Disseminated tuberculosis: Clinical presentation, diagnosis, and outcomes in a tertiary-care hospital in Saudi Arabia.

Background: Tuberculosis (TB) is the primary infectious cause of mortality worldwide. Although TB incidence and prevalence are declining, the use of immunosuppressive drugs and the growing prevalence of immunocompromising conditions such as comorbidities, malignancies, and the use of immunosuppressive agents are risk factors for disseminated TB (DTB). This study aims to identify the relevant clinical, laboratory, radiological, and histopathological features of DTB, as well as to assess the typical anatomical distributions and treatment outcomes of patients diagnosed with the disease at King Abdulaziz Medical City (KAMC). Methods: A retrospective chart review was conducted, including all patients diagnosed with miliary or DTB at KAMC with retrievable medical files. Results: The study included 55 patients, of whom 35 (63.6%) were male and the median age was 64 years old. 35 (63.6%) of the infected patients were timely diagnosed and eventually cured from the illness. The most common comorbid conditions were diabetes, chronic kidney disease, and immunocompromising conditions, which were present in 37 (67.2%), 12 (21.8%), and 11 (20%) of the patients, respectively. The most common presenting symptoms were fever and cough, present in 31 (56.3%) and 26 (47.2%) of the patients, respectively, followed by weight loss in 25 (45.4%), night sweats in 15 (27.2%), and shortness of breath in 14 (25.4%). Approximately two-thirds of the patients had pulmonary miliary TB (MTB) (38; 69.1%), followed by TB lymphadenitis (21; 38.2%), central nervous system involvement (13; 23.6%), skeletal involvement (11; 20%), gastrointestinal involvement (5; 9.1%), pleural involvement (3; 5.5%), and urogenital TB (2; 3.6%). The mortality rate was 14 (25.5%) patients. Conclusion: MTB is challenging to diagnose due to nonspecific clinical, laboratory, and imaging findings. Clinicians dealing with patients who are at risk of developing DTB should be aware of the typical presentations and abnormal clinical findings. They should also have a low threshold to initiate specific investigations for the disease, as early diagnosis and effective treatment is critical in reducing morbidity and mortality rates.

Low secondary attack rate after prolonged exposure to sputum smear positive miliary tuberculosis in a neonatal unit.

BACKGROUND: Several neonatal intensive care units (NICU) have reported exposure to sputum smear positive tuberculosis (TB). NICE guidelines give support regarding investigation and treatment intervention, but not for contact definitions. Data regarding the reliability of any interferon gamma release assay (IGRA) in infants as a screening test for TB infection is scarce. We report an investigation and management strategy and evaluated the viability of IGRA (T-Spot) in infants and its concordance to the tuberculin skin test (TST). METHODS: We performed an outbreak investigation of incident TB infection in a NICU after prolonged exposure to sputum smear positive miliary TB by an infant's mother. We defined individual contact definitions and interventions and assessed secondary attack rates. In addition, we evaluated the technical performance of T-Spot in infants and compared the results with the TST at baseline investigation. RESULTS: Overall, 72 of 90 (80%) exposed infants were investigated at baseline, in 51 (56.7%) of 54 (60%) infants, follow-up TST at the age of 6 months was performed. No infant in our cohort showed a positive TST or T-Spot at baseline. All blood samples from infants except one responded to phytohemagglutinin (PHA), which was used as a positive control of the T-Spot, demonstrating that cells are viable and react upon stimulation. 149 of 160 (93.1%) exposed health care workers (HCW) were investigated. 1 HCW was tested positive, having no other reason than this exposure for latent TB infection. 5 of 92 (5.5%) exposed primary contacts were tested positive, all coming from countries with high TB incidences. In total, 1 of 342 exposed contacts was newly diagnosed with latent TB infection. The secondary attack rate in this study including pediatric and adult contacts was 0.29%. CONCLUSION: This investigation highlighted the low transmission rate of sputum smear positive miliary TB in a particularly highly susceptible population as infants. Our expert definitions and interventions proved to be helpful in terms of the feasibility of a thorough outbreak investigation. Furthermore, we demonstrated concordance of T-Spot and TST. Based on our findings, we assume that T-Spot could be considered a reliable investigation tool to rule out TB infection in infants.

Clinical analysis of pregnancy complicated with miliary tuberculosis.

BACKGROUND: Pregnancy complicated with tuberculosis is increasingly common. The clinical characteristics of pregnancy complicated with miliary tuberculosis are summarized in this study. METHODS: A retrospective analysis of pregnant patients with miliary tuberculosis was performed in terms of epidemiology, demography, clinical characteristics, laboratory tests, treatment, and prognosis. RESULTS: Of the 23 patients that were included, 12 became pregnant after in vitro fertilization combined with embryo transfer (IVF-ET). The average gestational age at symptom onset was 13.96 weeks, and the average time from symptom onset to diagnosis was 33 days. Clinical symptoms included fever, dyspnoea, cough, headache, abdominal pain, and chest pain. Extrapulmonary tuberculosis occurred in 10 patients, respiratory failure in 11 patients, and ARDS in 9 patients. Chest HRCT showed diffusely distributed miliary nodules in all patients. Six patients were on mechanical ventilation, two underwent ECMO, and one died. Symptoms appeared in the first trimester of nine pregnancies after IVF-ET and in the second trimester of seven natural pregnancies. CONCLUSIONS: Miliary tuberculosis can occur in pregnant patients, especially in patients after IVF-ET. Symptoms often appear in the first trimester of pregnancy after IVF-ET and in the second trimester of natural pregnancy. Lacking specificity, the common clinical characteristics include elevated inflammation markers, anaemia, low lymphocyte count, and multiple miliary nodules shown on a chest HRCT scan. Half of patients with miliary tuberculosis may develop respiratory failure, and some may progress to ARDS. Therefore, infertile patients should be required to undergo TB screening before undergoing IVF-ET, and preventive anti-TB treatment should be given to patients with latent TB infections or untreated TB disease.Key MessageMiliary tuberculosis can occur in pregnant patients, especially in pregnant patients after IVF-ET. Symptoms often appear in the first trimester of pregnancy after IVF-ET and in the second trimester of natural pregnancy. Many patients develop respiratory failure or ARDS.

Tuberculosis miliar / Miliary tuberculosis

Introducción: La tuberculosis es considerada como la enfermedad infecciosa más importante del mundo, a pesar de los esfuerzos que se han invertido para su control. Es producida por el complejo mycobacterium tuberculosis. El órgano más afectado es el pulmón, aunque puede tener repercusión extrapulmonar. Objetivo: Presentar el caso de un paciente diagnosticado de tuberculosis miliar a través del esputo posbroncoscopia. Caso clínico: Se expone el caso de un paciente diagnosticado de una tuberculosis miliar al cual se le realizó broncoscopia diagnóstica y lavado bronquial para bacilo ácido alcohol resistente (BAAR), el cual fue negativo. El diagnóstico se obtuvo por esputo BAAR posbroncoscopia. Conclusiones: El esputo posbroncoscopia es una opción con adecuada rentabilidad en el diagnóstico de esta enfermedad infecciosa(AU)

Introduction: Tuberculosis is considered the most important infectious disease in the world, despite the efforts that have been invested to control it. It is produced by the mycobacterium tuberculosis complex. The most affected organs are the lungs, although it can have extrapulmonary repercussions. Objective: To report the case of a patient diagnosed with miliary tuberculosis through post-bronchoscopy sputum. Clinical case report: The case of a patient diagnosed with miliary tuberculosis is reported. This patient underwent diagnostic bronchoscopy and bronchial lavage for acid-alcohol-resistant bacillus (ABB), which was negative. The diagnosis was obtained by postbronchoscopy ARB sputum. Conclusions: Post-bronchoscopy sputum is an option, with adequate profitability in the diagnosis of this infectious disease(AU)

Prevalence and risk factors of paradoxical tuberculosis associated immune reconstitution inflammatory syndrome among HIV-infected patients in Beijing, China.

BACKGROUND: In this study, we aimed to describe the prevalence, clinical presentation and risk factors of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) cases in China. METHODS: We performed a descriptive analysis of demographic and clinical data of HIV/TB coinfected patients receiving ART at Beijing Ditan Hospital between January 2014 and October 2018. RESULTS: Of 199 patients included, 45 (22.6%) developed paradoxical TB-IRIS, and 19 (9.5%) TB-IRIS cases presented miliary TB. The pre-ART CD4 count lower than 50 cells/mm3 was found to be significantly associated with development of TB-IRIS. Similarly, patients with higher than 4-fold increase in CD4 cell count after antiretroviral therapy (ART) had significantly higher odds of having TB-IRIS. When patients aged 25-44 years were utilized as the control group, youths (< 25 years old) were more likely to have miliary TB. No significant difference was observed in the intervals from initiation of ART to IRIS presentation between miliary and non-miliary group. CONCLUSIONS: In conclusion, our data demonstrate that approximate one quarter of patients coinfected with TB and HIV develop paradoxical TB-IRIS after initial of ART therapy in China. Lower baseline CD4 count and rapid increase in CD4 count are the major risk factors associated with the occurrence of paradoxical TB-IRIS.

Predictors and outcomes of disseminated tuberculosis in an intermediate burden setting.

SETTING: University-affiliated hospital located in Porto, North Portugal, an area with a low to intermediate incidence of tuberculosis (TB). OBJECTIVE: To identify predictors and outcomes of disseminated TB (dTB). DESIGN: A cohort of patients diagnosed with TB between 2007 and 2013 was retrospectively analysed. Patients with dTB criteria were characterized and compared to single organ TB cases. Factors independently associated with dTB were determined by multivariate logistic regression analysis. RESULTS: A total of 744 patients were analysed, including 145 with dTB. Independent risk factors for dTB were pharmacological immunosuppression (OR 5.6, 95% CI 2.8-11.3), HIV infection (OR 5.1, 95% CI 3.1-8.3), chronic liver failure or cirrhosis (OR 2.3, 95% CI 1.4-4.1) and duration of symptoms (OR 2.3, 95% CI 1.4-3.8). Compared to single organ TB, the clinical presentation of dTB patients differed by the absence of haemoptysis (OR 3.2, 95% CI 1.3-8.4) and of dyspnoea (OR 1.9, 95% CI 1.2-3.1), presence of weight loss (OR 1.8, 95% CI 1.1-2.9), night sweats (OR 1.7, 95% CI 1.1-2.7) and bilateral lung involvement (OR 4.4, 95% CI 2.8-7.1). Mortality and time until culture conversion were higher for dTB patients, although not reaching statistical significance. CONCLUSION: Immunosuppressive conditions and chronic liver failure or cirrhosis were associated with increased risk of dTB. The haematogenous spread may be dependent on longer symptomatic disease and usually progresses with bilateral lung involvement.

Clinical Characteristics and Etiologies of Miliary Nodules in the US: A Single-Center Study.

BACKGROUND: Miliary nodules have been typically described as a radiological manifestation of disseminated tuberculosis. However, miliary nodules are known to occur in a wide variety of conditions. The primary objective of the study was to identify clinical characteristics and etiologies of miliary nodules within our institution. METHODS: Using International Classification of Diseases, Ninth and Tenth Revision codes, electronic medical records were used to retrospectively identify 53 patients who fulfilled criteria of miliary nodules over the last 10 years. Demographic and clinical data were extracted for all the patients in this cross-sectional study. RESULTS: The diagnosis of tuberculosis was made in 15 (28.3%) patients, sarcoidosis in 12 (22.6%), silicosis in 7 (13.2%), extrathoracic malignancy in 5 (9.4%), and histoplasmosis in 4 (7.6%) patients. Four of 9 HIV patients had histoplasmosis. There was 1 case each of hypersensitivity pneumonitis, Pneumocystis jiroveci pneumonia, Mycobacterium-avium complex, Epstein-Barr virus pneumonia, cryptococcosis, aspergillosis, and primary lung cancer. Sputum was positive for acid fast bacilli in 4 cases (28%), and bronchoscopy had a 57% successful yield in miliary tuberculosis. CONCLUSION: Our study is the largest single-center data review evaluating the etiology of miliary nodules within the United States; most of the data exist in case reports.

Changes in tuberculosis in human immunodeficiency virus infected patients in a Spanish tertiary hospital (1995-2013).

OBJECTIVE: Although the incidence of human immunodeficiency virus (HIV)-associated tuberculosis (TB) has decreased, changes in other characteristics of the disease are largely unknown. To describe the trends in TB in patients infected with HIV from 1995 to 2013. METHODS: We review all cases of TB in a tertiary hospital in Madrid, Spain. RESULTS: Among 1,284 patients diagnosed of TB, 298 (23%) were coinfected with HIV. The prevalence of HIV infection during the period of study has decreased from 40% to 14% (p for the trend < 0.001). Clinical presentation has also changed. Although pulmonary and extrapulmonary TB has remained unchanged, miliary presentation has significantly decreased (from 36% to 22%, p = 0.005). The 4-drug regimen was the preferable scheme, with higher implementation at the end of the study period (82% from 1995-1999 to 95% in 2010-2013, p = 0.43). Factors such as treatment failure (OR: 11.7; CI 95%: 3.12-44.1) and miliary form (OR: 2.8; CI 95%; 1.09-7.3) were independently associated with TB related mortality, while the longer duration of treatment was as a protective factor (OR 0.7; CI 95%: 0.6-0.8). CONCLUSIONS: HIV has decreased very significantly as a risk factor for the development of TB. Despite improvement in the treatment of both TB and HIV, and in overall mortality, deaths attributable to the disease in this population remain high mostly in miliary and relapsing forms.

[Miliary tuberculosis]. / La miliaire tuberculeuse,une série rétrospective marocaine.

INTRODUCTION: Tuberculosis miliary is a severe and rare form of tuberculosis. It is often due to a haematogenous spread of the bacillus of Koch and represents less than 2 % of tuberculosis. PATIENTS AND METHODS: We conducted a retrospective study of 81 cases of tuberculous miliary collected at the Department of respiratory diseases of the Ibn Rochd university hospital in Casablanca between September 2003 and November 2016. RESULTS: A female predominance was noted with 58 % of the cases. The average age was 36 years. The history of tuberculosis was found in eight cases and tuberculous tuberculosis in eleven cases, postpartum in five cases, diabetes in three cases and trisomy 21 in one case. The clinical picture was dominated by altered general status in all cases, and fever in 69 cases (86 %). Chest x-ray showed a miliary aspect in all cases, cardiomegaly in two cases, pyopneumothorax in three cases, and opacities excavated in five other cases. The intradermal tuberculin reaction, performed in all cases, was positive in 26 cases, and sputum oscillations were positive in 21 cases. The dissemination report found cerebromeningeal involvement in nine cases, with cerebral tuberculomas in five cases, pericarditis in four cases, mediastinal and peripheral adenopathies in nine cases each. Bouchut tubercles were found in nine cases. Antibacillary therapy was started as a matter of urgency, according to the national TB control program with the old regimen (2SHRZ/7RH) and the new regimen (2RHZEb/7RH) in all cases. The outcome was good in 55 cases (68.9 %), 17 patients were lost to follow-up, and 11 deaths were reported. CONCLUSION: We insist on this work on the severity of the tuberculous miliary and the need for early and urgent therapeutic management.

Pulmonary tuberculosis in a Pediatric Reference Hospital in Bogotá, Colombia.

BACKGROUND: In Colombia, epidemiological and clinical information related to pediatric tuberculosis (TB) is scarce. Data are needed to define the impact of the disease and to strengthen measures for detection and treatment. It is proposed to analyze the pediatric population diagnosed with pulmonary TB in a national reference institution. METHODS: Retrospective observational study including pediatric patients with pulmonary and miliary TB, and pulmonary and extrapulmonary involvement, treated between January 1, 2008 and December 31, 2016. A descriptive analysis of the selected variables was done. RESULTS: A total of 93 cases of diagnosed TB were identified, of which 61 cases were classified as pulmonary (65.6%). The location of TB occurred only in lungs in 51 patients (83.6%), was miliar in 3 (4.9%), pulmonary and extrapulmonary involvement in 7 patients (11.5%). The mean age was 7.5 years (0.5-18 years). Clinical criteria used for diagnosis was related to 98.3% of the cases, whereas radiological criteria in 90.2%. Bacteriological criterion was met in 42.6% of the cases. The most frequent symptoms were coughing (83.6%), fever (63.9%), and weight loss (26.2%); human immunodeficiency virus co-infection occurred in 3 cases (4.9%). During treatment, 5 mortality cases were recorded, although they were not attributable to TB. CONCLUSIONS: The epidemiological characterization of pediatric patients with pulmonary TB helps to achieve a better diagnostic approach in this population. Improving monitoring and follow-up activities in children with pulmonary TB, as well as promoting actions for adequate prevention and treatment is highly necessary.

Epidemiology of extrapulmonary and disseminated tuberculosis in a tertiary care center in Oman.

BACKGROUND: The incidence of extrapulmonary and disseminated tuberculosis (TB) cases is increasing worldwide, and this growth significantly impacts TB-related morbidity and mortality. Little is known about the host risk factors for extrapulmonary and disseminated TB. In this study, we examined those risk factors. MATERIALS AND METHODS: We conducted a retrospective review of all TB cases admitted to Sultan Qaboos University Hospital from 2006 to 2015. We compared extrapulmonary TB (EPTB) cases with pulmonary and disseminated TB cases. We evaluated the risk factors associated with the development of extrapulmonary and disseminated TB using logistic regression analysis. RESULTS: We reviewed 260 TB cases, of which EPTB comprised 37%, PTB comprised 53%, and disseminated TB comprised 10%. The most common sites of infection in the EPTB group were the lymph nodes and the abdomen. Disseminated TB and TB meningitis were more common in expatriates than in Omanis. Patients with EPTB were less likely to smoke compared to a patient with PTB. Patients with disseminated TB had a higher mortality when compared to patients with EPTB (adjusted odds ratio [OR], 0.004; 95% confidence intervals [CI]: 0.001-0.054;P = 0.001) and PTB (adjusted OR, 0.022; 95% CI: 0.004-0.115;P = 0.001). Human immunodeficiency virus (HIV) was the main risk factor for patients with disseminated TB when compared to patients with extrapulmonary and PTB. CONCLUSION: The rates of extrapulmonary and disseminated TB in Oman are higher than what has been recognized. Expatriates, patients with HIV, and smokers are at high risk for disseminated TB. In these patients, suspected extrapulmonary sites should be evaluated and sampled to exclude disseminated TB.

High Detection Rates of Urine Mycobacterium tuberculosis in Patients with Suspected Miliary Tuberculosis.

Objective The utility of detecting Mycobacterium tuberculosis in urine samples from patients with pulmonary tuberculous with diffuse small nodular shadows (suspected miliary tuberculosis (MTB)) is still unclear in Japan. A retrospective cross-sectional study was conducted to investigate the detection rates of M. tuberculosis in urine of patients with suspected MTB. Methods Among 687 hospitalized patients with tuberculosis, 45 with culture-confirmed suspected MTB and the data of culture and polymerase chain reaction (PCR) for M. tuberculosis in urine and sputum samples were investigated. The detection rates of M. tuberculosis in urine using cultures and PCR were calculated. The detection rate of urine was then compared with that of bone marrow aspiration. Results Fourteen patients with suspected MTB were ultimately analyzed. A diagnosis of miliary tuberculosis was suspected in all patients before anti-tuberculosis chemotherapy. Positive results by PCR (11 [78.6%] cases) and culture (8 [57.1%]) were obtained from urine samples. In patients with suspected MTB, there was no significant difference in the detection rates between M. tuberculosis in urine using a combination of PCR and culture (85.6% [12/14 cases]) and bone marrow aspiration (66.7% [8/12 cases]) (p>0.05). Conclusion Using PCR and culture, we demonstrated high detection rates of M. tuberculosis in the urine of patients with suspected MTB. A combination of PCR and culture compared favorably with the detection rates achieved with bone marrow aspiration. We believe that detection of M. tuberculosis from urine and sputum samples may be easy and safe for patients with disseminated tuberculosis infections such as definitive MTB.

Miliary Tuberculosis.

Miliary tuberculosis (TB) results from a massive lymphohematogenous dissemination of Mycobacterium tuberculosis bacilli and is characterized by tiny tubercles evident on gross pathology resembling millet seeds in size and appearance. The global HIV/AIDS pandemic and widespread use of immunosuppressive drugs and biologicals have altered the epidemiology of miliary TB. Considered to be predominantly a disease of infants and children in the pre-antibiotic era, miliary TB is increasingly being encountered in adults as well. The clinical manifestations of miliary TB are protean and nonspecific. Atypical clinical presentation often delays the diagnosis. Clinicians, therefore, should have a low threshold for suspecting miliary TB. Focused, systematic physical examination helps in identifying the organ system(s) involved, particularly early in TB meningitis, as this has therapeutic significance. Fundus examination for detecting choroid tubercles offers a valuable clinical clue for early diagnosis, as their presence is pathognomonic of miliary TB. Imaging modalities help in recognizing the miliary pattern, defining the extent of organ system involvement. Examination of sputum, body fluids, image-guided fine-needle aspiration cytology or biopsy from various organ sites, needle biopsy of the liver, bone marrow aspiration, and biopsy should be done to confirm the diagnosis. Cytopathological, histopathological, and molecular testing (e.g., Xpert MTB/RIF and line probe assay), mycobacterial culture, and drug susceptibility testing must be carried out as appropriate and feasible. Miliary TB is uniformly fatal if untreated; therefore, early initiation of specific anti-TB treatment can be lifesaving. Monitoring for complications, such as acute kidney injury, air leak syndromes, acute respiratory distress syndrome, adverse drug reactions such as drug-induced liver injury, and drug-drug interactions (especially in patients coinfected with HIV/AIDS), is warranted.

Miliary tuberculosis: a severe opportunistic infection in juvenile systemic lupus erythematosus patients.

INTRODUCTION: One of the main issues in juvenile systemic lupus erythematosus (JSLE) patients is infection, such as tuberculosis (TB). Of note, SLE patients are susceptible to pulmonary and extrapulmonary TB. However, to our knowledge, this contagious disease was rarely reported in pediatric lupus population, particularly diffuse or miliary TB. Therefore, from January 1983 to December 2011, 5,635 patients were followed-up at our Pediatric Rheumatology Unit and 285 (5%) of them met the American College of Rheumatology classification criteria for SLE. CASE REPORTS: Four (1.4%) of our JSLE patients had disseminated TB and were described herein. All of them were female gender, received BCG vaccination and did not have a history of TB household contact. The median of current age at TB diagnosis and the period between JSLE and TB diagnosis were 17 years old (range 14-20) and 5.5 years (range 2-7), respectively. All patients developed miliary TB during the course of the disease. The median of SLE Disease Activity Index 2000 (SLEDAI-2K) was 4 (2-16) and the patients were treated with immunosuppressive agents (glucocorticoid, azathioprine and/or intravenous cyclophosphamide). Two of them presented sepsis and TB diagnosis was only established at autopsy, especially with lungs, central nervous system and abdominal involvements. Anti-TB therapy (isoniazid, rifampicin and pyrazinamide) was indicated in the other two TB cases, however they deceased. DISCUSSION: Miliary TB is a rare and severe opportunist infection in pediatric lupus population. This study reinforces the importance of routine searches for TB in JSLE patients.

Miliary tuberculosis: a severe opportunistic infection in juvenile systemic lupus erythematosus patients / Tuberculose miliar: infecção oportunista grave em pacientes com lúpus eritematoso sistêmico juvenil

Abstract Introduction One of the main issues in juvenile systemic lupus erythematosus (JSLE) patients is infection, such as tuberculosis (TB). Of note, SLE patients are susceptible to pulmonary and extrapulmonary TB. However, to our knowledge, this contagious disease was rarely reported in pediatric lupus population, particularly diffuse or miliary TB. Therefore, from January 1983 to December 2011, 5,635 patients were followed-up at our Pediatric Rheumatology Unit and 285 (5%) of them met the American College of Rheumatology classification criteria for SLE. Case reports Four (1.4%) of our JSLE patients had disseminated TB and were described herein. All of them were female gender, received BCG vaccination and did not have a history of TB household contact. The median of current age at TB diagnosis and the period between JSLE and TB diagnosis were 17 years old (range 14-20) and 5.5 years (range 2-7), respectively. All patients developed miliary TB during the course of the disease. The median of SLE Disease Activity Index 2000 (SLEDAI-2K) was 4 (2-16) and the patients were treated with immunosuppressive agents (glucocorticoid, azathioprine and/or intravenous cyclophosphamide). Two of them presented sepsis and TB diagnosis was only established at autopsy, especially with lungs, central nervous system and abdominal involvements. Anti-TB therapy (isoniazid, rifampicin and pyrazinamide) was indicated in the other two TB cases, however they deceased. Discussion Miliary TB is a rare and severe opportunist infection in pediatric lupus population. This study reinforces the importance of routine searches for TB in JSLE patients.

Resumo Introdução Um dos principais problemas no lúpus eritematoso sistêmico juvenil (LESJ) é a infecção, como a tuberculose (TB). É importante observar que pacientes com LES são suscetíveis à tuberculose pulmonar e extrapulmonar. No entanto, de acordo com o que se sabe, essa doença contagiosa é raramente relatada na população pediátrica com lúpus, particularmente a TB difusa ou miliar. De janeiro de 1983 a dezembro de 2011, 5.635 pacientes foram acompanhados na Unidade de Reumatologia Pediátrica; 285 deles (5%) preencheram os critérios de classificação para LES do American College of Rheumatology. Relatos de caso Quatro (1,4%) de nossos pacientes com LESJ tinham tuberculose disseminada e foram descritos neste estudo. Todos eram do sexo feminino, receberam a vacina BCG e não tinham história de contato domiciliar com a TB. A mediana da idade no momento do diagnóstico da TB e o período entre os diagnósticos de LES e tuberculose foram de 17 anos (variação de 14 a 20) e 5,5 anos (variação de dois a sete), respectivamente. Todas as pacientes desenvolveram tuberculose miliar durante o curso da doença. A mediana no SLE Disease Activity Index 2000 (SLEDAI-2K) foi de 4 (2 a 16) e as pacientes foram tratadas com agentes imunossupressores (glicocorticoides, azatioprina e/ou ciclofosfamida intravenosa). Duas delas apresentaram sepse e o diagnóstico de tuberculose só foi determinado na necropsia, com envolvimento especialmente dos pulmões, do sistema nervoso central e do abdome. A terapia antituberculose (isoniazida, rifampicina e pirazinamida) foi indicada nos outros dois casos de TB; porém, as pacientes foram a óbito. Discussão A TB miliar é uma infecção oportunista rara e grave na população pediátrica com lúpus. Este estudo reforça a importância de pesquisas de rotina para TB em pacientes com LESJ.

Tuberculosis extrapulmonar, una revisión / Extrapulmonary tuberculosis

Hasta en un 25% de los casos de tuberculosis existe afectación extrapulmonar. Esta afectación es producida por la diseminación hematógena y linfática del bacilo de M. tuberculosis hacia otros órganos. Las localizaciones más frecuentes son la ganglionar, pleural y osteo-articular. El problema de estas formas de tuberculosis radica en la dificultad para llegar a su diagnóstico definitivo, ya que tanto los síntomas clínicos, como las pruebas de imagen pueden ser inespecíficos. La mayoría de las veces es necesario recurrir a pruebas diagnósticas invasivas como PAAF guiada con ecografía o TAC, para la recolección de muestras biológicas para su diagnóstico. A pesar del auge y el avance, en los últimos años, de los métodos moleculares para la detección precoz de ADN de la micobacteria, el cultivo sigue siendo el gold estándar que permite el diagnóstico microbiológico definitivo. El tratamiento de estas formas de tuberculosis, no va diferir de las pautas de tratamiento de las formas pulmonares. Se recomienda utilizar los mismos regímenes de antibióticos con una duración de 6 meses y únicamente prolongar la duración en las tuberculosis con afectación del sistema nervioso y en la espondilitis tuberculosa con afectación neurológica (AU)

Up to 25% of tuberculosis cases present extrapulmonary involvement. This is produced by haematogenous and lymphatic spread of the M. tuberculosis bacillus to other organs. The most common locations are the lymph nodes, pleura and the osteoarticular system. The problem with these types of tuberculosis is the difficulty in establishing a definitive diagnosis, since the clinical symptoms and results of imaging tests may be vague. It is often necessary to resort to invasive diagnostic testing such as ultrasound or CAT-guided FNAB, used to collect biological samples for diagnosis. Despite the growing use of and advances in recent years of molecular methods for early detection of mycobacteria DNA, cultures continue to be the gold standard that enable a firm microbiological diagnosis to be made. Treatment for these types of tuberculosis do not differ from treatment regimens for pulmonary forms of the same disease. The same antibiotic regimens for 6 months are recommended, and any extension of this period is advisable solely in tuberculosis affecting the central nervous system and in Pott’s disease (AU)

Immunological markers and hematological parameters among newly diagnosed tuberculosis patients at Jimma University Specialized Hospital.

BACKGROUND: Tuberculosis (TB) is a cause of 1.2-1.5 million deaths worldwide, including deaths from TB among HIV positive people. Determining the extent of immune cells belonging to cell mediated immunity and haematological parameters is critical to maximize the potential benefit of anti-tubercular treatment and case management. MATERIALS AND METHODS: Comparative cross sectional study was conducted to determine the white blood cell (WBC) count, CD4, CD8, haemoglobin (Hgb), red blood cell (RBC) count, mean corpuscular haemoglobin (MCHC), mean corpuscular volume (MCV) between newly diagnosed TB patients and apparently healthy controls (HCs). RESULTS: From consecutively enrolled 108 TB patients, pulmonary TB (PTB) accounted for 48(44.4%), TB lymphadenitis accounted for 48(44.4%), and disseminated/miliary TB accounted for 12(11.1%). Analysis of variance revealed that mean ± SD of CD4 count of male TB patients (650 ± 224cells/µl) was significantly lower than male control group (883 ± 256 cells/µl) (p= 0.001). In a similar manner, the mean CD4 count of female TB patients (793 ± 332cells/µl) was lower than female control group (975 ± 300 cells/µl) (p=0.001). There was no statistically significant difference in CD8 counts between cases and controls for both genders. Forty (37.0%) TB patients had developed anaemia of whom 22(55%) were among PTB, 13(32.5%) from tuberculous lymphadenitis and 5(20%) from disseminated TB. Morphologically, from all anaemia among TB patients, normocytic normochromic anaemia accounted for 15(37.5%) followed by normocytic hypochromic anaemia 13(30.4%). CONCLUSION: CD4 lymphopenia was significant among TB patients. Granulocyte count was increased. Mild anaemia was found major haematological abnormality among newly diagnosed TB patients.

Intestinal tuberculosis in a child living in a country with a low incidence of tuberculosis: a case report.

BACKGROUND: Relatively common in adults, intestinal tuberculosis is considered rare in children and adolescents. The protean manifestations of intestinal tuberculosis mean that the diagnosis is often delayed (sometimes even for years), thus leading to increased mortality and unnecessary surgery. The main diagnostic dilemma is to differentiate intestinal tuberculosis and Crohn's disease because a misdiagnosis can have dramatic consequences. CASE PRESENTATION: A 13-year-old Caucasian, Italian female adolescent attended the Emergency Department complaining of abdominal pain, a fever of up to 38 °C, night sweats, diarrhea with blood in stool, and a weight loss of about three kilograms over the previous two months. Physical examination revealed a marked skin pallor and considerable abdominal distension with relevant discomfort in all the abdominal quadrant. Laboratory tests revealed a decreased white blood cell count with anemia and increased C-reactive protein levels. The Mantoux tuberculin skin test was negative. A chest X-ray and an abdominal ultrasonography did not reveal any significant findings. The patient underwent colonoscopy that showed diffuse mucosal congestion and significant blood loss, and laparatomy showed small bowel and colon loops with a whitish appearance. A biopsy of the ileal mucosa revealed inflammation with noncaseating granulomas possibly due to bacterial infection. Given the suspicion of an opportunistic bacterial infection in a child with chronic inflammatory bowel disease (possibly Crohn's disease), treatment with a third-generation cephalosporin was started. However, the abdominal pain, fever and poor general condition persisted and so, after 11 days, the patient underwent total body computed tomography and magnetic resonance imaging of the brain. On the basis of the radiological findings, miliary tuberculosis was suspected and bronchoscopy was performed and resulted positive for Mycobacterium tuberculosis. Miliary tuberculosis was confirmed and an effective treatment with four drugs was started. CONCLUSION: This case shows that the manifestations of intestinal tuberculosis can be very difficult to diagnose and mimic those of Chron's disease. Total body computed tomography and laparotomy with an intestinal biopsy for the detection of Mycobacterium tuberculosis are the means of avoid the risks of a misdiagnosis in children with unexplained chronic abdominal problems.

Protection by BCG vaccine against tuberculosis: a systematic review of randomized controlled trials.

BACKGROUND: Randomized trials assessing BCG vaccine protection against tuberculosis have widely varying results, for reasons that are not well understood. METHODS: We examined associations of trial setting and design with BCG efficacy against pulmonary and miliary or meningeal tuberculosis by conducting a systematic review, meta-analyses, and meta-regression. RESULTS: We identified 18 trials reporting pulmonary tuberculosis and 6 reporting miliary or meningeal tuberculosis. Univariable meta-regression indicated efficacy against pulmonary tuberculosis varied according to 3 characteristics. Protection appeared greatest in children stringently tuberculin tested, to try to exclude prior infection with Mycobacterium tuberculosis or sensitization to environmental mycobacteria (rate ratio [RR], 0.26; 95% confidence interval [CI], .18-.37), or infants (RR, 0.41; 95% CI, .29-.58). Protection was weaker in children not stringently tested (RR, 0.59; 95% CI, .35-1.01) and older individuals stringently or not stringently tested (RR, 0.88; 95% CI, .59-1.31 and RR, 0.81; 95% CI, .55-1.22, respectively). Protection was higher in trials further from the equator where environmental mycobacteria are less and with lower risk of diagnostic detection bias. These associations were attenuated in a multivariable model, but each had an independent effect. There was no evidence that efficacy was associated with BCG strain. Protection against meningeal and miliary tuberculosis was also high in infants (RR, 0.1; 95% CI, .01-.77) and children stringently tuberculin tested (RR, 0.08; 95% CI, .03-.25). CONCLUSIONS: Absence of prior M. tuberculosis infection or sensitization with environmental mycobacteria is associated with higher efficacy of BCG against pulmonary tuberculosis and possibly against miliary and meningeal tuberculosis. Evaluations of new tuberculosis vaccines should account for the possibility that prior infection may mask or block their effects.

Extrapulmonary tuberculosis: 7 year-experience of a tertiary center in Istanbul.

BACKGROUND: Although a decreasing trend of tuberculosis (TB) was reported in Turkey, higher proportion of extrapulmonary tuberculosis (EPT) was revealed. MATERIAL AND METHODS: In this retrospective study, clinical and laboratory data of 141 EPT patients were evaluated for a seven-year period by using descriptive statistics, and parametric and non-parametric tests where appropriate. RESULTS: The most frequent types of EPT were meningeal TB (23%) and TB lymphadenitis (21%), respectively. Other types of EPT were skeletal, miliary, peritoneal, abscess, genitourinarial, cutaneous and gastrointestinal involvement which ranged between 18% and 1%. Mean age was 42 and female/male ratio was almost equal. All patients were born in Turkey. Although all of them were permanent residents of Istanbul, 73% of the patients came from East and Southeast Region of Turkey. For the patients, being older than 40 years old (p<0.01), having miliary TB (p<0.05) and high CRP levels (p<0.05) were found to be associated with mortality. CONCLUSIONS: EPT still remains as a significant morbidity and mortality reason in lower income populations and developing countries. In our study, although all patients were residents of Istanbul approximately two thirds of them have migrated from East and Southeast parts of the country. The relatively high prevalence of tuberculosis cases in Istanbul may be due to the permanent migration from other parts of the country. Early diagnosis and initiation of appropriate treatment are the keys for reducing morbidity and mortality in patients with EPT, particularly in the cases of older ages.