Changes in the activity or responsiveness of neuroendothelial mecha-nisms may trigger vascular injury with im-balance of angiogenesi

Collalti, Giulia

Gasperini, Maria Ludovica

Gigante, Antonietta

Iacolare, Andrea

Pellicano, Chiara

Rosato, Edoardo

English

IACOLARE, ANDREA

PELLICANO, CHIARA

Archivio della ricerca- Università di Roma La Sapienza

S-159Clinical and Experimental Rheumatology 2019Letters to the EditorsSkin perfusion of hands is associated with parasympathetic activity in systemic sclerosisSirs,Raynaud’s phenomenon (RP) and microvas-cular damage are the features of systemic sclerosis (SSc). Changes in the activity or responsiveness of neuroendothelial mecha-nisms may trigger vascular injury with im-balance of angiogenesis (1). The skin perfu-sion of hands, evaluated with laser Doppler perfusion imaging (LDPI), is reduced in SSc patients (2) and it decreases with the se-verity of capillaroscopic damage. In a previ-ous study abnormal skin perfusion showed a negative correlation with pulsatility and stiffness of digital arteries (3).In this pilot study we aimed to evaluate skin perfusion of the hands in SSc using LDPI and correlate it with autonomic activity. The protocol, according to Declaration of Hel-sinki, was approved by local Ethics Com-mittee. Twenty-five SSc patients [20 female, median age 47 (40-51)] were enrolled. Fif-teen patients had diffuse cutaneous systemic sclerosis (dcSSc) and sixteen had a history of digital ulcers, no patient had active digi-tal ulcers. Median value of modified Rod-nan skin score was 13 (11-18). The nailfold videocapillaroscopy showed an early capil-laroscopic pattern in 8 (32%) patients, ac-tive in 8 (32%) patients and late in 9 (36%) patients. Exclusion criteria were active digital ulcers, peripheral arterial diseases, diabetes, thrombophilia, cigarette smok-ing, cardiac arrhythmias and conduction disorders. Five patients were treated with bosentan for digital ulcers prophylaxis, no patient was treated with phosphodiesterase type 5 (PDE5) inhibitor. Calcium channel blockers therapy, bosentan and iloprost in-fusion was discontinued 72 hours before the LDPI. Baseline images were taken of dor-sum of both hands with Lisca Laser Doppler Perfusion Imager (Perimed AB, Stockholm, Sweden). The dorsum of the hand was di-vided into regions of interest (ROI) and ac-cording to our previous study we analysed fingers from the second to the fourth (4, 5): ROI1 included three fingers of the hand from the second to the fourth distally to the proximal interphalangeal finger joint and ROI2 included the area between the PIP (proximal interphalangeal) and the MCP (metacarpophalageal) joint (5). Perfusion has been expressed by arbitrary perfusion units (pU). All patients underwent to 24-h Holter monitoring and electrocardiography (ECG) to assess autonomic nervous system by heart rate variability (HRV) analysis. The time domain analysis was evaluated for the activity of the cardiac system. Parasympa-thetic system was represented by the square root of the mean of the sum of the squares of differences between adjacent NN intervals (RMSSD) while global autonomic activity was represented by the standard deviation of normal-to-normal RR intervals (SDNN) (6).All the results were expressed as median and CI (confidence interval). Group com-parisons were made by Kruskal-Wallis test. Spearman correlation coefficients (r) was used. p-values <0.05 were considered sig-nificant.The median value of perfusion of both hands was 61.3 (53.6–72.2) pU, the median value of ROI1 was 62.1 (54.5–70.2) pU, the median value of ROI2 was 93.7 (86.7–131.1) pU. The median value of SDNN was 122 (119-138) ms and the median value of RMSSD was 40 (37–53) ms.We have not observed correlation between SDNN and median value of perfusion of hands, ROI1 and ROI2. Conversely, we have observed a positive linear correla-tion between RMSSD and perfusion of hands (r=0.61, p<0.001) and ROI1 (r=0.51, p<0.01) (Fig. 1). There was no correlation between RMSSD and perfusion of ROI2.Impaired neuroendothelial mechanisms between vasoconstriction and vasodilata-tion are present in course of RP (7). HRV in SSc is reduced and plays a key role in de-termining and maintaining the mechanisms responsible for the vasodilation and vaso-constriction (8, 9). Recently we have dem-onstrated that parasympathetic activity is associate with vascular endothelial growth factor expression (10). In the present study skin perfusion is favoured by vasodilation mediated to parasympathetic system. First line of treatment in course of SSc is repre-sented by vasodilatory medications for RP and digital ulcers (11). We can suppose that the perfusion of the hands and especially of the distal phalanges is modulated by para-sympathetic activity.M.L. GASPERINI, MDA. GIGANTE, MDA. IACOLARE, MDC. PELLICANO, MDG. COLLALTI, MDE. ROSATO, MD, PhDDepartment of Translational and Precision Medicine, Sapienza University of Rome, Italy.Please address correspondence to: Dr Edoardo Rosato, Department of Translational and Precision Medicine, Sapienza University of Rome, Viale dell’Università 37, 00185 Rome, Italy.E-mail: edoardo.rosato@uniroma1.itCompeting interests: none declared.© Copyright CliniCal and ExpErimEntal rhEumatology 2019.References  1. ROMANO E, ROSA I, FIORETTO BS, GUIDUCCI S, MANETTI M, MATUCCI-CERINIC M: A new avenue in the pathogenesis of systemic sclerosis: the molecular interface between the endothelial and the nervous systems. Clin Exp Rheumatol 2019; 37 (Suppl. 119): S134-41.  2. BARBANO B, MARRA AM, QUARTA S et al.: In systemic sclerosis skin perfusion of hands is re-duced and may predict the occurrence of new digital ulcers. Microvasc Res 2017; 110: 1-4.  3. ROSATO E, GIGANTE A, BARBANO B et al.: In systemic sclerosis macrovascular damage of hands digital arteries correlates with microvascular dam-age. Microvasc Res 2011; 82: 410-5.  4. ROSATO E, BORGHESE F, PISARRI S, SALSANO F: Laser Doppler perfusion imaging is useful in the study of Raynaud’s phenomenon and improves the capillaroscopic diagnosis. J Rheumatol 2009; 36: 2257-63.  5. ROSATO E, ROSSI C, MOLINARO I, GIOVAN-NETTI A, PISARRI S, SALSANO F: Laser Doppler perfusion imaging in systemic sclerosis impaired re-sponse to cold stimulation involves digits and hand dorsum. Rheumatology 2011; 50: 1654-8.Fig. 1. Linear positive correlation between RMSSD and median perfusion of both hands (A) and ROI1 (B).S-160 Clinical and Experimental Rheumatology 2019Letters to the Editors  6. Task Force of the European Society of Cardiol-ogy and the North American Society of Pacing and Electrophysiology: heart rate variability: standards of measurement, physiological interpretation and clinical use. 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Skin perfusion of hands is associated with parasympathetic activity in systemic sclerosis

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Skin perfusion of hands is associated with parasympathetic activity in systemic sclerosis

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