Misdiagnosis of Inclusion Body Myositis: Two Case Reports and a Retrospective Chart Review

Amaiak Chilingaryan; Richard A. Rison; Said R. Beydoun

Disclosures

J Med Case Reports. 2015;9(169) 

In This Article

Discussion

s-IBM is both a myodegenerative and neurodegenerative disease with β-amyloid-related deposits and an inflammatory disease with endomysial lymphocytic infiltration. Accumulation of misfolded proteins and inadequate intracellular repair mechanisms characterize the disease.[10] There is also expression of major histocompatibility complex (MHC) class I molecules.[3] A 43 kDa muscle protein, recently identified as cytosolic 5′-nucleotidase 1A, was discovered in 2013 as an autoantigen for s-IBM autoantibodies.[11–13] This finding indicates the potential role of humoral immunity in the pathogenesis of the disease in addition to a cytotoxic T-cell-mediated component. Furthermore, identification of this target of s-IBM autoantibodies could lead to the development of a diagnostic blood test, potentially eliminating the need for invasive testing such as muscle biopsy.

Although muscle biopsy can confirm the diagnosis of s-IBM, the results may be negative owing to sampling error or to end-stage muscle wasting. Endomysial inflammation and degeneration with misfolded protein aggregates and/or inclusions[10] and atrophic fibers[14] are often present. Congo red staining or immunofluorescence shows amyloid β-pleated sheets in and around vacuoles.[3] There are rimmed vacuoles within the myofibril. In cases where the inclusion bodies are not found, the presence of inflammation alone can lead to an erroneous diagnosis of PM.[4,15] If there is no definite diagnosis, then biopsy should be repeated.

Currently, there is no cure for s-IBM. Some patients may initially show a limited response to corticosteroids. Other treatments available for inflammatory myopathies have efficacy in s-IBM in specific cases.[3,16] Patients with dysphagia may benefit from intravenous immunoglobulin (IVIG) therapy, along with balloon dilation or botulinum toxin injection.[16–20] Although this disease is rare and incurable, making the correct diagnosis is crucial to directing the patient to physical therapy for weakness, gait training, and education to prevent falls. Occupational therapy may improve a patient's ability to engage in activities of daily living. Appropriate patients with swallowing complaints should be referred to a speech therapist for proper education regarding diet consistency and aspiration precautions. Patients may be assured that s-IBM is not a motor neuron disease or a rapidly deteriorating myopathic condition that is life-threatening.[6]

Our university neuromuscular clinic sees approximately six new patients with s-IBM each year. The median age of the predominantly male population in our present report was 69 years, and patients' ages ranged from 43 to 85 years. The median time from symptom onset to final diagnosis was 54 months and ranged from 6 months to 20 years, reflective of the slow disease course that helps to differentiate s-IBM from other disease mimickers. Experienced neurologists and neuromuscular specialists can diagnose s-IBM based on its topography of weakness of quadriceps and forearm flexors, but the diagnosis is often missed, delayed, or incorrect. Common misdiagnoses are PM, immune-mediated neuromuscular disease, entrapment neuropathies, and motor neuron disease. Erroneous diagnosis can lead to inappropriate therapy, as illustrated by some of the cases described here and in a previous report of patients who received years of corticosteroids and immunosuppressive medication and experienced serious side effects.[6] IVIG was previously used for treatment of s-IBM until a controlled clinical trial showed lack of efficacy.[2] Needless surgical treatments for radiculopathy or entrapment neuropathy have occurred, as illustrated by patient 5 in our series.

Although s-IBM is a well-recognized neuromuscular diagnosis that is seen in neurology and neuromuscular specialty clinics, it is well known that it can masquerade as other disorders.[6] The cases described here confirm and highlight the fact that s-IBM is still difficult to diagnose and remains frequently misdiagnosed. Our data show that the time to diagnosis averaged 5.83 years, a delay similar to that described by Lotz and coworkers in 1989.[21] The fact that this has remained unchanged for 25 years is disappointing but not entirely surprising, given the symptoms and neurological topography, including asymmetric weakness, finger flexor weakness, loss of grip strength, gait difficulty, and dysphagia, that overlap with those of non-s-IBM conditions. The electrodiagnostic findings in our clinical neurophysiology laboratory in this case series also coincide with previous reports of mixed patterns, which may confuse non-neuromuscular clinicians.

We find several pitfalls in the diagnosis of s-IBM. First is an overreliance on electrophysiology. Second, muscle biopsies sometimes do not have all the cardinal histological features, including endomysial inflammation, newer findings of MHC class II upregulation and invasion of non-necrotic muscle fibers by lymphocytes, and mitochondrial changes.[22–24] Also, clinicians may be misled by an incomplete biopsy appearance, with patchy inflammatory changes being more florid early and patchy degenerative changes more florid later in the disease course. A third pitfall arises when patients present early with either atypical symptoms, such as camptocormia or foot drop, or an incomplete clinical picture. Clues to look for in a clinical examination include long finger flexor and quadriceps weakness, as confirmed in our present study. It has been suggested that s-IBM can be made by clinical diagnosis alone.[25] To the general practice clinician, however, we recommend that all cases of suspected s-IBM be referred to a center specializing in neuromuscular disease so that an appropriate diagnosis can be made and inappropriate treatments are avoided.

Limitations of our study include the relatively small number of patients. Our present study of 20 patients is only half the number of the series previously reported by Lotz and colleagues (40 patients).[21] Also, our study may have university and/or tertiary geographic referral bias, along with limitations of our single-center experience. We do hope that our aforementioned clinical points are clear, however, regarding potential misdiagnosis and the importance of correct diagnosis.

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