Etiology of SLE and Idiopathic Inflammatory Myopathies

Kostas N. Botsoglou, MD: The etiology of these chronic autoimmune conditions, including lupus and idiopathic inflammatory myopathies, is unknown. However, it’s multifactorial, and many observational studies have suggested a role for genetic, hormonal, immunologic, and environmental factors. In lupus, the clinical manifestation may be mediated either directly or indirectly by antibody formation, and that’s the creation of the immune complexes. Antibodies can also be seen on cell surface antigens, such as those of the phospholipid beta-2 glycoprotein complex. These antibodies are involved in thromboembolic events as well as obstructive complications. When it comes to the skin lesions in lupus, this again is thought to be of multifactorial origin. It is and suspected that ultraviolet light has local effects on the skin and may increase the degree of autoimmunity. In terms of the inflammatory myopathies, this includes dermatomyositis, polymyositis, the antisynthetase syndrome, immune-mediated necrotizing, and inclusion body myositis; they share the common feature of immune-mediated muscle injury. The clinical and histopathologic distinctions between these conditions suggest that that different pathogenic processes are part of the underlying myopathies. However, the precise mechanism leading to tissue injury in the inflammatory myopathies is still not completely defined.

The manifestations in these conditions are heterogeneous. Patients can present with a simple skin lesion to a severe organ involvement. Specifically, in lupus, we can see skin lesions consistent with a malar rash or discoid lesions. We may see scarring or nonscarring patchy alopecia, oral or nasal ulcers, as well as inflammatory joint symptoms, which tend to be polyarticular and symmetric. In addition, patients with muscular manifestations typically present with a gradual onset of proximal muscle weakness, and this is usually manifested by elevated muscle enzymes. Extra-muscular presentations can include cutaneous manifestations; lung involvement, such as interstitial lung disease; and systemic features, such as rheumatoid arthritis or systemic sclerosis.

A differential diagnosis that should be considered in patients with these autoimmune conditions can include mixed connective tissue disease, characterized by overlapping features of SLE [systemic lupus erythematous], systemic sclerosis, and polymyositis. Another consideration should be vasculitis and malignancies, such as leukemia or myelodysplastic syndromes. Specifically for the myopathies, we should rule out any myopathy related to hypothyroidism, muscular dystrophies, and drug-induced or metabolic myopathies.

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