Seronegative Polyarthritis in Association With Anti-NXP2 Antibodies: A Case Series

Article Figures & Data

Table 1.

Clinical features of 3 patients with anti-NXP2 isolated polyarthritis.

	Patient 1	Patient 2	Patient 3
Sex	Female	Female	Female
Age at diagnosis, yrs	51	58	22
Ethnicity	French Canadian	French Canadian	French Canadian
Comorbidities	None	OA, hypothyroidism, fever, and abdominal pain due to CMV infection 2 months prior	ADHD, migraines
Family medical history	JIA (daughter)	Colon cancer (mother), lung cancer (father)	Unknown
Length of follow-up, months	32	11	13
Smoking	–	–	–
Muscle strength (MRC-5 scale)	5/5	5/5	5/5
Myalgia	–	–	+
Dysphagia	–	–	–
DM skin rash	–	–	–
Polyarthritis (joints)	MCP-PIP (bilateral)	PIP, wrists, ankles (bilateral)	MCP-PIP (bilateral)
Raynaud phenomenon	–	–	–
ANA (pattern)	1/640 (speckled)	1/320 (speckled)	1/640 (diffuse)
ENA	–	–	–
dsDNA	–	–	–
C3 and C4	–	–	–
aPL^{^a}	–	–	–
RF	–	–	–
Anti-CCP	–	–	–
Myositis panel (titer)	Anti-NXP2 (3+)	Anti-NXP2 (3+)	Anti-NXP2 (2+)
CK, IU/L (normal range 24-184)	52	34	390
CRP, mg/L (Normal < 10)	5.3	3.0	5.1
HIV screening	–	–	–
QFT	–	–	–
MRI	–	–	–
EMG	Not done	–	–
Muscle biopsy	Not done	Not done	–
Nailfold capillaroscopy	Dilated dysmorphic capillaries, no specific DM pattern	Dilated dysmorphic capillaries, no specific DM pattern	–
Cancer screening	Colonoscopy, pap smear, mammogram, abdominal US	PET scan, colonoscopy, mammogram, abdominal US CA 19-9, CA 15-3, CA 125, CEA	PET scan
IS treatment	MTX, HCQ	MTX, HCQ	Prednisone, MTX, HCQ, TOF
Status at last follow-up	Remission	Remission	Polyarthritis significantly improved

↵^a aPL: anti-β₂ glycoprotein, anticardiolipin, and lupus anticoagulant antibodies. ADHD: attention deficit and hyperactivity disorder; ANA: antinuclear antibodies; Anti-CCP: anticyclic citrullinated peptide antibody; anti-NXP2: antinuclear matrix protein 2; aPL: antiphospholipid antibody; CA: cancer antigen; CEA: carcinoembryonic antigen; CK: creatine kinase; CMV: cytomegalovirus; CRP: C-reactive protein; DM: dermatomyositis; EMG: electromyography; ENA: extractable nuclear antigens; HCQ: hydroxychloroquine; IS: immunosuppressive; JIA: juvenile idiopathic arthritis; MCP: metacarpophalangeal; MRI: magnetic resonance imaging; MRC: Medical Research Council scale for muscle power evaluation; MTX: methotrexate; OA: osteoarthritis; PET: positron emission tomography; PIP: proximal interphalangeal; QFT: QuantiFERON-TB (Qiagen); RF: rheumatoid factor; TB: tuberculosis; TOF: tofacitinib; US: ultrasound.

Table 2.

Phenotype of anti-NXP2 positive myositis in the literature.

Disease entities	JDM IIM (DM > PM)
Epidemiology	Increased prevalence far from the equator zone No consistent age or sex pattern 18-25% of cases of JDM 1.6-17% of cases of IIM
Pathology	Increased capillary C5b-9 deposition Increased ischemic muscle damage
Muscle features	Severe weakness: proximal and distal Prominent myalgia and dysphagia Higher CK levels
Cutaneous features	Calcinosis, especially in JDM Distal ulcerations and edema Occasionally heliotrope and V-sign rash
Joint features	Polyarthritis described in 50-100% of myositis cases Severe arthralgias Small joints (hands and wrists) and large joints (shoulders, knees, ankles)
Systemic features	Reduced risk of ILD Increased risk of gastrointestinal vasculitis in JDM
Malignancy	Increased risk of malignancy, mostly in older males No specific association to a cancer subtype
Serology	Positive ANA (diffuse or speckled pattern) Commercial myositis assays (Euroimmun) have excellent specificity (100%) and sensitivity (84%) when compared to immunoprecipitation, the gold standard
Prognosis	No evidence of overall decreased survival Increased risk of poor treatment response Disease tends to relapse

ANA: antinuclear antibody; anti-NXP2: antinuclear matrix protein 2; CK: creatine kinase; DM: dermatomyositis; IIM: idiopathic inflammatory myopathies; ILD: interstitial lung disease; JDM: juvenile dermatomyositis; PM: polymyositis.