Correlation of nailfold capillaroscopy findings with history of digital ulcer on same finger: Results of SCLEROCAP study.

Systemic sclerosis may be complicated by digital ulcers. Nailfold capillaroscopy on one finger might reflect an increased risk of digital ulcer (DU). In the present study we studied the correlations between a history of ulcer and capillary findings on the finger. METHOD: This study is part of Sclerocap, a multicenter study aiming at validating prospectively the prognostic value of Maricq's and Cutolo's capillaroscopic classifications during a three-year longitudinal follow-up. A history of past or present digital ulcer was recorded at inclusion and nailfold capillaroscopy was performed. Elementary findings as well as Cutolo and Maricq's classifications were assessed. RESULTS: 387 patients were included in Sclerocap (327 females, 60 males) and 3096 fingers were examined by capillaroscopy at inclusion: 316 fingers (10%) belonging to 113 patients had a history of DU. Late Cutolo's stage was statistically correlated with a history of DU, both by univariate: OR 2.08 [1.09-3.96] and multivariate analysis: OR 1.97 [1.06-3.63]. Among the elemental abnormalities, only edema and decreased capillary density were correlated with a history of DU by multivariate analysis: respectively OR 1.92 [1.17-3.16] and 0.65 [0.49-0.85]. CONCLUSION: This cross-sectional study in a large cohort of patients with systemic sclerosis shows a correlation between a history of digital ulcer and edema, a decrease in capillary density and the late stage in Cutolo's classification. The extent of capillary abnormalities on one finger is associated with a history of local digital ulcer. Capillaroscopy might be used to predict the risk of DU but these results need first to be confirmed by prospective studies.

Correlation between capillaroscopic classifications and severity in systemic sclerosis: results from SCLEROCAP study at inclusion.

OBJECTIVES: We assessed the correlation between severity of systemic sclerosis (SSc) and current staging systems based on nailfold capillaroscopy. METHODS: SCLEROCAP is a multicenter prospective study including consecutive scleroderma patients who have a yearly routine follow-up with capillaroscopy and digital blood pressure measurement. Capillaroscopy images were read by two observers blinded from each other, then by a third one in the case of discordance. A follow-up of 3 years is planned. The present study assessed the correlation between severity of systemic sclerosis (SSc) and current staging systems based on nail fold capillaroscopy at enrollment in the SCLEROCAP study. Univariate and multivariate logistic regression analysis was performed for both the Maricq and Cutolo classifications. RESULTS: SCLEROCAP included 387 patients in one year. Maricq's active and Cutolo's late classifications were very similar. In multivariate analysis, the number of digital ulcers (OR for 2 ulcers or more, respectively 2.023 [1.074-3.81] and 2.596 [1.434-4.699]) and Rodnan's skin score >15 (OR respectively 32.007 [6.457-158.658] and 18.390 [5.380-62.865]) correlated with Maricq's active and Cutolo's late stages. Haemoglobin rate correlated with Cutolo's late stage (hemoglobin<100 vs. >120 g/dl: OR 0.223 [0.051-0.980]), and total lung capacity with Maricq's active one: increase in 10%: OR0.833 [0.717-0.969]. CONCLUSIONS: The correlations found between capillaroscopy and severity of SSc are promising before the ongoing prospective study definitively assesses whether capillaroscopy staging predicts complications of SSc. Only two capillaroscopic patterns seem useful: one involving many giant capillaries and haemorrhages and the other with severe capillary loss.

Lower-limb Ulcers in Systemic Sclerosis: A Multicentre Retrospective Case-control Study.

Lower-limb ulcers in systemic sclerosis patients are rarely reported. The aim of this study was to describe the main causes and outcomes of lower-limb ulcers in systemic sclerosis patients and to assess factors associated with ischaemic causes (arterial disease and/or microvascular impairment). A retrospective, multicentre, case-control study was conducted in 2013 and 2014, including 45 systemic sclerosis patients presenting lower-limb ulcers between 2008 and 2013. The estimated prevalence of lower-limb ulcers among systemic sclerosis patients was 12.8%. Ulcers were related to venous insufficiency in 22 cases (49%), ischaemic causes in 21 (47%) and other causes in 2 (4%). Complete healing was observed in 60% of cases in a mean time of 10.3 months; 59% relapsed during a mean follow-up of 22 months. Ischaemic lower-limb ulcer outcomes were poor, with a 28.6% amputation rate. Logistic-regression multivariate analyses between ischaemic lower-limb ulcer cases and matched systemic sclerosis-controls identified past or concomitant digital ulcer and cutaneous sclerosis of the feet as independent risk factors associated with ischaemic lower-limb ulcers.

Reproducibility of capillaroscopic classifications of systemic sclerosis: results from the SCLEROCAP study.

Objectives: Subgroups of capillaroscopic scleroderma landscape have been correlated with stages of SSc: two groups for Maricq's classification (slow and active), and three for Cutolo's classification (early, active and late). We report inter- and intra-observer agreement for these classifications as a preliminary step in the multicentre prospective SCLEROCAP study, which aims to assess the classification and single capillaroscopic items as prognostic tools for SSc. Methods: SCLEROCAP included 385 patients. Agreement was studied in the first 100 patients, who were independently rated twice by two observers, blind to patients' characteristics; 30 of the patients were rated once by six observers. After consensus meetings, these ratings were held again. Kappa and intraclass correlation coefficients were used to assess agreement. Results: Interobserver agreement on 100 patients was moderate for Maricq and Cutolo classifications [κ 0.47 (0.28, 0.66) and 0.49 (0.33, 0.65), respectively], and became substantial after consensus meetings [0.64 (0.50, 0.77) and 0.69 (0.56, 0.81)]. Intra-observer agreement between two observers was moderate to substantial: κ 0.54 (0.33, 0.75) and 0.70 (0.57, 0.83) for Maricq's classification; 0.57 (0.38, 0.77) and 0.76 (0.65, 0.87) for Cutolo's. Thirty patients were rated once by each of six observers, and agreement was moderate to substantial: κ 0.57 ± 0.10 (Maricq) and 0.61 ± 0.12 (Cutolo). Agreement was substantial for bushy, giant capillaries and microhaemorrhages, moderate for capillary density and low for oedema, disorganization and avascular areas. Conclusion: The moderate reproducibility of Maricq and Cutolo classifications might hamper their prognostic value in SSc patients. Consensus meetings improve reliability, a prerequisite for better prognostic performances. A focus on giant capillaries, haemorrhages and capillary density might be more reliable.

Systemic sclerosis with normal or nonspecific nailfold capillaroscopy.

BACKGROUND: In systemic sclerosis (SSc), a specific nailfold videocapillaroscopy (NVC) pattern is observed in 90% of cases and seems to be associated with severity and progression of the disease. OBJECTIVE: To describe the characteristics of SSc patients with normal or nonspecific (normal/nonspecific) NVC. METHODS: In a retrospective cohort study, clinical features and visceral involvements of 25 SSc cases with normal/nonspecific NVC were compared to 63 SSc controls with the SSc-specific NVC pattern. RESULTS: Normal/nonspecific NVC versus SSc-specific NVC pattern was significantly associated with absence of skin sclerosis (32 vs. 6.3%, p = 0.004), absence of telangiectasia (47.8 vs. 17.3%, p = 0.006) and absence of sclerodactyly (60 vs. 25.4%, p = 0.002), and less frequent severe pulmonary involvement (26.3 vs. 58.2%, p = 0.017). CONCLUSION: Normal/nonspecific NVC in SSc patients appears to be associated with less severe skin involvement and less frequent severe pulmonary involvement.

Systemic sclerosis is associated with lower limb vascular stiffness and microvascular impairment: results from a prospective study.

OBJECTIVE: Systemic sclerosis (SSc) is a connective tissue disease characterized by microangiopathy. Peripheral arterial disease, increasingly studied during SSc, is responsible for digital ulcers, associated with a high risk of amputation. The aim of our study was to assess the frequency of lower limb arterial impairment in SSc patients by measuring ankle-brachial index (ABI), toe pressure (TP), and toe-brachial index (TBI). METHODS: Systemic sclerosis patients were included prospectively during 1 year in Tenon and Saint-Antoine Hospitals, Paris. Clinical and biological data were recorded. For each patient, ABI, TP, and TBI were measured and an arterial duplex ultrasonography was prescribed in case of abnormal results. RESULTS: Eighty-six patients were included (94% women, median age 62 years). Only 24% of them had no lower limb hemodynamic vascular abnormalities; 44% had an isolated microvascular abnormality (normal ABI and TBI<0.75); 31% had at least a macrovascular injury associated or not with microvascular impairment (abnormal ABI) and 12.6% had a TP<50 mmHg. During follow-up, there was a trend towards association of low TBI with more major adverse event (all-cause mortality, non-fatal stroke, non-fatal myocardial infarction, and lower limb ischemic manifestations) than normal TBI. CONCLUSION: By measuring ABI and TP, we showed that 76% of SSc patients had hemodynamic arterial lower limb abnormalities related to macro- and/or microvascular impairment and that 28% had vascular stiffness. In SSc patients, ABI is not an accurate tool to detect lower limb arterial disease, likely due to underlying micro- and macrovascular changes. Key Points • The presence of lower limb macro-and/or microvascular involvement was detected in 76% of SSc patients. • In SSc patients, ABI is not an accurate tool to detect lower limb arterial disease, likely due to underlying microvascular changes and frequent arterial stiffness.

Malignancy and chronic leg ulcers: the value of systematic wound biopsies: a prospective, multicenter, cross-sectional study.

OBJECTIVE: To determine the frequency of skin cancers associated with chronic leg ulcers (CLUs) presumably of vascular origin and failing to heal (ie, increased wound area or depth) despite 3 months or more of appropriate treatment. DESIGN: Prospective cross-sectional study. SETTING: Ambulatory or hospitalized patients from 17 dermatology departments. PATIENTS: Between January 1, 2006, and May 31, 2008, a total of 144 patients consulted for CLUs, attributed to venous and/or peripheral arterial disease(s), increasing in wound size, that is, larger area and/or depth, despite appropriate standard treatment for at least 3 months. MAIN OUTCOME MEASURES: At inclusion, at least two 6-mm punch biopsies, 1 at the wound edge and 1 in the wound bed, in the most clinically suspicious areas, were systematically performed. The primary end point was the skin cancer frequency diagnosed in at least 1 wound biopsy specimen obtained at inclusion. RESULTS: The 144 patients included had 154 CLUs. The overall skin cancer frequency in the CLUs was 10.4%: 9 squamous cell and 5 basal cell carcinomas, 1 melanoma, and 1 leiomyosarcoma; 56.3% had persisted for at least 3 years. Univariate analyses retained older age, abnormal excessive granulation tissue at wound edges, high clinical suspicion of cancer, and number of biopsies, but not wound area or duration, as being significantly associated with skin cancer in 1 or more biopsy specimens. CONCLUSIONS: The combined primary ulcerated cancer or malignant transformation frequency was sufficiently high in CLUs referred to tertiary care centers to consider systematic biopsy of a wound refractory to 3 months or more of appropriate treatment.

Cutaneous microvascular blood flow and reactivity in patients with homozygous sickle cell anaemia.

Homozygous sickle cell anaemia (SS disease) involves a high prevalence of skin ulcerations, and background experience concerning the cutaneous microcirculatory flux and reactivity in this disease is very limited. We investigated, by laser-Doppler velocimetry, the microcirculatory cutaneous blood flow and vasoreactivity in 17 patients with SS disease but no cutaneous trophic changes, vs. the corresponding values in 18 normal matched controls. The laser-Doppler probe was placed on the foot dorsum, and recordings were made in the supine and dependent positions, and after post-ischaemic hyperaemia. The venoarteriolar reflex was calculated as the difference between the fluxes in the supine and dependent positions. In both positions, patients with SS disease exhibited clear vasodilation, with larger cutaneous fluxes than those of the controls (P=0.024 and 0.0009, respectively). The venoarteriolar reflex, expressed as a percentage of the resting supine flux, was lower in the patients (P=0.0004). These impairments of the microcirculatory fluxes, which combine a vasodilated state with abnormal vasoreactivity, resemble those observed in patients with chronic venous insufficiency and might be crucial in determining the pathogenesis of the skin ulcerations that occur in SS disease. Laser-Doppler velocimetry seems a suitable non-invasive technique for investigating such cutaneous microangiopathy.