A rare coexistence of sarcoidosis with overlap syndrome and sarcoidosis with primary biliary cholangitis and Sjogren's syndrome: Two distinct case reports.

Sarcoidosis and the overlap syndrome of autoimmune hepatitis and primary biliary cholangitis (PBC) share common clinical, biological, and histological features. The simultaneous occurrence of these diseases have been reported in few cases and suggests that a common pathway which may contribute to granuloma formation in both conditions. We report the cases of two female patients having an association of sarcoidosis and inflammatory liver diseases. The first case is of a 61-year-old woman had been monitored for an overlap syndrome of PBC and autoimmune hepatitis (AIH). Therefore, treatment with azathiprine has been initiated associated with ursodeoxycholic acid (UDCA). Azathioprine had to be discontinued due to digestive intolerance, specifically chronic diarrhea and abdominal pain. The patient remained clinically stable on UDCA and her liver function tests were stable for years, until she developed symptoms of progressive dyspnea without any other associated signs. Chest computed tomography (CT) revealed mediastinal enlargement, bilateral pulmonary nodules, and symmetrical adenomegalies in the mediastinum. The bronchoalveolar lavage (BAL) revealed increased cellularity, with a notable elevation in lymphocyte count (48 %) and a CD4/CD8 ratio of 4. The patient underwent mediastinoscopy; a biopsy of the right laterotracheal (4R) adenomegaly was performed. Histological examination of the lymph node showed epithelioid and giant-cell tuberculoid lymphadenitis without necrosis, compatible with sarcoidosis. Ophthalmological and cardiac assessments were normal. Plethysmography test was normal and there was no need for corticosteroid treatment; a surveillance was planned. Treatment with UDCA was pursued. The second case is of a 50-year-old woman with no medical history presented symptoms including dry eyes and mouth, inflammatory-type polyarthralgia affecting knees and wrists, bilateral Raynaud's phenomenon, right hypochondrium pain, and worsening dyspnea over six months. Liver analysis showed elevation of alkaline phosphatase (ALP) to three times upper limit of normal (ULN) and gamma-glutamyltransferase (GGT) to 5 times ULN. This cholestasis was associated with an increase in transaminase activity to 5 times ULN for over six months. Immunological tests revealed positive anti-nuclear antibodies (ANA), anti-Ro52, anti-M23E, and anti-centromere antibodies. Chest-CT showed multiple bilateral bronchiolar parenchymal micronodules mostly in the upper and posterior regions without any mediastinal adenomegaly. Bronchial endoscopy was normal, and biopsies indicated chronic inflammation. The BAL revealed increased cellularity, characterized by a high lymphocyte count (51.7 %) and a CD4/CD8 ratio of 2.8. Biopsy of minor salivary gland revealed grade 4 lymphocytic sialadenitis. Skin biopsy revealed an epithelioid granuloma without caseous necrosis. Liver biopsy performed in the presence of cytolysis and moderate hepatic insufficiency, revealed granulomatous hepatitis and cholangitis lesions along with septal fibrosis suggestive of PBC. The diagnosis of cutaneous and pulmonary sarcoidosis with PBC and Sjögren's syndrome was retained. The spirometry and diffusing capacity for carbon monoxide value were normal. Treatment involved UDCA, corticosteroids, and azathioprine, leading to clinical and biological improvement. Sarcoidosis shares some clinical manifestations with autoimmune liver diseases, primarily PBC. A hepatic granuloma with a different appearance and location can guide the diagnosis. Early diagnosis and appropriate management can avoid serious complications and improve prognosis.

Esophageal leiomyomas presenting as a mediastinal mass.

Although benign tumors of the esophagus are very rare, the leiomyomas are frequently recorded. Most of them are small, asymptomatic and without risk of malignant degeneration. These benign tumors are usually discovered fortuitously on endoscopy. Sometimes, they may manifest clinically by dysphagia, hematemesis or other signs. They may mimic the esophageal cancer, which is more frequent, or some mediastinal tumors. The diagnosis can be oriented by the barium swallow esophagogram or other imaging methods, yet, only the histological examination gives the confirmation of the diagnosis. We report the case of a 50-year-old man, non-smoker, complaining of dysphagia, epigastric pain and deterioration of general condition. The clinical and radiological presentation mimicked a mediastinal tumor. Surgery was performed, and histological examination concluded to two leiomyomas of the esophagus.

Breathing pattern during sequential swallowing in healthy adult humans.

Sequential liquid swallowing is a common daily occurrence during which coordination of deglutition and breathing are highly regulated to avoid pulmonary aspiration and to maintain hematosis. We studied the effects of sequential water swallowing (SWS) at fixed swallowing rates and with regular succession of swallows on respiration in healthy subjects. Thirty-one normal adults (19 men, 12 women) with a mean age of 27.96 ± 3.68 yr were explored at rest and during SWS (at 12 and 24 swallows/min). Respiration was recorded by intranasal air pressure changes and timing of deglutition by an acoustic method. Oxygen saturation [arterial O2 saturation from pulse oximetry ( SpO2 )] was monitored with a finger probe. During SWS, we determined the respiratory phase (inspiration or expiration) before and after each ingestion cycle (IC; period of sustained apnea including 1 or more swallows). We also measured inspiratory time (TI), expiratory time (TE), respiratory cycle duration (TT), respiratory rate (RR) and SpO2 at rest and during SWS. We showed that respiration was interrupted by sequential swallows determining a succession of ICs that were often preceded and followed by expiration. During SWS, TI decreased and TE increased compared with rest ( P < 0.01). However, TT, RR, and SpO2 did not change. It seems that the preferential coupling of swallowing with expiration during SWS is favored by an increase in TE to ensure airway protection, although the repetitive swallows, RR, and SpO2 were not altered during SWS. These data may be useful to study the effects of aging and pathological conditions on swallowing and breathing coordination during SWS. NEW & NOTEWORTHY Sequential water swallowing induces ingestion cycles that are often preceded and followed by expiration. Moreover, inspiratory time decreases and expiratory time increases during sequential swallowing compared with rest without changes in ventilatory cycle duration, respiratory rate, and oxygen saturation.

The Z-score: A new tool in the interpretation of spirometric data.

Spirometry is an important tool in the diagnosis and management of patients with respiratory pathology. An appropriate interpretation of the spirometric data requires the use of a population-specific reference equation. However, the most widely used equations were established in European populations with limited age groups. The extrapolation of these equations, based on a specific population, and their uses for a different population led to measurement and interpretation biases. In 2012, an international working group conducted a multicenter study and published new reference equations called The Global Lung Initiative (GLI). These enabled the modeling of spirometric parameters from a very large sample collected in several ethnic groups using modern statistical techniques to establish continuous equations for all ages and in many countries. The GLI also recommends the use of a new statistical tool for the expression of results: The Z-score. This tool allows to express, in a simple way: how many standard deviations a subject is deviated from its reference value. The Z-score is calculated by the ratio of the difference between the measured value and that predicted with the residual standard deviation. This simple approach has reduced the false positive results found by the use of the conventional limits of 80% compared to a predicted value or 0.70 in absolute value for the definition of bronchial obstruction that remain still used.

Preoperative assessment in pulmonary resection surgery.

Pulmonary resection can be associated with a significant risk of morbidity and mortality, which depends on the nature and extent of pulmonary resection but also on the patient himself. This risk can be apprehended by a preoperative assessment which estimates the immediate operative risk as well as the physiological state and the post-operative quality of life which can require more conservative therapies. Currently, preoperative exploration of a patient is based on various technological tools, which can range from simple electrocardiogram or simple spirometry to a complex exploration such as a cardiorespiratory effort test. These multiple evaluation tools require the rationalization of good practice processes according to international recommendations, taking into account the patient's specificity and the country context. This approach makes it possible to prioritize examinations according to their availability and accessibility in order to identify patients with high operative risk and to offer them an appropriate therapeutic choice.

Role of metalloproteinases MMP-2 in asthma.

Background - Many metalloproteinases (MMPs) play a role in the pathogenesis and modulation of the severity of asthma. MMP-9 is the predominant in asthma but other MMPs are involved such as the MMP-2. Aim - To determine the role of single nucleotide polymorphism of the gene MMP2 in susceptibility to asthma and its severity. Methods - Study case-control with prospectively enrolled patients with asthma and healthy subjects. We determined within two groups genotypes corresponding to the MMP2 polymorphism in -735C / T position, using a polymerase chain amplification technique associated with a polymorphism in the length of restriction fragments. Results - We included 150 patients with asthma and 150 healthy controls. Comparison of allele and genotype frequencies of the studied polymorphisms between patients and controls showed that there was no association between the SNP-735C / T and susceptibility to asthma and its severity. Conclusion - The role of MMP 2 in asthma remains unclear and no study has been conducted till date, to determine the role of MMP-2 -735C/T gene polymorphism in asthma. This study does not disprove such association. Further studies are needed to clarify the exact role the pathogenesis of asthma.

Contribution of fixed-dose combinations in the treatment of tuberculosis.

Background - The introduction of fixed-dose combinations (FDCs) of TB treatment in Tunisia is recent (July 2009). WHO and the National Tuberculosis Programme recommend the use of fixed-dose combination (FDC) tablets for the treatment of tuberculosis (TB). The effectiveness of ADF has been demonstrated, however the risk of relapse and tolerance were controversial. Objective - Through a retrospective study, we evaluate, the contribution of FDCs compared with dissociated treatment (TD) (efficacy, tolerance and the occurrence of relapses). Patients and methods - This is a retrospective study conducted in the Department of Pneumology la Rabta. Are included patients with pulmonary tuberculosis (TB) first attack. Two groups were studied: Group I (TC) treated between July 2009 and June 2011 who received ADF. Group II (TD) treated between July 2008 and June 2009 who received TB dissociated treatment. Results - One hundred and seventy one patients were included: 122 in the TC group with an average age of 39.2 years and 49 patients in the TD group with an average age of 38.2 years. Male predominance was observed in the two groups (82/75.5%). The period of apyrexia was below 7 days at more than 80% of patients in the two groups. Sputum smears conversion were obtained between one and two months (median 52,8 vs 55,8 days) in both groups with no significant difference (p = 0.06). The rate of smears conversion at 2 months was 74% in TC group versus 65.3 % (p = 0.12). Eighty patients (65%) of the TC group and 29 patients (59%) of the TD group had one or more adverse effects to treatment without significant difference (p = 0.270). The most common adverse effects were those related to digestive system (17.2% vs 6.1%), liver toxicity (7.4% vs 4.1 %) and urticaria (9.8% vs 8.1%). The treatment successful rate was: 73.7 % in TC group and 77.5 % in TD group. There was no significant difference in treatment compliance, neither in relapse rate nor in the death rate. Conclusion - This study demonstrated non-inferiority of the effectiveness of ADF with a comparable safety. Its effects in the prevention of relapse and resistance BK remain unproven.

Drug Rash with Eosinophilia and Systemic Symptoms to antituberculosis treatment.

Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome reflects a serious hypersensitivity reaction to drugs. This syndrome is an uncommon adverse reaction due to antituberculosis drugs and is sometimes difficult to identify the culprit agent. We report a case of a 45-year-old woman who received combined antituberculosis drugs (RHZE) for lymph node tuberculosis. Clinical manifestations included fever, dyspnea, rash, hypereosinophilia and visceral involvement (liver involvment). After symptom resolution and biology normalization, anti-tuberculosis drugs were reintroduced successively one after another. Systemic symptoms reappeared with the four anti-tuberculosis drugs. The clinical outcome was favorable with second line antituberculosis treatment.

[Infuenzae A (H1N1): about 189 cases]. / Grippe A (H1N1): à propos de 189 cas.

BACKGROUND: Influenza A (H1N1) is a contagious acute respiratory infection caused by a subtype influenza virus A (H1N1). The later had caused a pandemic in 2009. Despite its low mortality, the disease was more severe in some subgroups. OBJECTIVES: Describe confirmed cases of influenza A (H1N1) addressed to the pulmonary department of the Rabta hospital and identify risk factors. METHODS: During the pandemic influenza A (H1N1), pulmonary department of Rabta hospital was identified among the centers to receive and detect new cases in addition to hospitalization of severe ones. All subjects had nasal and pharyngeal swabs. The authors distinguished non-severe and severe cases; hospitalization was indicated for severe forms. RESULTS: From September 2009 to March 2010, influenza A (H1N1) has been confirmed in 189 patients. The average age was 27.3 years [2-72 years]. Sex ratio was 1.2. Contagion was found in all patients. Twenty-two patients were hospitalized for the severe form. Mean age was 56 years, sex ratio was 0.47. Among them, 20 patients had at least one co-morbidity. Most frequently found risk factors were diabetes (9 cases), chronic respiratory disease (9 cases) and pregnancy (6 cases). All patients received ozeltamivir. The dose was doubled in severe cases. Nonspecific antibiotic therapy was prescribed in 11 cases. Seven patients were hospitalized in intensive care unit, among whom 4 died. Mortality in severe forms was 18% and overall mortality 2.1%. CONCLUSIONS: Through this Tunisian series, we emphasize the potential severity of influenza A (H1N1). This justifies a systematic vaccination of subjects at risk even away from pandemic period.

[Diagnosis approach of pulmonary embolism]. / Strategie diagnostique au cours de l'embolie pulmonaire.

BACKGROUND: Pulmonary embolism (PE) is a fairly common condition that can be fatal. The variability of presentation sets clinician up for potentially missing the diagnosis. Routine laboratory findings are nonspecific and are not helpful in diagnosis of PE.Diagnosis is based on clinical prediction rule in combination with laboratory tests such as the D-dimers test leading to the realization ofa confirming examination. AIM: To precise the confirming examinations of PE and propose analgorithm based on clinical prediction rules in combination with D-Dimers. METHODS: A Pub Med search was conducted using the following keywords: pulmonary embolism,computed tomogramphy pulmonary angiography, scintigraphy and D Dimer. The study was based on are view of 18 studies including meta analysis, reviews and original articles referring recent strategy diagnosis of pulmonary embolism. RESULTS: Ventilation/perfusion scan is a type of examination that is used less often because it is not a widespread technology. However,it may be useful in patients who have an allergy to iodinated contrast.Ultrasonography of the legs, also known as leg doppler, in search of deep venous thrombosis (DVT) may help the diagnosis approach particularly when other exams are not available or contraindicated.This may be a valid approach in pregnancy. The gold standard for diagnosing PE is pulmonary angiography. It is used less often due to wider acceptance of multi detector CT scans, which are non-invasive.A normal ventilation/perfusion scan rules out the diagnosis of PE with negative predictive value of 97%. There is no consensus in pregnancy. Finally, the MRI has a low and insufficient sensibility to diagnose PE. CONCLUSION: D Dimers, multidetector CT, ventilation/ perfusion scintigraphy and ultrasonography of the legs are the most useful examinations to diagnose PE. Many algorithms were established depends on medical experience and examination availability

[Sarcoidosis in Tunisia: epidemiologic and clinical study]. / Sarcoïdose en Tunise: partcularités épidémiologiques et cliniques.

BACKGROUND: The epidemiologic study of sarcoidosis is problematic and differing incidences across the world are reported. In Tunisia, the incidence of this affection is yet unknown. This is at least attributable to the lack of large series and the overshadowing presence of tuberculosis. AIM: To determine presenting signs, symptoms and investigations particularities. METHODS: We report a retrospective series patients with sarcoidosis followed up in the Rabta university hospital between 1991 and 2005 and try to determine presenting signs, symptoms and investigations particularities. RESULTS: 131 patients (79 women and 52 men) with a median age of 47 ± 14 years were reviewed. They were symptomatic in 95 % of cases. Cutaneous symptoms were present at onset in 56.8 %, respiratory symptoms in 48.6 % and general symptoms in 41.6 %. Thoracic presentation was observed in 81.3%. Chest X-ray changes and tomodensitometry showed that type II and III were predominant. Lung function was disturbed in 58.5% of the cases. Extrathoracic involvement, observed in 89.3 % of the cases, was largely dominated by cutaneous lesions. Histopathological lesions provided diagnosis in 66.6%. CONCLUSION: The relative high frequency of dermatological lesions suggests genetic or even environmental predisposition to develop sarcoidosis such as sunlight exposition.