There has long been debate on what is the most sensitive and specific marker that distinguishes Dermatomyositis (DM) from Polymyositis (PM) or Inclusion Body Myositis (IBM), and further whether anti-synthestase syndromes (ASS) should be included under DM.
Where subjects present with a skin rash and muscle weakness with one of 5 DM specific autoantibodies, i.e. Mi-2, NXP-2, MDA-5, TIF-1gamma or SAE, the diagnosis of DM is straightforward. Given the difficulty in obtaining muscle biopsies within the NHS, particularly in DGHs, most Rheumatologists would settle for a diagnosis of DM in this scenario, particularly if the EMG too is characteristic of a myopathy.
But what if DM presents without a skin rash, as it can in approximately 8% of subjects. The distinction between DM one one hand and PM, IBM and ASS on the other is more than academic, firstly because of a higher association of cancer with the former, and secondly because of increasing reports of efficacy of JAK inhibitors for DM but not the other conditions.
In this situation, two tests can be useful. The first requires a muscle biopsy, and the second is included in the DM specific autoantibody panel.
First, the staining of the sarcoplasm of muscle for Myxovirus Resistance Protein A (MxA) is highly sensitive (76%) and 100% specific for DM. This is a Type I interferon induced protein and therefore an interferon signature. It is not seen in PM, IBM or ASS. Unlike the latter three, DM is an interferonopathy (which is why it responds to JAK inhibitors).
While other interferon signatures such as RIG-1 and ISG-15 are also quite specific for DM, as indeed are muscle biopsy findings of perifascicular atrophy (PFA) and deposition of membrane attack complex on capillaries, none of these are as sensitive as MxA. (While ASS also displays PFA on biopsy, the characteristic necrotic and regenerating fibres in perifascicular fibres sets it apart from the mainly degenerative fibres seen in DM).
The other useful marker of Dermatomyositis sine (without) dermatitis is the muscle specific antibody NXP-2. This is seen in fully 86% of subjects who have DM without skin involvement at presentation, but only in 28% of subjects who have DM with rash. Therefore, a subject presenting with myositis, but no rash and a positive NXP-2 should be treated as DM rather than PM. In a minority of such subjects, a typical rash may appear after many months or even years.
DM sine dermatitis should not be confused with amyopathic DM, which is characterised by rash and lung involvement without muscle involvement. Most such subjects are positive for MDA-5 and have a severe lung phenotype.
References
1. https://jamanetwork.com/journals/jamaneurology/fullarticle/2764337
2. https://pubmed.ncbi.nlm.nih.gov/30267437/
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