Digital ulcers and cutaneous subsets of systemic sclerosis: Clinical, immunological, nailfold capillaroscopy, and survival differences in the Spanish RESCLE Registry.
Digital ulcers (DU) are the most common vascular complication of systemic sclerosis (SSc). We compared the characteristics between patients with prior or current DU with those never affected and evaluated whether a history of DU may be a predictor of vascular, organ involvement, and/or death in patients with SSc.



Data from SSc patients with or without prior or current DU were collected by 19 referral centers in an ongoing registry of Spanish SSc patients, named Registro de ESCLErodermia (RESCLE). Demographics, organ involvement, autoimmunity features, nailfold capillary pattern, survival time, and causes of death were analyzed to identify DU related characteristics and survival of the entire series and according to the following cutaneous subsets-diffuse cutaneous SSc (dcSSc), limited cutaneous SSc (lcSSc), and SSc sine scleroderma (ssSSc).



Out of 1326, 552 patients enrolled in the RESCLE registry had prior or current DU, 88% were women, the mean age was 50 ± 16 years, and the mean disease duration from first SSc symptom was 7.6 ± 9.6 years. Many significant differences were observed in the univariate analysis between patients with and without prior/current DU. Multivariate analysis identified that history of prior/current DU in patients with SSc was independently associated to younger age at SSc diagnosis, diffuse cutaneous SSc, peripheral vascular manifestations such Raynaud's phenomenon, telangiectasia, and acro-osteolysis but no other vascular features such as pulmonary arterial hypertension or scleroderma renal crisis. DU was also associated to calcinosis cutis, interstitial lung disease, as well as worse survival. Multivariate analysis performed in the cutaneous subsets showed that prior/current DU were independently associated: (1) in dcSSc, to younger age at SSc diagnosis, presence of telangiectasia and calcinosis and rarely a non-SSc pattern on nailfold capillaroscopy; (2) in lcSSc, to younger age at SSc diagnosis, presence of Raynaud's phenomenon as well as calcinosis cutis, interstitial lung disease, and higher incidence of death from all causes; and (3) in ssSSc, to younger age at first SSc symptom and greater incidence of death from all causes.



Digital ulcers develop in patients with SSc younger at diagnosis, mainly in patients with dcSSc and lcSSc, and they are associated to other peripheral vascular manifestations such as Raynaud's phenomenon, telangiectasia, and acro-osteolysis but also to calcinosis, and interstitial lung disease. History of DU in SSc leads to worse survival, also noticeable for lcSSc and ssSSc subsets but not for dcSSc patients.
Department of Internal Medicine, Corporació Sanitària Universitària Parc Taulí, Universidad Autónoma de Barcelona, Sabadell, Barcelona, Spain. Electronic address: ctolosa@tauli.cat.
Carles
C
Tolosa-Vilella
Department of Internal Medicine, Corporació Sanitària Universitària Parc Taulí, Universidad Autónoma de Barcelona, Sabadell, Barcelona, Spain.
Maria Lluisa
ML
Morera-Morales
Department of Internal Medicine, Hospital Valld'Hebron, Barcelona, Spain.
Carmen Pilar
CP
Simeón-Aznar
Department of Internal Medicine, Corporació Sanitària Universitària Parc Taulí, Universidad Autónoma de Barcelona, Sabadell, Barcelona, Spain.
Begoña
B
Marí-Alfonso
Department of Internal Medicine, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain.
Dolores
D
Colunga-Arguelles
Unit of Autoimmune Systemic Diseases, Department of Internal Medicine, Hospital Clínico San Cecilio, Granada, Spain.
José Luis
JL
Callejas Rubio
Department of Internal Medicine, Hospital Universitario de Bellvitge, Barcelona, Spain.
Manuel
M
Rubio-Rivas
Department of Internal Medicine, Complejo Hospitalario Universitario de Vigo, Pontevedra, Spain.
Maika
M
Freire-Dapena
Department of Internal Medicine, Hospital Valld'Hebron, Barcelona, Spain.
Alfredo
A
Guillén-Del Castillo
Department of Autoimmune Systemic Diseases, Hospital Clinic, Barcelona, Spain.
Nerea
N
Iniesta-Arandia
Unit of Connective Tissue Diseases, Department of Internal Medicine, Hospital Virgen del Rocio, Sevilla, Spain.
Maria Jesús
MJ
Castillo-Palma
Department of Internal Medicine, Hospital de Cruces, Barakaldo, Vizcaya, Spain.
Marivi
M
Egurbide-Arberas
Department of Internal Medicine, Hospital de Cabueñes, Gijón, Spain.
Luis
L
Trapiellla-Martínez
Department of Internal Medicine, Hospital Virgen de las Nieves, Granada, Spain.
José A
JA
Vargas-Hitos
Department of Internal Medicine, Hospital La Fe, Valencia, Spain.
José Antonio
JA
Todolí-Parra
Department of Internal Medicine, Hospital Universitari Mútua Terrassa, Barcelona, Spain.
Mónica
M
Rodriguez-Carballeira
Department of Internal Medicine, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain.
Adela
A
Marin-Ballvé
Consorci Hospitalari de Vic, Barcelona, Spain.
Xavier
X
Pla-Salas
Department of Internal Medicine, Hospital La Paz, Madrid, Spain.
Juan José
JJ
Rios-Blanco
Department of Internal Medicine, Hospital Valld'Hebron, Barcelona, Spain.
Vicent
V
Fonollosa-Pla
D000328:Adult; D000368:Aged; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D020678:Microscopic Angioscopy; D008875:Middle Aged; D012042:Registries; D012595:Scleroderma, Systemic / Q000150:complications* / Q000401:mortality / Q000503:physiopathology; D012883:Skin Ulcer / Q000209:etiology* / Q000401:mortality / Q000503:physiopathology; D013030:Spain / Q000453:epidemiology; D015996:Survival Rate
Anti-centromere antibodies; Anti-topoisomerase I antibodies; Diffuse cutaneous SSc; Digital ulcers; Limited cutaneous SSc; Nailfold capillaroscopy; SSc sine scleroderma; Survival; Systemic sclerosis