F. Ravera

Timing of transition between capillaroscopic patterns in systemic sclerosis.

OBJECTIVE To investigate the timing of transition through different patterns of nailfold microvascular damage in patients with systemic sclerosis (SSc). METHODS In this medium-term longitudinal study, 38 SSc patients (median disease duration 12 months) with the early scleroderma pattern of microangiopathy seen on baseline nailfold videocapillaroscopy (NVC) were followed up by NVC for a median of 84 months. The evolution of the NVC pattern over time was monitored and recorded. RESULTS At the end of followup, the NVC pattern was still that of early scleroderma in 47% of the patients. The active scleroderma pattern was seen in 34%, the late scleroderma pattern in 13%, and a normal pattern in 5%. The mean± SD time of progression from the early to the active pattern and from the early to the late pattern was of 28 ± 20 months and 36± 29 months, respectively. In the subgroup of patients whose microangiopathy progressed from the early to the late NVC pattern, the time of progression from the early to the active pattern was only 8± 1 months (P = 0.01), demonstrating that there is a subset of patients with rapid progression of microangiopathy. Clinical symptoms progressed in accordance with the nailfold morphologic changes in 60% of the SSc patients. CONCLUSION The results of this longitudinal study demonstrate dynamic transition of microvascular damage through different NVC patterns of microangiopathy in ∼50% of SSc patients. It is recommended that patients exhibiting rapid progression from the early to the active NVC pattern (<1 year) should be monitored closely, since the evidence suggests that they are at risk of rapid progression to the advanced (late) NVC pattern of microangiopathy that is associated with further clinical manifestations of SSc.

Longterm treatment with endothelin receptor antagonist bosentan and iloprost improves fingertip blood perfusion in systemic sclerosis.

Objective. To evaluate the longterm effects of endothelin-1 (ET-1) antagonism on peripheral blood perfusion (PBP) in patients with systemic sclerosis (SSc). Methods. Twenty-six patients with SSc already receiving cyclic intravenous iloprost (ILO) for severe Raynaud phenomenon were enrolled. Thirteen patients continued the treatment for a further 3 years (ILO group) and 13 patients, because of the appearance of digital ulcers, received in addition bosentan (BOS; 125 mg twice/day) for 3 years (ILO + BOS group). Both PBP at fingertips and nailfold microangiopathy were evaluated yearly by laser Doppler flowmetry and nailfold videocapillaroscopy, respectively. Results. A progressive significant increase of PBP was observed in the ILO + BOS group during the 3 followup years (p = 0.0007, p = 0.0002, p = 0.01, respectively). In contrast, an insignificant progressive decrease of PBP was observed in the ILO group. Difference of perfusion between the PBP evaluations at basal temperature and at 36°C (to test capillary dilation capacity), was found progressively decreased during the 3-year followup only in the ILO group (p = 0.05, p = 0.26, p = 0.09, respectively). A progressive increase of nailfold capillary number was observed only in the ILO + BOS group after 2 and 3 years of followup (p = 0.05). Conclusion. Longterm treatment of SSc patients with ET-1 antagonism, in combination with ILO, seems to increase fingertip blood perfusion, as well as both capillary dilation capacity and number.

Prospective capillaroscopy-based study on transition from primary to secondary Raynaud’s phenomenon: preliminary results

The objective of this prospective study was to investigate the transition from primary (PRP) to secondary (SRP) Raynauds phenomenon (RP), in a large cohort of patients affected by isolated RP. A total of 2065 patients with RP were investigated by clinical interview, laboratory examinations, and nailfold videocapillaroscopy (NVC). Patients with negative NVC at first visit were yearly followed to monitor either the appearance of specific morphological alterations at NVC, or clinical manifestations of an underlying disease. Capillary abnormalities at NVC were scored, as well as the qualitative patterns of microangiopathy (Early, Active and Late). NVC was found negative at first visit in 1500 subjects; among them, 412 patients were evaluable and they were followed for a mean time of 5±4 years (range 2-13 years). Sixty-eight patients (16%) achieved a diagnosis of SRP during follow-up, showing normal or not specific capillary alterations at NVC 4% of patients (the diagnosis was undifferentiated connective tissue diseases), Early scleroderma-pattern 57%, Active scleroderma-pattern 7%, Late scleroderma-pattern 12%, and scleroderma-like pattern 18% of patients. The time of transition from normal/not specific capillary alterations to Early scleroderma-pattern was 4.4±3.8 years. Enlarged capillaries (diameter between 20 and 50 microns) and mild reduction of capillary density were found the more frequent markers at first NVC visit in patients who progressed to a scleroderma pattern (P=0.01). This study demonstrates in a large cohort, that almost 16% of patients initially diagnosed as affected by RP with negative NVC may transit to SRP during a mean follow-up of 4.4 years. PRP patients showing major notspecific alterations of nailfold capillaries at first NVC should be strictly monitored at least once a year since at higher risk of transition to SRP.

Coexistence of osteopoikilosis with seronegative spondyloarthritis and Raynaud's phenomenon: first case report with evaluation of the nailfold capillary bed and literature review.

Osteopoikilosis (OPK) is a rare autosomal dominant bone disorder characterized by numerous hyperostotic areas that tend to localize in periarticular osseous regions. It is usually asymptomatic and is often diagnosed incidentally during X-rays. OPK may be an isolated finding or associated with other pathologies, e.g. skin manifestations, rheumatic and/or skeletal disorders. We report a literature review and, for the first time, the coexistence of OPK with seronegative spondyloarthritis and Raynauds phenomenon in a 48-year old female. To the best of our knowledge, this is the first case of OPK studied by videocapillaroscopy, demonstrating the absence of specific microvascular abnormalities of nailfold capillaries.

AB0194 Peripheral Blood Perfusion as Evaluated by Laser Speckle Contrast Analysis in Different Areas of Hands in Primary Raynaud's Phenomenon and Healthy Subjects

Background Laser speckle contrast analysis (LASCA) is a technique to assess blood perfusion in different body areas (1-2). Objectives To investigate peripheral blood perfusion (BP) by LASCA in different areas of hands in primary Raynauds phenomenon (PRP) patients and healthy subjects (CNT), looking for differences between the groups. Methods 31 PRP patients (LeRoy criteria) (3) (mean age 48±18 years, mean Raynaud duration 6±2 years) and 51 CNT (mean age 51±16 years) were enrolled, after informed consent. BP was bilaterally assessed by LASCA at the level of fingertips, periungual areas, dorsal and palmar surface of proximal phalanges, dorsum and palm of both hands, and the BP was calculated as perfusion units (PU) (1,2). All subjects stayed in a room at constant temperature (23°C) for 20 minutes before the analysis. PRP subjects discontinued treatment with oral vasodilators, if present, at least seven days before the examination. Statistical analysis was carried out by non parametric tests. Results PRP patients showed a statistically significant lower BP than CNT at the level of fingertips (median 86 and 181 PU, respectively, p<0.0001), periungual (median 75 and 142 PU, respectively, p<0.0001), palmar aspect of proximal phalanges (median 71 and 129 PU, respectively, p<0.0001), and palm areas (median 61 and 108 PU, respectively, p<0.0001). On the contrary, the two groups displayed similar BP values at the level of the other areas of hands (dorsum and dorsal phalanges). The gradients of BP fingertip-phalanx-palm and periungual-phalanx-dorsum were significantly lower in PRP patients when compared with CNT (p<0.0001). Conclusions This study demonstrates that blood perfusion is reduced only in selected areas of the hands (where microcirculation is prevalent), sparing dorsal surface of phalanges and dorsum of hands (where macrocirculation is predominant). Therefore, present results are in agreement with the fact that macrocirculation is usually not involved in PRP (4). References Ruaro B, et al. Ann Rheum Dis 2014;73:1181-5. Sulli A, et al. Ann Rheum Dis 2014;73:2059-61. LeRoy EC, et al. Clin Exp Rheumatol.1992;10:485-8. Cutolo M et al. Nat Rev Rheumatol. 2010;6:578-87. Disclosure of Interest None declared

SAT0177 Primary Raynaud's Phenomenon and Nailfold Videocapillaroscopy: Age-Related Changes in Capillary Morphology

Background Primary Raynauds phenomenon (PRP) represents a benign condition observed in healthy subjects. It is usually due to an exaggerated response to the physiological cold-induced vasospasm [1]. Objectives To detect by nailfold videocapillaroscopy (NVC) the presence of age-related capillary morphological patterns in a large cohort of subjects with PRP. Methods 877 subjects affected by PRP (median age 44 years; median disease duration 3 years) performed NVC during their normal clinical screenings and they were divided into three groups (age<35 years, 305 patients; 35< age<55 years, 318 patients; age>55 years, 254 patients). Two fields (3 mm) per finger of both hands were analyzed in the central area of the nailfold, and the qualitative score for several capillaroscopic parameters, usually observed in PRP patients, was evaluated (i.e. number of apical ectasias, irregular ectasias, efferent branch ectasias, microhaemorrhages, tortuosity, as well as subpapillary venous plexus visibility) [2]. The statistical analysis was performed by non-parametric tests. Results Patients with irregular ectasias, as well as patients with efferent branch ectasias, seem significantly younger than those without (median age 40 vs 48 years, and 36 vs 47, p<0.0001). In particular, irregular ectasias are present in 40% of patients with age<35 years, 37% 3555 years (p<0.0001); efferent branch ectasias are present in 49% of patients with age<35 years, 31% 3555 years (p<0.0001). Furthermore, patients with efferent branch ectasias have a longer disease duration than those without (median 4 vs 3 years, p=0.03). The presence of irregular and efferent branch ectasias would seem to exclude the presence of apical ectasias, in fact 99% of subjects with irregular ectasias do not show apical ectasias, and 87% of subjects with efferent branch ectasias do not show apical ectasias (p<0.0001). Moreover, 78% of patients with efferent branch ectasias show even irregular ectasias (p<0.0001). Patients with microhaemorrhages are significantly younger than those without (median age 42 vs 45 years, p=0.05), and 80% of patients without microhaemorrhages even do not show irregular and efferent branch ectasias (p<0.0001). The subpapillary venous plexus seems more easily visible in subjects with age<35, as well as in those with age>55 years (p<0.0001). A statistically significant negative correlation was found between apical and irregular ectasias (p<0.0001), apical ectasias and efferent branch ectasias (p=0.02), apical ectasias and tortuosity (p=0.0005), microhaemorrhages and tortuosity (p<0.0001), efferent branch ectasias and tortuosity (p=0.02). Finally, a statistically significant positive correlation was found between irregular and efferent branch ectasias (p<0.0001), irregular ectasias and microhaemorrhages (p<0.0001), efferent branch ectasias and microhaemorrhages (p<0.0001). Conclusions Aspecific abnormalities in nailfold microvasculature could be present in subjects with PRP with a different age distribution. The possible relationship with younger age and local trauma/damage, and/or as related to hypoxic conditions linked to the intensity/duration of the PRP are under further investigation. References LeRoy EC, Clin Exp Rheumatol 1992;10:485-8. Smith V,Pizzorni C. In Atlas of Capillaroscopy in Rheumatic Diseases. M. Cutolo Ed, Elsevier 2010. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3539

FRI0480 Laser Speckle Contrast Analysis Assessment of Blood Perfusion in Several Skin Areas of Systemic Sclerosis Patients Looking for Correlations with Nailfold Microangiopathy Extent

Background In systemic sclerosis (SSc), blood perfusion (BP) may be evaluated by laser speckle contrast analysis (LASCA), as well as nailfold microangiopathy may be assessed by nailfold videocapillaroscopy (NVC) (1-3). Objectives To investigate BP by LASCA in different skin areas of SSc patients, looking for possible correlations with the extent of the nailfold microvascular damage. Methods Seventy SSc patients (mean age 62±14 years, mean disease duration 7±5 years) and 70 sex and age matched healthy subjects (CNT) were enrolled during their regular clinical follow-up. After informed consent, BP was assessed by LASCA at the level of face and dorsal and palmar regions of the hands in both SSc patients and CNT. Afterward, different regions of interest (ROIs) were created at the level of the hands (fingertips, periungual areas, dorsum and palm of both hands), as well as of the face (forehead, tip of nose, zygomas and perioral regions), and the average BP evaluated as perfusion units (PU) (1). NVC was performed to detect the proper pattern of nailfold microangiopathy (“early”, “active” or “late”) and to calculate the microangiopathy evolution score (MES) (2-4). Statistical analysis was carried out by non parametric tests. Results SSc patients showed a statistically significant lower median BP than CNT at the level of fingertips (median 86 and 189 PU, respectively, p<0.0001), periungual (69 and 140 PU, respectively, p<0.0001) and palm areas (78 and 111 PU, respectively, p<0.0001). On the contrary, both groups displayed similar BP values at the level of dorsum of hands, whole face, as well as at different ROIs of the face. The median BP difference between fingertips and palm was lower in SSc patients than in CNT (11 and 67 PU, respectively, p<0.0001), as it was the gradient between the dorsum and periungual areas (25 and 69 PU, respectively, p=0.0009). A significant progressive decrease of BP was observed at the level of fingertips (median 103, 86 and 80 PU, respectively, p=0.004), periungual (median 86, 65, and 57 PU, respectively, p=0.007) and palm areas (median 92, 82, and 67 PU, respectively, p=0.02) in SSc patients in relation to the progressive pattern of nailfold microangiopathy (“early”, “active”, and “late”), as well a statistically significant negative correlation between BP and MES in the same areas was detected (r=0.49, p<0.0001, (r=0.30, p=0.01, and r=0.35, p=0,003, respectively). Conclusions As assessed by LASCA technique, BP is significantly lower in SSc patients in comparison with healthy subjects at the level of fingertips, periungual areas, and palm of hands, and a statistically significant negative correlation exists between nailfold microangiopathy extent and BP at the level of the same skin areas in SSc patients. Both combined investigations might optimize the follow-up of SSc patients. References Ruaro B, et al. Ann Rheum Dis 2013; Aug 16, [Epub ahead of print]. Cutolo M, et al. Rheumatology 2004;43:719-26. Sulli A, et al. Arthritis Rheum. 2012;64:821-5. Sulli A, et al. Ann Rheum Dis. 2008;67:885-7. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5922

FRI0391 Evaluation of peripheral blood perfusion by laser speckle contrast analysis in systemic sclerosis patients: comparison with laser doppler flowmetry.

Background Systemic sclerosis (SSc) is characterized by early impairment of the microvascular system and decrease in peripheral blood perfusion (PBP) (1,2). Objectives The aim of this study was to asses PBP by new technique laser speckle contrast analysis (LASCA) in SSc patients with different patterns of nailfold microangiopathy, checking for any correlations between LASCA and laser Doppler flowmetry (LDF) techniques (1-3). Methods Sixty-one SSc patients and 61 sex and age-matched healthy subjects were enrolled, after informed consent was signed. PBP was analysed by LASCA in both SSc patients and healthy subjects, by creating eight regions of interest (ROI) at the fingertips of the 2nd-5th finger bilaterally, after a 30 second recording of whole hand: the average perfusion was scored as perfusion units (PU). PBP was measured also by LDF at the central area of the fingertips, through a 30 second recording for each fingertip (2). Peripheral microangiopathy was detected and scored by nailfold videocapillaroscopy (NVC), assessing the proper pattern of microvascular damage (Early, Active, or Late), calculating the microangiopathy evolution score (MES) (4-6). Patients enrolled into the study were not taking vasoactive drugs. Non-parametric tests were used for the statistical analysis. Results PBP was significantly lower in SSc patients than in healthy subjects, as evaluated by both LASCA (median 85 and 187 PU, respectively; p<0.0001) and LDF techniques (median 71 and 185 PU, respectively; p<0.0001). PBP was progressively lower in SSc patients with an “Early”, “Active” or “Late” NVC pattern, as evaluated by both LASCA (median 90, 84 and 78 PU, respectively; p=0.04) and LDF techniques (median 86, 75 and 63 PU, respectively; p=0.002). A negative correlation was found between MES and PBP values, as evaluated by both LASCA (p=0.006) and LDF (p=0.002) methods. A strong positive correlation was found between LASCA and LDF in the evaluation of PBP values, in healthy subjects and in SSc patients (p<0.0001). Intra-operator reproducibility was 95% for LASCA and 87% for LDF assessment. Conclusions As evaluated by LASCA, PBP was found lower in SSc patients than in healthy subjects, and was found progressively lower in SSc patients with worsening pattern of nailfold microangiopathy. There was a significant positive correlation between LASCA and LDF in the assessment of PBP. However, LASCA is less time consuming than LDF and shows lower intra-operator variability. References Cutolo M, et al. Nat Rev Rheumatol 2010; 6, 578-87. Cutolo M, et al. J Rheumatol 2010; 37:1174-80. Draijer M et al. Laser Med Sci 2009; 24: 639-51. Sulli A, et al Arthritis Rheum. 2012; 64: 821-5. Sulli A, et al. Ann Rheum Dis 2008; 67:885-7. Smith V, et al. Ann Rheum Dis 2010; 69:1092-6. Disclosure of Interest: None Declared

AB0486 High frequency ultrasound and laser doppler flowmetry for the evaluation of digital dermal thickness and fingertip blood perfusion in systemic sclerosis patients

Background Modified Rodnan skin score (mRss) and high frequency ultrasound (US) are employed to evaluate dermal thickness (DT) in systemic sclerosis (SSc) patients (1-3). Laser Doppler flowmetry (LDF) is used to assess and measure the peripheral blood perfusion (4). Objectives The aim of this study was to identify possible correlations between finger dermal thickness (DT) using both US and mRss, and fingertip blood perfusion (FBP) in SSc patients. Methods Forty-nine consecutive SSc patients and 37 healthy subjects (CNT) were enrolled, after informed consent. US was performed in both SSc patients and CNT to evaluate DT (ultrasound-DT) at the level of the dorsum of the middle phalanx of the third finger on both right and left hand, and the average value was recorded in millimetres. After double blind evaluation of US pictures, the intra-operator reproducibility in measuring DT was found of 95%. DT was also assessed by mRss in SSc patients at the level of the dorsum of the fingers bilaterally, and the average score of the fingers was calculated. LDF was performed in both SSc patients and CNT. FBP was detected at the level of the fingertips bilaterally, and the results were expressed as perfusion units (PU). The same operator (BR) performed the examination, and there was a 88% reproducibility of the LDF assessment. Statistical analysis was carried out by non parametric tests. Results SSc patients showed higher ultrasound-DT as well as lower FBP at the level of the fingers, than healthy subjects (p<0.0001). A negative correlation was observed between FBP and both ultrasound-DT (r=-0.36, p=0.02) and mRss values (r=-0.41, p=0.002). A positive statistically significant correlation was observed between left and right finger ultrasound-DT (r=0.68, p<0.0001), as well as between ultrasound-DT and mRss (r=0.55, p<0.0001). Conclusions A significant negative correlation between finger DT, evaluated by either US or mRss, and FBP, evaluated by LDF, is detectable with reliability in SSc patients. References Clements PJ, et al. J Rheumatol 1993; 20: 1892-6. Moore TL, et al. Rheumatology 2003; 42: 1559-63. Kaloudi O et al. Ann Rheum Dis. 2010; 69:1140-3. Cutolo M, et al. J Rheumatol 2010; 37:1174-80. Disclosure of Interest None Declared

AB0488 Nailfold videocapillaroscopy and laser speckle contrast analysis: in search of a correlation between microvascular damage and blood perfusion.

Background Microvascular impairment and decreased peripheral blood perfusion are typical aspects of systemic sclerosis (SSc) (1,2). It is not clear if there is a correlation between nailfold microangiopathy and blood perfusion (BP) in different skin areas of the body in SSc patients. Objectives The aim of this study was to identify, in SSc patients, possible correlations between nailfold microangiopathy extent and BP degree in three different body areas (periungual, dorsum of hand and zygoma). Methods Fifty SSc patients (mean age 57±10SD years) were enrolled after written informed consent. All patients were assessed by nailfold videocapillaroscopy (NVC) to assess the proper pattern of microvascular damage (“early”, “active”, or “late“), and calculate the microangiopathy evolution score (MES) (3-5). BP was analysed by the new technique laser speckle contrast analysis (LASCA) by creating regions of interest (ROIs) at the periungual areas of the fingers, dorsum of hands and zygomas bilaterally: the average perfusion was scored as perfusion units (PU) (6). Patients enrolled into the study were not taking vasoactive drugs since at least one month before LASCA assessment. Non-parametric tests were used for the statistical analysis. Results A statistically significant progressive decrease of BP was observed by LASCA in SSc patients with different “early”, “active”, or “late” NVC pattern of microangiopathy at the level of periungual areas (p<0.001). No statistically significant difference was observed between the three NVC patterns and BP at the level of both dorsum of hands and zygomas. A significant negative correlation was confirmed between MES and BP at periungual area (r=-0.48, p<0.0001). On the contrary, no statistically significant correlation was found between MES and BP at the level of both dorsum of hands and zygomas. Conclusions A significant correlation between nailfold microangiopathy extent (evaluated by NVC) and BP degree (evaluated by LASCA) seems to exist in SSc patients at the periungual level, but not at dorsum of hands and zygomas. References Cutolo M, et al. Nat Rev Rheumatol 2010; 6, 578-87. Murray AK, et al. Arthritis Rheum 2006; 54: 1952-60. Sulli A, et al Arthritis Rheum. 2012; 64: 821-5. Sulli A, et al. Ann Rheum Dis 2008; 67:885-7. Smith V, et al. Ann Rheum Dis 2010; 69:1092-6. Draijer M et al. Laser Med Sci 2009; 24: 639-51. Disclosure of Interest None Declared