Lyme borreliosis and other tick-borne diseases. Guidelines from the French scientific societies (II). Biological diagnosis, treatment, persistent symptoms after documented or suspected Lyme borreliosis.

The serodiagnosis of Lyme borreliosis is based on a two-tier strategy: a screening test using an immunoenzymatic technique (ELISA), followed if positive by a confirmatory test with a western blot technique for its better specificity. Lyme serology has poor sensitivity (30-40%) for erythema migrans and should not be performed. The seroconversion occurs after approximately 6 weeks, with IgG detection (sensitivity and specificity both>90%). Serological follow-up is not recommended as therapeutic success is defined by clinical criteria only. For neuroborreliosis, it is recommended to simultaneously perform ELISA tests in samples of blood and cerebrospinal fluid to test for intrathecal synthesis of Lyme antibodies. Given the continuum between early localized and disseminated borreliosis, and the efficacy of doxycycline for the treatment of neuroborreliosis, doxycycline is preferred as the first-line regimen of erythema migrans (duration, 14 days; alternative: amoxicillin) and neuroborreliosis (duration, 14 days if early, 21 days if late; alternative: ceftriaxone). Treatment of articular manifestations of Lyme borreliosis is based on doxycycline, ceftriaxone, or amoxicillin for 28 days. Patients with persistent symptoms after appropriate treatment of Lyme borreliosis should not be prescribed repeated or prolonged antibacterial treatment. Some patients present with persistent and pleomorphic symptoms after documented or suspected Lyme borreliosis. Another condition is eventually diagnosed in 80% of them.

Lyme borreliosis and other tick-borne diseases. Guidelines from the French Scientific Societies (I): prevention, epidemiology, diagnosis.

Lyme borreliosis is transmitted en France by the tick Ixodes ricinus, endemic in metropolitan France. In the absence of vaccine licensed for use in humans, primary prevention mostly relies on mechanical protection (clothes covering most parts of the body) that may be completed by chemical protection (repulsives). Secondary prevention relies on early detection of ticks after exposure, and mechanical extraction. There is currently no situation in France when prophylactic antibiotics would be recommended. The incidence of Lyme borreliosis in France, estimated through a network of general practitioners (réseau Sentinelles), and nationwide coding system for hospital stays, has not significantly changed between 2009 and 2017, with a mean incidence estimated at 53 cases/100,000 inhabitants/year, leading to 1.3 hospital admission/100,000 inhabitants/year. Other tick-borne diseases are much more seldom in France: tick-borne encephalitis (around 20 cases/year), spotted-fever rickettsiosis (primarily mediterranean spotted fever, around 10 cases/year), tularemia (50-100 cases/year, of which 20% are transmitted by ticks), human granulocytic anaplasmosis (<10 cases/year), and babesiosis (<5 cases/year). The main circumstances of diagnosis for Lyme borreliosis are cutaneous manifestations (primarily erythema migrans, much more rarely borrelial lymphocytoma and atrophic chronic acrodermatitis), neurological (<15% of cases, mostly meningoradiculitis and cranial nerve palsy, especially facial nerve) and rheumatologic (mostly knee monoarthritis, with recurrences). Cardiac and ophtalmologic manifestations are very rarely encountered.

[Specific cyclo-oxygenase-2 inhibitors in cardiovascular pathology]. / Inhibiteurs spécifiques de la cyclooxygénase-2 en patholologie cardiovasculaire.

Cyclo-oxygenase catalyses the conversion of arachidonic acid and O2 into prostaglandins. Its two isoenzymes, COX-1 and COX-2, have different functions. COX-1 is expressed in constituent form in most tissues where it controls the production of arachidonic acid metabolites which maintain the physiological tissue integrity. By contrast, COX-2 is only induced in response to inflammatory stimuli, resulting in the production of inflammation mediating prostaglandins. Conventional non-steroidal anti-inflammatories inhibit both enzymes in a non-specific manner. The recent development of specific COX-2 inhibitors, which retain the same anti-inflammatory efficacy but do not have the gastric side effects of conventional treatment related to COX-1 inhibition, gives them a greater safety margin. However, coronary events are observed in patients treated with COX-2 inhibitors. This risk, seemingly confirmed at least at higher dosages, has been attributed to a disequilibrium in the balance of thromboxane A2/prostacyclin (TxA2/PGI2) which they induce. Paradoxically, COX-2 inhibitors also have several favorable effects on atheromatous plaque progression and its inflammatory component, not only in vitro but also therapeutically, including situations where platelet activation and arterial thrombosis are predominant, such as in acute coronary syndrome. The salt retention induced by COX-2 inhibitors could also be the origin of an increase in blood pressure, and in susceptible subjects it could provoke cardiac decompensation. These multiple cardiovascular risks tinge the safety profile of COX-2 inhibitors, especially in elderly subjects and those with multiple pathology, for whom extra surveillance is required.

[Mediators of reactive hyperemia]. / Facteurs de l'hyperémie réactionnelle.

Reactive hyperemia is a protective adaptive phenomenon, which quickly restores blood flow distal to a transient arterial occlusion. It involves the vascular tone regulation mechanisms of the ischaemic distal territory as a whole, but also its proximal control (flow-mediated dilation). The resulting vasodilatation differs from one vascular bed to another, and also between the large proximal arteries and the distal arterioles in the microcirculation. Thus, although both are elicited by a similar transient occlusion of brachial blood flow, non-invasive investigation of reactive hyperemia in the humeral circulation differs from assessment of endothelial function with the flow-mediated arterial dilation. Indeed, whereas nitric oxide (NO) plays the key-role in the later, several mediators are involved in the former, including myogenic and metabolic factors, prostaglandins, K + ATP channels, adenosine and NO which is only one of the many components of this complex regulation mechanism.

[Cardiac side effects of anti-HIV agents]. / Complications cardiaques des médicaments au cours de l'infection par le VIH.

Both nature and prognosis of cardiac complications occurring in patients infected by the Human Immunodeficiency Virus-1 (HIV-1) have changed considerably since the introduction of highly acive and anti-retroviral triple therapy ("HART"). Opportunist cardiac infections have thus been displaced and side effects of drugs now occupy the primary aetiological role. Torsades de pointe may be exceptionally triggered by anti-infectious agents such as pentacarinat or trimethoprime-sulfamethoxazole, as are those induced by the association of ketoconazole and terfenadine or cisapride, the dangers of which are well known and the prevention more effective, especially with the association with HIV antiproteases which inhibit the cytochrome P450. The diagnosis of iatrogenic myocardial dysfunction is more difficult, except when it occurs acutely as with phosphonoformate (Foscarnet), or interleukine-2. Progressive cardiomyopathy caused by -interferon and dideoxynucleosides (zidovudine, didanosine and zalcitabine), reversible on withdrawal of the drug responsible in half the cases, should be distinguished from those due to the HIV itself (therapeutic relay) or to another associated cause (alcohol, coronary artery disease). The coronary complications of diseases treated by antiproteases usually occur in smokers whose cholesterol and triglyceride levels are rapidly increased with HAART. In a series of 9 patients (amongst 700 treated with the antiproteases), after the acute phase of myocardial infarction during which the interventional approach is often preferred, the medium-term prognosis is relatively good, on condition that the patients correct the hyperlipidaemia and give up smoking.

Recurrent subcutaneous infection due to Scopulariopsis brevicaulis in a liver transplant recipient.

We describe a case of recurrent Scopulariopsis brevicaulis subcutaneous infection, which occurred 6 years after the patient underwent liver transplantation. Combined surgery and long-term oral therapy with terbinafine resulted in a favorable outcome, although this is not the rule in the previously reported S. brevicaulis infections in immunocompromised patients.

Reduced reactive hyperemia in HIV-infected patients.

BACKGROUND: Given that several pathology-based studies reported some degree of coronary and arterial vasculopathy in HIV-infected patients, we investigated whether abnormal vascular reactivity may also be found in these patients. METHODS: Vascular reactivity was assessed noninvasively using finger-skin blood-flow monitoring by laser-Doppler flow measurement in 10 HIV-infected-patients (mean CD4 T-cell count, 350+/-84 cells/mm3) with cardiac symptoms (previous myocardial infarction or left-ventricular dysfunction) and/or HIV-related protease inhibitor-induced hyperlipemia (group 1, symptomatic), 19 HIV-infected patients free of cardiac disease, hyperlipemia, and previous opportunistic infections (mean CD4 T-cell count, 333+/-175 cells/mm3; group 2, asymptomatic), and 19 healthy control subjects (group 3). Laser-Doppler flow was measured at baseline, during postocclusive hyperemic response following transient interruption of brachial blood flow (reactive hyperemia), during transcutaneous delivery of acetylcholine (Ach) using iontophoresis (endothelium-dependent dilation) and after sublingual nitroglycerin administration (endothelium-independent dilation). RESULTS: During reactive hyperemia, the absolute increase in flow was found to be lower in asymptomatic HIV-infected patients than in controls (median values [25th-75th percentile]: asymptomatic: 300 [200-400]; versus controls: 600 [400-750] arbitrary units [AU]; p< or =.0001). This abnormality was more pronounced in symptomatic patients (100 [100-200]; p< or =.0001). There was also a reduced peak/baseline flow ratio (symptomatic: 1.14 [1.1-1.2]; asymptomatic: 1.40 [1.25-1.5]; versus controls: 1.83 [1.6-2.2]; p<.0001 for both comparisons) and a reduced hyperemic response, as assessed by the curve of area under the flow versus time from deflation to the end of the hyperemic response (symptomatic: 1850 [1100-2225]; asymptomatic: 6000 [2850-7950]; versus controls: 23,735 [16,000-31, 800] AU x sec; p<.0001 for both comparisons). Although there was no statistically significant difference in acetylcholine (Ach)-induced increases in flow between asymptomatic HIV patients and controls (peak/baseline flow ratio: 6 [4.4-10] versus 5.3 [4-8]; p =.47), a trend to lower values was seen in symptomatic patients (4.4 [1.2-5]; p =.06). Administration of 0.4 mg sublingual nitroglycerin resulted in increases in flow without statistically significant difference between patients and controls: peak/baseline flow ratio for symptomatic: 2.4 [1.9-2.7]; asymptomatic: 2.1 [1.75-2.34] versus controls: 1.97 [1.8-2.4]; p =.2 and.83, respectively). CONCLUSIONS: Postischemic reactive hyperemia is reduced in HIV-infected patients. In addition, there was is trend for a reduced response to Ach only in those with cardiac disease and/or hyperlipemia.

Hemorheology in asymptomatic HIV-infected patients.

Although cardiac and vascular complications have been recognized among patients infected with the Human Immunodeficiency Virus-1 (HIV-1), their vascular biology and rheology have not been studied. Rheology of red blood cells (RBC) was assessed with an erythroaggregometer in 22 HIV-1 infected asymptomatic patients (pts) and 17 healthy HIV negative controls (C). All participants were normotensive, nondiabetics, had normal lipid levels and had an hematocrit ranging from 37 to 44% and hemoglobin levels > or = 12 g/100 ml. Patients had a shorter RBC aggregation characteristic time than controls (1.49 +/- 0.17 vs. 2.04 +/- 0.41 s, p = 0.001) and an increased disaggregation shear rate (166 +/- 34.9 vs. 122 +/- 25.4 s(-1), p = 0.001). This hyperaggregation tendancy was associated with increased gamma-globulin (18.3 +/- 3.3 vs. 13.7 +/- 1.9 g/l, p = 0.01) and fibrinogen (3.52 +/- 0.57 vs 3.03 +/- 0.48 g/l, p = 0.003) levels and with an increased erythrocyte sedimentation rate (ESR) (25 +/- 14.3 vs. 12.3 +/- 7.5 mm, p = 0.02). Even in patients with ESRs ranging within normal values (< or = 20 mm), the aggregation characteristic time was found lower in patients than in controls (p = 0.004). There was no correlation between these rheological changes and the CD4+ T-cell count. The 17 patients receiving an antiviral therapy had lower CD4+ T-cell counts than their 5 untreated counterparts (244.7 +/- 167 vs. 410 +/- 106/mm3, p = 0.025), and a higher disaggregation shear rate (177.4 +/- 38.2 vs. 127 +/- 25.4, p = 0.01). Thus, an impairment of rheological characteristics is observed in asymptomatic HIV-I infected patients in association with changes in plasma proteins.