To the Editor:
Antinuclear matrix protein 2 (anti-NXP2) are dermatomyositis (DM)-specific autoantibodies.1 A recent metanalysis outlined their association with muscle weakness, myalgia, dysphagia, edema, and calcinosis.2 We report 3 cases of seronegative polyarthritis, without myositis or DM rash, attributed to anti-NXP2 autoantibodies (Table 1).
Clinical features of 3 patients with anti-NXP2 isolated polyarthritis.
Written informed consent from study patients were obtained as part of their participation in the Canadian Inflammatory Myopathy Study. Approval by our local ethics committee (Comité d’Éthique, Centre de Recherche du CHUM, Université de Montréal) was not required for case reports with fewer than 4 patients.
Case 1. A 51-year-old female presented with acute polyarthritis of the hands. Examination did not show muscle weakness or DM rash. She had normal inflammatory markers and creatine kinase (CK). Serological tests demonstrated positive antinuclear antibody (ANA; 1/640 speckled) and anti-NXP2 (3+) on a myositis panel (Euroimmun). Magnetic resonance imaging (MRI) of the thighs did not show inflammatory hypersignals. Nailfold capillaroscopy showed dystrophic capillaries without a definite DM pattern. Cancer screening was negative. Her polyarthritis resolved with a short course of prednisone, followed by methotrexate (MTX) and hydroxychloroquine (HCQ).
Case 2. A 58-year-old female presented with acute polyarthritis in her hands, wrists, and ankles. Muscle strength was normal and there was no DM rash. She had normal inflammatory markers and CK. Serological tests demonstrated positive ANA (1/320 speckled) and anti-NXP2 (3+). MRI and electromyography (EMG) were normal. Nailfold capillaroscopy showed dystrophic capillaries without a specific DM pattern. Cancer screening was negative. She was successfully treated with prednisone, followed by MTX and HCQ.
Case 3. A 22-year-old female developed polyarthritis and edema in both hands. She also reported mild upper limb myalgia over the last 3 months. Examination did not reveal muscle weakness (Medical Research Council scale 5/5) or DM rash. She had normal inflammatory markers and mildly elevated CK (390 U/L, normal range 24-184). Serological tests demonstrated positive ANA (1/640 diffuse) and anti-NXP2 (2+). Muscle MRI, EMG, nailfold capillaroscopy, and quadriceps muscle biopsy were normal. Full-body positron emission tomography scan was negative. She was successfully treated with a combination of prednisone, MTX, HCQ, and tofacitinib.
In 1997, Oddis et al discovered anti-NXP2 autoantibodies, formerly named anti-MJ, in patients with juvenile DM (JDM).3 In 2002, their target was identified as a nuclear matrix protein that contributes to RNA metabolism and nuclear architecture.4 These autoantibodies were initially associated with a severe JDM clinical phenotype including refractory myositis, calcinosis, joint contractures, intestinal vasculitis, and polyarthritis.5
Our 3 cases presented with a unique phenotype of acute polyarthritis, normal inflammatory markers, and no cutaneous or muscular features of DM. We searched for articles regarding the clinical characteristics of anti-NXP2 autoantibodies (PubMed, MEDLINE, EMBASE) and summarized the data in Table 2. To our knowledge, no cases of isolated seronegative polyarthritis have been reported to date with anti-NXP2 autoantibodies. Indeed, polyarthritis has exclusively been described with concomitant myositis as reported in 2 of 4 (50%),6 3 of 6 (50%),7 and all 4 (100%) cases8 in recent case series. In 2020, Tansley et al highlighted that commercial myositis assays for anti-NXP2 autoantibodies have an excellent correlation with immunoprecipitation, the gold standard.9 This, in addition to a positive speckled or diffuse ANA pattern, strongly exclude the issue of false positive anti-NXP2 results.
Phenotype of anti-NXP2 positive myositis in the literature.
Our cases highlight that anti-NXP2 autoantibodies may present clinically with isolated seronegative polyarthritis. We suggest testing for these autoantibodies in the presence of acute polyarthritis, isolated positive ANA, and normal inflammato Although none of our patients had cancer, clinicians should remain careful as this antibody has been associated with a higher cancer risk.10
ACKNOWLEDGMENT
The authors would like to thank Dr. Martial Koenig for kindly reviewing the nailfold capillaroscopies of our patients.
Footnotes
The authors declare no conflicts of interest relevant to this article.
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