REVIEW Clinical Medicine 2017 Vol 17, No 4: 322–8 Idiopathic inflammatory myopathies – a guide to subtypes, diagnostic approach and treatment A u t h o r s : A l e x a n d e r O l d r o y d , A J a m e s L i l l e k e r B a n d H e c t o r C h i n o y C The idiopathic infl ammatory myopathies are a group of condi- E p i d e m i o l o g y tions characterised by infl ammation of muscles (myositis) and other body systems. The diagnosis can be challenging because The IIMs are relatively rare conditions with an overall reported incidence of 11/million person-years (10 for men and 13 for of the many potential clinical features and extra-muscular 3 manifestations, which may be seemingly unrelated. An accu- women) and a prevalence of 14/100,000. ABSTRACT rate diagnosis requires up-to-date understanding of the clini- The peak age range of IIM onset is 45–60 years for adults and cal manifestations, different clinical subtypes and appropriate 5–15 years for children. Apart from inclusion body myositis (IBM), all IIM subtypes occur more commonly in women interpretation of investigations, including newly described 4 serological subtypes. This review will detail the approach to (ratio 2:1); IBM occurs twice as commonly in men as women. the diagnosis of an idiopathic infl ammatory myopathy, based on up-to-date knowledge. The recently updated classifi cation S u b t y p e s criteria and treatment options will also be described. Traditionally, the IIMs have been divided into subtypes according to their clinical features. Recent advances have K E Y W O R D S : Dermatomyositis , idiopathic infl ammatory myopa- identified that more clinically distinct subtypes exist than were thies , inclusion body myositis , myositis , polymyositis originally recognised. Introduction Dermatomyositis and polymyositis The idiopathic inflammatory myopathies (IIMs) are a group Dermatomyositis (DM) and polymyositis (PM) are both characterised by myositis (muscle inflammation) and systemic of autoimmune conditions characterised by inflammation 5,6 of muscle (myositis) and other organ systems, resulting in involvement. Myositis usually involves the proximal widespread organ dysfunction, increased morbidity and early musculature of the limbs leading to weakness and fatigue, mortality. Knowledge of the clinical manifestations of the IIMs especially on tasks such as standing from a seated position or and our ability to treat them have dramatically progressed reaching up for highly placed objects. since publication of the Bohan and Peter criteria in 1975.1,2 T h i s The systemic manifestations (ie involvement of organs other review aims to outline the clinical features of the IIMs, current than skeletal muscle) are important aspects of each disease. Possible systemic features include dysphagia, 7 dysphonia, classification criteria, the association of autoantibodies to 8 9 clinical features and current recommended treatment. interstitial lung disease (ILD), subcutaneous calcification, dilated cardiomyopathy, arrhythmias, atrioventricular defects and constitutional features, such as fatigue, fever and weight loss. DM is particularly associated with an increased risk of Authors: A NIHR academic clinical fellow (rheumatology), Centre for cancer development (cancer-associated myositis). Musculoskeletal Research, University of Manchester, Manchester, Myositis can occur without any other systemic manifestations. UK and NIHR Manchester Biomedical Research Centre, Central This so-called ‘lone PM’ is a rare occurrence and can pose a Manchester NHS Foundation Trust, Manchester Academic Health diagnostic challenge in differentiating this from other causes of Science Centre, Manchester, UK ; B clinical research fellow, NIHR muscle weakness. Manchester Biomedical Research Centre, Central Manchester NHS DM can be distinguished from PM by its typical cutaneous Foundation Trust, Manchester Academic Health Science Centre, features, which include Gottron’s papules (Fig 1 ), Gottron’s sign, Manchester, UK and Greater Manchester Neurosciences Centre, heliotrope rash (Fig 2 ), V-sign rash, mechanic’s hands (Fig 3 ), Salford Royal NHS Foundation Trust, Manchester Academic Health shawl sign rash and erythroderma. 10,11 Gottron’s papules are Science Centre, Salford, UK ; C senior clinical lecturer (rheumatology), red, scaly papules that occur over the dorsal aspect of the NIHR Manchester Biomedical Research Centre, Central Manchester metacarpophalangeal, proximal and distal interphalangeal NHS Foundation Trust, Manchester Academic Health Science joints, whereas Gottron’s sign is the same red, scaly papular Centre, Manchester, UK and Salford Royal NHS Foundation Trust, rash occurring elsewhere on the body. These cutaneous lesions Manchester Academic Health Science Centre, Salford, UK typically worsen with sun exposure. 322 © Royal College of Physicians 2017. All rights reserved. CMJv17n4-Oldroyd.indd 322 7/12/17 10:54 AM Idiopathic inflammatory myopathies Fig 1. Gottron’s papules over metacarpophalangeal and interphalangeal joints in a patient with dermatomyositis. Reproduced with permission from 11 Dugan et al. Fig 3. Mechanic’s hands: scaling, cracking and fi ssuring with bleeding along the lateral and palmar aspects of the fi ngers. Reproduced with permission from Dugan et al. 11 J u v e n i l e D M Juvenile DM has similar clinical features to adult DM and is characterised by myositis, cutaneous features and systemic and feet. 14 Fever, Raynaud’s phenomenon and mechanic’s involvement in patients under the age of 18 years.12 Features hands are also characteristic of the antisynthetase syndrome. particular to juvenile DM include cutaneous ulcerations, Antisynthetase syndrome is defined by the presence of an calcinosis cutis and vasculopathy. antisynthetase autoantibody and ≥1 of the following: > m y o s i t i s A m y o p a t h i c D M > I L D DM can exist without myositis, this uncommon subtype is > R a y n a u d ’ s p h e n o m e n o n termed clinically amyopathic DM. 13 Apart from muscle > M e c h a n i c ’ s h a n d s involvement, the clinical features of clinically amyopathic DM > a r t h r i t i s are the same as typical DM in terms of risk of ILD, cutaneous > f e v e r . manifestations and malignancy. Hypomyopathic disease may be seen in DM patients with magnetic resonance or muscle biopsy Immune-mediated necrotising myopathy evidence of myositis without weakness. Confusingly, patients may also present with histological features of DM without an Immune-mediated necrotising myopathy (IMNM), a rare overt rash (dermatomyositis sine dermatitis). but severe IIM subtype, is characterised by muscle necrosis and regeneration resulting in proximal muscle weakness. 15 In contrast to the previously discussed IIMs, inflammatory Antisynthetase syndrome infiltrates on muscle biopsy are not a predominant feature. The antisynthetase syndrome is a particularly severe IIM IMNM can be idiopathic, may follow viral infections or be subtype associated with myositis, ILD and inflammatory associated with statin use, malignancy or connective tissue symmetrical polyarthritis of the small joints of the hands diseases (CTDs), particularly scleroderma. The statin-associated form of IMNM is associated with autoantibodies directed against HMGCR (3-hydroxy-3-methyl-glutaryl-coenzyme A reductase) and characteristically does not improve despite withdrawal of the statin. IMNM is also associated with presence of the anti-signal recognition particle autoantibody. In the cancer-associated cases, treatment of malignancy (if possible) can lead to resolution of the myopathy. Inclusion body myositis IBM is a condition characterised by both inflammatory and degenerative changes within the muscle. 16 IBM occurs in patients aged over 50 years. The muscle weakness pattern is notable for both proximal and distal involvement with asymmetry being a common feature. The pattern of muscle weakness particular to IBM is early involvement of the finger flexors, ankle dorsiflexors and knee extensors. Head drop and camptocormia may manifest Fig 2. Heliotrope rash over the left eyelid with associated periorbital due to axial muscle involvement. Dysphagia occurs in over half of 17 oedema. Reproduced with permission from Dugan et al. 11 all patients with IBM. The condition follows a slowly progressive © Royal College of Physicians 2017. All rights reserved. 323 CMJv17n4-Oldroyd.indd 323 7/12/17 10:54 AM Alexander Oldroyd, James Lilleker and Hector Chinoy course and is unresponsive to immunotherapy. High degrees of Typical presentation of IIMs disability are seen, especially due to falls and weakness of grip. Diagnosis of an IIM can be straightforward if a patient presents Association with cancer with typical muscle weakness, clear multisystem involvement and a consistent serological profile. However, many patients in The association between the IIMs and increased risk of cancer clinical practice present with non-specific clinical features, such has been well reported. 18–23 The risk of cancer in the IIMs is as fever, fatigue, myalgia and arthralgia. between 2 and 7 times higher than the general population. Acute or subacute symmetrical muscle weakness of the The risk is highest in DM (2–7 times higher) compared to PM proximal arm and leg muscles is typical of the IIMs. Muscle (2 times higher). The risk of malignancy is highest in the year weakness may cause a patient to complain about difficulty in prior to and the year after IIM onset. DM confers a particularly combing their hair or progressive difficulty in rising from a higher risk of lung, ovarian and breast cancer, whereas PM chair. Weakness of other muscle groups may cause dysphonia is more associated with non-Hodgkin lymphomas, lung and or dysphagia. bladder cancer. As previously described, a diagnosis of DM can be suspected Current cancer screening recommendations for a patient newly in the presence of muscle weakness and typical DM cutaneous diagnosed with PM or DM comprise comprehensive history features. and examination, including rectal, breast, pelvic and testicular A patient may first present with an extra-muscular examination.