Predictive risk factors for autoimmune thyroid diseases in patients with pernicious anemia.

BACKGROUND: Patients with pernicious anemia (PA) have a higher prevalence of other autoimmune diseases. We assessed the correlation between PA and autoimmune thyroid diseases (AITD), and evaluated the risk factors for this association. METHODS: A longitudinal study was conducted involving patients with PA between 2010 and 2017. RESULTS: A total of 86 patients with PA were evaluated, 74 (86%) female, with a median age of 51.5 years. Thyroid abnormalities were detected in 45 (52.3%) patients, including 28 (32.3%) hypothyroidism, 3 (3.5%) hyperthyroidism and 20 (23.3%) thyroperoxidase antibody positivity. Logistic regression analysis identified risk factors for having AITD in PA patients: weight loss (OR 12.03; 95% CI 1.06-137.02, P=0.045), diabetes mellitus (OR 4.68, 95% CI 1.15-26.58, P=0.047) and gastric antibodies positivity (OR 5.05, 95% CI 1.45-18.24, P=0.013). CONCLUSION: PA and AITD are frequently associated, suggesting all patients with PA should be investigated for occult thyroid disease, especially those with weight loss, diabetes mellitus and gastric autoantibodies.

Bernard-Soulier syndrome associated with 22q11.2 deletion and clinical features of DiGeorge/velocardiofacial syndrome.

: Bernard-Soulier syndrome (BSS) is a rare autosomal recessive bleeding disorder caused by a defective function of glycoprotein (GP) Ib-V-IX complex. Among the genes encoding the 4 receptor subunits (GPIbα, GPIbß, GPV and GPIX), the GPIbß gene is located on chromosomes 22q11.2. We report a case of a girl with BSS associated with clinical features of 22q11.2 deletion syndrome (22q11.2DS) with phenotypic spectrum of DiGeorge syndrome/velocardiofacial syndrome. She has a history of life-long bleeding tendency, tetralogy of Fallot, hypothyroidism, mild facial dysmorphic signs and macrothrombocytopenia. The BBS and 22q11.2DS association could be explained by the fact that the constitutional hemizygosity of 22q11.2 may unmask an autosomal recessive disorder caused by alterations of the nondeleted GPIbß allele. We suggest that all patients with 22q11.2DS and bleeding manifestations should be always tested for BSS.

Effect of circadian variation on neutrophil mobilization to the peripheral blood in benign constitutional neutropenia.

Benign constitutional neutropenia (BCN) is an asymptomatic condition characterized by mild chronic neutropenia in patients with no history of recurrent infections. Most patients are referred for further testing, increasing health care costs. We present an alternative form of assessment of individuals with BCN based on neutrophil circadian variation. The objective of this study was to evaluate whether circadian variations of neutrophil counts would result in neutrophil values higher than neutropenia threshold in individuals with BCN. Absolute neutrophil counts (ANCs) were evaluated in 102 patients with BCN (<1500 cells/µL) and 60 age- and sex-matched controls. Paired blood counts were performed in the early morning and in the early afternoon. We observed a significant difference between morning and afternoon ANC in BCN patients (879 cells/µL, 95% CI 745-1028, p < 0.001), as well as in the controls (619 cells/µL, 95% CI 443-796, p < 0.001). The ANC increase between the two evaluations was significantly greater in BCN patients compared with controls: 83% and 27%, respectively (p < 0.001). The ANC increment was higher in the groups with a lower morning ANC: 105%, 63%, and 27% in the <1000, 1000-1500, and >1500 cells/µL groups, respectively (p < 0.001). Of all BCN patients, 73% presented with >1500 cells/µL in the afternoon and 16% improved from the <1000 cells/µL to the 1000-1500 cells/µL category. In conclusion, neutrophil circadian variation measurement allows many BCN patients to be excluded from the neutropenia threshold. We identified a simple, easy, and feasible way to assess neutrophil reserve in patients with BCN with a potential reduction in costs of the assessment.

Impact of vitamin D deficiency on increased blood eosinophil counts.

OBJECTIVE/BACKGROUND: Vitamin D has been increasingly recognized as an immunomodulatory agent. Its deficiency has been associated with immune-mediated diseases such as asthma, rhinitis, and atopic dermatitis. These allergic conditions are dependent on T-helper type 2 (Th2) cells secreting interleukins, overproduction of immunoglobulin E (IgE), and eosinophil activation. We investigated the association between serum vitamin D levels and blood absolute eosinophil count. METHODS: We carried out a cross-sectional study of 669 men and women referred to a clinical pathology laboratory who underwent 25-hydroxyvitamin D testing and complete blood count analysis on the same day. RESULTS: Vitamin D levels were stratified into four ranges: severely deficient (<10ng/mL), deficient (≥10ng/mL and <20ng/mL), insufficient (≥20ng/mL and <30ng/mL), or sufficient (≥30ng/mL). The mean/median eosinophil count in the four groups was 267/254cells/µL, 245/238cells/µL, 191/159cells/µL, and 182/146cells/µL, respectively, (p=.001). The difference was significant between the severe deficiency group and each of the other three groups (p=.012, p=.002, and p=.001, respectively). There was no statistical difference among the four groups in terms of total leukocyte counts (p=.151), neutrophils (p=.177), or lymphocytes (p=.582). CONCLUSION: Vitamin D deficiency was associated with higher blood eosinophil count. These results support the possible role of vitamin D in the eosinophil immune response.

Treatment of idiopathic light chain deposition disease: complete remission with bortezomib and dexamethasone.

Light chain deposition disease (LCDD) is a rare clinical entity characterized by the deposition of light chain immunoglobulins in different tissues and primarily affects the kidneys, followed by the liver and heart. This disease often manifests as nephrotic syndrome with marked proteinuria and rapid deterioration of renal function. More than 50% of cases are secondary to multiple myeloma or other lymphoproliferative diseases, with a well-established treatment aimed at controlling the underlying disease. In rare cases, there is no detection of an associated hematological disease, referred to as idiopathic LCDD. In these cases, there is no evidence-based consensus on the therapeutic approach, and management is based on the clinical experience of reported cases. Here we report a case of idiopathic LCDD treated with bortezomib and dexamethasone with complete hematologic responses, significant reduction of proteinuria, and improved renal function.

Treatment of idiopathic light chain deposition disease: complete remission with bortezomib and dexamethasone / Tratamento da doença de depósito de cadeia leve idiopática: remissão completa com bortezomib e dexametasona

Abstract Light chain deposition disease (LCDD) is a rare clinical entity characterized by the deposition of light chain immunoglobulins in different tissues and primarily affects the kidneys, followed by the liver and heart. This disease often manifests as nephrotic syndrome with marked proteinuria and rapid deterioration of renal function. More than 50% of cases are secondary to multiple myeloma or other lymphoproliferative diseases, with a well-established treatment aimed at controlling the underlying disease. In rare cases, there is no detection of an associated hematological disease, referred to as idiopathic LCDD. In these cases, there is no evidence-based consensus on the therapeutic approach, and management is based on the clinical experience of reported cases. Here we report a case of idiopathic LCDD treated with bortezomib and dexamethasone with complete hematologic responses, significant reduction of proteinuria, and improved renal function.

Resumo A doença de deposição de cadeia leve (DDCL) é uma entidade clínica rara caracterizada pela deposição de cadeias leves das imunoglobulinas em diferentes tecidos e afeta principalmente os rins, seguido pelo fígado e coração. Manifesta-se frequentemente como síndrome nefrótica com proteinúria marcante e rápida deterioração da função renal. Mais de 50% dos casos são secundários ao mieloma múltiplo ou outras doenças linfoproliferativas, tendo seu tratamento bem estabelecido, voltado para o controle da doença de base. Em casos raros, não há detecção de uma doença hematológica associada, sendo referida como DDCL idiopática. Nestes casos, não há um consenso baseado em evidências sobre a abordagem terapêutica, tendo sua conduta baseada na experiência clínica dos casos relatados. Aqui, nós relatamos um caso de DDCL idiopática tratado com bortezomib e dexametasona atingindo resposta hematológica completa, redução significativa da proteinúria e recuperação da função renal.

Aminotransferases analysis in patients with dengue serotype IV / Análise das aminotransferases em pacientes com dengue sorotipo IV

OBJECTIVE: To evaluate the aminotransferase levels inpatients with dengue serotype IV. METHODS: We conducteda cross-sectional analysis of 3,596 people with laboratory confirmed dengue. RESULTS: The analysis showed that 49.2%(1,768) had normal aminotransferase levels, 43.4% (1,559)had changes in levels by up to three times the upper limit ofnormal, 7.0% (253) had elevations three times the referencevalue and 0.4% (16) developed acute hepatitis. Patients withthrombocytopenia and hemoconcentration had major changesin the levels of enzymes (p<0.05). Women were more susceptibleto those changes than men (p<0,05). The average AST and ALTwere higher in dengue hemorrhagic type (147.51±137.74U/Land 111.54±81.27U/L) as compared to dengue fever(55.18±52.06U/L and 60.39±57.50U/L) (p<0.05). Leukopenicpatients had aminotransferases average lower compared toindividuals without any drop in overall white blood cellcount (p<0.05). A total of 224 patients were submitted tohospitalization, with the AST average of 88.18±100.47U/Land ALT 77.95±88.38U/L, which is higher than the average inambulatory patients (p<0.05). CONCLUSION: A significantnumber of patients was found with altered levels of enzymes,which requires clinical laboratory monitoring for an extendedperiod.

OBJETIVO: Avaliar os níveis de aminotransferases em pacientes com dengue sorotipo IV. MÉTODOS: Foi realizada uma análise transversal de 3.596 pessoas com dengue confirmada laboratorialmente. RESULTADOS: A análise mostrou que49,2% (1.768) tinham níveis normais de aminotransferases,43,4% (1.559) mostraram alterações nos níveis em até três vezes o limite superior da normalidade, 7,0% (253) apresentaram elevações três vezes o valor de referência e 0,4% (16) desenvolveram hepatite aguda. Os doentes com trombocitopenia e hemoconcentração tiveram grandes alterações nos níveis enzimáticos(p<0,05). As mulheres foram mais suscetíveis a essas alterações do que os homens (p<0,05). As médias de AST e ALT foram maiores na dengue do tipo hemorrágica (147,51±137,74U/Le 111,54±81,27U/L) em comparação com dengue clássica(55,18±52,06U/L e 60,39±57,50U/L) (p<0,05). Pacientes leucopênicos tiveram a média de aminotransferases menor em comparação com os indivíduos sem qualquer queda na contagem global de glóbulos brancos (p<0,05). Um total de 224pacientes foi submetido a hospitalização, com a média de AST88,18±100,47U/L e ALT 77,95±88,38U/L, o que é mais elevado do que a média em doentes ambulatórios (p<0,05). CONCLUSÃO:Um número significativo de pacientes foi identificado com níveis alterados de enzimas, o que exige acompanhamento clínico e laboratorial por um período prolongado.

Differences between Risk Factors Associated with Tuberculosis Treatment Abandonment and Mortality.

OBJECTIVES: To identify the risk factors that were associated with abandonment of treatment and mortality in tuberculosis (TB) patients. METHODS: This study was a retrospective longitudinal cohort study involving tuberculosis patients treated between 2002 and 2008 in a TB reference center. RESULTS: A total of 1,257 patients were evaluated, with 69.1% men, 54.4% under 40 years of age, 18.9% with extrapulmonary disease, and 9.3% coinfected with HIV. The risk factors that were associated with abandonment of treatment included male gender (OR=2.05; 95% CI=1.15-3.65) and nonadherence to previous treatment (OR=3.14; 95% CI=1.96-5.96). In addition, the presence of extrapulmonary TB was a protective factor (OR=0.33, 95% CI=0.14-0.76). The following risk factors were associated with mortality: age over 40 years (OR=2.61, 95% CI=1.76-3.85), coinfection with HIV (OR=6.01, 95% CI=3.78-9.56), illiteracy (OR=1.88, 95% CI=1.27-2.75), the presence of severe extrapulmonary TB (OR=2.33, 95% CI=1.24-4.38), and retreatment after relapse (OR=1.95, 95% CI=1.01-3.75). CONCLUSIONS: Male gender and retreatment after abandonment were independent risk factors for nonadherence to TB treatment. Furthermore, age over 40 years, coinfection with HIV, illiteracy, severe extrapulmonary TB, and retreatment after relapse were associated with higher TB mortality. Therefore, we suggest the implementation of direct measures that will control the identified risk factors to reduce the rates of treatment failure and TB-associated mortality.

Comparison of clinical and laboratory characteristics between children and adults with dengue

Over the past several years, the epidemiological profile of dengue has been changing progressively and is currently characterized by an increase in the number of cases in children under 15 years of age. This study was aimed at comparing the clinical and laboratory features between adults and children with dengue; therefore, we performed a cross-sectional analysis of 5686 individuals with laboratory-confirmed dengue who sought treatment at a healthcare facility in Rio de Janeiro, Brazil from 2010 to 2011. A multivariate analysis indicated that myalgia (OR = 2.58; CI 95% = 2.08-3.18), retro-orbital pain (OR = 1.36; CI 95% = 1.15-1.62), nausea (OR = 1.92; CI 95% = 1.60-2.30), and arthralgia (OR = 3.64; CI 95% = 2.72-4.89) were the most frequent clinical symptoms in adults, whereas vomiting (OR = 0.52; CI 95% = 0.43-0.61) and skin rash (OR = 0.46; CI 95% = 0.25-0.85) were the most prevalent symptoms in children. Adults exhibited a higher hemoconcentration (OR = 3.04; CI 95% = 2.53-3.65), thrombocytopenia (OR = 2.17; CI 95% = 1.80-2.60), increased erythrocyte sedimentation rate (OR = 1.81; CI 95% = 1.53-2.14), and increased ALT (OR = 3.13; CI 95% = 2.44-4.02) than did children. In addition, adults exhibited a higher frequency of the severe forms of the disease (OR = 1.74; CI 95% = 1.12-2.72) and hospitalization (OR = 2.21; CI 95% = 1.59-3.06) relative to children. Based on these results, this study demonstrated significant differences in the clinical and laboratory presentations and disease severity between adults and children affected by dengue.

Comparison of clinical and laboratory characteristics between children and adults with dengue.

Over the past several years, the epidemiological profile of dengue has been changing progressively and is currently characterized by an increase in the number of cases in children under 15 years of age. This study was aimed at comparing the clinical and laboratory features between adults and children with dengue; therefore, we performed a cross-sectional analysis of 5686 individuals with laboratory-confirmed dengue who sought treatment at a healthcare facility in Rio de Janeiro, Brazil from 2010 to 2011. A multivariate analysis indicated that myalgia (OR=2.58; CI 95%=2.08-3.18), retro-orbital pain (OR=1.36; CI 95%=1.15-1.62), nausea (OR=1.92; CI 95%=1.60-2.30), and arthralgia (OR=3.64; CI 95%=2.72-4.89) were the most frequent clinical symptoms in adults, whereas vomiting (OR=0.52; CI 95%=0.43-0.61) and skin rash (OR=0.46; CI 95%=0.25-0.85) were the most prevalent symptoms in children. Adults exhibited a higher hemoconcentration (OR=3.04; CI 95%=2.53-3.65), thrombocytopenia (OR=2.17; CI 95%=1.80-2.60), increased erythrocyte sedimentation rate (OR=1.81; CI 95%=1.53-2.14), and increased ALT (OR=3.13; CI 95%=2.44-4.02) than did children. In addition, adults exhibited a higher frequency of the severe forms of the disease (OR=1.74; CI 95%=1.12-2.72) and hospitalization (OR=2.21; CI 95%=1.59-3.06) relative to children. Based on these results, this study demonstrated significant differences in the clinical and laboratory presentations and disease severity between adults and children affected by dengue.

Thrombotic thrombocytopenic purpura associated with mixed connective tissue disease: a case report.

Thrombotic thrombocytopenic purpura (TTP) is a multisystemic disorder characterized by microangiopathic hemolytic anemia and thrombocytopenia, which may be accompanied by fever, renal, or neurologic abnormalities. Cases are divided into acute idiopathic TTP and secondary TTP. Autoimmune diseases, especially systemic lupus erythematosus, in association with TTP have been described so far in many patients. In contrast, TTP occurring in a patient with mixed connected tissue disease (MCTD) is extremely rare and has only been described in nine patients. We describe the case of a 42-year-old female with MCTD who developed thrombocytopenia, microangiopathic hemolytic anemia, fever, and neurological symptoms. The patient had a good clinical evolution with infusion of high volume of fresh frozen plasma, steroid therapy, and support in an intensive care unit. Although the occurrence of TTP is rare in MCTD patients, it is important to recognize TTP as a cause of thrombocytopenia and hemolytic anemia in any patient with autoimmune diseases. Prompt institution of treatment remains the cornerstone of treatment of TTP even if plasma exchange is not available like what frequently happens in developing countries.