A genome-wide association study of pulmonary tuberculosis in Morocco.

Although epidemiological evidence suggests a human genetic basis of pulmonary tuberculosis (PTB) susceptibility, the identification of specific genes and alleles influencing PTB risk has proven to be difficult. Previous genome-wide association (GWA) studies have identified only three novel loci with modest effect sizes in sub-Saharan African and Russian populations. We performed a GWA study of 550,352 autosomal SNPs in a family-based discovery Moroccan sample (on the full population and on the subset with PTB diagnosis at <25 years), which identified 143 SNPs with p < 1 × 10(-4). The replication study in an independent case/control sample identified four SNPs displaying a p < 0.01 implicating the same risk allele. In the combined sample including 556 PTB subjects and 650 controls these four SNPs showed suggestive association (2 × 10(-6) < p < 4 × 10(-5)): rs358793 and rs17590261 were intergenic, while rs6786408 and rs916943 were located in introns of FOXP1 and AGMO, respectively. Both genes are involved in the function of macrophages, which are the site of latency and reactivation of Mycobacterium tuberculosis. The most significant finding (p = 2 × 10(-6)) was obtained for the AGMO SNP in an early (<25 years) age-at-onset subset, confirming the importance of considering age-at-onset to decipher the genetic basis of PTB. Although only suggestive, these findings highlight several avenues for future research in the human genetics of PTB.

[Organizing pneumonia associated with primary biliary cirrhosis]. / Pneumonie organisée associée à une cirrhose biliaire primitive.

INTRODUCTION: Primary biliary cirrhosis is a hepatic auto-immune disease which is rarely associated with respiratory complications. CASE REPORT: A 40-year-old woman had a 5-year history of primary biliary cirrhosis. Two years previously, she had begun to experience a chronic cough and dyspnea. On clinical examination, the patient had fever, jaundice and basal pulmonary crackles. Chest X-ray showed bilateral slowly migrating and spreading airspace consolidation refractory to antibiotics. Microbiological investigations evidenced no abnormalities. Routine biological studies revealed an inflammatory syndrome, a mild neutrophilic hyperleukocytosis without hypereosinophilia and a mild hepatitis picture with cholestasis. Antineutrophil cytoplasmic antibody testing and anti-nuclear factor testing were negative. Fibreoptic bronchoscopy showed diffuse bronchial inflammation with no specific pathological pattern at bronchial biopsy. The bronchoalveolar lavage revealed a mixed cellular pattern. The chest computed tomography revealed peribronchial pulmonary consolidation with septal and pleural thickening, suggestive of an organizing pneumonia. The patient was treated with oral corticosteroids which resulted in a prompt clinical improvement and complete resolution of radiographic pulmonary abnormalities within two months. Treatment continued for six months and no relapse was noticed during the six months following the end of treatment. CONCLUSIONS: This case of organizing pneumonia highlights the importance of physicians considering this condition in women with primary biliary cirrhosis complaining of respiratory symptoms in the context of unresolved pneumonia.

[Adverse effects of BCG revaccination: 12 cases]. / Complications de la revaccination par le BCG: 12 observations.

INTRODUCTION: Calmette-Guérin bacillus (BCG) is a live attenuated strain used in tuberculosis vaccination. Local and systemic side-effects, although rare, are associated with BCG vaccine. They are common in cases of overdose and with poor vaccination techniques. These complications also occur in some cases of revaccination. PATIENTS AND METHODS: This was a retrospective study over a period of 5 years between January 2000 and March 2005. 12 patients presenting complications following revaccination with BCG were observed. Patients were revaccinated with BCG following a negative intradermal reaction test. The following parameters were recorded: age, gender, history, vaccination method, type of complication, treatment and outcome. RESULTS: There were 10 men and 2 and women of mean age 21 years (19 to 23 years). Mean time to consultation was 4 weeks. Complications comprised subcutaneous abscess in 8 cases, deep chronic ulcers in 4 cases complicated by humeral osteitis in one case. The dose administered was 0.1 ml in 9 patients and 1 ml in 3 others (i.e. 10 times the recommended dose). Six patients had extensive and progressive ulceration, with one positive culture, the presence of a granuloma with caseum necrosis and one case of humeral osteitis, and specific treatment was given. DISCUSSION: Revaccination is no longer recommended by the WHO since efficacy is considered to be low or even nil. Intradermal injection is the reference method for BCG vaccination. Technical errors such as injection of an excessively high dose of the vaccine or subcutaneous administration of the vaccine solution increase the incidence of adverse effects. In our study, three patients erroneously received 1 ml of vaccine and the injection was too deep in 9 cases. There are few reports in the literature concerning the underlying mechanisms of these post-revaccination accidents; two major physiopathological mechanisms, infectious and immunological, are discussed. There is no consensus regarding treatment of these complications. Six of the 12 patients received specific therapy for 6 months.

[Sequestration of the posterobasal segment of the right lower pulmonary lobe]. / Séquestration du segment postérobasal du lobe pulmonaire inférieur droit.

Pulmonary sequestration is a rare congenital malformation that receives its blood supply from a systemic artery. We report a case of pulmonary sequestration treated by ligature of the anomalous artery without pulmonary resection. Pulmonary sequestration must be treated surgically before the occurrence of severe complications.

[Pulmonary artery aneurysms in Behcet syndrome]. / Anévrysmes artériels pulmonaires au cours du syndrome de Behçet.

Behcet syndrome is a systemic disease with venous tropism, generally expressed by thrombosis and phlebitis. Arterial involvement is more exceptional but can lead to aneurysm of the pulmonary artery, generally not more than three. We report a patient with Behcet syndrome who developed multiple aneurysms of the pulmonary artery and discuss the clinical, radiological aspects as well as the disease course and therapeutic management.

[Chronic alveolar syndrome]. / Syndrome de condensation alvéolaire chronique.

We report a case of primary pulmonary Hodgkin's disease in a 20 year-old woman. The chest x-ray showed a chronic alveolar syndrome. The diagnosis was established from a pulmonary biopsy. The radiological features and the options for diagnosis of primary pulmonary Hodgkin's disease are discussed.

[A rare cause of posterior mediastinal tumors: extramedullary hematopoiesis]. / Une cause rare des tumeurs du médiastin postérieur: l'hématopoïèse extra-médullaire.

We report a case of a patient with intrathoracic extramedullary hematopoiesis presenting as a posterior mediastinal tumor, without associated myelofibrosis. Pathophysiology and the options for diagnosis and treatment in this condition are discussed.

[Multifocal tuberculosis: fatal outcome due to toxic drug reactions]. / La tuberculose multifocale.

We report a case of multifocal tuberculosis with the following features: - skin involvement with multiple gommes disseminated on the left upper limb, the left flank, the right hypocondrium, and the right leg; - nodal involvement including the left supraclavicular, left axillary, right laterotracheal, pre and subcarineal, ceoeliomesenteric, and liver hilus nodes; splenic involvement; right pleural involvement; - spondylodiscitis of T11-T12 and of the head of the right fibula; - peritoneal involvement leading to ascitis; - multi-organ involvement. This 43-year-old woman had not particular history: no diabetes, no renal failure, no long-term corticosteroid treatment, no immunosuppressor treatment, negative HIV-1 and HIV-2 serology. Treatment with anti-tuberculosis agents led to severe drug reactions causing death due to hepatic encephalitis.

[Mediastinitis caused by Klebsiella pneumoniae with a pharyngeal portal]. / Médiastinite à Klebsiella pneumoniae à point de départ pharyngé.

We report a case of Klebsiella pneumoniae medisatinitis secondary to a retrophyarygeal abscess in a 40-year-old patient. The patient was treated with antibiotics and pleural drainage. Surgery was not necessary and the clinical course was favorable. We recall the pathophysiological and clinical aspects of this now uncommon condition and discuss the prognosis and therapeutic options.