Myasthenia-Inflammatory Myopathy (MG-IM)

Clinical History:

This 60-year-old patient presented with complaints of worsening hand weakness (particularly finger extensors). The weakness initially involved the right hand approximately 2 years ago, but it now also involves the left hand. His past medical history is significant for recent clinical diagnosis of myasthenia gravis. MRI of the right forearm revealed abnormal signal in forearm musculature concerning for a myopathic process. The patient’s past medical history is significant for hyperlipidemia, hypertension and hypothyroidism. Laboratory studies demonstrated positive IgG autoantibodies to titin, mild elevation of CPK (355), normal/negative CRP, ESR, NT5c1A, myositis specific autoantibodies, HMGCR, SSB, SSA and rheumatoid factor.

Muscle biopsy showed morphologic alterations seen in images #1 and #2 of formalin-fixed paraffin embedded tissue sections. No rimmed vacuoles, congophilic inclusions or TDP43-positive protein aggregates were seen to suggest the presence of sporadic Inclusion Body Myopathy. No morphologic evidence of vasculitis was present.

In the context of this patient’s clinical history and morphologic features seen in images #1 and #2, what is your diagnosis?

Answer:

Inflammatory myopathies may occur in patients with other autoimmune disorders (overlap myositis). The concurrence of myasthenia gravis and inflammatory myopathy is uncommon.

• It has been estimated that 20-40% of patients with AChR autoantibodies have titin autoantibodies.
• The presence of titin autoantibodies is enriched in patients with thymic neoplasm-related myasthenia gravis.
• The overlapping clinical features of myasthenia gravis and inflammatory myopathy often result in delay in early diagnosis. The presence of elevated creatine kinase (CPK), myopathic features on electrodiagnostic studies, muscle edema on MRI, and involvement of other organ systems (interstitial lung disease, arthritis/arthralgias, Raynauds phenomenon and skin lesions) are of diagnostic utility as these are not typically present in myasthenia gravis.
• The distribution and degree of muscle weakness in patients with MG-IM can vary and has been characterized as: isolated focal, diffuse distal predominant, and proximal.

Reference(s) / Additional Reading:

• Garibaldi M, Fionda L, Vanoli F, Leonardi L, Loreti S, Bucci E, Di Pasquale A, Morino S, Vizzaccaro E, Merlonghi G, Ceccanti M, Lucchini M, Mirabella M, Andreetta F, Pennisi EM, Petrucci A, Salvetti M, Antonini G. Muscle involvement in myasthenia gravis: Expanding the clinical spectrum of Myasthenia-Myositis association from a large cohort of patients. Autoimmun Rev. 2020 Apr;19(4):102498. doi: 10.1016/j.autrev.2020.102498. Epub 2020 Feb 14. PMID: 32062029.
• Lauletta A, Fionda L, Merlonghi G, Leonardi L, Morino S, Bucci E, Tufano L, Alfieri G, Costanzo R, Rossini E, Salvetti M, Antonini G, Garibaldi M. Distal upper limb involvement in myasthenia-myositis association. Neurol Sci. 2023 Feb;44(2):719-722. doi: 10.1007/s10072-022-06489-8. Epub 2022 Nov 7. PMID: 36336775.