Thalidomide-induced bronchiolitis obliterans organizing pneumonia in a patient with multiple myeloma.

Thalidomide, which is an angiogenesis inhibitor and immunomodulator that reduces tumor necrosis factor-alpha, has regained value in the treatment of multiple myeloma. Serious pulmonary complications due to thalidomide use remain relatively uncommon. We describe a case of bronchiolitis obliterans organizing pneumonia (BOOP) due to thalidomide. A 51-year-old man with IgG lambda myeloma was treated with thalidomide and dexamethasone. Seven days after the beginning of chemotherapy, the patient presented a fever and a persistent cough. Auscultation revealed crackles in both pulmonary bases. The chest X-ray showed a diffuse bilateral alveolar-interstitial syndrome. Computed tomography scan revealed bilateral pulmonary involvement, with bilateral interstitial alveolar infiltration and ground-glass pattern consolidations. Pulmonary infection, malignant tumor, and lung involvement of multiple myeloma were excluded through various tests. Thalidomide-induced BOOP was suspected, and the drug was withdrawn and replaced by Melphalan. The patient had complete resolution of his symptoms and radiologic pulmonary involvement on discontinuation of the drug. In the absence of other etiologies, physicians should be cognizant of this potential complication in patients receiving thalidomide who present with respiratory symptoms.

Acute Respiratory Failure as the First Manifestation of Antisynthetase Syndrome.

We report the case of a 40-year-old man with acute respiratory failure syndrome that later proved to be an initial manifestation of antisynthetase syndrome. The diagnosis of this rare combination of a connective tissue disease and an acute respiratory failure is difficult in a previously asymptomatic patient. Early diagnosis and immunosuppressive therapy started precociously prevented the disease progression and resulted in a good outcome.

Vitamin D deficiency and interleukin-17 relationship in severe obstructive sleep apnea-hypopnea syndrome.

PURPOSE: We aimed to assess Vitamin D (VD) abnormalities in patients with severe obstructive sleep apnea-hypopnea syndrome (OSAHS), to study its association with clinical and polygraphic data, and to correlate VD levels with interleukin-17 (IL-17). METHODS: Ninety-two patients with severe OSAHS were consecutively enrolled between September 2014 and February 2016 and compared to age-, sex-, and body mass index (BMI)-matched controls. Anthropometric parameters and medical history were collected. The serum levels of VD and IL-17 were determined by radioimmunoassay and enzyme-linked immunosorbent assay, respectively. RESULTS: Ninety-two severe OSAHS patients and thirty controls were enrolled in the study. All OSAHS patients had VD deficiency. The mean level of VD was at 7.9 ng/ml among OSAHS group versus 16.8 ng/ml among control group. IL-17A levels were elevated (20.3 pg/ml) in OSAHS group compared to healthy group (10.05 pg/ml). VD levels were negatively correlated with nocturia severity (r = -0.26; P = 0.01) and positively correlated with mean O2 saturation (r = 0.59; P = 0.02) and lowest O2 saturation (r = 0.3; P = 0.03). IL-17 levels were positively correlated with nocturia severity (r = 0.24; P = 0.03) and negatively correlated with mean O2 saturation (r = -0.42; P = 0.03). A significant negative association was observed between IL-7 and VD levels (r = -0.64, P = 0.2 10-4). The magnitude of this correlation was higher for important nocturia, lower MSaO2, or higher BMI. CONCLUSIONS: VD deficiency in patients with severe OSAHS is common with a negative association between IL-17 and VD serum levels. Hypoxia could play an important role in this association. Further studies are needed to clarify this relationship.

Evaluation of Tuberculin Skin Test Positivity and Early Tuberculin Conversion among Medical Intern Trainees in Tunisia.

BACKGROUND: As healthcare workers (HCWs), medical trainees are at a high-risk for acquisition of tuberculosis (TB) infection and disease. To our knowledge, there are no published data about TB infection among medical trainees in Tunisia.To determine the tuberculin skin test (TST) positivity and tuberculin conversion among a group of medical trainees in different departments at our institution. MATERIALS AND METHODS: We performed a prospective study using the TST. The study was conducted in two steps: 1) an initial TST survey and 2) an evaluation of the TST conversion rates. RESULTS: Among 114 participants, the TST was positive (≥10 mm) in 26.3% and negative (<5 mm) in 57%. The conversion rate of TST was 4%, which was only observed among the trainees assigned to the pulmonary departments. The significant predictor variables of TST positivity were a history of nosocomial TB exposure and training in a high-risk area. CONCLUSION: Despite the small number of participants, the high TB conversion rate among the trainees is alarming. This population represents an important target group for a latent tuberculosis infection screening program in countries with limited resources such as Tunisia.

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.

Sit-to-stand test and 6-min walking test correlation in patients with chronic obstructive pulmonary disease.

BACKGROUND: The 6-min walking test (6MWT) is one of the most commonly used tests to assess exercise capacity during chronic obstructive pulmonary disease (COPD). However, it is a relatively time-consuming test. Many authors assessed the usefulness of simpler methods, as the sit-to-stand test (STST), to estimate exercise capacity. PURPOSE: To demonstrate the feasibility of STST, in comparison to 6MWT, for the evaluation of functional status in Tunisian COPD patients and evaluate its correlation to the severity of the disease. METHODS: We studied patients with COPD (Global Initiative for Chronic Obstructive Lung Disease A-D). All patients had plethysmography and manual quadriceps femoris muscle strength evaluation. Each patient completed a 6MWT and a STST. During the tests, dyspnea severity (Borg scale), heart rate, pulsed oxygen saturation, and blood pressure were measured. RESULTS: In 49 patients with stable COPD (mean age 67.06 ± 8.4 years, mean forced expiratory volume in the first second 46.25% ± 19.64%), 6MWT and STST were correlated with each other (r = 0.47, P = 0.001). During 6MWT and STST, the rise in heart rate, systolic blood pressure, and severity of dyspnea were statistically significant compared to baseline (P < 0.05). However, cardiorespiratory stress was lower after STST than after 6MWT (P < 0.05). A statistically significant positive correlation was noted between the 6MWT distance and forced vital capacity (r = 0.357, P < 0.05). The 6MWT was negatively correlated with dyspnea severity at baseline (r = -0.289, P < 0.05) and with BODE index (r = -0.672, P < 0.01). STST was correlated only with age (r = 0.377, P < 0.01). No correlation was found between both tests and quadriceps femoris strength. CONCLUSION: As like as 6MWT, STST can determine functional status during COPD. In addition, it is less time consuming and produces less hemodynamical stress compared to 6MWT. STST can be used as an alternative for 6MWT in patients with COPD.

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.

First isolation of Mimivirus in a patient with pneumonia.

BACKGROUND: Mimiviridae Mimivirus, including the largest known viruses, multiply in amoebae. Mimiviruses have been linked to pneumonia, but they have never been isolated from patients. To further understand the pathogenic role of these viruses, we aimed to isolate them from a patient presenting with pneumonia. METHODS: We cultured, on Acanthamoeba polyphaga amoebae, pulmonary samples from 196 Tunisian patients with community-acquired pneumonia during the period 2009-2010. An improved technique was used for Mimivirus isolation, which used agar plates where the growth of giant viruses is revealed by the formation of lysis plaques. Mimivirus serology was tested by microimmunofluorescence and by bidimensional immunoproteomic analysis using Mimivirus strains, to identify specific immunoreactive proteins. The new Mimivirus strain genome sequencing was performed on Roche 454 GS FLX Titanium, then AB SOLiD instruments. RESULTS: We successfully isolated a Mimivirus (LBA111), the largest virus ever isolated in a human sample, from a 72-year-old woman presenting with pneumonia. Electron microscopy revealed a Mimivirus-like virion with a size of 554 ± 10 nm. The LBA111 genome is 1.23 megabases, and it is closely related to that of Megavirus chilensis. Furthermore, the serum from the patient reacted specifically to the virus compared to controls. CONCLUSIONS: This is the first Mimivirus isolated from a human specimen. The findings presented above together with previous works establish that mimiviruses can be associated with pneumonia. The common occurrence of these viruses in water and soil makes them probable global agents that are worthy of investigation.

[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.