Inflammatory autoimmune myopathies

Inflammatory autoimmune myopathies are a group of systemic autoimmune diseases with three distinct clinical expressions: polymyositis (PM), dermatomyositis (DM) and inclusion myositis. Although the criteria for classification are essentially based on the clinical manifestation, autoantibodies (AAb) have been described and may also be very useful in the diagnosis of PM and DM. A distinction must be made between the specific auto-antibodies of these myosites and those associated with “overlap syndrome” in which the patient presents the symptoms of myositis and another autoimmune disease.

Polymyositis

Clinically, PM is characterized by the association of inflammatory myopathy, interstitial pneumonitis, polyarthritis, and cutaneous manifestations of Raynaud’s syndrome type and hyperkeratosis with fissuring (or “mechanic’s hand” syndrome).

From a biological viewpoint, the Ab’s most frequently encountered in the course of PM are anti-tRNA synthetases, hence the term “anti-synthetase syndrome” (ASS); these auto-Abs, of which the most important is the anti-Jo1, generate cytoplasmic fluorescence under indirect immunofluorescence (IFI) of Hep-2/200 cells. The group of anti-synthetases also includes: anti-PL7, PL12, EJ and OJ.

If evidence of the presence of an anti-synthetase is found under IFI, it is essential that its presence is verified by a confirmation technique (Immunodot, ELISA…).
In some cases, the polymyositis may be associated with another autoimmune disease, hence the term “overlap syndrome”:

Anti-PM/Scl (identifying PM75 and PM100 proteins) is a very useful Ab in the diagnosis of “scleromyositis” (polymyositis + scleroderma); Under IFI, its presence may be indicated by ‘speckling’ of the nucleolus on Hep-2/2000 but in this case, too, its presence must be confirmed by another technique.

Anti-Ku is also found in the context of sclerodomyositis or lupus/myositis but is not specific (positivity in the course of other autoimmune diseases).

Dermatomyositis

Clinically, DM combines myositis and characteristic cutaneous signs: periorbital edemas, purplish maculopapular rash in the joints (Gottron’s sign) and erythema of the neckline or back. The most important DM is anti-Mi2, with a speckled finely granular appearance under IFI, which very specific to DM; the prognosis for anti-Mi DM is more favourable than for SAS.

Other antibodies can be found in the context of dermatomyositis: anti-MDA5 (which is often associated with moderate muscular disorders and with which cutaneous and pulmonary affections will predominate), TIF1Υ (often found in a neoplastic context: lung, breast or ENT), anti-NXP2 or P140/MJ (associated with juvenile dermatomyositis).

Necrotizing myopathies

Clinically, these myopathies are distinguished by particularly severe myogenic attacks (massive increase of muscular enzymes), with acute onset, during which the extra-muscular manifestations are less frequent.

Two types of auto-Abs have been described in this myositis: anti-SRP (giving the cytoplasm a finely granular vacuolated appearance under IFI) and more recently anti-HMGcoA reductase (initially demonstrated in patients who have been treated by statins, these Abs have also been demonstrated in statin-naive patients).

As is often the case with autoimmunity, it is essential that the results of the IFI are verified in the clinical, pathological and anatomical context and in the light of the complete blood analysis (muscle enzyme elevation: CPK, aldolase), with an effective dialogue between clinicians and biologists dialogue being the key to a successful diagnosis.