Sparing effect of hemiplegia on skin fibrosis and microvascular involvement: Reports of two cases of systemic sclerosis and review of the literature Nicola Ughi, MD a,n , Simon A. Hervey, MD b , Roberta Gualtierotti, MD a , Silvana Zeni, MD a , Ariane L. Herrick, MD c , Francesca Ingegnoli, MD, PhD a , Pierluigi Meroni, MD a a Division of Rheumatology, Department of Clinical Sciences and Community Health, Gaetano Pini Orthopedic Institute, University of Milano, Piazza Cardinal Ferrari 1, Milano 20122, Italy b Eastbourne District General Hospital, Eastbourne, East Sussex, UK c Centre for Musculoskeletal Research, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK article info Keywords: Hemiplegia Systemic sclerosis Scleroderma Scleroderma spectrum disease Connective tissue disease Nailfold capillaroscopy abstract Objectives: The sparing effect of hemiplegia in rheumatic diseases has been described, but reports on systemic sclerosis (SSc)-spectrum disorders are unusual. SSc-spectrum disorders are complex diseases of unknown origin characterized by multisystem involvement, skin and organ fibrosis, microvascular alterations, and immunologic abnormalities. We describe two cases of patients with hemiplegia who developed Raynaud's phenomenon and skin fibrosis of the non-paretic limb. Methods: Clinical, laboratory, and investigation findings of two cases with hemiplegia who developed scleroderma spectrum disorders of the non-paretic limb are presented. A review of the medical literature was performed in PubMed for all articles in English. Results: A total of 46 reports from 1935 to 2012 were identified, especially on osteoarthritis and rheumatoid arthritis. Only two case reports on patients with SSc describe asymmetric SSc skin involvement and unilateral acro-osteolysis on x-ray images of the non-paretic limb. By contrast, we report the first description of capillaroscopic microvascular changes in patients with hemiplegia and asymmetric SSc skin involvement. Conclusions: Our cases point out the potential role of a “cross-talk” between the nervous system and the skin in SSc-spectrum disorders and suggest future directions for research in studies of pathogenesis. & 2014 Elsevier Inc. All rights reserved. Introduction Systemic sclerosis (SSc)-spectrum disorders are complex diseases of unknown origin characterized by skin and multiorgan fibrosis, microvascular alterations, and immunologic abnormalities such as autoantibody production. SSc-spectrum disorders are often multi- system, causing lung and gastrointestinal and other major internal involvement, although nervous system impairment is uncommon [1]. The sparing effect of hemiplegia in rheumatic diseases has been reported, especially in rheumatoid arthritis (RA) [2–4], but rarely in patients with SSc. We describe two cases of patients with hemiplegia who developed Raynaud's phenomenon (RP), skin fibrosis, and microvasculature abnormalities of the non-paretic limb. Methods In addition to the presented cases, in order to identify pre- viously published cases of patients with a diagnosis of hemiplegia and SSc and other rheumatic diseases, a search was performed using PubMed for all articles published in English, and this was supplemented by manually searching bibliographies of these articles. The keywords used in our search are as follows, and the Boolean operators “AND” and “OR” were used in combining more keywords to increase the specificity and reduce the sensitivity of our search: “Raynaud” (OR “Raynaud's phenomenon” OR “Raynaud phenomenon” OR “Raynaud's disease” OR “Raynaud disease”), AND “systemic sclerosis” (OR “scleroderma”), “mixed connective tissue disease,” “undifferentiated connective tissue disease,” “rheumatic disease,” AND “hemiplegia.” A total of 46 case reports were identified (Table). Contents lists available at ScienceDirect journal homepage: www.elsevier.com/locate/semarthrit Seminars in Arthritis and Rheumatism http://dx.doi.org/10.1016/j.semarthrit.2014.10.011 0049-0172/& 2014 Elsevier Inc. All rights reserved. n Corresponding author. E-mail addresses: nicola.ughi@gpini.it, nicolaughi@gmail.com (N. Ughi). Seminars in Arthritis and Rheumatism 44 (2015) 597–601