Objective To describe systemic sclerosis (SSc) with myopathy in patients without classic SSc-specific and SSc-overlap autoantibodies (aAbs), referred to as seronegative scleromyositis.
Methods Twenty patients with seronegative scleromyositis diagnosed by expert opinion were analysed retrospectively for SSc features at myositis diagnosis and follow-up, and stratified based on HEp-2 nuclear patterns by indirect immunofluorescence (IIF) according to International Consensus of Autoantibody Patterns. Specificities were analysed by protein A−assisted immunoprecipitation. Myopathy was considered an organ involvement of SSc.
Results SSc sine scleroderma was a frequent presentation (45%) at myositis diagnosis. Myositis was the most common first non-Raynaud manifestation of SSc (55%). Lower oesophagal dysmotility was present in 10 of 11 (91%) investigated patients. At follow-up, 80% of the patients met the American College of Rheumatology/EULAR SSc classification criteria. Two-thirds of patients had a positive HEp-2 IIF nuclear pattern (all with titers ≥1/320), defining three novel scleromyositis subsets. First, antinuclear antibody (ANA)-negative scleromyositis was associated with interstitial lung disease (ILD) and renal crisis. Second, a speckled pattern uncovered multiple rare SSc-specific aAbs. Third, the nuclear dots pattern was associated with aAbs to survival of motor neuron (SMN) complex and a novel scleromyositis subset characteriszed by calcinosis but infrequent ILD and renal crisis.
Conclusions SSc skin involvement is often absent in early seronegative scleromyositis. ANA positivity, Raynaud phenomenon, SSc-type capillaroscopy and/or lower oesophagal dysmotility may be clues for scleromyositis. Using HEp-2 IIF patterns, three novel clinicoserological subsets of scleromyositis emerged, notably (1) ANA-negative, (2) ANA-positive with a speckled pattern and (3) ANA-positive with nuclear dots and anti-SMN aAbs.
- Autoimmune Diseases
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Contributors Conceptualisation and design: OL-C, AB-D, MS, MJF, YT and J-LS. Acquisition of data: OL-C, AB-D, SH, JB-T, A-MM, FZ, J-PM, JN, ER, J-RG, TG, MK, FJ, IR, IT, MS, MJF, YT and J-LS. Analysis and interpretation: OL-C, AB-D, SH, AM, VL, JB-T, MK, MH, MS, MJF, YT and J-LS. Critical revision of the manuscript for important intellectual content: all authors.
Funding This research was supported in part by the University of Montreal Scleroderma Research Chair (J-LS); by grants from Canadian Institutes of Health Research (J-LS, MK) (#MOP-142211), Sclérodermie Québec, Scleroderma Society of Ontario, Scleroderma Society of Canada, the Scleroderma Association of Saskatchewan, Scleroderma Manitoba, and the Scleroderma Association of British Columbia (J-LS, MK, SH, OL-C); by donations from Mrs Gisèle Sarrazin-Locas in support of the Autoimmunity Research Laboratory; and by a Japan Society for the Promotion of Science KAKENHI Grant-in-Aid for Scientific Research #15K08790 (MS). Dr Senécal holds the University of Montreal Scleroderma Research Chair.
Competing interests None declared.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available upon reasonable request.
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