[Off label uses of tigecycline]. / Les utilisations hors-autorisation de mise sur le marché de la tigécycline.

INTRODUCTION: Tigecycline is a relatively new antibiotic that have very limited valid indications. When no other alternative is available, this drug is widely used off label with promising results. The objective of this study is to summarize the different off label uses of tigecycline so that we can decide when and how to prescribe it in the absence of guidelines. MATERIAL AND METHODS: This study a revue of the literature collecting all the articles concerning the off label uses of tigecycline. RESULTS: Tigecycline was widely prescribed, off label, to treat infections with controversial results. Randomised clinical trials were conducted to evaluate its use to treat pneumonia. The results for this indication have a respectable level of evidence. For the other indications, the data collected was insufficient to support tigecycline prescription. In fact, different protocols were used which makes it hard to evaluate the efficacy and to conclude to the best treatment regimen. A tendency to prescribe high doses of the molecule was noted in different studies. When prescribed off label, tigecycline prescriptions were associated with a higher mortality and incidence of side effects. CONCLUSION: The tigecycline remains a valid option for the treatment of infections dues to multi-resistant bacteria especially when other alternatives are scarce or in cases of renal failure.

[Allopurinol-induced DRESS complicated by hemophagocytic lymphohistiocytosis]. / DRESS à l'allopurinol compliqué d'un syndrome d'activation macrophagique.

BACKGROUND: Drug hypersensitivity syndrome is among the most severe drug hypersensitivity reactions and in rare cases it may progress to hemophagocytic lymphohistiocytosis. Herein, we report a case of allopurinol-induced drug reaction with eosinophilia and systemic symptoms complicated by hemophagocytic lymphohistiocytosis. CASE REPORT: An 18-year-old girl presented with maculopapular rash associated with cervical lymphadenopahy appearing 3 weeks after treatment with allopurinol. Her hemodynamic status at admission was unstable. Cutaneous examination revealed an itchy maculopapular rash, which was purpuric at certain sites, together with facial edema. The diagnosis of drug hypersensitivity was suggested and was confirmed by histological examination of a skin biopsy. Allopurinol was stopped. Two weeks later, however, eosinophilia was noted. Further, four days after discontinuation of allopurinol, in view of the laboratory signs of bicytopenia, hyponatremia, hypertriglyceridemia and hyperferritinaemia, as well as the presence of hemophagocytosis in bone marrow, a diagnosis was made of lymphohistiocytosis hemophagocytic syndrome complicating a drug reaction with eosinophilia and systemic symptoms. Moreover, viral serology tests were negative. The patient was given intravenous immunoglobulin and the outcome was good. DISCUSSION: The literature contains only very few reports of drug reaction with eosinophilia and systemic symptoms complicated by hemophagocytic lymphohistiocytosis. The incriminated drugs were vancomycin, lamotrigine and phenobarbital. To our knowledge, there has only been one report of allopurinol-induced drug reaction with eosinophilia and systemic symptoms complicated by hemophagocytic lymphohistiocytosis.

[Bartonella quintana meningoencephalitis in an immunocompetent: rare case]. / Méningo-encéphalite à Bartonella quintana chez un sujet immunocompétent : une observation rare.

INTRODUCTION: Bartonella quintana (Bq) is responsible of various clinical pictures. Neuromeningeal complications are rarely reported. CASE: A 20-year-old woman was admitted for fever, headache lasting for 5 days. On admission, she was febrile at 39.3°C and had a stiff neck. Symptoms, contact with animals, biological tests and lumbar puncture (PL) rendered viral meningitis a likely diagnosis. She had received symptomatic treatment and the outcome was favorable. Three days later, the patient had headache, agitation and confusion with fever. The PL noted 130/mm(3) whites, 90% lymphocytes. The albuminorachie was 0.98 g/L, glucorachie was normal. The patient was treated with 400 mg of ofloxacine/day, seven days. Serologic tests for B. quintana were reactive. The outcome was favorable. CONCLUSION: B. quintana infection should be considered in neurological symptoms of unknown etiology.

[Macrophage activation syndrome: rare complication of murine typhus]. / Syndrome d'activation macrophagique: complication rare de typhus murin.

INTRODUCTION: Typhi is one of the rickettsial species endemic in the Mediterranean countries and is associated with the zoonotic infection of murine typhus, which may have a complicated course especially in adult patients. The association with macrophage activation syndrome (MAS) has rarely been reported in the medical literature. CASE REPORT: We describe a case of murine typhus in a diabetic woman complicated with MAS, who was effectively treated with cyclin and parenteral immunoglobulin. CONCLUSION: The murine typhus can be exceptionally complicated with SAM. This infection should be suspected in front of the discovery of SAM.

Optineurin in patients with Amyotrophic Lateral Sclerosis associated to atypical Parkinsonism in Tunisian population.

Amyotrophic Lateral Sclerosis (ALS) is a heterogeneous disorder and the phenotypic variability goes far beyond the used clinical stratification parameter. Evidence has emerged that ALS may coexist with distinct neurodegenerative diseases in single cases. We aim to study the clinical features of two familial cases of ALS carriers of two distinct variants harbored in the Optineurin (OPTN) gene. We included definite familial ALS followed up in the Department of Neurology of Razi University Hospital, Tunisia, and selected according to Byrne criteria. Preliminary screening for the four main ALS genes (SOD1, C9ORF72, TARDBP, FUS) was conducted. Given the negative results, we proceeded to NGS target-re-sequencing with a custom panel including genes associated with ALS-FTD, Alzheimer's, and Parkinson's diseases. Both families are carriers of two different OPTN variants and they present very different ALS clinical features. The first family comprises two siblings diagnosed with ALS and Corticobasal syndrome (ALS-CBS) at an early age of onset and carriers of OPTN p.E135X in the homozygous state. The proband for the second family was diagnosed with ALS at an early age of onset presenting as progressive muscular atrophy with rapid progression. Genetic analysis revealed the presence of the homozygous variant p.R520H. Our findings highlight the peculiarity of genetic Tunisian drift. Indeed, genes with a recessive mode of inheritance may explain part of ALS diversity in clinical features. Therefore, the screening of the OPTN gene is highly recommended among inbreeding populations such as the Tunisian one.

[Visceral leishmaniasis in immunocompetent adults. About six cases]. / La leishmaniose viscérale de l'adulte immunocompétent. À propos de six cas.

OBJECTIVE: Studying the epidemiological variations of visceral leishmaniasis in Tunisia and proving the importance of parasitological investigations to raise the diagnosis. PATIENTS AND METHODS: Six patients hospitalised during the period between January 1998 and January 2009 at Fattouma Bourguiba Teaching Hospital in Monastir, five men and an only one woman, aged from 26 to 70 years old, originating from the central and eastern regions of the country. Epidemiological, clinical, biological and therapeutic data were obtained from the patient's medical files. RESULTS: The major clinical symptoms were fever, weakness and spleen enlargement. Biological data revealed the presence of anaemia in every case and leucopoenia associated or not associated with thrombopenia in four cases. The diagnosis of visceral leishmaniasis was confirmed by the identification of the parasite in the blood or in the bone marrow. All patients were treated with two courses of antimoniate of meglumine separated by a 6-week interval. The outcome was positive and the patients were cured. CONCLUSION: Visceral leishmaniasis is increasing among adults in Tunisia. Moreover, it is spreading outside its epidemiological area in the north to reach the central and southern regions. It should be raised when fever and spleen enlargement occur. Biological data are hardly specific. Diagnosis is based on finding the parasite in human fluids, mainly by molecular techniques. The rapid establishment of a specific treatment is vital.

Mediterranean spotted fever as a cause of septic shock.

Mediterranean spotted fever is a generally benign disease but with the potential of serious manifestations. We report a case of Mediterranean spotted fever in a 56-year-old woman, with pet dog exposure, who presented with a septic shock pattern. Based on clinical symptoms, history, and laboratory results, the diagnosis of Mediterranean spotted fever was suspected and the outcome was favorable with doxycycline treatment. Although rickettsiae remain an uncommon cause of the sepsis syndrome, it is important to consider it, especially as people are now traveling to endemic areas more frequently.

[Pulmonary thrombosis as a complication of Mediterranean spotted fever]. / Une fièvre boutonneuse méditerranéenne compliquée d'une embolie pulmonaire.

INTRODUCTION: Thromboembolic complications were uncommon in mediterranean spotted fever. OBSERVATION: We report a case of 55-years- old man who was admitted for mediterranean spotted fever. Two days later, the patient developed chest pain due to a pulmonary thrombosis confirmed by angio-CT. The outcome was good with heparin therapy. The investigation for another cause of thrombosis was negative. CONCLUSION: Mediterranean spotted fever is usually a moderately severe self-limited illness. Pulmonary thrombosis was uncommon associated with severe disease.

Epidemiological, clinical and laboratory features of murine typhus in central Tunisia.

OBJECTIVE: Murine typhus is an endemic zoonosis. It is difficult to diagnose because of its non-specific clinical manifestations. Our objective was to describe the epidemiological, clinical, laboratory, and treatment features of murine typhus. METHODS: We conducted a retrospective study of 73 adult patients hospitalized for murine typhus from 2006 to 2011. The diagnosis was confirmed by a single titer of IgM≥128 or by seroconversion to typhus group antigen identified by indirect fluorescent assay. RESULTS: The mean age of patients was 33.1 years (range, 13-68 years). Thirty-eight patients (52%) lived in rural or suburban areas; neither fleabites nor exposure to rats were reported. The most common clinical symptoms were: fever, headache, and myalgia. A maculopapular and non-confluent rash was observed in 47 patients (64.4%). No inoculation eschar was observed in any patient. Eight patients presented with interstitial pneumonia and two with lymphocytic meningitis. The diagnosis was confirmed by indirect fluorescence assay in every case. A single titer of IgM ≥ 128 was found in 62 (84.9%) cases. The other 11 cases were diagnosed by seroconversion. All patients were given antibiotics. Tetracyclines were prescribed in 57 cases (78%). The two patients presenting with meningitis were treated with fluoroquinolone. The outcome was favorable for all patients and no relapse was observed. CONCLUSION: The features of murine typhus are non-specific. The definitive diagnosis is based on serologic testing by indirect fluorescent assay. Cyclins were the most prescribed antibiotics.

[Tuberculosis of finger bones: three cases]. / Tuberculose digitale : à propos de trois cas.

Tuberculosis dactylis is exceptional. We report tuberculous dactylitis in three women who were 51, 44, and 62-year-old, respectively. The diagnosis was suspected on chronic and insidious clinical presentation, and confirmed by histology. Disease course was favourable with antibuberculosis regimen but two patients had permanent hand disability. Clinical and therapeutic issues are discussed in the context of an endemic country.

Rhino-orbito-cerebral mucormycosis: five cases.

INTRODUCTION AND OBJECTIVE: Mucormycosis is an invasive fungal infection usually observed in immunocompromised patients. Mucormycosis is rapidly fatal without an early diagnosis and treatment. We report five patients of rhino-orbital-cerebral mucormycosis and a literature review. DESIGN: The medical records of five patients presenting with rhino-orbital-cerebral mucormycosis, admitted between January 1995 and December 2007, were analyzed. All patients underwent tissue biopsy. The histologic sections revealed the presence of non-septate hyphae of the order Mucorales. RESULTS: The five patients, three men and two women, between 27 and 61 years of age, were all diabetic. The main symptoms were exophthalmia (five patients), facial swelling (four patients), periorbital cellulitis (four patients), and cranial nerve palsy (four patients). Anterior rhinoscopy revealed palatine or nasal necrotic lesions in four patients. All presented with diabetic ketoacidosis and CT scan revealed rhino-orbital-cerebral involvement in every patient. All patients were given intravenous amphotericin B. Four patients underwent surgical debridement of necrotic tissue. Two patients survived. CONCLUSIONS: Mucormycosis is usually a fatal infection in diabetic patients. Early diagnosis should be based on imaging data and histology. Amphotericin B must be rapidly initiated and associated with aggressive surgical debridement to reduce mortality.