The efficacy of Allium ampeloprasum L. in reducing neutrophil recovery time in childhood cancer with febrile neutropenia: a randomized, double-blind, placebo-controlled trial.

INTRODUCTION: Febrile neutropenia is a serious complication of cancer chemotherapy that can result in delays in treatment. This study evaluates the efficacy of A. ampeloprasum L. at neutrophil recovery time in children with chemotherapy-associated febrile neutropenia. METHODS: This single-center, parallel-group, double-blind, randomized clinical trial was conducted at an oncology hospital. Patients selected among childhood cancers with febrile neutropenia. Overall, 97 febrile neutropenic children were enrolled. The intervention group (n=49) was given A. ampeloprasum L. in capsules (500 mg twice daily) for seven days plus supportive care. The control group (n=48) was treated similarly with supportive care and placebo capsules. Total white blood cell (WBC) and absolute neutrophil counts (ANC) were checked daily and neutrophil recovery time in both groups was compared. RESULTS: Patients in the intervention group experienced shorter neutrophil recovery compared to the control group (4.02 ± 2.32 days vs. 6.38 ± 2.80 days, respectively, P less than 0.001). The intervention group was discharged from the hospital earlier than the control group with a mean of two days, but it did not reach statistical significance (P=0.133). Mean WBC and ANC were not significantly different in the two groups. Herbal medicine was well tolerated, and no adverse effect was reported. CONCLUSIONS: A fresh, lyophilized extract from deciduous leaves of A. ampeloprasum L. can effectively shorten the ANC recovery time leading to an earlier release from the hospital. The trial was registered in the Iranian Registry of Clinical Trials with registration No. IRCT2015051615666N2 (http://www.irct.ir/).

Cardioprotective effects of deferoxamine in acute and subacute cardiotoxicities of doxorubicin: a randomized clinical trial.

BACKGROUND: Cardiotoxicity is a major concern following doxorubicin (DOX) use in the treatment of malignancies. We aimed to investigate whether deferoxamine (DFO) can prevent acute cardiotoxicity in children with cancer who were treated with DOX as part of their chemotherapy. RESULTS: Sixty-two newly-diagnosed pediatric cancer patients aged 2-18 years with DOX as part of their treatment regimens were assigned to three groups: group 1 (no intervention, n = 21), group II (Deferoxamine (DFO) 10 times DOX dose, n = 20), and group III (DFO 50 mg/kg, n = 21). Patients in the intervention groups were pretreated with DFO 8-h intravenous infusion in each chemotherapy course during and after completion of DOX infusion. Conventional and tissue Doppler echocardiography, serum concentrations of human brain natriuretic peptide (BNP), and cardiac troponin I (cTnI) were checked after the last course of chemotherapy. Sixty patients were analyzed. The level of cTnI was < 0.01 in all patients. Serum BNP was significantly lower in group 3 compared to control subjects (P = 0.036). No significant differences were observed in the parameters of Doppler echocardiography. Significant lower values of tissue Doppler late diastolic velocity at the lateral annulus of the tricuspid valve were noticed in group 3 in comparison with controls. By using Pearson analysis, tissue Doppler systolic velocity of the septum showed a marginally significant negative correlation with DOX dose (P = 0.05, r = - 0.308). No adverse effect was reported in the intervention groups. CONCLUSIONS: High-dose DFO (50 mg/kg) may serve as a promising cardioprotective agent at least at the molecular level in cancer patients treated with DOX. Further multicenter trials with longer follow-ups are needed to investigate its protective role in delayed DOX-induced cardiac damage. Trial registration IRCT, IRCT2016080615666N5. Registered 6 September 2016, http://www.irct.ir/IRCT2016080615666N5 .

Severe acute respiratory syndrome coronavirus-2 Alpha variant (B.1.1.7), original wild-type severe acute respiratory syndrome coronavirus 2, and cytomegalovirus co-infection in a young adult with acute lymphoblastic leukemia, case report, and review of the possible cytomegalovirus reactivation mechanisms.

BACKGROUND: Like other viral infections, severe acute respiratory syndrome coronavirus-2 infection could affect different human body systems, including host immune responses. Three years after its pandemic, we learn more about this novel coronavirus. As we expected, different co-infections with various organisms, such as viruses, bacteria, and even fungi, have been reported. However, concurrent infection with two severe acute respiratory syndrome coronavirus-2 strains and cytomegalovirus is extremely unusual. We have only a rudimentary understanding of such co-infections and their long-term consequences for patients with cancer. CASE PRESENTATION: An 18-year-old young Iranian adult with acute lymphoblastic leukemia presented with abdominal pain, diarrhea, nausea, and vomiting following a recent history of severe acute respiratory syndrome coronavirus-2 infection. The patient never experienced respiratory symptoms, and the chest imaging study was normal on admission. His primary laboratory investigation revealed prerenal azotemia and severe abnormal liver function tests (blood urea nitrogen 32 mg/dL, creatinine 1.75 mg/dL, prothrombin time 66 s, partial thromboplastin time 44.5 s, international normalized ratio 5.14, total bilirubin 2.9 mg/dL, and direct bilirubin 2.59 mg/dL). Cytomegalovirus disease was diagnosed by polymerase chain reaction in his blood and stool samples. The patient's gastrointestinal signs and symptoms improved shortly after receiving intravenous ganciclovir treatment. His gastrointestinal symptoms continued intermittently for weeks despite maintenance valganciclovir prescription, necessitating frequent hospitalizations. The patient was complicated by the recurrence of gastrointestinal symptoms during the sixth hospitalization, even though he had no respiratory symptoms, and the nasopharyngeal test revealed severe acute respiratory syndrome coronavirus-2 Wuhan strain for the first time. Remdesivir and valganciclovir were administrated due to persistent enteritis and evidence of intestinal tissue invasion by severe acute respiratory syndrome coronavirus 2 and cytomegalovirus on multiple intestinal biopsies, which led to partial clinical responses. Cytomegalovirus and severe acute respiratory syndrome coronavirus-2 fecal shedding continued for more than 6 months despite repeated antiviral therapy, and the Wuhan and Alpha strains were also detected in his nasopharyngeal samples through repeated sampling (confirmed by four nasopharyngeal sampling and multiple stool specimens and several intestinal biopsies). Finally, during the Delta-variant (B.1.617.2) outbreak in Iran, the patient was admitted again with febrile neutropenia and decreased level of consciousness, necessitating respiratory support and mechanical ventilation. During the Delta-variant peak, the patient's nasopharyngeal sample once more tested positive for severe acute respiratory syndrome coronavirus 2. The patient died a few days later from cardiopulmonary arrest. CONCLUSION: The coronavirus disease 2019 pandemic has encountered patients with cancer with critical diagnostic and treatment challenges. Patients who are immunocompromised may co-infect with multiple severe acute respiratory syndrome coronavirus-2 strains and cytomegalovirus, and even with timely diagnosis and treatment, the prognosis may be poor.

The survival of childhood leukemia: An 8-year single-center experience.

BACKGROUND: The survival of childhood leukemia has improved. We aimed to report the survival rate and the associated factors in children with acute leukemia during an 8-year follow-up. AIMS: This study investigates the 8-year survival rates of children with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) in Shiraz, the largest oncology center in Southern Iran. We also aimed to assess the independent factors associated with higher mortality in childhood leukemia. METHODS: Children 0-18 years with acute leukemia were followed from 2013 to 2021 in Shiraz, Iran. The 8-year overall survival (OS) and event-free survival (EFS) rates were estimated by the Kaplan-Meier method. Independent factors associated with survival were assessed by the Cox regression hazard modeling. RESULTS: We included 786 children, with 43.5% female, and a mean age of 6.32 ± 4.62 years. Patients with AML compared to ALL experienced more relapse (34.6% vs. 22.5%, p = .01) and death (31.7% vs. 11.3%, p < .001). The cumulative 8-year OS and EFS were 81% (95% confidence interval (CI), 74.3% to 86.1%) and 68.3% (95% CI, 63.5% to 72.7%) in ALL patients and 63.5% (95% CI, 52.1% to 72.9%) and 43% (95% CI, 33.1% to 52.6%) in AML patients. Multivariable analysis revealed that hepatomegaly (hazard ratio = 4, 95% CI, 1.0 to 22.3, p = .05) was the main independent risk factor of death in ALL patients. No definite risk factor was defined for AML patients. CONCLUSION: The survival of childhood leukemia has recently increased dramatically in low-middle income countries. Hepatomegaly was introduced as a potential risk factor for lower survival in ALL patients. Further multicenter studies are needed to confirm the validity of this association.

Comparative Effectiveness of Peg-Asparaginase and L-Asparaginase on Coagulation Markers Among Pediatric Patients with Acute Lymphoblastic Leukemia.

BACKGROUND: Asparaginase (ASP), a chemotherapy component in the acute lymphoblastic leukemia (ALL) treatment, could impair normal coagulation state. Usually, a decline in the levels of several coagulation factors occurs which ultimately could lead to thrombotic events and abnormal coagulation tests. In this study, we aimed to compare the effects of two different subtypes of ASP, pegylated asparaginase (PEG-ASP) and L-asparaginase (L-ASP) on coagulation markers and test among 40 pediatric patients with ALL. METHODS: In this cohort study a total of 40 pediatric patients with newly diagnosed ALL were enrolled and divided into two groups by simple randomization. In group A, 20 patients received PEG-ASP while in group B, 20 patients received L-ASP during the induction treatment. Coagulation markers included prothrombin time (PT), partial thrombin time (PTT), protein-C (Pr-C), protein-S (Pr-S), and antithrombin III (ATIII) and were assessed before start and after of induction chemotherapy. RESULTS: Coagulation profile including PT, PTT, INR, Pr-C, Pr-S, and ATIII before start of treatment were not statistically significant between the two groups. Anticoagulant factors decreased significantly after consuming both drugs. Tests for PT and INR of those who took L-ASP decreased significantly. Overall, when comparing the changes of the six studied factors, ATIII and Pr-C were the significant factors which were different between groups. CONCLUSIONS: ASP has a negative effect on anticoagulant factors including (ATIII, Pr-C, Pr-S). Additionally, the negative effect of L-ASP on anticoagulant factors was more prominent than PEG-ASP. Therefore, the risk of thrombosis probably was negligible in PEG-ASP in comparison with L-ASP.

The Cerebrospinal Fluid Concentration of Methyltetrahydrofolate and Serum Folate in Children with Developmental Delay, Regression, and/or Refractory Epilepsy.

BACKGROUND AND OBJECTIVES: Folate is an important vitamin with a significant role in cell metabolism processes, and its deficiency is associated with several diseases. In addition, cerebral folate deficiency is associated with neurodevelopmental disorders. Studying the association of serum and cerebral folate deficiency with childhood neurodevelopmental disorders such as refractory epilepsy, developmental delay, and regression can be an important step towards the improvement of symptoms of such disorders. MATERIALS AND METHODS: In this cross-sectional study, from February to October 2018, 60 children aged 6 months to 5 years; known cases of idiopathic refractory epilepsy; were selected randomly. After recording demographic, and clinical characteristics, cerebrospinal fluid (CSF) and blood samples were taken from the patients and sent to a laboratory for measurement of 5-methyltetrahydrofolate (5MTHF), folate, and homocysteine levels. RESULTS: Sixty patients completed the study, including 33 boys (55%) and 27 girls (45%). Mean ± SD of the studied population was 26.93 ± 19.97 months. Eighteen children (30%) had refractory epilepsy, 11 (18.3%) had developmental delay, 12 (20%) had refractory epilepsy and developmental delay, and 19 (31.7%) had refractory epilepsy and developmental regression. The results of brain magnetic resonance imaging (MRI) were normal in 47 (78.3%) children and atrophic in 13 (21.7%) children. Mean ± SD of serum level of homocysteine was 9.14 ± 8.58 µmol/L, that of folate was 11.60 ± 6.89 nmol/L, and that of 5MTHF was 69.23 ± 54.16 nmol/L. CONCLUSION: Measurement of serum folate, homocysteine, and CSF level of 5MTHF are of great importance in patients with developmental disabilities.

Comparison of the clinical features and outcome of children with hemophagocytic lymphohistiocytosis (HLH) secondary to visceral leishmaniasis and primary HLH: a single-center study.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of excessive inflammation. We aimed to describe the clinical and laboratory findings of HLH patients secondary to Visceral leishmaniasis (VL) and their treatment outcome during a 4-year follow-up period compared to primary HLH. METHOD: Forty children with primary HLH confirmed by genetic study and 20 children with HLH secondary to VL confirmed by a blood or bone marrow polymerase chain reaction from 2014 to 2018 in Shiraz, Fars province, Southern Iran, were enrolled. RESULTS: The median age at diagnosis was 11.5 months (range 1-170), and 56.7% were male. Fever and splenomegaly were the most frequent clinical presentations. 93.3% of the subjects had an HScore > 169, which had a good correlation with HLH-2004 criteria (r = 0.371, P = 0.004). Patients with primary HLH experienced more thrombocytopenia (P = 0.012) and higher alanine transaminase (P = 0.016), while patients with VL-associated HLH had higher ferritin (P = 0.034) and erythrocyte sedimentation rate (P = 0.011). Central nervous system (CNS) involvement occurred in 38.3% of patients. The mortality rate was higher in patients with CNS disease (61% vs. 35%, P = 0.051). The 3-yr overall survival rate was 35.9%. (24% in primary HLH and 100% in VL-associated HLH, P < 0.001). In Cox regression analysis, platelet count < 100,000/ µ l (hazard ratio 4.472, 95% confidence interval 1.324-15.107, P = 0.016) correlated with increased mortality in patients with primary HLH. CONCLUSION: VL is a potential source of secondary HLH in regions with high endemicity. Treatment of the underlying disease in VL-associated HLH is sufficient in most cases, with no need to start etoposide-based chemotherapy.

Feasibility and Therapeutic Potential of Combined Peptide Receptor Radionuclide Therapy With Intensive Chemotherapy for Pediatric Patients With Relapsed or Refractory Metastatic Neuroblastoma.

BACKGROUND: Recent evidence has demonstrated high expression of somatostatin receptors in neuroblastoma (NB) cells. Because of this, we endeavored to evaluate the diagnostic performance and clinical efficacy of 68Ga-DOTATATE PET/CT and peptide receptor radionuclide therapy (PRRT) using 177Lu-DOTATATE combined with chemotherapy in pediatric NB patients. PATIENTS AND METHODS: In total, 14 pediatric patients with histopathologically confirmed NB underwent 68Ga-DOTATATE PET/CT. Among them, the patients who were refractory or relapsed after therapy with 131I-MIBG and had intensive uptake of 68Ga-DOTATATE were referred for PRRT using 177Lu-DOTATATE. Treatment response based on follow-up imaging was classified into complete response, partial response, stable disease, and progressive disease. After each cycle of PRRT, laboratory tests were performed for evaluation of hematological, renal, and hepatic toxicities. The CTCAE (Common Terminology Criteria for Adverse Events; version 4.03) was used for grading adverse event. Curie score and International Society of Pediatric Oncology Europe Neuroblastoma score were used for semiquantitative analysis of scans of patients who underwent PRRT. In addition, overall survival was calculated as the time interval between the date of the first cycle and the end of follow-up or death. RESULTS: Overall, 14 refractory NB children including 7 boys and 7 girls with a median age of 5.5 years (ranged from 4 to 9) underwent 68Ga-DOTATATE PET/CT. PET/CT was positive in 10/14 patients (71.4%), and the median number of detected lesions in positive patients was 2 (range, 1-13). Of 14 patients, 5 patients underwent PRRT, including 3 boys and 2 girls. A total of 19 PRRT cycles and 66.4 GBq 177Lu-DOTATATE were given. Among these 5 patients, 2 showed an initial complete response, which relapsed a few months later, 1 showed a partial response, and 2 showed progressive disease. According to the Kaplan-Meier test, the overall survival was estimated at 14.5 months (95% confidence interval, 8.9-20.1). In evaluation of PRRT-related toxicity according to the CTCAE, 4 patients showed grade 1, and 1 showed grade 2 leukopenia. Two patients showed grade 1, and 2 others showed grade 2 anemia. Two patients showed grade 1, and 3 patients showed grade 2 thrombocytopenia. Serum creatinine in 1 patient increased to grade 1. CONCLUSIONS: Combination of 177Lu-DOTATATE with chemotherapeutic agents might achieve worthwhile responses with low toxicity, encouraging survival in NB patients who have relapsed or are refractory to conventional therapy, including 131I-MIBG therapy. Imaging with 68Ga-DOTATATE PET/CT in such patients has a relatively high detection efficacy, demonstrating its potential use as an alternative imaging tool to conventional modalities such as 123I/131I-MIBG. However, further well-designed trials are highly warranted.

Effect of chamomile on chemotherapy-induced neutropenia in pediatric leukemia patients: A randomized triple-blind placebo-controlled clinical trial.

OBJECTIVE: Chemotherapy-induced neutropenia is one of the main side effects of acute lymphoblastic leukemia (ALL) treatment. In this trial, we evaluated the efficacy of chamomile in management of neutropenia. MATERIALS AND METHODS: This randomized triple-blind placebo-controlled clinical trial was carried out in 2-18-year-old children with ALL. Participants in each group daily received 2.5 ml of either chamomile syrup or placebo syrup for a period of 30 days. Participants' white blood cell (WBC), and absolute neutrophil count (ANC), as well as their quality of life were evaluated. RESULTS: The study was completed with a total of 40 patients. An increasing trend of ANC was observed in the treatment group despite the decreasing trend in placebo group, which was statistically significant between the two groups (P Interaction=0.019, 95% confidence intervals=15.076-171.324). No serious side effects were reported. CONCLUSION: Using chamomile syrup as a complementary therapy in children with leukemia could improve their immunity (as it increased WBC) by minimizing chemotherapy-induced neutropenia.

Extramedullary manifestations in acute lymphoblastic leukemia in children: a systematic review and guideline-based approach of treatment.

OBJECTIVE: Acute lymphoblastic leukemia (ALL) may present with signs and symptoms related to extramedullary involvement, therefore, leads to delayed diagnosis of ALL in children. This study aims to consider the extramedullary manifestations of ALL in children and their proper treatment. METHOD: The databases were searched for all relevant subjects including "acute lymphoblastic leukemia", "clinical presentation", "unusual presentation", "childhood acute lymphoblastic leukemia", "presenting features of ALL", "extramedullary presentation", and "atypical presentation" from April 1968 to June 2020. The Inclusion criteria for this review study were all cases reported, case series, and studies about extramedullary presentations of ALL in pediatrics. Eighty-seven studies had inclusion criteria. All reported studies were analyzed given their extramedullary presentations, age, sex, treatment option, and prognostic factors. A two-sided P-value less than 0.05 was considered statistically significant. RESULT: In this review study, the extramedullary initial signs and symptoms of ALL were related to musculoskeletal system 17 (19.5%) especially bony symptoms and hypercalcemia. The additional extramedullary presentations of ALL in order of frequency include; renal involvement, 17 (19.5%), hepatic symptom 12 (13.8%), orbital presentation 10 (11.5%), neurologic signs 8 (9%), dermatological manifestations 5 (5.8%), oral presentations 5 (5.8%), hypereosinophilia 5 (5.8%), abdominal manifestation 3 (3.5%), pericardial involvement 2 (2.3%), and the other miscellaneous presentations 3 (3.5%). CONCLUSION: The clinicians must become familiar with these extramedullary presentations of ALL in pediatrics to avoid the delayed diagnosis of this disease and increase the probable chance of survival by early detection.

The Effect of Viola Odorata L. Oil for Fever in Children: A Randomized Triple-blinded Placebo-controlled Clinical Trial.

INTRODUCTION: Finding non-systemic antipyretic option in cancer patients who simultaneously receive several other drugs seems be logical. This study was designed to evaluate complementary therapy with Viola odorata L. oil for fever control in febrile neutropenic children. METHODS AND MATERIALS: In a randomized placebo controlled clinical trial, 41 febrile children were divided into two groups. Children in the active drug group received viola oil (20 drops) to be rubbed on the peripheral margin of the patient umbilicus. Primary outcome measure of the study was the mean axillary temperature in the 30, 60, and 240 minutes after the intervention. RESULTS: The mean temperature reduced significantly in the viola group after 30 minutes of administration (p =0.005), while there was no significant change in the placebo group (p =1.00). The number of patients who received paracetamol as the rescue treatment was significantly lower in the viola group than that in the placebo group (5 vs. 17, p =0.001). CONCLUSION: The results of our study showed the safety and efficacy of complementary therapy with Viola odorata L. oil for fever control in febrile neutropenic children during hospital course.

Successful treatment of refractory metastatic neuroblastoma with panobinostat in combination with chemotherapy agents and iodine-131-meta-iodobenzylguanidine therapy.

INTRODUCTION: Neuroblastoma commonly required multimodal therapy containing surgery, chemotherapy, radiotherapy, and immunotherapy. CASE REPORT: In our case, who had refractory metastatic neuroblastoma, we use histone deacetylase inhibitor (panobinostat) in combination with chemotherapy agents and iodine-131-meta-iodobenzylguanidine (MIBG) therapy. MANAGEMENT AND OUTCOME: This approach leads to successfully treat the patient. MIBG scan and bone marrow examination after therapy revealed no evidence of tumor. Now, she underwent autologous transplantation six months ago and free of tumor. CONCLUSION: Panobinostat can cause apoptosis induction in refractory metastatic neuroblastoma in combination with MIBG therapy and chemotherapy.

A novel frame-shift deletion in FANCF gene causing autosomal recessive Fanconi anemia: a case report.

BACKGROUND: Fanconi anemia (FA) is a heterogeneous genetic disorder characterized by congenital anomalies, early-onset bone marrow failure, and a high predisposition to cancers. Up to know, different genes involved in the DNA repair pathway, mainly FANCA genes, have been identified to be affected in patients with FA. CASE PRESENTATION: Here, we report clinical, laboratory and genetic findings in a 3.5-year-old Iranian female patient, a product of a consanguineous marriage, who was suspicious of FA, observed with short stature, microcephaly, skin hyperpigmentation, anemia, thrombocytopenia and hypo cellular bone marrow. Therefore, Next Generation Sequencing was performed to identify the genetic cause of the disease in this patient. Results revealed a novel, private, homozygous frameshift mutation in the FANCF gene (NM_022725: c. 534delG, p. G178 fs) which was confirmed by Sanger sequencing in the proband. CONCLUSION: Such studies may help uncover the exact pathomechanisms of this disorder and establish the genotype-phenotype correlations by identification of more mutations in this gene. It is the first report of a mutation in the FANCF gene in Iranian patients with Fanconi anemia. This new mutation correlates with a hematological problem (pancytopenia), short stature, and microcephaly and skin hyperpigmentation. Until now, no evidence of malignancy was detected.

Gynecomastia as a late complication of childhood cancer and its treatment that can affect the quality of life of male survivors.

Childhood cancer is relatively rare, and nowadays it is curable in more than 80% of children. Childhood cancer therapy is directed not only at improving survival but recently, we also concentrate on reducing late effects. We want children who have a diagnosis of cancer to survive and have an excellent quality of life. Gynecomastia and fertility outcome of the survivors of childhood malignancies should be considered in the follow-up of teen agers and young adults and should be approached in an accurate manner and managed in comprehensive teams.

The Curative Role of Bitumen in Traditional Persian Medicine

AIM: Bitumen is a natural substance effusing from rocks' notches in some highland areas; it has been known as an effective remedy for treating some illnesses. Considering pain relieving properties of bitumen in traditional Persian medicine (TPM) sources, this study aims to review the viewpoints of TPM sages regarding bitumen in the context of traditional Persian medicine. It also provides applicable information for interested researchers to conduct well-designed clinical trials and evaluate therapeutic effects of bitumen claimed in TPM sources. MATERIAL AND METHOD: Various databases including Embase, SID, IRANDOC, IranMedex, Scopus and PubMed were searched with keywords "bitumen" and "Shilajit". Furthermore, main traditional Persian medicine sources including Avicenna's "Canon of medicine", "Continens Liber" by Razes, "The storehouse of medicaments" by Aghili, "Gift for the faithful" by Momen Tonekaboni and "Measure for medicine" written by Muhammad Akbar Shah Arzani were reviewed with Persian keywords "Moomiaii" and "Mumnaei" Results: According to TPM sources, bitumen was used by Iranian's physicians to treat a wide range of diseases. It was known especially as an effective remedy to improve gastrointestinal digestive problems. CONCLUSION: Bitumen is cited in traditional Persian medicine sources as an effective remedy for treatment of a wide range of diseases, especially GI disorders and bone pain. Recent studies showed the beneficial effects of bitumen in treatment of wound healing, however using it in medical practice for other health dilemma should be confirmed by conducting well-designed clinical studies in the future.

ASSOCIATION OF POTENTIAL CELIAC DISEASE AND REFRACTORY IRON DEFICIENCY ANEMIA IN CHILDREN AND ADOLESCENTS.

BACKGROUND: Celiac disease is an enteropathy caused by dietary gluten. The combination of serologic, genetic and histologic data has led to description of other categories of this disease. OBJECTIVE: There are a number of patients with iron deficiency anemia (IDA) that do not respond to iron treatment and may be repeated for many times, Therefore, we aimed to investigate celiac disease in this group. METHODS: In this cross sectional transverse prospective study from August 2011 to February 2013, in a Pediatric care clinic affiliated to Shiraz University of Medical Sciences, 184 children including 92 IDA patients who responded to treatment using iron supplement, 45 non-responding iron deficient patients, and 47 healthy individuals, with the maximum age of 18 years, with written consent from their parents, participated in serologic screening (with Anti-TTG antibody and anti-Endomysial antibody) for celiac disease. Patients with at least one positive serology test underwent multiple mucosal biopsy from bulb and duodenum. RESULTS: Among 184 participants, 19 (10.3%) subjects had positive serologic test for celiac disease, including 13 (28.9%) patients in the group with refractory IDA, 5 (5.4%) patients in the group with treated IDA, and 1 patient in the healthy group. The frequency of positive serologic test in the group with IDA resistant to treatment was prominently higher than the other two groups (P<0.001). Among the patients with positive serologic celiac test who underwent endoscopy and biopsy, no histologic evidence of celiac disease was seen. They were diagnosed as potential celiac disease. CONCLUSION: Frequency of potential celiac disease in patients with refractory IDA was higher than control the subjects. Therefore, we recommend serologic screening for early detection and minimizing the complications of celiac disease and repeated iron therapy for this group.

Potencial associação da doença celíaca com anemia ferropriva refratária em crianças e adolescentes / Association of potential celiac disease and refractory iron deficiency anemia in children and adolescents

ABSTRACT BACKGROUND: Celiac disease is an enteropathy caused by dietary gluten. The combination of serologic, genetic and histologic data has led to description of other categories of this disease. OBJECTIVE: There are a number of patients with iron deficiency anemia (IDA) that do not respond to iron treatment and may be repeated for many times, Therefore, we aimed to investigate celiac disease in this group. METHODS: In this cross sectional transverse prospective study from August 2011 to February 2013, in a Pediatric care clinic affiliated to Shiraz University of Medical Sciences, 184 children including 92 IDA patients who responded to treatment using iron supplement, 45 non-responding iron deficient patients, and 47 healthy individuals, with the maximum age of 18 years, with written consent from their parents, participated in serologic screening (with Anti-TTG antibody and anti-Endomysial antibody) for celiac disease. Patients with at least one positive serology test underwent multiple mucosal biopsy from bulb and duodenum. RESULTS: Among 184 participants, 19 (10.3%) subjects had positive serologic test for celiac disease, including 13 (28.9%) patients in the group with refractory IDA, 5 (5.4%) patients in the group with treated IDA, and 1 patient in the healthy group. The frequency of positive serologic test in the group with IDA resistant to treatment was prominently higher than the other two groups (P<0.001). Among the patients with positive serologic celiac test who underwent endoscopy and biopsy, no histologic evidence of celiac disease was seen. They were diagnosed as potential celiac disease. CONCLUSION: Frequency of potential celiac disease in patients with refractory IDA was higher than control the subjects. Therefore, we recommend serologic screening for early detection and minimizing the complications of celiac disease and repeated iron therapy for this group.

RESUMO CONTEXTO: A doença celíaca é uma enteropatia causada pelo glúten na dieta. A combinação de dados sorológicos, genéticos e histológicos proporcionou a descrição de outras categorias desta doença. OBJETIVO: Há pacientes com anemia por deficiência de ferro que não respondem ao tratamento com ferro mesmo que repetido por muitas vezes. O objetivo deste trabalho foi investigar a presença de doença celíaca nestes indivíduos. MÉTODOS: Realizado estudo prospectivo com cruzamento secional transversal, de agosto de 2011 a fevereiro de 2013, em uma clínica de cuidados pediátricos afiliados a Shiraz University Medical Sciences, com 184 crianças incluindo 92 pacientes com anemia por deficiência de ferro que responderam ao tratamento com ferro suplementar, 45 não respondedores e 47 indivíduos sadios, com idade máxima de 18 anos, todos com consentimento informado dos pais. Todos participaram da triagem sorológica (com anticorpos anti-TTG e anticorpo antiendomísio) para doença celíaca. Pacientes com pelo menos um teste de sorologia positiva foram submetidos a biópsia da mucosa múltipla do bulbo e duodeno. RESULTADOS: Entre os 184 participantes, 19 (10,3%) tinham teste sorológico positivo para doença celíaca, incluindo 13 (28,9%) pacientes no grupo com a anemia por deficiência de ferro refratária, 5 (5,4%) pacientes no grupo com anemia por deficiência de ferro tratados e respondedores e 1 paciente do grupo saudável. A frequência de teste sorológico positivo no grupo com anemia por deficiência de ferro resistente ao tratamento foi destacadamente maior do que os outros dois grupos (P<0,001). Entre os pacientes com teste sorológico positivo para doença celíaca submetidos a endoscopia e biópsia, não foi vista nenhuma evidência histológica de doença celíaca. Foram diagnosticados como potencial doença celíaca. CONCLUSÃO: Potencial frequência de doença celíaca em pacientes com anemia por deficiência de ferro refratária foi maior do que nos controles. Portanto, recomendamos testes sorológicos de triagem para a detecção precoce, minimizando as complicações da terapia de ferro repetidas para este grupo.