Acta Dermato-Venereologica 98-8CompleteContent | Page 7

735 CLINICAL REPORT Clinical Characteristics of Pruritus in Systemic Sclerosis Vary According to the Autoimmune Subtype Greta GOURIER 1,2 , Chloé THÉRÉNÉ 1 , Margaux MAZEAS 2 , Claire ABASQ-THOMAS 1 , Emilie BRENAUT 1 , Flavien HUET 1 , Haitham SONBOL 1 , Elize CAMPILLO 2 , Julie LEMERLE 2 , Elisabeth PASQUIER 3 , Emmanuelle LE MOIGNE 3 , Alain SARAUX 4 , Valérie DEVAUCHELLE-PENSEC 4 , Laurent MISERY 1# and Yves RENAUDINEAU 2# 1 Department of Dermatology, 2 Laboratory of Immunology and Immunotherapy, INSERM U1227, 3 Department of Internal Medicine, Pneumology and Vascular Medicine, and 4 Department of Rheumatology, INSERM U1227, CHRU Brest, Brest, France # These authors have contributed equally as senior authors. Pruritus is a frequent symptom in systemic sclerosis (SSc), with a prevalence of 40–65%, but its patho­ physiology is poorly understood. This study investiga- ted the immunological component of pruritus. Fifty-six patients with SSc responded to a standardized ques- tionnaire regarding both SSc disease and pruritus cha- racteristics. Among patients with SSc, those with pru- ritus did not display a particular immunological profile (inflammatory, humoral, and/or cellular factors), but pruritus was, in most cases, concomitant with the de- velopment of SSc. Thus, pruritus characteristics were evaluated further, according to the detection of anti- centromere autoantibodies (ACA), into ACA+ (n  = 17) and ACA– (n  = 19). The ACA+ subgroup was characteri- zed by a longer evolution of SSc and pruritus, pruritus present outside the sclerotic area, and a shorter daily duration of pruritus. In conclusion, the concomitant appearance of the 2 processes and the differences ob- served between ACA+ and ACA– subgroups support the presence of an immunological component in pruritus. Key words: systemic sclerosis; pruritus; itch; autoantibodies; inflammation; autoimmunity; quality of life. Accepted May 29, 2018; Epub ahead of print Jun 1, 2018 Acta Derm Venereol 2018; 98: 735–741. Corr: Yves Renaudineau, Laboratory of Immunology and Immunotherapy, Brest University Medical School Hospital, BP 824, FR-29609, Brest, Fran- ce. E-mail: [email protected] S ystemic sclerosis (SSc) is a rare and complex au- toimmune connective tissue disease characterized by vascular changes and fibrosis of the skin and viscera, resulting in organ failure and irreversible injury (1). The disease process starts with vascular injury and endothelial activation, leading, in turn, to an uncontrolled inflamma- tory reaction, which triggers fibroblast activation (2, 3). In this complex disease, environmental factors (e.g. ex- posure to silica and solvent) seem to be the main factors in genetically primed individuals (4). In addition, recent results from genome-wide association studies (GWAS) have further shown different SSc subtypes confined to specific autoantibody profiles, including anti-centromere antibodies (ACA) or anti-topoisomerase/scl70 antibodies (5). The prevalence of SSc, ranging from 150 to 443 cases per million, vary substantially in different regions of the world, with higher reports in North America and SIGNIFICANCE Key points related to the study: - Systemic sclerosis and pruritus appear in most of the cases concomitantly. - This study unmasks different characteristics of pruritus according to the autoimmune subtype of systemic sclero- sis. - Pruritus characteristics are less severe when anti-centro- mere antibodies are detected. Australia compared with Japan and France (6). A sex bias toward women is observed in SSc (female to male sex ratio approximately 4:1). The most common organ complications associated with SSc are gastrointestinal (90%) followed by mus- culoskeletal problems (65%), interstitial lung disease (40%), pulmonary arterial hypertension (15%) and renal crisis (5–10%). Regarding skin involvement, SSc is characterized by skin fibrosis (> 90%), Raynaud’s phenomenon (90%), telangiectasia (75%), ulcers (40%) and calcinosis (25%) (1). Chronic pruritus represents a common, but infrequently reported, skin symptom in SSc, with a prevalence of 43–62% (7–9), compared with 7–14% for chronic pruritus in the general population (10–13). In primary care consultations, pruritus repre- sents the main complaint in 0.6–1.0% of cases (13–15). Pruritus, or itch, is defined as “an unpleasant sensa- tion, which provokes the desire to scratch” (16). This unpleasant sensory experience is difficult to explore due to its multidimensional aspects, including sensory, cognitive, affective and motivational components (17). From the neurological point of view, 2 types of unmyeli- nated fibres leading to pruritus are described (18). First, histamine-sensitive fibres have an important role in the transmission of most types of acute pruritus, including urticaria. Secondly, non-histamine-sensitive peripheral C-nerve fibres are involved in the transmission of most types of chronic pruritus. Of particular note, these pruri- ceptors are distinct from the C-nerve fibres that transmit pain (nociceptors). Emerging arguments further support the possibility of cross-talk between the sensory nervous system and the immune signalling pathways to influ- ence mammalian behaviour through the emergence of neurophysiological reflexes, especially on the skin with This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2018 Acta Dermato-Venereologica. doi: 10.2340/00015555-2980 Acta Derm Venereol 2018; 98: 735–741