Clin Rheumatol DOI 10.1007/s10067-006-0313-3 ORIGINAL ARTICLE Francesca Ingegnoli . Valentina Galbiati . Silvana Zeni . Laura Meani . Lenka Zahalkova . Chiara Lubatti . Amedeo Soldi . Erberto Paresce . Antonella Murgo . Calogero Crapanzano . Flavio Fantini Use of antibodies recognizing cyclic citrullinated peptide in the differential diagnosis of joint involvement in systemic sclerosis Received: 17 February 2006 / Revised: 6 April 2006 / Accepted: 7 April 2006 / Published online: 3 May 2006 # Clinical Rheumatology 2006 Abstract Objective: To determine the prevalence of anti- cyclic citrullinated peptide (CCP) antibodies in systemic sclerosis (SSc) and to assess any association between the presence of anti-CCP, radiographic features, and clinical manifestations. Materials and methods: Anti-CCP anti- bodies and rheumatoid factor (RF) were tested in serum samples from 75 patients with SSc (64 women and 11 men), with a mean age of 59.4 years (range 24–85) with either diffuse (dcSSc) and limited (lcSSc) cutaneous involvement. As a control group, 22 age- and sex-matched healthy controls (HCs) were examined. Standard radio- graphs of the hands and wrists were examined in each patient. Results: The presence of anti-CCP was found in sera of 10.6% (8/75) patients with SSc (lcSSc 3 of 44, 6.8%; dcSSc 5 of 31, 16.1%). None of the HCs was positive for anti-CCP. The positivity of RF was observed in 19 of 75 (25.3%) SSc patients (lcSSc 10 of 44, 22.7%; dcSSc 9 of 31, 29%). Statistically significant association was found between anti-CCP positivity and the presence of arthritis (p<0.0001) and marginal erosions (p=0.001). Conclusion: Our data show that joint involvement is a common presenting feature of SSc. In this report, we show that anti-CCP antibodies can be detected also in patients with SSc, but they are generally less commonly present than in adults with rheumatoid arthritis (RA). Thus, the finding of high titers of anti-CCP antibodies may help to define the diagnosis of overlap syndrome SSc/RA and facilitate diagnosis and appropriate treatment. Keywords Anti-cyclic citrullinated peptide antibodies . Radiologic features . Systemic sclerosis Introduction Systemic sclerosis (SSc) is a multisystem disorder of connective tissue characterized by increased biosynthesis of matrix proteins by interstitial fibroblasts. The excessive collagen deposition in affected organs can lead to micro- vascular damage and fibrosis of the skin and internal organs. During the disease course, many patients developed musculoskeletal involvement which is manifest clinically as myalgias, muscle atrophy, arthralgia and/or arthritis, and/or flexion contractures, with subsequent loss of joint function [1]. These patients may particularly often have joint manifestations which may be the presenting feature of SSc in 24–97% of cases and range from arthralgias to a symmetrical polyarthritis clinically indistinguishable from that of rheumatoid arthritis (RA) [2, 3]. Flexion contractures, especially in the fingers, wrists, and elbows, are usually attributed to the appearance of tight and hidebound of the skin and tethering of the skin to underlying tissue with impairment of movement and function. On the other hand, joint involvement in SSc could depend either on periarticular fibrosis or synovitis, histological documented, or even on an overlapping rheumatoid arthritis [3–5]. Because these changes in the superficial tissues constitute the clinical hallmark of the disease, it remains unclear whether the rheumatic complaints were truly arthritic or merely a consequence of the skin tightening itself, but it is important to be able to identify the source of a patient’ s disability between joint, cutaneous, and subcu- taneous involvement, as the treatment may differ [5]. F. Ingegnoli (*) . V. Galbiati . S. Zeni . L. Meani . L. Zahalkova . C. Lubatti . A. Soldi . E. Paresce . A. Murgo . F. Fantini Department of Rheumatology, Istituto Gaetano Pini, University of Milan, Piazza Cardinal Ferrari, 1- 20122 Milan, Italy e-mail: francesca.ingegnoli@unimi.it Tel.: +39-02-58296746 Fax: +39-02-58318176 C. Crapanzano UO di Patologia Clinica, Laboratorio analisi, Istituto Gaetano Pini, Milan, Italy 26: (2007) 510–514