[Nail-fold capillaroscopy in dermatology]. / La capillaroscopie péri-unguéale en dermatologie.

Nail-fold capillaroscopy is a non-invasive tool to study the microcirculation and is increasingly being used in dermatology, angiology and rheumatology. More recently, the use of video-capillaroscopy has allowed computer storage of capillaroscopic images (video-capillaroscopy), enabling evaluation of changes in capillaroscopic abnormalities during the follow-up of patients with systemic sclerosis or mixed connective tissue disease. Qualitative and quantitative assessment of the nail-fold dermal capillaries and of their organization can readily distinguish between a normal capillaroscopic pattern in primary Raynaud phenomenon and a specific sclerodermic pattern in secondary Raynaud phenomenon carrying a very high risk of systemic sclerosis. Apart from its important role as a diagnostic tool for distinguishing between primary and secondary Raynaud phenomenon, capillaroscopy is now used to predict the risk of development of digital ulcers and of future visceral complications in patients with systemic sclerosis. Moreover, nail-fold capillaroscopy is essential for differential diagnosis between connective tissue diseases, for the etiologic diagnosis of digital necrosis and diffuse interstitial lung disease, and in sclerodermiform syndromes.

Measurement of the cutaneous blood flow reserve in normal humans by laser-Doppler flowmetry.

AIM: To assess the normality of the cutaneous blood flow reserve (CR). METHODS: To explore the feasibility and reproducibility of laser-Doppler flowmetry for CR measurement, we prospectively measured CR in 17 healthy subjects on the dorsum of the foot and pulp of the big toe. CR was defined as the sum of the venoarteriolar reflex (VAR), i.e. postural vasoconstriction, and postischemic reactive vasodilation (H), expressed as % of the resting supine flux and assessed by using laser-Doppler flowmetry. RESULTS: For the dorsal foot, VAR%+/-SEM was 61+/-14, H%, 752.5+/-214 and CR, 813.5+/-217. On the pulp of the big toe, VAR% was 61.6+/-4.7, H%, 588.2+/-174 and CR, 649.9+/-176. CR measurement variability was assessed by calculating the inter-individual coefficient of variation of CR, which was 1.1 for both the dorsal foot and pulp of the big toe. Reproducibility was assessed by calculating the CR intraclass correlation coefficient, which was 0.49 for the dorsal foot and 0.64 for the pulp of the big toe. CONCLUSIONS: The CR is proposed as a new parameter for assessing the microvascular integrity and contractile reserve of the skin. Laser-Doppler flowmetry is suitable for this non-invasive evaluation. The method displayed large variability, and its reproducibility varied from moderate for the dorsal foot, to substantial for the toe. Further studies are necessary to demonstrate its clinical usefulness.

Cutaneous microvascular effects of mid-term hormone replacement therapy in healthy postmenopausal women: a prospective placebo controlled trial.

OBJECTIVE: To study the mid-term effects of Hormone Replacement Therapy (HRT) on cutaneous microcirculatory blood flow and reactivity in healthy postmenopausal women. DESIGN: In a double-blind placebo controlled randomized study, 16 healthy postmenopausal women received either placebo or HRT (micronized estradiol: 1 mg/day, day 1-28, promegestrone: 0.25 mg/day, day 14-28). This regimen was completed 6 times. Cutaneous microcirculatory blood flow was recorded by laser-Doppler velocimetry on the foot dorsum, in the supine and then dependent positions, and after post-ischemic hyperemia. RESULTS: At day 0, the two groups were similar and none of the following data differed significantly between treated and placebo group: (supine flux: 11.8 +/- 1.8 u vs. 13.2 +/- 3.9, venoarteriolar reflex: 5.6 +/- 1.3 vs. 6 +/- 3.3, and post-ischemic hyperemia: 35.2 +/- 3.9 vs.48.3+/-11). At the end of the study (day 26-28 of 6th cycle), the supine flux was 9.8 +/- 2.1 in the HRT group vs.12.9 +/- 6 in the placebo group (NS), the venoarteriolar reflex, 1.2 +/- 2 vs. 7+/-1.7 (p=0.04), and post ischemic hyperemia, 31.8 +/- 5.4 vs. 39.5 +/- 4.6 (NS). Intragroup values did not change significantly for any of the microcirculatory parameters measured, which remained stable throughout the 6 months of the study. Intergroup values for these parameters did not change either, except for the venoarteriolar reflex, which was lower at the end of the study in the HRT (EP period, cycle 6 day 26-28) than placebo group (p=0.04). CONCLUSIONS: HRT does not impair the resting supine cutaneous microcirculation blood flow or post-ischemic hyperemia.

[Treatments of progressive systemic sclerosis]. / Evolution des traitements de fond de la sclérodermie.

Progressive Systemic Sclerosis (PSS) is still an incurable disease but there are treatments for it, and the list of proposed treatments is long. The methodology of trials concerning PSS is complex, due to the low prevalence of the disease and therefore its financial interest for pharmaceutical companies, the lack of simple end points for efficacy, and the large number of clinical expressions with various prognoses. These causes explain why most open studies are fiercely positive, and why controlled studies are so rare. The progress made during the last 10 years concern 1) the diagnosis, which is now made earlier due to capillaroscopy and antibody assays, especially of anticentromere antibodies, 2) better knowledge of the prognosis, due to the classification of PSS into limited and the diffuse forms which have different prognoses, and 3) the recognition of a serious complication of the disease, ie. pulmonary hypertension, which can now be detected by non-invasive methods. All these improvements will also improve the methodology of future trials of drugs for treating PSS. In this ocean of uncertainties, some treatments have a valid background, and 3 visceral locations of PSS can be efficiently treated: renal involvement, with angiotensin-converting enzyme inhibitors, respiratory involvement, with D-penicillamine, and pulmonary hypertension, with prostacyclin derivatives. Corticosteroids are suspected to increase the risk of renal complications. Calcium blockers are considered a useful symptomatic treatment of the associated Raynaud's phenomenon and of the risk of digital necrosis, and may also constitute a treatment of PSS itself. A recent trial conducted by the French Microcirculation Society and its acrosyndrome Study Group considered the effects of an oral derivative of prostacyclin. Beneficial effects were: a reduction of the risk of digital necroses, improved overall wellbeing, less necessity for hospitalizations, fewer giant capillaries, and a dramatic fall in the level of von-Willebrand factor.

[Cannabis and tobacco: cofactors favoring juvenile obliterative arteriopathy]. / Cannabis et tabac. Co-facteurs favorisant l'artériopathie oblitérante juvénile.

The causal effect of cannabis, associated or not with smoking, in juvenile thromboangiitis disorders such as Leo Buerger disease, has been suggested. We describe here a case of a 30-year-old woman who smoked cannabis and developed intermittent claudication of the lower limbs. Female sex and proximal localization of the lesions (external iliac artery) are not usually described in "cannabis arteritis". Cannabis would be involved not only in the pathogenesis of juvenile obstructive arteriopathy, but also in the development of atheromatous lesions in the young subject.

Leg ulcers and hydroxyurea: forty-one cases.

BACKGROUND: Hydroxyurea is an antitumor agent used to treat chronic myeloproliferative disorders. Leg ulcerations have been reported in patients undergoing long-term hydroxyurea therapy for myeloproliferative diseases. To better define this dermatological adverse effect of hydroxyurea therapy and to try to understand the pathophysiological process of this disease, we collected medical information for such patients in a multicenter retrospective study. OBSERVATIONS: Forty-one patients (mean age, 67 years) developed leg ulcerations while undergoing hydroxyurea therapy (mean therapy duration, 5 years). The sex ratio was 1, and there was no underlying vascular disease. Hematologic abnormalities were identified. Complete recovery from the ulcerations occurred quickly after withdrawal of treatment in 33 (80%) of the cases. CONCLUSIONS: This longest-reported series of patients confirms the role of hydroxyurea therapy in the onset of leg ulcerations. Healing or improvement requires cessation of treatment. Cutaneous atrophy and impaired wound healing may explain the relationship between hydroxyurea and leg ulcers. In addition, the megaloblastic erythrocytes resulting from the presence of hydroxyurea may circulate poorly through the capillary network. A prospective study in hematologic centers would be valuable.

Clinical significance of subcutaneous calcinosis in patients with systemic sclerosis. Does diltiazem induce its regression?

OBJECTIVE: To establish whether diltiazem reduces subcutaneous calcinosis (SCC) in patients with systemic sclerosis (SSc), and whether this calcinosis is related to other signs or symptoms. METHODS: 47 patients with SSc were evaluated and divided into two groups according to the presence or absence of SCC. RESULTS: Among the 12 patients with SCC who were treated with diltiazem and had sequential hand radiographs (differential time between the two radiographs: 7.8+/-4 years), there was a slight radiological improvement in three patients only. More patients with SCC had anticentromere antibodies than patients without (p = 0.003), fewer had anti-Scl 70 antibodies (p = 0.01), more had telangiectasia and giant capillaries ( p + 0.04 and 0.048 respectively), and SCC patients had significantly fewer capillaries at the nailfold (p = 0.03). CONCLUSION: These results do not clearly indicate that diltiazem is effective in calcinosis associated with SSc. Among the patients with SSc, those who also had SCC exhibited a distinctive autoimmune profile and more severe cutaneous capillary injury than those without SCC.

Importance of cutaneous postural reflex vasoconstriction in patients with atherosclerotic occlusive disease of the lower extremities.

OBJECTIVE: The present study was designed to measure the cutaneous postural vasoconstrictive reflex (PVR) in normal controls and patients with atherosclerotic occlusive disease of the lower extremities, and to determine its diagnostic and prognostic relevance. EXPERIMENTAL DESIGN: The postural vasoconstrictive reflex was recorded in 34 patients with atherosclerotic occlusive disease of the lower limbs and 27 normal controls, using laser-Doppler flowmetry. Patients also had ankle and toe pressure measurements and transcutaneous oximetry (TcPO2). SETTING: University hospital. RESULTS: The PVR on the pulp of the big toe was 20+/-7 arbitrary perfusion units in normal controls, 9.4+/-12 in patients with claudication, and -19 +/- 5 in patients with rest pain and/or gangrene, who differed from the claudicant and control groups (p=0.001 and 0.0001 respectively). The sensitivity of negative PVR in the big toe was 89% for the diagnosis of rest pain and/or gangrene, and its specificity, 83%. The severity of foot ischaemia and PVR values exhibited a significant inverse correlation (r=-0.56, p<0.0001). All patients with a poor outcome, ie. death and/or major amputation within 100 days of follow-up, had a negative PVR, and all patients with a positive PVR had a good 100-day prognosis without even a minor amputation. CONCLUSIONS: Laser-Doppler provides useful additional information in the assessment of foot ischaemia severity by showing that postural vasoconstriction is impaired in patients with severe atherosclerotic occlusive disease of the lower limbs, resulting in increased skin microcirculatory flow during leg dependency.

Abnormal IgG cardiolipin antibody titers in patients with Raynaud's phenomenon and/or related disorders: prevalence and clinical significance.

BACKGROUND: The prevalence of antibodies to cardiolipin (a-CL) in patients with Raynaud's phenomenon (RP) and/or related disorders (rD) is not known. OBJECTIVE: The purpose of this study was to determine the prevalence of these antibodies. METHODS: We assayed IgG a-CL in 230 consecutive patients with RP/rD and compared the results with those in a series of 230 control blood donors. RESULTS: Sixteen percent of patients were a-CL positive versus 7.8% of the control donors (p = 0.014). The prevalence of a-CL positivity was 8.7% for primary RP, 10.5% for secondary RP, 8% for chilblains, 25% for essential acrocyanosis, 20% for connective tissue diseases, and 17% for undifferentiated connective tissue diseases. Among patients with digital necrosis, 24% were a-CL positive. CONCLUSION: The prevalence of abnormal a-CL titers is higher in patients with RP/rD than in control donors, especially in patients with a connective tissue disease.

Haemodynamics of patients with severe lower limb arterial disease: the critical aspects of critical ischaemia.

OBJECTIVES: To compare the value of ankle and toe pressures as regards the diagnosis of critical ischaemia, its prognosis, and the need for vascular surgery. DESIGN: University hospital-based retrospective study. MATERIALS AND METHODS: Fifty-seven patients (23 women and 34 men) with gangrene or rest pain had a haemodynamic evaluation combining ankle systolic pressure, toe pressure and cutaneous oximetry (tcPO2) with long-term follow-up (until death, for 44%). RESULTS: After 2 years of follow-up, actuarial rates were 49 and 79% for survival and limb salvage, respectively. Ankle and toe pressures gave rise to different subsets of patients, p < 0.001, mainly because of the existence of a group of patients with very distal foot arterial disease. Low ankle pressure was linked to the risk of major amputation. Low toe pressure was linked to a great need for vascular surgery. Diabetes increased the risk of minor amputation. CONCLUSIONS: The concept of critical ischaemia remains clinically relevant. Haemodynamic quantitative data strengthen this concept, but ankle and toe pressures are not interchangeable parameters. For these reasons, toe pressures should be changed from a recommended to a mandatory haemodynamic parameter in the definition of critical ischaemia.

Nailfold capillary microscopy in patients with anticardiolipin antibodies: a case-control study.

BACKGROUND AND DESIGN: This case-control study was undertaken to determine whether anticardiolipin antibodies (ACA) are responsible for particular abnormalities in nailfold capillary microscopy (NCM). Cases comprised 33 consecutive patients positive for ACA (24 women and 7 men). Controls comprised the same number of ACA-negative patients, with the same sex ratio, the same diagnosis and the most similar duration of disease possible. Clinical data, serum samples and NCM recordings were obtained from all patients and controls. RESULTS: In each group, 22 patients had connective-tissue-related disorders and 11 various other diseases. In ACA-positive patients, the mean IgG ACA titre was 39 +/- 58 IgG phospholipid units. Cases and controls displayed various cutaneous manifestations. In ACA-positive patients, there were Raynaud's phenomenon (54%), cutaneous vasculitis (24%), scleroderma changes (18%), photosensitivity (9%), a history of digital gangrene (6%), malar rash (6%), acrocyanosis (6%), chilblains (3%), livedo reticularis (3%) and purpura (3%). Cases and controls exhibited numerous NCM abnormalities. In ACA-positive patients, they included haemorrhages (54%), oedema (24%), bushy capillaries (21%), disordered capillaries (18%), capillary bed disorganization (12%), capillary rarefaction (9%), giant capillaries (6%) and 'desert areas' (3%). There were no correlations between the ACA titres on the one hand and the number of cutaneous manifestations or NCM abnormalities on the other. CONCLUSIONS: ACA-positive patients frequently exhibit clinical skin lesions and abnormal NCM. In this study, these lesions and NCM abnormalities resembled those of the matched ACA-negative controls.

Raynaud's phenomenon together with antinuclear antibodies: a common subset of incomplete connective tissue disease.

BACKGROUND: The frequency of incomplete connective tissue disease (ICTD) is unknown. OBJECTIVE: Our purpose was to determine the frequency of Raynaud's phenomenon (RP) and antinuclear antibodies (ANA) in patients without definite connective tissue disease. METHODS: A series of 165 consecutive patients with RP was investigated. RESULTS: Fifty-one patients had primary RP; 60 had secondary RP; 54 patients were classified as having ICTD, 35 of whom had ANA and 19 of whom did not. Of the 35 patients who had ICTD with ANA, 29 were women and six were men. Their clinical findings were as follows: 17 had nonerosive arthritis, 14 had a nailfold capillary scleroderma pattern, 12 had puffy fingers, 10 had anticentromere antibodies, nine had sicca syndrome, seven had pernio, seven had esophagitis, six had fingertip ulceration, five had telangiectasia, four had malar eruption, four had myalgia, four had weight loss, four had exertional dyspnea, and three had photo-sensitivity. No patient exhibited life-threatening visceral complications or antitopoisomerase antibodies. CONCLUSION: In this series ICTD was more frequent than definite connective tissue disease. Many patients with RP have ICTD that is sometimes chronic.

[Leg volumetry: a precise method for quantification in phlebology]. / La volumétrie: une méthode précise de quantification en phlébologie.

UNLABELLED: Chronic venous insufficiency is usually quantified by venous pressure measurement, which is an invasive method. Air plethysmography has also been used, but it is expensive, time consuming and only suitable for sophisticated research laboratories. Leg volumetry might be suitable for routine use, as it is simple, inexpensive, fast, non invasive and can be performed by non medical personnel. Here, we only evaluated its practicability, accuracy and reproducibility. PATIENTS: The study group included 28 legs of 14 healthy volunteers, and 22 legs of 11 patients suffering from varicose veins. METHOD: The device used was a plexiglass boot, 50 cm high, 20 cm wide. It was filled with water at 24 +/- 2 degrees C. The leg was immersed and the volume of water displaced recorded. RESULTS: Normal legs displaced a volume of 2,449 +/- 153 ml (mean +/- SD), range: 2,080-2,720, and variability 6.2%. Patients' legs displaced a volume of 2,576 +/- 290, range: 2,110-3,120, (p = 0.05 vs normals) and variability 11.2%. Accuracy was 0.7%, as from 2 consecutive measurements of the same patients' legs by 2 different observers. Intra-individual variability was 1.3%, as recorded in 12 repeated measurements of the same leg on different mornings. In normal legs, the difference between morning and evening volumes was statistically significant (18 +/- 15 ml, p = 0.0001), a finding consistent with the deterioration of the venous function in normal extremities during daily activities. CONCLUSION: This simple, cheap, objective, non-invasive reproducible and accurate method of leg volume measurement might be useful in routine practice for chronic venous insufficiency quantification.

[Distal arteritis of the legs: lumbar sympathectomy]. / Artérite distale des membres inférieurs: sympathectomie lombaire.

Among atheromatous occlusive arterial disease of the lower limbs, chronic sub-popliteal arterial occlusions refer an heterogenous group of patients. In this medical condition, lumbar sympathectomy constitutes a classical possible treatment. Actually, the beneficial effect of sympathectomy has never been confirmed by controlled randomised trials. In this particular and uncomfortable situation, it is only possible to list non indications for sympathectomy: asymptomatic patient, claudication, critical ischemia, limb salvage, and combination with vascular surgery. Lumbar sympathectomy deserves a controlled evaluation in patients with a small foot ischemic ulceration without hemodynamic critical ischemia i.e. systolic toe pressure > 30 mm Hg and/or ankle systolic pressure > 50 mm Hg.

Long-term follow-up study of 164 patients with definite systemic sclerosis: classification considerations.

To evaluate the usefulness of recently proposed schemes of classification for systemic sclerosis an extensive cross-sectional study of a series of 164 consecutive patients with long-term systemic sclerosis was undertaken. There were 47 cases of proximal sclerosis, 93 of distal sclerosis and 24 of complete CREST syndrome. The study included clinical, visceral, immunological and follow-up data. In addition, a quantitative clinical score was calculated for each patient, thus providing indications for prognosis. Data were expressed according to three conventional systems of classification: The ARA system, the diffuse versus limited systemic sclerosis system and the early cutaneous involvement system. The most reliable indications of severe outcome were: proximal sclerosis, trunk skin involvement, presence of anti Scl 70 autoantibody, pulmonary and/or heart involvement and age. Diagnosis and prognosis were not generated by the same items. Prognosis indicators proved more accurate for groups than for individuals. Mortality was 1 death per 149 patient X years of follow-up from diagnosis. We conclude that the ARA criteria for classification should be recognized as a standard, but patients with complete CREST syndrome should be included in the distal group. Other systems of classification, principally 2-way versus 3-way criteria, allow different subsets of patients that correlate with prognosis and the severity of the disease, and could be used for therapeutic purposes.

Clinical correlations and prognosis based on hyaluronic acid serum levels in patients with progressive systemic sclerosis.

The serum levels of hyaluronic acid (sHA) were measured using an affinoimmunoenzymatic assay in patients with distal (n = 16) and proximal (n = 15) progressive systemic sclerosis (PSS) and in 31 controls. The severity of PSS was evaluated using a standardized organ-involvement score. The mean sHA was significantly higher in the patients with PSS than in controls (mean +/- SD:80 +/- 43.4 micrograms/l vs. 42.3 +/- 19.1 micrograms/l, P less than 0.001). sHA was significantly higher in patients with proximal PSS than in patients with distal PSS (106.4 +/- 44.6 micrograms/l vs. 55.4 +/- 23.8 micrograms/l, P less than 0.001). A positive correlation was found between sHA and the disease score (r = 0.67, P less than 0.001). sHA was also correlated with lung diffusion capacity for carbon monoxide (r = 0.70, P less than 0.001), but only in the those patients who had abnormal lung function, and therefore presumably had lung PSS involvement. We suggest that sHA could be an indicator of the degree of systemic involvement in PSS. Its prognostic value and possible use in the follow up of patients with PSS remain to be clarified.