 criteria. Among these, joint involvement was prominent (n = 6; 75%). CONCLUSION: To our knowledge, this is the largest cohort study of pediatric SLE to test the performances of all 3 classification criteria. The SLICC 2012 criteria yielded the best sensitivity, whereas the ACR 1997 criteria had the best specificity. SLICC 2012 criteria performed better than EULAR/ACR 2019 criteria. Separation of different hematological manifestations in the SLICC 2012 criteria might have contributed to the higher performance of this criteria set.

Evaluation of the thicknesses of cartilage and enthesis in familial Mediterranean fever and enthesitis-related arthritis.

OBJECTIVE: Subclinical inflammation is still a controversial issue in inflammatory diseases. There is no reliable, easy, and cheap inflammation marker in daily clinical practices currently. This study aims to predict clinical remission using cartilage and tendon thicknesses. METHODS: Eleven patients with Familial Mediterranean Fever (FMF) who had musculoskeletal involvement before and 11 patients with Enthesitis-Related Arthritis (ERA) were included in this study. They were on remission with clinical and laboratory evaluations for at least three months. Demographic and clinical features of the subjects, including age, sex, body mass index, disease duration, age at onset, medical treatment, and laboratory evaluations, were all noted. Healthy children of the same age were included as the control group. The thicknesses of the bilateral knee, second metacarpophalangeal and ankle joints cartilages, quadriceps, superior and inferior patellar, and the Achilles tendons were measured with a linear probe. A total of 198 joint and 264 tendon thicknesses were measured. RESULTS: The thicknesses of metacarpophalangeal, knee, and ankle cartilages were higher in the FMF group than in the others. In the FMF group, the quadriceps tendon thickness was higher than in the ERA group, and the superior patellar tendon thickness was higher than in the control group (p<0.05). CONCLUSION: According to our preliminary findings, an increased thickness of the cartilage and tendon in FMF patients may be an indicator of subclinical inflammation. Increased thickness of the enthesis in FMF patients may also indicate that enthesitis-related arthritis will also develop in the future.

Evaluation of factors affecting the duration of disease-modifying anti-rheumatic drugs application in patients with enthesitis-related arthritis.

OBJECTIVE: Treatments for enthesitis-related arthritis (ERA) consist of a mono- or combination therapy with non-steroidal anti-inflammatory drugs, disease-modifying anti-rheumatic drugs (DMARDs), and biological agents, and they are primarily based on adult studies and studies on other forms of juvenile idiopathic arthritis, depending on whether there is axial or peripheral involvement. We use DMARDs frequently in our daily practice, even in patients with axial involvement. The main reason for this is that the health insurance system in Turkey does not allow the use of Tumor Negrosis Factor (TNF) blockers as the first line of treatment. The aim of this study is to evaluate the factors affecting the duration of DMARDs application in patients with ERA. METHODS: Fifty-two patients with ERA were accepted in this retrospective cohort study. These patients did not have an inflammatory bowel disease, reactive arthritis or undifferentiated arthritis, psoriasis, and familial Mediterranean fever. Demographic characteristics, medical history, the initial and follow-up physical examination, initial Juvenile Spondyloarthritis Disease Activity Index (JSpADA), initial laboratory tests, radiographic tests, Juvenile Arthritis Damage Index-articulary (JADI-A) and extra-articulary (JADI-E) on the last admission, and data on medical treatments were recorded from the registered data. The univariate Cox proportional hazards regression analyses was used to determine factors affecting the non-response time of ERA patients to DMARDs before the biological treatment was started. RESULTS: Twenty-seven patients (52%) achieved remission with DMARDs, while 25 (48%) patients did not. The age at diagnosis (HR=1.12; p=0.247); gender (HR=2.53; p=0.210); family history of ankylosing spondylitis (HR=1.17; p=0.730); inflammatory back pain (HR=0.57; p=0.175); the shoulder (HR=0.75 p=0.706), hip (HR=0.45; p=0.129), and small-joint involvement (HR=1.53; p=0.439); sacroiliitis with physical examination (HR=0.90; p=0.814) and magnetic resonance imaging (MRI) (HR=2.84; p=0.110); enthesitis (HR=0.83; p=0.670); presence of uveitis (HR=2.04; p=0.342); presence of HLA-B27 (HR=1.39; p=0.524); initial high acute phase reactants levels(HR=1.89; p=0.183); initial JSpADA score (HR=0.98; p=0.944); and last JADI-A (HR=1.41; p=0.060) score did not affect the duration of DMARDs treatment before switching to biological treatments. CONCLUSION: In our study, the absence of factors affecting the duration of DMARDs application in patients with ERA showed that DMARDs may still be applied as the first line of treatment.

Elemental mercury intoxication in 7 patients admitted to a pediatric rheumatology clinic.

Paç Kisaarslan A, Sözeri B, Bastug F, Gündüz Z, Yel S, Nalçacioglu H, Sahin N, Özdemir Çiçek S, Poyrazoglu H, Düsünsel R. Elemental mercury intoxication in 7 patients admitted to a pediatric rheumatology clinic. Turk J Pediatr 2019; 61: 786-790. Mercury (Hg) is a toxic heavy metal that can be classified into three groups; organic (methyl), inorganic (mercuric), and elemental (metallic) mercury(Hg0). Mercury intoxication occurs mostly with the elemental form which can potentially damage the function of any organ, or any subcellular structure. The target organ of mercury is the brain, but peripheral nerve function, renal function, immune function, endocrine and muscle function, and several types of dermatitis have been described. We present 7 patients admitted to a pediatric rheumatology clinic with severe extremity pain. One of the patients had acrodynia, two of them had hypertension, two of them had tubulopathy, and three of them had neuropathy. The treatments were Dimercaptosuccinic acid and metalcaptase. In this report, we emphasize that mercury intoxication should be kept in mind with unexplained extremity pain. Timely diagnosis and treatment may prevent severe morbidity and mortality.

Brucella melitensis in blood cultures of two newborns due to exchange transfusion.

Brucellosis is a zoonotic infection, transmitted to humans primarily by consumption of unpasteurized milk and milk products. Transmission by blood transfusion is possible but very unusual. Herewith we present two newborns with positive blood cultures for Brucella melitensis after exchange transfusions. However, the standard tube agglutination titers against Brucella were not elevated and the newborns did not develop brucellosis. It is suggested that, in areas endemic for brucellosis, blood donors should be questioned about symptoms of brucellosis, and if suspected, serological tests for brucellosis should be indicated before blood transfusion. At the same time, the prevalence of the disease among animals should be reduced with effective animal disease control programs.