Spleen size evaluation in children: Time to define splenomegaly for pediatric surgeons and pediatricians.

BACKGROUND: We determined the range of normal spleen dimensions evaluated by ultrasonography (US) in children according to sex and age and the relationship between splenic measurements, auxological data and body proportions, in order to define splenomegaly parameters in support of the surgical mini-invasive approaches in pediatrics. METHODS: We prospectively examined 317 caucasian children of both sexes. The patients were divided into three groups: 0-3 years; 4-10 years; 11-18 years. Sex, weight, height/length, body mass index (BMI), waist circumference and xipho-pubic distance were determined for each child. US spleen evaluation included longitudinal/antero-posterior/transverse diameters, transverse area and volume. Spleen volume/abdominal volume, longitudinal spleen diameter/longitudinal left kidney diameter and longitudinal spleen diameter/xipho-pubic distance ratios were also calculated. RESULTS: For caucasian subjects, in different age groups spleen volume, transverse area and diameter increased while the spleen/abdominal volume ratio decreased significantly (p<0.001). A significant (p<0.001) decrease in longitudinal spleen diameter/xipho-pubic distance ratio was noted between the 0-3 years group and both 4-10 and 11-18 years group. Age and auxological data, except BMI, showed a high correlation with spleen dimension (r≥0.8). CONCLUSIONS: The current concept of splenomegaly is not applicable in pediatric surgery. A dedicated classification of splenomegaly is needed for children and would improve the safety and feasibility of treatment.

Clinical efficacy and safety of ruxolitinib in the management of myelofibrosis: A single institution experience in Taiwan.

OBJECTIVE: Myelofibrosis (MF) is a pathologic entity of myeloproliferative neoplasm (MPN) characterized by bone marrow fibrosis, extramedullary hematopoiesis, splenomegaly, and constitutional symptoms that severely affect the quality of life accompanied with the risk of leukemia development. Conventional treatment is usually ineffective and has limited impact on prolongation of survival. Dysregulated Janus kinase (JAK) signaling is common in MPN. In two randomized controlled trials, ruxolitinib, a potent pan-JAK inhibitor, has been shown to be highly effective in patients with intermediate- and high-risk MF. METHOD: We retrospectively analyzed the therapeutic outcome of 10 MF patients treated with ruxolitinib in our institute. Basic clinical data, JAK2V617F mutational status and Myelofibrosis Symptoms Assessment Form (MF-SAF) to evaluate disease-related symptoms were recorded initially, and at every visit. RESULT: Among these patients, only half of the patients harbored JAK2V617F mutation. After treatment with ruxolitinib, all patients had reduction of splenic size and reached nadir by week 24. Nine patients had body weight increment, and four of them had body weight increment more than 10%. Seven patients had their total symptom score reduced by more than 50% after therapy. The efficacy of ruxolitinib was irrelevant to JAK2V617F mutational status. Adverse events were mainly hematological and easily manageable. DISCUSSION AND CONCLUSION: Ruxolitinib is both safe and efficacious in a cohort of Asian patients with MF. The efficacy of ruxolitinib is irrelevant to the mutational status of JAK2V617F.

Feasibility of a newborn screening and follow-up programme for sickle cell disease among South Gujarat (India) tribal populations.

OBJECTIVES: To evaluate the feasibility of a newborn screening and follow-up programme for sickle cell disease (SCD) among tribal populations of south Gujarat, India. METHODS: A total of 5467 newborn babies were screened over 2 years using High-performance liquid chromatography, with diagnosis by molecular analysis. The SCD babies were followed-up clinically and haematologically regularly for 1.5 to 5 years to describe the course of the disease. RESULTS: Thirty-three babies (0.60%) were sickle homozygous, 13 (0.23%) were-sickle-ß-thalassaemia, 687 (12.5%) were sickle heterozygous, and 4736 were unaffected. The parents of SCD babies were educated and counselled for home care. There were 32 babies (69.5%) who could be clinically and haematologically followed-up; 7 babies (21.8%) presented with severe clinical complications, whereas 18 (56.2%) babies were asymptomatic till the last follow-up. The variation in clinical presentation was seen in spite of the presence of ameliorating factors, such as high fetal haemoglobin, Xmn-I polymorphism, and α-thalassaemia. CONCLUSION: In addition to demonstrating the possibility of establishing a newborn screening programme for sickle cell disorders among tribal populations, this study has shown that the disease is not always mild among tribal groups in India, as previously believed. There is a need, therefore, for increasing awareness among these tribal groups about the disease, and for regular monitoring of affected babies to reduce morbidity and mortality and to understand the natural course of the disease.

Sonographic assessment of spleen size in Turkish migrants with Familial Mediterranean fever in Germany.

OBJECTIVES: Familial Mediterranean fever (FMF) can be associated with splenomegaly. Prospective quantitative data are lacking. We performed a sonographic assessment of spleen size in patients with FMF and healthy control participants to assess its diagnostic value. METHODS: Patients with FMF according to the criteria of Livneh et al (Arthritis Rheum 1997; 40:1879-1885) who were in an asymptomatic interval and control participants were prospectively included in this study in Germany and underwent sonographic measurement of the spleen as well as a structured interview and a physical examination. Patients and controls were Turkish migrants. RESULTS: Thirty-six patients and 27 controls were included. Patients and controls did not differ significantly in age (mean ± SD, 34.8 ± 9.7 versus 33.3 ± 10.0 years, respectively; P = .56), sex, height, weight, or body mass index (26.7 ± 4.7 versus 26.1 ± 4.3 kg/m(2); P = .63). Spleen size was greater in patients than controls in width (4.3 ± 1.0 versus 3.7 ± 0.7 cm; P = .008) and also length (12.1 ± 1.9 versus 10.5 ± 1.4 cm; P = .001). Twenty-six of 36 patients (72.2%) had a history of appendectomy compared to 3 of 27 controls (11.1%; P < .001). The combination of an enlarged spleen (length >11 cm and/or width >4 cm) gave specificity of 100% (95% confidence interval, 87%-100%) and a positive predictive value of 100% (95% confidence interval, 78%-100%) for the diagnosis of FMF in our study. CONCLUSIONS: Spleen size as evaluated by sonography is larger in patients with FMF compared to healthy controls. Most patients with FMF included in this study had undergone appendectomy. Familial Mediterranean fever should be considered as a differential diagnosis in Turkish migrants in Germany if the spleen is enlarged and a history of appendectomy is reported.

Malaria endemicity in an Orang Asli community in Pahang, Malaysia.

An epidemiological cross-sectional study was undertaken to determine the endemicity of malaria among the Orang Asli population of Raub, Pahang. Malaria endemicity was measured in terms of the prevalence of parasitaemia and splenomegaly. A total of 520 Orang Asli were examined. The point prevalence of malaria was 24.2% (95% CI 20.7-25.1), with Plasmodium falciparum (67.5%) being the predominant species. Children < 12 years were at least 3.7 times more likely to be parasitaemic compared to those older. The prevalence of malaria among children 2-<10 years was 38.1% (95% CI 31.6-50.0). Spleen rate among children 2-<10 years old was 22.3% (95% CI 17.1-28.3). The average enlarged spleen size was 1.2. These findings classify the study area as being mesoendemic. Malaria control activities among the Orang Asli should focus on protecting vulnerable subgroups like young children. Measuring the level of malaria endemicity at regular intervals is fundamental in evaluating the effectiveness of malaria control programs.

Splenic enlargement and abdominal scarification in childhood malaria. Beliefs, practices and their possible roles in management in Benin City, Nigeria.

BACKGROUND: To achieve sustainable reduction in malaria burden in Africa, cultural practices that foster increased malaria burden must be addressed. In Edo state Nigeria, scarification/tattooing on the left hypochondrium presumably over an enlarged spleen arising mainly from malaria is widely practiced. This practice is deleterious, diversionary and causes complications. AIMS AND OBJECTIVES: This was a cross-sectional and descriptive study to evaluate the beliefs and practice, regarding abdominal wall scarification in children and within the context of malaria control; It was carried out among experienced women in child care selected from Egor Local Government Area of Edo State, Nigeria. METHODS: Information relating to beliefs, knowledge and their practices including possible socio-cultural/economic determinants were obtained with use of questionnaire. RESULTS: Of the 400 questionnaires administered 394 were responded to. The modal age bracket was 26 - 30 years (Range, 18 - 56 years) Respondents were mainly Binis Esan and Ibos amongst others. About 27.0% of respondents considered the spleen a "bag of worms". Other views included "collection of bad blood" 27.2% and as a sickness of its own, 14.7%. Named causes of splenomegaly were fever, 59.6% and evil spirit, 15.5%. Over 45.0% of respondents would consult the herbalists for splenomegaly. Less educated (X2 = 40.0, p<0.005), women over 40 years of age (X2 = 13.5, p< 0.05) and Esan/Bini ethnic groups (X2 = 15.6, p <0.05) are more prone to the practice. Reasons for widespread use included perceived effectiveness, low cost and accessibility. Information on scarification was obtained mainly from family members, 49.5%, neighbours, 25.1%; and friends/colleagues, 16.7% CONCLUSION/RECOMMENDATIONS: Practice of scarification is deep rooted and widespread in the study location. It has potentials to negate efforts involved in malaria control. Education including public enlightenment campaign should effectively check the practice.

Spleen enlargement and genetic diversity of Plasmodium falciparum infection in two ethnic groups with different malaria susceptibility in Mali, West Africa.

The high resistance to malaria in the nomadic Fulani population needs further understanding. The ability to cope with multiclonal Plasmodium falciparum infections was assessed in a cross-sectional survey in the Fulani and the Dogon, their sympatric ethnic group in Mali. The Fulani had lower parasite prevalence and densities and more prominent spleen enlargement. Spleen rates in children aged 2-9 years were 75% in the Fulani and 44% in the Dogon (P<0.001). There was no difference in number of P. falciparum genotypes, defined by merozoite surface protein 2 polymorphism, with mean values of 2.25 and 2.11 (P=0.503) in the Dogon and Fulani, respectively. Spleen rate increased with parasite prevalence, density and number of co-infecting clones in asymptomatic Dogon. Moreover, splenomegaly was increased in individuals with clinical malaria in the Dogon, odds ratio 3.67 (95% CI 1.65-8.15, P=0.003), but not found in the Fulani, 1.36 (95% CI 0.53-3.48, P=0.633). The more susceptible Dogon population thus appear to respond with pronounced spleen enlargement to asymptomatic multiclonal infections and acute disease whereas the Fulani have generally enlarged spleens already functional for protection. The results emphasize the importance of spleen function in protective immunity to the polymorphic malaria parasite.

Survival advantage in female patients with sickle cell anaemia.

OBJECTIVE: To evaluate the clinical and laboratory features of adult sickle cell anaemia patients in Nigeria. DESIGN: A cross-sectional study. SETTING: Haematology clinic of the University College Hospital, Ibadan, Nigeria. SUBJECTS: Sixty nine adult sickle cell anaemia patients randomly sampled. RESULTS: The mean steady state haematocrit, HbA2 and HbF were 22%, 4.6% and 7% respectively. Twenty five per cent of the patients had never received blood transfusion and a similar proportion recorded an infrequent occurrence of painful crises. CONCLUSION: An improved survival was observed with female patients showing an age related survival advantage over the males. Persistent splenomegaly was observed less frequently in the Nigerian sickle cell population despite the high frequency of alpha thalassaemia in the region. This was thought to be due to the lower levels of HbF in this population.

The genetic basis of hyperreactive malarious splenomegaly.

Hyperreactive malarious splenomegaly (HMS) represents an abnormal immune response to recurrent malaria, characterized by excessive production of both IgM and IgG antibodies. It has both a racial and a familial distribution in various parts of the world. Immune responses to many foreign antigens, including those of malaria, are under genetic control of the major histocompatibility locus (MHC), through the influence of HLA antigens on regulatory T-lymphocyte activity. It is therefore likely that this region also contains the genetic determinants for HMS, which would be reflected in associations between HMS and particular HLA antigens or haplotypes. Genetic studies of the Watut people of Papua New Guinea have not shown any association between HMS and a wide range of red cell and serum polymorphisms. However, HMS in this group is associated with the class II HLA antigen DR2, and with high levels of HLA heterozygosity. Formal genetic analysis of family data also points to a sex-linked gene as a further determinant of overresponsiveness to malaria in the Anga. These findings suggest that more than one genetic system may be involved in the development of HMS, and that the combined effects of several genetic determinants may be responsible for the extraordinarily high frequency of HMS found in the Upper Watut Valley.

Ethnic differences in the prevalence of splenomegaly and malaria in The Gambia.

Significant variations in the prevalence of splenomegaly were found among members of the three main ethnic groups resident in North Bank Division, The Gambia. Among young children splenomegaly and malaria were less prevalent in Mandinkas than in Wollofs or Fulas, suggesting that some genetic or environmental factors protect Mandinka children from this infection. Among older children and adults splenomegaly was found most frequently in Fulas. Six of 22 adults with very large spleens had a high serum IgM level and probably had the hyperreactive malarial splenomegaly (tropical splenomegaly) syndrome. Four of these six subjects were Fulas. This finding, together with the results of a previous study in Nigeria, suggest that Fulas have a predisposition to this condition.