Acute Upper and Lower Extremity Weakness

Clinical History:

• History: 68-year-old man with 1 week of bilateral proximal upper and lower extremity weakness and 1 month of facial, eyebrow, neck, chest, and back rash (initially diagnosed as seborrheic dermatitis)
• PMH: HTN, PVD, asthma, hyperlipidemia, GERD, type 1 DM with retinopathy, IgA deficiency, hypothyroidism, former light smoker
• FH: Stroke, diabetes, arthritis, cancer, macular degeneration, heart disease
• Meds: Atorvastatin, insulin, levothyroxine, zolpidem; treated with Solu-Medrol and prednisone
• Physical exam: Mild-moderate proximal weakness, lower extremity edema
• MRI: Diffuse heterogeneous edema of bilateral quadriceps, adductors, and sartorius, suspicious for inflammatory myopathy
• Labs: CK peaked at 1570, trending down to 680; aldolase 20; mildly elevated CRP; ANA, Lyme, and RF negative; HMGCR Ab, MG panel, extended myositis and ENA panels pending

The primary pathology shown here is:

A. Necrotizing myopathic process

B. Eosinophil mediated inflammatory process

C. T-cell mediated inflammatory process

D. Macrophagic myofasciitis

Answer:

A. Necrotizing myopathic process

Pathology of necrotizing myopathy seen in this case:

• Basophilic (regenerating) fibers and mildly vacuolated hypereosinophilic (necrotic) fibers.
• No significant inflammatory cell infiltrate.
• Alkaline phosphatase dark regenerating fibers.
• Compliment C5b-9 (Membrane Attack Complex) positive necrotic fibers.

This is a setup for necrotizing myopathy. Common etiologies:

• Toxic myopathy (e.g. statin therapy)
• Immune-mediated necrotizing myopathy (IMNM; often with positive SRP or HMGCR serology)
• Partially treated idiopathic (acquired) inflammatory myopathy (myositis)
• Other etiologies include antisynthetase syndrome, and paraneoplastic, metabolic, endocrine (thyroid), or infectious (viral) myopathies.

However this month, all of the cases have the same history! It’s one patient with 4 concurrent, likely related diagnoses:

• Vasculitis of small muscular artery
• Myopathic changes
• Chronic active neurogenic changes
• MxA reactivity with perimysial pathology

Reference(s) / Additional Reading:

• Conticini E. Inflammatory muscle involvement in systemic vasculitis. Autoimmun Rev. 2022;21(3):103029.
• Waisayarat J. Sarcoplasmic Myxovirus Resistance Protein A. J Inflamm Res. 2023;16:5417-5426.
• Xing C. Myxovirus resistance protein A (MxA) expression in myositides. Muscle Nerve. 2024;69(5):548-555.
• Biopsy Diagnosis of Peripheral Neuropathy, 2nd Edition. JM Bilbao and RE Schmidt, eds. Springer, New York. 1995, 484 pp.