When Muscle Enzymes Understate the Disease: Anti-NXP2–Positive Dermatomyositis with Progressive Dysphagia

Background

Anti-nuclear matrix protein 2 (NXP2)-positive dermatomyositis (DM) is associated with a clinically important phenotype that may include prominent muscle involvement and dysphagia. Early recognition can be challenging when cutaneous manifestations precede or initially overshadow systemic symptoms. We present a newly diagnosed case of anti-NXP2-positive DM in which evolving characteristic skin findings, proximal weakness, and progressive dysphagia prompted recognition of an inflammatory myopathy despite only modest creatine kinase elevation.

Case Presentation

A 54-year-old woman presented to rheumatology with a progressive rash, myalgias, proximal weakness, and dysphagia. Her symptoms began with a pruritic erythematous eruption involving the fingers that subsequently spread to the hands, elbows, upper chest, and face, with reported prior periorbital involvement. The eruption was initially treated as eczema with topical corticosteroids and a two-week course of systemic prednisone, resulting in partial cutaneous improvement. She subsequently reported deep muscle discomfort with activity and progressive dysphagia, initially to solids and later to both solids and liquids. At rheumatology evaluation, approximately two weeks after completing systemic corticosteroids, examination demonstrated Gottron papules/sign, heliotrope rash, and Shawl sign. Strength was reduced to 4+/5 in the bilateral deltoids and hip flexors.

Laboratory evaluation demonstrated a high-titer antinuclear anti-body (>1:2560) with a nuclear dot pattern and isolated anti-NXP2 positivity on an extended myositis panel. Creatine kinase was modestly elevated at 352 U/L, with mild AST elevation and no substantial elevation of systemic inflammatory markers. Integration of the characteristic cutaneous findings, objective proximal weakness, symptoms, and serology supported a diagnosis of anti-NXP2-positive dermatomyositis. High-dose prednisone and mycophenolate mofetil were initiated, with intravenous immunoglobulin under consideration if dysphagia or overall disease control remains inadequate. Given the diagnosis of adult-onset DM, CT imaging of the chest, abdomen, and pelvis and age-appropriate cancer screening were initiated.

Discussion

Dermatomyositis may initially resemble common dermatologic conditions, delaying recognition of systemic disease. In this case, the evolution from predominantly cutaneous manifestations to objective proximal weakness and progressive dysphagia, together with anti-NXP2 positivity, supported the diagnosis despite modest CK elevation. This presentation underscores the importance of integrating the evolving clinical phenotype with physical examination, muscle enzymes, and myositis-specific antibodies rather than relying on CK levels alone. Progressive dysphagia warrants close monitoring because it may reflect clinically significant muscle involvement. In adults with newly diagnosed DM, assessment of malignancy risk and appropriate cancer screening should also be incorporated into the evaluation.

Conclusion

This case demonstrates that dermatomyositis should remain in the differential diagnosis when characteristic cutaneous findings evolve alongside proximal muscle weakness or dysphagia, even when CK elevation is modest. Recognition of the evolving clinical phenotype and appropriate use of myositis-specific antibodies may facilitate timely diagnosis, treatment, and evaluation for associated complications.