Pyruvate kinase deficiency in 29 Turkish patients with two novel intronic variants.

Pyruvate kinase (PK) is a key enzyme of anaerobic glycolysis. The genetic heterogeneity of PK deficiency (PKD) is high, and over 400 unique variants have been identified. Twenty-nine patients who had been diagnosed as PKD genetically in seven distinct paediatric haematology departments were evaluated. Fifteen of 23 patients (65.2%) had low PK levels. The PK:hexokinase ratio had 100% sensitivity for PKD diagnosis, superior to PK enzyme assay. Two novel intronic variants (c.695-1G>A and c.694+43C>T) have been described. PKD should be suspected in patients with chronic non-spherocytic haemolytic anaemia, even if enzyme levels are falsely normal. Total PKLR gene sequencing is necessary for the characterization of patients with PKD and for genetic counselling.

COVID-19 disease in children and adolescents following allogeneic hematopoietic stem cell transplantation: A report from the Turkish pediatric bone marrow transplantation study group.

BACKGROUND: Data on the risk factors and outcomes for pediatric patients with SARS-CoV-2 infection (COVID-19) following hematopoietic stem cell transplantation (HSCT) are limited. OBJECTIVES: The study aimed to analyze the clinical signs, risk factors, and outcomes for ICU admission and mortality in a large pediatric cohort who underwent allogeneic HSCT prior to COVID-19 infection. METHOD: In this nationwide study, we retrospectively reviewed the data of 184 pediatric HSCT recipients who had COVID-19 between March 2020 and August 2022. RESULTS: The median time from HSCT to COVID-19 infection was 209.0 days (IQR, 111.7-340.8; range, 0-3845 days). The most common clinical manifestation was fever (58.7%). While most patients (78.8%) had asymptomatic/mild disease, the disease severity was moderate in 9.2% and severe and critical in 4.4% and 7.6%, respectively. The overall mortality was 10.9% (n: 20). Deaths were attributable to COVID-19 in nine (4.9%) patients. Multivariate analysis revealed that lower respiratory tract disease (LRTD) (OR, 23.20, p: .001) and lymphopenia at diagnosis (OR, 5.21, p: .006) were risk factors for ICU admission and that HSCT from a mismatched donor (OR, 54.04, p: .028), multisystem inflammatory syndrome in children (MIS-C) (OR, 31.07, p: .003), and LRTD (OR, 10.11, p: .035) were associated with a higher risk for COVID-19-related mortality. CONCLUSION: While COVID-19 is mostly asymptomatic or mild in pediatric transplant recipients, it can cause ICU admission in those with LRTD or lymphopenia at diagnosis and may be more fatal in those who are transplanted from a mismatched donor and those who develop MIS-C or LRTD.

Evaluation of the Viscoelastic Properties of Lower-Extremity Muscles of Pediatric Hemophilia Patients Using Myotonometric Measurements.

This study aimed to evaluate the viscoelastic properties of lower-extremity muscles in pediatric hemophilia (FVIII-IX) patients. The study included 20 severe- and moderate-type right-dominant hemophilia patients diagnosed with hemophilia A-B and 20 healthy children. Viscoelastic properties (tone, stiffness, elasticity) of the lower-extremity muscles were measured using a MyotonPRO device. The physical characteristics of the pediatric hemophilia patients (mean age: 11.9 ± 3.95 years) and the control group (mean age: 12.6 ± 3.41 years) were found to be similar. A difference was observed only in the elasticity of the right vastus lateralis (p < 0.05) by means of the viscoelastic properties of the lower-extremity muscles. The results were similar in other muscle groups (p > 0.05). The dominant-side vastus lateralis muscle elasticity (the ability of the muscle to regain its original shape after contraction or removal of an external force) of hemophilia patients was found to be lower compared to healthy children. The fact that 45% of hemarthroses occur in the knee joint and that recurrent bleeding may affect the flexibility of the vastus lateralis, which is the main muscle within the quadriceps muscle group and responsible for the stabilization of the patella, can be associated with the study results.

Coexistence of Bloom Syndrome and Kostmann Disease and a Novel Mutation.

Bloom syndrome (BS) is a rare autosomal recessive inherited disorder. Patients with BS have photosensitivity, telangiectatic facial erythema, and stunted growth. They usually have mild microcephaly, and distinctive facial features such as a narrow, slender face, micrognathism, and a prominent nose. Kostmann disease (KD) is a subgroup of severe congenital neutropenias. The diagnosis of severe congenital neutropenia is based on clinical symptoms, bone marrow findings, and genetic mutation. Here, we report a female patient with a triangular face, nasal prominence, and protruding ears presenting with recurrent infections and severe neutropenia. Molecular genetic testing revealed a compound heterozygous variant in the HCLS-1-associated protein X-1 gene [(c.130_131insA) p.(trp44*), c.430 dup(p.Val144fs)] and a new homozygous variant in Bloom Syndrome RecQ like helicase gene [c.2074+2T>C p.(?)]. She was diagnosed with both BS and KD. To the best of our knowledge, this is the first case of coexisting BS and KD in a patient ever reported.

Clinical Characteristics and Outcomes of Cancer Cases Among Syrian Refugees From Southern Turkey.

Importance: Cancer was a common noncommunicable disease in Syria before the present conflict and is now a major disease burden among 3.6 million Syrian refugees in Turkey. Data to inform health care practice are needed. Objective: To explore sociodemographic characteristics, clinical characteristics, and treatment outcomes of Syrian patients with cancer residing in the southern border provinces of Turkey hosting more than 50% of refugees. Design, Setting, and Participants: This was a retrospective hospital-based cross-sectional study. The study sample consisted of all adult and children Syrian refugees diagnosed and/or treated for cancer between January 1, 2011, and December 31, 2020, in hematology-oncology departments of 8 university hospitals in the Southern province of Turkey. Data were analyzed from May 1, 2022, to September 30, 2022. Main Outcomes and Measures: Demographic characteristics (date of birth, sex, and residence), date of first cancer-related symptom, date and place of diagnosis, disease status at first presentation, treatment modalities, date and status at last hospital visit, and date of death. The International Statistical Classification of Diseases and Related Health Problems, Tenth Revision and International Classification of Childhood Cancers, Third Edition, were used for the classification of cancer. The Surveillance, Epidemiology, and End Results system was applied for staging. The diagnostic interval was defined as the number of days from first symptoms until the diagnosis. Treatment abandonment was documented if the patient did not attend the clinic within 4 weeks of a prescribed appointment throughout the treatment. Results: A total of 1114 Syrian adult and 421 Syrian children with cancer were included. The median age at diagnosis was 48.2 (IQR, 34.2-59.4) years for adults and 5.7 (IQR, 3.1-10.7) years for children. The median diagnostic interval was 66 (IQR, 26.5-114.3) days for adults and 28 (IQR, 14.0-69.0) days for children. Breast cancer (154 [13.8%]), leukemia and multiple myeloma (147 [13.2%]), and lymphoma (141 [12.7%]) were common among adults, and leukemias (180 [42.8%]), lymphomas (66 [15.7%]), and central nervous system neoplasms (40 [9.5%]) were common among children. The median follow-up time was 37.5 (IQR, 32.6-42.3) months for adults and 25.4 (IQR, 20.9-29.9) months for children. The 5-year survival rate was 17.5% in adults and 29.7% in children. Conclusions and Relevance: Despite universal health coverage and investment in the health care system, low survival rates were reported in this study for both adults and children with cancer. These findings suggest that cancer care in refugees requires novel planning within national cancer control programs with global cooperation.

A Novel Deletion in FERMT3 Causes LAD-III in a Turkish Family.

Leukocyte adhesion deficiency-III (LAD-III) is an extremely rare autosomal recessive syndrome caused by mutations in FERMT3, the gene encoding kindlin-3. The genetic alterations in this gene lead to abnormal expression or activity of kindlin-3 in leukocytes and platelets. Kindlin-3 acts as an important regulator of integrin activation. LAD-III has features of the bleeding syndrome of Glanzmann and also of leukocyte adhesion deficiency. In this study, we report on two families, one of Turkish and one of Syrian origin, with clinical features of LAD-III, loss of kindlin-3 protein expression, and a functional leukocyte defect. A novel, homozygous deletion in FERMT3 (c.921delC, p.Ser307Argfs*21) was found in the Turkish patient. The parents were carriers of the mutation, consistent with an autosomal recessive inheritance. A common c.1525C > T (p.Arg509*) mutation was found in the Syrian patient. In conclusion, beside the variant c.1525C > T in the FERMT3 gene, which was previously found in more than 15 patients in Anatolia, our study is the first to identify the novel homozygous variant c.921delC in the FERMT3 gene.

Hematopoietic stem cell transplantation activities and HRQOL of refugee or asylum seeker children in Turkey: A multicenter study.

BACKGROUND: Refugee or asylum seekers (RAS) children are at increased risk of physical, developmental, and behavioral health issues. The aim of this study was to evaluate clinical and psychosocial outcomes of hematopoietic stem cell transplantation (HSCT) in RAS children and compare health-related quality of life (HRQOL) to those of Turkish peers. METHODS: This retrospective study included patients who underwent HSCT aged 0-18 years and completed 100-day post-transplant. The PedsQL 4.0 Generic Core Scale was used in children over 5 years old to compare HRQOL. RESULTS: A total of 166 RAS patients (M/F: 106 /60) underwent 174 HSCTs (six patients had two, and one had three HSCT) compared to 66 Turkish patients. The mean age of the patients in the RAS group was 7.8 ± 4.9 years and similar to controls. A total of 124 patients (75%) were from Syria, and 49 (25%) were from other countries in the Middle East and Africa. The cause of migration was war in 121 (74%) RAS patients. Complications of HSCT were no different between the groups. However, the rate of neutropenic sepsis was significantly higher in the RAS group (p = 0.004). The total scores of HRQOL were not different between RAS and controls. In the RAS group, ratings of social functioning were lower in patients with consanguinity or non-malignant disease or who had match-related donors. DISCUSSION: Identifying areas of difficulty in subscales of HRQOL may help physicians to classify patients who need additional supportive care. Regular monitoring and supporting physical needs may result in better functional outcomes after HSCT.

The effects of close kinetic chain exercises on proprioception and physical activity level in pediatric patients with hemophilia.

INTRODUCTION: Knee joint proprioception is affected, and lower extremity functioning declines over time in patients with hemophilia A. AIM: To investigate the effects of a structured exercise programme consisting of the close kinetic chain (CKC) exercises on proprioception and physical activity level in pediatric patients with hemophilia. METHODS: A total of 21 patients with hemophilia A who had at least one target knee joint were randomized into three groups: Study Group (SG, n = 7), Conventional Treatment Group (CTG, n = 7) and Control Group (CG, n = 7). The SG received a structured, lower limb-specific exercise protocol consisting of CKC exercises 2 days a week for 12 weeks, in addition to prophylactic treatment. The CTG received exercise training as described in the published literature. The CG continued to receive prophylactic treatment during the study period. Proprioception was measured using a digital goniometer before and after treatment in open and closed kinetic chain positions (CKCPs). The Five Times Sit to Stand (STS), Timed Up and Go (TUG) and Functional Independence Score in Hemophilia were used for the assessment of physical activity level. RESULTS: A significant pre/post-treatment difference was found among the groups in proprioception (p = .001) and physical activity level (TUG p = .008, STS p = .001, FISH p = .006). Improvements in proprioception and physical activity level were greater in the SG compared to the other two groups (p < .05). CONCLUSION: Compared to conventional exercise, the structured exercise protocol consisting of CKC exercise training produced improvements in proprioception and physical activity in patients with hemophilia A.

Taste Alteration in Children With Acute Lymphoblastic Leukemia Undergoing Maintenance Treatment.

The purpose of the present study is to examine taste alteration in children with acute lymphoblastic leukemia (ALL) undergoing maintenance treatment. The population of the study was comprised of children with ALL between the ages of 7 and 18 who received maintenance treatment. The study sample was included 72 children (children with ALL:36 and healthy children: 36) determined by power analysis. This was a cross-sectional study. The children in both groups were applied to the taste test by the researcher. It was determined that there is a statistically significant difference ( P <0.05) between sweet (sucrose), salty (sodium chloride), sour (citric acid), and bitter (quinine hydrochloride) taste test score averages of the children with ALL and healthy children and that the 4 taste test score averages are lower in the experiment group. The taste alterations were determined in the present study for children with ALL undergoing maintenance treatment. Problems of children with cancer such as loss of appetite, negative attitude toward food or weight loss can be reduced or prevented when taste alteration is determined in children with cancer thereby improving the feeding of the children thereby increasing their quality of life.

Kindlin3-Dependent CD11b/CD18-Integrin Activation Is Required for Potentiation of Neutrophil Cytotoxicity by CD47-SIRPα Checkpoint Disruption.

The CD47-signal regulatory protein-alpha (SIRPα) immune checkpoint constitutes a therapeutic target in cancer, and initial clinical studies using inhibitors of CD47-SIRPα interactions in combination with tumor-targeting antibodies show promising results. Blockade of CD47-SIRPα interaction can promote neutrophil antibody-dependent cellular cytotoxicity (ADCC) toward antibody-opsonized targets. Neutrophils induce killing of antibody-opsonized tumor cells by a process identified as trogoptosis, a necrotic/lytic type of cancer cell death that involves trogocytosis, the antibody-mediated endocytic acquisition of cancer membrane fragments by neutrophils. Both trogocytosis and killing strictly depend on CD11b/CD18-(Mac-1)-mediated neutrophil-cancer cell conjugate formation, but the mechanism by which CD47-SIRPα checkpoint disruption promotes cytotoxicity has remained elusive. Here, by using neutrophils from patients with leukocyte adhesion deficiency type III carrying FERMT3 gene mutations, hence lacking the integrin-associated protein kindlin3, we demonstrated that CD47-SIRPα signaling controlled the inside-out activation of the neutrophil CD11b/CD18-integrin and cytotoxic synapse formation in a kindlin3-dependent fashion. Our findings also revealed a role for kindlin3 in trogocytosis and an absolute requirement in the killing process, which involved direct interactions between kindlin3 and CD18 integrin. Collectively, these results identified a dual role for kindlin3 in neutrophil ADCC and provide mechanistic insights into the way neutrophil cytotoxicity is governed by CD47-SIRPα interactions.

Outcomes of Eltrombopag Treatment and Development of Iron Deficiency in Children with Immune Thrombocytopenia in Turkey

Objective: Immune thrombocytopenia (ITP) is a rare autoimmune disease and hematologic disorder characterized by reduced platelet counts that can result in significant symptoms, such as bleeding, bruising, epistaxis, or petechiae. The thrombopoietin receptor agonist eltrombopag (EPAG) is a second-line agent used to treat chronic ITP purpura in adults and children. Materials and Methods: The present retrospective study evaluated the efficacy, safety, and side effects of EPAG treatment in pediatric patients with acute refractory and chronic immune thrombocytopenia, particularly focusing on iron-deficiency anemia. Results: The diagnosis was chronic ITP in 89 patients and acute refractory ITP in 16 patients. The mean age of patients was 9.5±4.5 years (minimum-maximum: 1.2-18 years) at the beginning of EPAG treatment. The overall response rate was 74.3% (n=78). The mean time for platelet count of ≥50x109/L was 11.6±8 weeks (range: 1-34 weeks). The treatment was stopped for 27 patients (25.7%) at an average of 6.8±9 months (range: 1-38 months). The reason for discontinuation was lack of response in 18 patients, nonadherence in 4 patients, and hepatotoxicity in 2 patients. Response to treatment continued for an average of 4 months after cessation of EPAG in 3 patients. Conclusion: Results of the current study imply that EPAG is an effective therapeutic option in pediatric patients with acute refractory and chronic ITP. However, patients must be closely monitored for response and side effects during treatment, and especially for iron deficiency.

Secondary severe thrombocytosis in a patient who underwent splenectomy due to hereditary spherocytosis and its treatment using hydroxyurea.

Thrombocytosis is a frequently seen condition during childhood. While it usually develops secondarily due to reasons such as infection or anemia, it may rarely develop due to clonal causes. Thrombocytosis becomes a life-threatening condition by causing severe complications such as hemorrhage and thrombosis development. Treatment is not recommended in patients who are asymptomatic and with a platelet count below 1,500,000/mm3, however, treatment is required in cases who are symptomatic and with a platelet count above 1,500,000/mm3 in conditions such as primary thrombocytosis. This article present the outcomes of a patient who was treated using low-dose hydroxyurea when he developed severe thrombocytosis after splenectomy.

Evaluation of Platelet Parameters in Children with Autism Spectrum Disorder: Elongated Collagen-Adenosine Diphosphate and Collagen-Epinephrine Closure Times.

Changes related to the serotonin system play a key role in the etiology of autism spectrum disorder (ASD). Although we know that platelets are associated with the serotonin system, their relation to ASD has not yet been elucidated. In this study, we aim to investigate platelet parameters in children with ASD. Forty patients with ASD according to Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5) and 30 healthy controls were included in the study. A complete blood count was done to measure parameters relating to platelet morphology. Moreover, prothrombin time (PT) and activated partial thromboplastin time (aPTT) were evaluated. Lastly, platelet functions were assessed with a platelet functions analyzer 100 (PFA-100) device by measuring collagen-ADP and collagen-epinephrine (EPI) closure times. There was not a significant difference between the groups in terms of platelet count, mean platelet volume (MPV), platelet distribution width, plateletcrit, PT, or aPTT parameters for ASD patients when compared to the control group (P > 0.05). However, MPV in severe ASD, as quantified by the Childhood Autism Rating Scale, was found to be significantly lower when compared to mild to moderate ASD (P = 0.047). Moreover, in terms of platelet functions, the elongation in collagen-ADP and collagen-EPI closure times were significantly higher for the ASD group (P = 0.044). These results may suggest an impairment in platelet functions rather than in platelet morphology for children with ASD. Considering these results, further investigation of thrombocyte functions in the ASD may lead to a better understanding of the pathogenesis of ASD and to the development of our limited knowledge of this disorder. Autism Res 2019, 12: 1069-1076. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Serotonin is a chemical that is found in brain as wells as in blood cells that function in blood clotting in the human body. There are problems related to serotonin in brains of people who have autism. Thus, blood clotting cells may also be affected in people who have autism. In this study, we compare blood clotting functions of children with autism with that of healthy controls.

Investigation of Dynamic Thiol/Disulfide Homeostasis in Children With Acute Immune Thrombocytopenia.

Oxidative stress may play a role in the pathogenesis of immune thrombocytopenia (ITP), but the role of dynamic thiol/disulfide homeostasis has not been studied. The objective of this study was to assess whether there is a change in thiol/disulfide homeostasis in children with acute ITP. A total of 40 children with acute ITP and 50 healthy age-matched and sex-matched controls were included in this study. Serum total thiol and native thiol levels have been measured with a novel automatic spectrophotometric method. The amount of dynamic disulfide bonds and related ratios were calculated from these values. The average total thiol and native thiol levels of the patient group were found to be significantly lower than those levels of controls (P<0.01). However, intravenous immunoglobulin (IVIG) treatment with 1 g/kg/d prevented these reductions. disulfide level was slightly, but not significantly, depressed in ITP patients, but it recovered following IVIG treatment. We detected no marked changes in disulfide/total thiol, disulfide/native thiol, and native thiol/total thiol ratios between groups. These results are the first to demonstrate that thiol/disulfide homeostasis plays a role in ITP pathogenesis, and IVIG treatment can prevent the reduced thiol levels in children.

Refugee children with beta-thalassemia in Turkey: Overview of demographic, socioeconomic, and medical characteristics.

AIM: Since the beginning of the Syrian civil war, more than 3.5 million Syrians have been under temporary protection status in Turkey. Because beta-thalassemia (BT) is a prevalent disorder in the Mediterranean countries, we decided to estimate the prevalence of and make an overview of the demographic, socioeconomic, medical characteristics, and healthcare problems of refugee children with BT. PATIENTS: Eighteen Turkish Pediatric Hematology Oncology Centers (PHOC) with 318 refugee children from 235 families participated in the study. The mean age of the patients was 8.1 ± 4.8 years (0.5-21 years). The mean time after immigration to Turkey was 2.5 ± 1.5 years (range, 0.1-7 years). Seventy-two (22.6%) of them were born and diagnosed with BT in Turkey. On physical examination, 82 patients (26%) were underweight and 121 patients (38%) were stunted. The appearance of a thalassemic face was reported for 207 patients (65.1%). Hepatomegaly and splenomegaly were reported in 217 (68.2%) and 168 (52.8%) patients, respectively. The median ferritin level was 2508 ng/mL (range, 17-21 000 ng/mL) at the first admission, and 2841 ng/mL (range, 26-12 981 ng/mL) at the last visit after two years of follow-up in a PHOC (P > 0.05). The most frequently encountered mutation was IVSI-110 (G>A) (31%). Before immigration, only 177 patients (55.6%) reported the use of chelators; after immigration it increased to 268 (84.3%). CONCLUSION: Difficulties in communication, finding a competent translator capable in medical terminology, nonregular use of medications, and insensitivity to prenatal diagnosis were preliminary problems. The current extent of migration poses emerging socioeconomic and humanitarian challenges for refugee patients with BT.

Respiratory Distress and Severe Anemia in a Child With Idiopathic Pulmonary Hemosiderosis.

Idiopathic pulmonary hemosiderosis is an infrequent cause of pulmonary hemorrhage in children. It is classically defined by the triad of recurrent hemoptysis, iron-deficiency anemia, and diffuse parenchymal infiltration without an obvious cause. The pathogenesis remains unexplained, diagnosis may be difficult, and the clinical course exceedingly variable. A 4-year-old girl was admitted to the hospital with complaints of dyspnea, and skin and mucous membrane pallor. The suspicion of idiopathic pulmonary hemosiderosis led to the use of corticosteroid therapy with rapid improvement in clinical condition and discharge from hospital.

Clinical Presentation, Prognostic Factors, and Outcome in Neutropenic Enteropathy of Childhood Leukemia.

Leukemia patients are at risk for neutropenic enteropathy (NEP) because of the effects of intensified chemotherapy. Medical records of 18 patients having 20 episodes of NEP were reviewed retrospectively. Primary diagnosis was acute lymphoblastic leukemia in 12 and myeloblastic leukemia in 6 cases. According to prognosis, 3 patients were in the standard-risk group, 6 in the moderate-risk group, and 9 in the high-risk group. Ultrasonography detected increased bowel wall thickness in 6 patients. Abdominal x-ray revealed air-fluid levels (n=8), pneumatosis intestinalis, pneumoperitoneum (n=1), and portal venous gas (n=1). All patients received medical treatment, and 1 with unrelieved hematochezia required resection of the cecum. Two cases with appendicitis and another 1 with pneumoperitoneum responded to antibiotics and recovered without surgery. The mortality rate was 30% and related to sepsis-induced complications. The presence of hypokalemia, hypoalbuminemia, metabolic acidosis, and admission to the intensive care unit were more common in patients with mortality (P=0.01). In conclusion, NEP should be kept in mind as a treatable but potentially lethal complication of childhood leukemia. Radiologic findings should be interpreted in conjunction with clinical picture. A conservative approach should be used in all cases but surgery can be considered in some situations.

Initial Lymphocyte Count as Prognostic Indicator for Childhood Immune Thrombocytopenia.

Acute ITP is a benign, self-limiting disease. Chronic ITP is diagnosed when thrombocytopenia persists beyond 12 months. The main objective of the present study was to examine whether absolute lymphocyte counts at diagnosis has predictive value with chronic ITP. A total of 601 patients diagnosed as ITP between 1995 and 2014 were retrospectively evaluated. CBCs with differential counts were performed at presentation for 601 patients. Absolute lymphocyte counts at presentation were independently predictive of disease duration. The male to female ratio was almost 1:1 and 25.9 % (156/601) of the patients had chronic ITP. We determined that age >6.75 year, platelet counts >6.950/mm3 and absolute lymphocyte counts ≤2.050/mm3 was associated with a significant risk for developing chronic ITP. Absolute lymphocyte counts at the time of diagnosis were predictive variables for the development of chronic ITP. Further researches are needed to confirm the current finding and to assess the underlying pathophysiology with the course of the ITP in observational studies.

Cutaneous side effects of doxycycline: a pediatric case series.

OBJECTIVE: Brucellosis is highly endemic in Turkey and doxycycline is commonly used for its treatment. The present study aimed at documenting the cutaneous side effects of doxycycline in pediatric brucellosis patients in Turkey. MATERIALS AND METHODS: Pediatric patients with brucellosis that were treated between February 2014 and January 2016 were analyzed retrospectively, and those that developed doxycycline-related cutaneous side effects were identified. Demographic data, epidemiological history, physical examination findings, laboratory test results, anti-brucellosis treatment regimen, duration of follow up and outcome were recorded. RESULTS: Among the 189 brucellosis patients, 141 treated with doxycycline plus rifampicin. Seven patients (5%) (two female and five male) developed doxycycline-related cutaneous side effects. Mean duration of treatment before the onset of cutaneous side effects was 9.5 weeks. Doxycycline therapy was continued in five of these patients and was changed in two patients. In the patients that continued to receive doxycycline the cutaneous side effects gradually improved. CONCLUSIONS: Cutaneous side effects of doxycycline should always be a consideration, especially in regions in which brucellosis is endemic and doxycycline is commonly used to treat it.