Association study of genes controlling IL-12-dependent IFN-γ immunity: STAT4 alleles increase risk of pulmonary tuberculosis in Morocco.

BACKGROUND: Only a minority of individuals infected with Mycobacterium tuberculosis develop clinical tuberculosis. Genetic epidemiological evidence suggests that pulmonary tuberculosis has a strong human genetic component. Previous genetic findings in Mendelian predisposition to more severe mycobacterial infections, including by M. tuberculosis, underlined the importance of the interleukin 12 (IL-12)/interferon γ (IFN-γ) circuit in antimycobacterial immunity. METHODS: We conducted an association study in Morocco between pulmonary tuberculosis and a panel of single-nucleotide polymorphisms (SNPs) covering 14 core IL-12/IFN-γ circuit genes. The analyses were performed in a discovery family-based sample followed by replication in a case-control population. RESULTS: Out of 228 SNPs tested in the family-based sample, 6 STAT4 SNPs were associated with pulmonary tuberculosis (P = .0013-.01). We replicated the same direction of association for 1 cluster of 3 SNPs encompassing the promoter region of STAT4. In the combined sample, the association was stronger among younger subjects (pulmonary tuberculosis onset <25 years) with an odds ratio of developing pulmonary tuberculosis at rs897200 for GG vs AG/AA subjects of 1.47 (1.06-2.04). Previous functional experiments showed that the G allele of rs897200 was associated with lower STAT4 expression. CONCLUSIONS: Our present findings in a Moroccan population support an association of pulmonary tuberculosis with STAT4 promoter-region polymorphisms that may impact STAT4 expression.

[Report of a case of isolated tuberculous arthritis of the knee: a difficult diagnosis in adolescents]. / L'arthrite tuberculeuse isolée du genou, un diagnostic difficile chez l'adolescent: rapport de cas.

Tuberculosis is a major global public health problem. Osteoarticular tuberculosis is very rare. In half of the cases it affects the vertebrae. Symptoms are insidious over a prolonged period and isolation of the pathogen is difficult, mostly leading to difficult and delayed diagnosis. We here report a new case of tuberculous arthritis of the knee in a teenager in whom the mean time between symtom onset and definitive diagnosis based on the detection of Mycobacterium tuberculosis genome by Xpert MTB/RIF test was eight months. This study emphasizes the importance of bacteriological sampling and diagnostic methods by molecular assay in early and definitive diagnosis of tuberculous arthritis.

[Probable post-traumatic aneurism of ascending thoracic aorta: about a case]. / Anévrysme de l'aorte thoracique ascendante post traumatique probable: à propos d'un cas.

Thoracic aortic aneurysms are relatively rare. Etiologies are dominated by atherosclerosis, elastic tissue dystrophies and trauma. We report the case of a 50-year old patient with a personal history of severe chest trauma occurring at age 25 years during parachute training. He presented with neurosensory signs of arterial hypertension. Chest X-ray showed aneurysmal dilatation of the thoracic aorta. Transthoracic echocardiography, CT angiography and MRI objectified ascending aortic aneurysm. The assessment of extent and etiological research were negative. The anatomopathological examination of surgical specimen showed nonspecific lesions.

[Spontaneous pneumomediastinum in an asthmatic patient]. / Pneumomediastin spontané chez un asthmatique.

Spontaneous pneumomediastinum is a rare disease. It especially affects young adults. The onset is usually sudden, involving chest pain, subcutaneous emphysema and dyspnea. We report the case of a 24-year old asthmatic patient with pneumomediastinum after coughing effort. The patient presented with acute respiratory failure associated with retrosternal chest pain. Chest X-ray confirmed the diagnosis of pneumomediastinum. The patient evolved favorably within 4 days after exsufflation, oxygen therapy and conventional medical treatment.

[A rare cause of posterior mediastinal tumors: mediastinal hydatid cyst]. / Une cause rare des tumeurs du médiastin postérieur: le kyste hydatique médiastinal.

Mediastinal hydatid cyst is extremely rare even in endemic areas, representing 0-4% of all hydatid cyst locations. We report the case of a 50-year old patient admitted to our Department with a mass in the left dorsal paraspinal region; chest X-ray showed posterior left basal opacity. Chest CT scan showed posterior mediastinal mass located in the left costovertebral gutter extending from D9 to D11. MRI confirmed the existence of a posterior mediastinal mass with endocanalar extension and spinal cord compression, first evoking cystic schwannoma. These radioclinical data were consistent with a neoplastic origin; a transparietal biopsy was performed which showed a paucicellular specimen composed of translucent eosinophilic material with appearance just barely compatible with hydatid cyst. Hydatic serology was positive. The diagnosis of hydatid cyst was retained and the patient underwent thoracotomy which revealed mediastinal hydatid cyst, confirmed by histologic examination. The postoperative course was uneventful. Mediastinal location of hydatid cyst is very rare and poses a problem in differential diagnosis with other mediastinal tumors.

[Severe pulmonary involvement in hypocomplementemic urticarial vasculitis (HUV)]. / Atteinte pulmonaire sévère au cours de la vascularite hypocomplémentémique urticarienne.

Pulmonary involvement in hypocomplementemic urticarial vasculitis (HUV) or Mac Duffie syndrome is extremely rare with a poor prognosis. We report the case of a 55-year-old female patient treated for HUV over a period of 20 years. The diagnosis was confirmed on the basis of urticarial lesions, ocular inflammation, positive C1q-p test by immunodiffusion, with low rate of C1q. The patient was treated with cycles of cyclophosphamide, corticoids and rituximab as she developed class III dyspnea (NYHA classification ). The clinico-radiological and functional assessment showed thoracic distension and severe obstructive pulmonary disease which found no significant improvement with systemic treatment Aerosol therapy was started and the patient had a marked clinical improvement. Pulmonary involvement in Mac Duffie hypocomplementemic urticarial vasculitis worsens the patient short-term vital prognosis. The knowledge of the different types of pulmonary involvement opens new therapeutic prospects.

[Pleuropulmonary metastasis revealing a malignant melanoma of the conjunctiva in a young subject]. / Métastases pleuropulmonaires révélant un mélanome malin de la conjonctive chez un sujet jeune.

Melanoma of the conjunctiva is a rare tumor with incidence from 0,03 to 0,08 cases per 100000 white population. Metastatic malignant melanoma represents approximately 5% of all secondary malignant lung tumors. We report the unexpected discovery of a pulmonary and pleural metastasis from a conjunctival melanoma in a young subject.