The IIM are systemic connective tissue diseases, and many other organ systems can be involved, resulting in a wide range of possible presentations and symptoms that can mimic many other disorders. Thus, the differential diagnosis of IIM includes the many disorders associated with muscle complaints and is considerably challenging, not only because of the plethora of conditions to be considered, but also because IIM are so rare that few clinicians are thoroughly familiar with these diseases. One begins with clearly defining the patient’s primary problems. Since patients may use “weakness” and “pain” interchangeably, questions should focus on (1) distinguishing myalgias from true weakness, which is often painless, by focusing on the patients’ functional abilities (what they can and cannot do in their daily routine) (2); the location of weakness (proximal muscles in PM and DM vs. distal muscles in IBM and other disorders; symmetric weakness in PM and DM vs. asymmetric muscle involvement in IBM and other disorders) (3); the time frame and tempo of symptom progression and whether atrophy is present, signifying a chronic course most consistent with dystrophies (4); and any associated nonmuscular symptoms such as fatigue, low-grade fevers, rashes, breathing or swallowing difficulties, arthritis or arthralgias, which suggest a systemic disease, such as IIM.

Next, one needs to consider possible causes. Has the individual been exposed to any myotoxins, licit or illicit drugs, botanical or other over-the-counter preparations that could result in myopathy, or a metabolic abnormality such as hypokalemia? Has the patient had any recent unusual exposure, infection, or travel? Are there any symptoms or findings that suggest thyroid or parathyroid disease, diabetes, or an underlying malignancy? Is there a family history of a similar disorder that would suggest a dystrophy or inherited myopathy?

Criteria to define the IIM syndromes and distinguish them from other myopathies were proposed more than 30 years ago (4) and remain useful today. Since these are diagnoses of exclusion, one must first do an evaluation directed by the history and physical examination findings to exclude the many other causes of myopathy. Once this has been accomplished, a diagnosis of IIM can be made using the findings of acute or subacute symmetric proximal muscle weakness, significant elevation of muscle enzymes, characteristic EMG abnormalities, and muscle biopsy findings or rashes consistent with IIM (Table 13.1). In unclear cases, additional clues that can assist in making the diagnosis of IIM include the presence of antinuclear antibodies (ANA) or myositis autoantibodies (5), a family history of autoimmune disease, detection of inflammatory changes in muscles by magnetic resonance imaging (MRI) (6), or a clinical response to immunosuppressive therapy (Table 13.2).

Inclusion body myositis is the most common IIM occurring in patients older than 50 years. Patients with IBM usually fulfill the IIM criteria, but in contrast, have more slowly progressive weakness of the quadriceps and distal muscles of the arms, in a somewhat asymmetric fashion; lower elevations of serum CK levels; and characteristic amyloid deposits and rimmed vacuoles within myocytes seen on light microscopy. Some inflammatory changes may be present, but amyloid deposition predominates. Although some patients may initially improve with immunosuppressive treatments, most have a gradual and relentless progression of muscle weakness.

Cancer-associated myositis is another IIM disorder, and on the basis of population studies (7), can be considered if both diagnoses are made within 2 years of one another. Treating the underlying cancer generally also treats the myositis. Although molecular genetic studies have identified genes responsible for many dystrophies, metabolic, and mitochondrial myopathies, some patients continue to defy diagnostic evaluations and remain enigmas.