Aim
Drug‐induced Raynaud's phenomenon (RP) has long been associated with the use of different drugs, including cancer chemotherapy or β‐adrenoceptor blockers. However, sources report extremely ...variable prevalence and the level of evidence for each class is heterogeneous. Moreover, new signals are emerging from case reports and small series. Our objective was therefore to review available evidence about this adverse drug effect and to propose a mechanistic approach of drug‐induced RP.
Methods
A systematic review of English and French language articles was performed through Medline (1946–2015) and Embase (1974–2015). Further relevant papers were identified from the reference lists of retrieved articles.
Results
We identified 12 classes of drugs responsible for RP, with a variety of underlying mechanisms such as increased sympathetic activation, endothelial dysfunction, neurotoxicity or decreased red blood cell deformability. Cisplatin and bleomycin were associated with the highest risk, followed by β‐adrenoceptor blockers. Recent data suggest a possible involvement of tyrosine kinase inhibitors (TKI), through an unknown mechanism.
Conclusion
Drug‐induced RP is a probably underestimated adverse drug event, with limited available evidence regarding its prevalence. Although rare, serious complications like critical digital ischaemia have been reported. When these treatments are started in patients with a history of RP, careful monitoring must be made and, if possible, alternative therapies that do not alter peripheral blood flow should be considered.
Obstructive sleep apnea (OSA) is highly prevalent in conditions characterized by fluid overload. Chronic venous insufficiency (CVI) is associated to fluid overload that might interfere with OSA ...occurrence and severity.
A total of 180 patients with symptomatic CVI completed the Berlin questionnaire and were assessed for the presence of symptoms and signs of OSA and fluid shift.
According to the Berlin questionnaire, 59 patients (33%) had high risk of OSA. The predictors of having a positive Berlin questionnaire were male sex, body mass index and symptoms possibly related to fluid shift.
Patients with CVI, a disease characterized by fluid overload, present high risk of OSA, which might be related to fluid shift.
•Chronic venous insufficiency (CVI) presented high risk of OSA.•Patient-reported signs of fluid overload and shift have been correlated with OSA.•CVI patients with clinically detectable fluid overload may have higher risk of OSA.
Vascular lesions are frequent in Behçet's disease, and among them, deep venous thrombosis may occur in up to one-third of patients. Treatment is based on immunosuppressive drugs in addition to ...anticoagulants. We report the case of a young woman who presented with an acute iliofemoral venous thrombosis. Acute treatment with endovascular thrombectomy and catheter-directed fibrinolysis failed, probably because of the inflammatory status of the vessel wall. Recanalization with stenting of the obstructed common femoral and iliac veins 1 year later was successful under immunosuppressive therapy. This case suggests that endovascular treatment of venous thrombosis in Behçet's disease may be conducted successfully in nonactive venous lesions under immunosuppressive therapy.
Finger systolic blood pressure measurement (FSBP) has been shown helpful in the detection of distal arterial insufficiency in upper limbs. This work assesses the possibility to measure FSBP on the ...2nd phalanx instead of the first one in order to improve its sensitivity and to verify this would not alter the repeatability of the measurement.
In this multicenter study, FSBP was measured twice in all fingers but the thumbs in consecutive systemic sclerosis patients on the first phalanx and the second phalanx in alternate order using laser-Doppler flowmetry.
Thirty-seven patients were enrolled. The repeatability of FSBP was excellent and similar on the first and 2nd phalanxes with coefficients of variation respectively of 7.1% and 7.6%. While the correlation between the FSBP at the two sites was fair (Pearson coefficient 0.69; p < 0.001). The agreement was poor, with a mean difference of 14 mm Hg between the two sites. Significantly higher differences were found in fingers with digital ulcers. The ROC curves showed a better prediction of the 2nd phalanx measurements.
FSBP has an excellent repeatability whatever the site of phalanx. However, measurements performed on the 2nd phalanx have a better sensitivity for the prediction of digital ulcers.
•Finger Systolic Blood Pressure with laser doppler detect significant arterial disease in systemic sclerosis patients.•FSBP has an excellent repeatability of the measurements whatever the warming method used and the site of measurement.•Measurements performed on the second phalanx exhibit an excellent repeatability.Measurements performed on the second phalanx have a better sensitivity for the prediction of digital ulcers.
Objective
To evaluate the prevalence and clinical correlates of peripheral arterial disease of the upper limbs in patients with systemic sclerosis (SSc), as detected with finger brachial pressure ...index (FBPI) measurements.
Methods
This work is based on the baseline data of the SCLEROCAP multicenter cohort of SSc patients. Finger systolic blood pressure was measured with laser Doppler flowmetry, and the FBPI was obtained as its ratio over the ipsilateral brachial systolic blood pressure. An FBPI of <0.70 was used as the diagnostic criterion for occlusive arterial disease of the upper limbs. Thus, the prevalence of defined arterial disease as well as its clinical, biologic, and capillaroscopic correlates were evaluated.
Results
Among 326 enrolled patients, 177 (54.3%) met the criterion for arterial disease (FBPI <0.70). No association was found with the type of SSc nor with the type of associated antinuclear antibodies, but a significant association was found with the duration of the disease (P < 0.001), the capillaroscopic pattern (P < 0.001), and most strikingly with the presence of digital ulcers (42.9% versus 13.4%; P < 0.001). A quantitative relationship was found between the FBPI and the prevalence of digital ulcers and was shown to be independent from the capillaroscopic pattern.
Conclusion
This cross‐sectional study shows a high prevalence of arterial disease of the upper limbs in patients with SSc. FBPI appears to be a strong and independent predictor of digital ulcers. This study suggests that both macro‐ and microangiopathy are contributing to the ischemic damage of the fingertips.
Aim
Peripheral vasoconstriction has long been described as a vascular adverse effect of β‐adrenoceptor blockers. Whether β‐adrenoceptor blockers should be avoided in patients with peripheral vascular ...disease depends on pharmacological properties (e.g. preferential binding to β1‐adrenoreceptors or intrinsic sympathomimetic activity). However, this has not been confirmed in experimental studies. We performed a network meta‐analysis in order to assess the comparative risk of peripheral vasoconstriction of different β‐adrenoceptor blockers.
Method
We searched for randomized controlled trials (RCTs) including β‐adrenoceptor blockers that were published in core clinical journals in the Pubmed database. All RCTs reporting peripheral vasoconstriction as an adverse effect of β‐adrenoceptor blockers and controls were included. Sensitivity analyses were conducted including possibly confounding covariates (latitude, properties of the β‐adrenoceptor blockers, e.g. intrinsic sympathomimetic activity, vasodilation, drug indication, drug doses). The protocol and the detailed search strategy are available online (PROSPERO registry CRD42014014374).
Results
Among 2238 records screened, 38 studies including 57 026 patients were selected. Overall, peripheral vasoconstriction was reported in 7% of patients with β‐adrenoceptor blockers and 4.6% in the control groups (P < 0.001), with heterogeneity among drugs. Atenolol and propranolol had a significantly higher risk than placebo, whereas pindolol, acebutolol and oxprenolol had not.
Conclusion
Our results suggest that β‐adrenoceptor blockers have variable propensity to enhance peripheral vasoconstriction and that it is not related to preferential binding to β1‐adrenoceptors. These findings challenge FDA and European recommendations regarding precautions and contra‐indications of use of β‐adrenoceptor blockers and suggest that β‐adrenoceptor blockers with intrinsic sympathomimetic activity could be safely used in patients with peripheral vascular disease.
Digital skin ulcers are a severe complication of systemic sclerosis. The first‐line treatment is intravenous iloprost, but it induces dose‐limiting adverse effects. Local administration of ...treprostinil through skin iontophoresis may be a safe alternative. We conducted a 2‐stage, randomized, placebo‐controlled single‐ascending‐dose study in healthy volunteers and patients with systemic sclerosis‐related digital ulcer. We further explored the effect of the procedure on skin blood flux. In a first group of healthy subjects, treprostinil and placebo iontophoresis were performed at 3 locations (ie, 6 skin sites): the sole of the foot, the leg, and the fingers. We used a 1‐mg/mL hydrogel of treprostinil. We then randomly treated systemic sclerosis‐related digital ulcers in a 3:1 ratio of treprostinil or placebo. We used concentrations from 0.1 to 1 mg/mL. All adverse events were recorded and rated according to the Common Terminology Criteria for Adverse Events (CTCAE), whereas skin microvascular blood flux was recorded with laser speckle contrast imaging. Among the 12 healthy volunteers, we observed 60 local adverse effects: burns, skin pain, erythema, and pruritus, graded 1 or 2 on the 5‐point CTCAE scale. Treprostinil iontophoresis significantly increased skin blood flux on the leg (AUC0‐4 h at 88 460% ± 6436% versus 12 730% ± 3397% baseline flux.min respectively; P < .001) and on the sole of the foot (AUC0‐3 h at 20 124% ± 6119% versus 3142% ± 3036% baseline flux.min, respectively; P = .018) with a trend on the finger. Among 5 patients with systemic sclerosis‐related digital ulcer, 2 resolutive local adverse effects were reported. Iontophoresis of treprostinil hydrogel was safe in systemic sclerosis patients with digital ulcer.
Objectives
To propose a scale of severity for post-thrombotic venous lesions (PTVLs) after ilio-femoral deep venous thrombosis and to compare the grade with the results of endovascular treatment of ...ilio-femoral PTVLs.
Methods
In this retrospective monocentric observational study, we included 95 patients treated for ilio-femoral PTVLs. We proposed a four-grade scale evaluating the severity of PTVLS caudal to the common femoral vein based on CT phlebography and per-operative phlebography. For most patients, venous patency was assessed with color duplex ultrasonography and the clinical efficacy of the intervention using the Villalta and CIVIQ scores.
Results
Recanalization was successful in 100% of patients with a morbidity rate of 4%. After a mean follow-up of 21 months, the overall primary patency was 75%, the assisted primary patency 82%, and the secondary patency 93%. Secondary patency was 100% for grade 0–1, 90% for grade 2, and 63% for grade 3 (
p
< 0.002). There was no correlation between the extension of stenting caudally of the common femoral vein and venous patency. The mean improvements in the Villalta and CIVIQ-20 scores were, respectively, 4.6 (
p
< 0.0001) and 18 (
p
< 0.0001); scores were not correlated with the grade of PTVLs in the thigh.
Conclusion
Venous patency after endovascular treatment of ilio-femoral PTVLs was strongly linked to the severity of PTVLs caudal to the common femoral vein but not to the extent of stenting.
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