Disease Info

Overview – What are IIMs?
Clinical overview of the diseases

Idiopathic inflammatory myopathies (IIMs) are a large heterogeneous group of autoimmune diseases whose common denominator is the involvement of striated skeletal muscles.
IIMs are chronic, systemic diseases that may also affect the skin, joints and lungs. Recent advances have led to a subdivision of this group into four main categories:

1. Dermatomyositis 
2. Immune-mediated necrotizing myopathies
3. Inclusion body myositis
4. Overlap myositis, including antisynthetase syndrome and scleromyositis 

Epidemiology   

IIMs incidence is about 8 cases per million inhabitants per year. They have been described in the five continents. It has increased during the last 50 years, which may reflect progress in diagnostic performance but also true modification of the epidemiology. Adult onset is about 10-fold more frequent than juvenile onset. Women are about 2-fold more frequently affected than men. 

Clinical overview of the disease  

Myopathy (proximal muscle weakness, dysphagia and/or elevated serum levels of creatine kinase) is the common denominator of IIMs. However, IIMs are systemic disease whose symptoms also include skin rash, polyarthritis, interstitial lung disease, Raynaud’s phenomenon and/or myocarditis. These extra-muscular symptoms can inaugurate the disease while myopathy can be absent (amopathic forms) or may be very mild (hypomyopathic forms). 

Risk factors and possible causes  

The causes of IIMs are partially known and depend on the subtypes of IIMs. 

Immunogenetics factors explain only about 20% of the disease. IIMs are not genetic myopathies. 

Several environmental factors have been highlights and linked with different subgroups of IIMs:  

• A cancer is associated with IIMs in 10% of the case (especially dermatomyositis and necrotizing myopathy without antibodies, see below “diagnosis”)
• Ultraviolet radiation plays a role in the onset and relapses of dermatomyositis
• Viral infections have been linked with the onset of several subtypes of IIMs
• Some drugs have been associated with the onset of IIMs. The most common are statins (associated with autoimmune necrotizing myopathies with anti-HMGCR autoantibodies) and immune checkpoint inhibitors (associated with a peculiar form of IIMs)
• Smoking has been involved in antisynthetase syndrome with anti-Jo1 antibodies

MULTIDISCIPLINARY DIAGNOSIS AND MULTIDISCIPLINARY TEAMS TREATMENT IN IDIOPATHIC INFLAMMATORY MYOPATHIES (IIM)
Speakers Prof. Louise Diederichsen, ePAGs Olga Drápalová and Silke Schlüter, moderator Prof. Ingrid Lundberg.
Sept. 25th, 2024 – 16.00 CEST.

Common symptoms  

– Myopathy in IIMs typically affects the upper and lower limb–girdles. It consists in weakness, leading to difficulty to walk, climb stairs and carry heavy loads. In up to two third of the cases, myopathy affects swallowing muscles (dysphagia). The severity of the myopathy varies widely, ranging from normal strength to loss of walking ability and/or impossibility to eat. Myalgia can be present or absent, being  not a reliable sign of myopathy.
The serum levels of creatine kinase (a muscle enzyme) is generally increased. The onset is generally over several months. Yet, in some cases, myopathy occurs over several years that can lead to a misdiagnosis of a genetic myopathy. A peculiar form of IIMs, inclusion body myositis, is characterized by weakness prevailing on finger flexors and quadriceps muscles. 

– Skin involvement is present in half of the patients. It consists of a rash over the eyelids (heliotrope rash), rashes and/or papules on the extensor surfaces of joints (Gottron’s sign and/or papules) that are mostly seen in patients with dermatomyositis. It can masquerade lupus rash. Hyperkeratosis and fissures of the fingers of the hands (mechanic’s hands) and/or the feet (hiker’s feet) are mainly seen in antisynthetase syndrome. It can masquerade psoriasis. Skin thickening is mainly seen in scleromyositis.

– Joint involvement affects 30% of the patients. It consists of inflammatory arthralgia and/or arthritis of the small joints of the hands and/or feet. It is more frequent in antisynthetase syndrome, dermatomyositis and scleromyositis. It can masquerade rheumatoid arthritis, but is usually non-erosive.  

 – Lung involvement affects 30% of the patients. It consists of cough and/or dyspnea. It is more frequent in antisynthetase syndrome, dermatomyositis and scleromyositis. A high resolution chest CT scan and pulmonary function tests are necessary to diagnose and monitor this involvement. It can masquerade idiopathic fibrosis

– Raynaud’s phenomenon affects 30% of the patients. It is more frequent in antisynthetase syndrome, dermatomyositis and scleromyositis. Digital ulcer tips can occur. It can be distinguished from primary Raynaud’s phenomenon with capillaroscopy.  

– Heart involvement affects about 9 % of the patients. It consists of chest pain, dyspnea and or stroke. Echocardiography, ECG and sometimes cardiac MRI are needed to diagnose and monitor this involvement. 

When to see a doctor  

Weakness, skin rash, arthralgia, cough, dyspnea, Raynaud’s phenomenon are the main signs that should lead to a consultation. 

Diagnosis (PATH/ TESTS / DIFFERENTIAL DIAGNOSIS) 

In a patient with one or more of the signs listed above, two diagnostic tools should be considered. They should be performed in an expert center for IIMs. 

Autoantibodies detection. IIMs are autoimmune diseases. The majority of the patients have autoantibodies that can be detected in the blood. About twenty different autoantibodies can be detected with commercial kits and have been shown to be useful for diagnosing and classifying IIMs.  

Recorded Webinars

The most frequent autoantibodies in IIMs are:  

• Dermatomyositis: anti-Mi2, -TIF1-y, -NXP2, -SAE, -MDA5 
• Antisynthetase syndrome: anti-Jo-1, -PL7, -PL12, -OJ, -EJ, -KS, -Ha, -Zo
• Autoimmune necrotizing myopathies: anti-SRP, -HMGCR 
• Scleromyositis: anti-U1-RNP, -PM/Scl, -Ku, -U3-RNP 

In around 20% of patients, no autoantibodies are detected. These patients are believed to have autoantibodies which have not yet been discovered or for which no available detection technique exists in current practice. 

Muscle biopsy. Muscle biopsy consists in the removal of a small piece of the skeletal muscle for histological (and sometimes biochemical and/or molecular examination). Despite the progress in autoantibodies detection, it is still a crucial step in the diagnosis and the classification of IIMs.  

Treatment overview  

Treatment should be started as soon as possible in coordination with an expert center for IIMs. The aims of the treatment are to: 

– Induce and maintain remission (or low disease activity) of the disease. The control of the activity of the disease is mandatory in order to restore functionality and to prevent disease damages (see below). This aim will be achieved using:  

1-Induction treatment. Corticosteroids are usually used to achieve remission (or low disease activity). They are generally given at high dose (1 mg/kg/day orally, sometimes in intravenous bolus). To limit the risk of long-term side effects of corticosteroids, these drugs are gradually tapered and eventually discontinued when possible.  

2-Maintenance treatment. To maintain remission upon corticosteroids tapering, immunomodulatory drugs are prescribed, generally starting at the same time as corticosteroids. These drugs will be pursued for several years. The choice of the immunomodulatory drug depends on the subtype of the IIMs and of the organ involvement. The prevention of the flares with photo-protection (especially in dermatomyositis), tobacco cessation (especially in antisynthetase syndrome) are also important measures. 

– Limit and reverse the damage of the disease. As opposed to disease activity, damage is the cumulation of residual manifestations associated with sequelae that do not respond to immunomodulators. They include sarcopenia, skin depigmentation, calcinosis… Early initiation and tight control of the disease limits the risk of damage. Exercise is effective to reverse muscle damage and should be systematically implemented. Surgery can be used to treat calcinosis. 

– Research and treat an associated cancer. In 10% of the patients, a cancer is associated with IIMs. In these cases, the treatment of the cancer will generally also treat the IIM. The risk of an associated cancer depends on the IIMs subtype. Cancer screening and monitoring should be performed at diagnosis and in some cases up to 3 years after diagnosis depending on the risk. 

– Restore functionality. Myositis can have a dramatic impact on functionality and activities of daily life. Early treatment, including active physical and occupational therapy from the start can minimize this impact. 

– Prevent comorbidities. The risk of infections, cardiovascular events and/or osteoporosis is increased in IIMs because of the disease and its treatments. This risk can be decreased with vaccinations, diet, exercises and some preventive drugs when needed. 

 – Cope with the disease. Therapeutic education, and interaction with peers through patients’ associations are crucial supports to cope with IIMs. 

Prognosis  

Current treatments are generally needed for several years to maintain the control of IIMs. Several studies have indicated that the prognosis of IIMs has improved over the last decades. Yet, important improvements in the delay of diagnosis and the current conventional cares are needed to increase life expectancy and quality of life that are still significantly affected by these diseases. 

New guidelines (since state of the art) 

Antibodies
Damoiseaux J, et al. ENMC 256th Workshop Study Group. 256th ENMC international workshop: Myositis specific and associated autoantibodies (MSA-ab): Amsterdam, The Netherlands, 8-10 October 2021. Neuromuscul Disord. 2022. 

Capillaroscopy 
Piette Y, et al. Standardised interpretation of capillaroscopy in autoimmune idiopathic inflammatory myopathies: A structured review on behalf of the EULAR study group on microcirculation in Rheumatic Diseases. Autoimmun Rev. 2022. 

Management of IIM
Oldroyd AGS, et al. British Society for Rheumatology guideline on management of paediatric, adolescent and adult patients with idiopathic inflammatory myopathy. Rheumatology (Oxford). 2022.

Bader-Meunier B, et al. French Network of rare autoimmune, autoinflammatory diseases FAI2R. French expert opinion for the management of juvenile dermatomyositis. Arch Pediatr. 2019. 

Romero-Bueno F, et al. Recommendations for the treatment of anti-melanoma differentiation-associated gene 5-positive dermatomyositis-associated rapidly
progressive interstitial lung disease. Semin Arthritis Rheum. 2020.

 AWMF Leitlinienregister 

DeWane ME, et al. Dermatomyositis: Clinical features and pathogenesis. J Am Acad Dermatol. 2020.

Waldman R, et al. Dermatomyositis: Diagnosis and treatment. J Am Acad Dermatol. 2020.

Lim D, et al. Current concepts and advances in dermatomyositis: a dermatological perspective. Clin Exp Rheumatol. 2023.

Patient organisations 

Denmark. The myositis group in under the umbrella of the Arthritis Association
Tove Wolf – tovewolf(at)mail.tele.dk – Linda Rath –  lindarath(at)email.dk 

Czech Republic. The Czech Myositis Working Goup (CMWK) operates under the umbrella of the Czech League against Rheumatism  (CLAR)
Olga Drápalová – olga.drapalova(at)revmaliga.cz 

Germany. The German Myositis-Group (Myositis-Gruppe) within the German Society for Neuromuscular Diseases (Deutsche Gesellschaft für Muskelkranke e.V.  – DG)  
Silke Schlüter: silke.schlueter(at)dgm.org 

Dutch. Dutch Myositis Working Group (DMWG) under the umbrella of Spierziekten Nederland (Dutch Patient association for neuromuscular diseases)
Ingrid de Groot: Ingrid.de.groot(at)upcmail.nl 

Sweden. The Swedish Myositis Working Group (Riksförening för myositsjukdomar) within the Swedish Rheumatism Association (Reumatikerförbundet)  
Anneli Dihkan – anneli(at)eneby.nu 

United Kingdom. Myositis UK
Irene Oakley – irene(at)myositis.org.uk 

Begium, Flemish. CIB-Liga (Chronische Inflammatoire Bindweefselziekten), under the umbrella of ReumaNet 

Portugal. myositis group is under umbrela of – Associação Portuguese de Doentes Neuromusculares 

France. AFM TELETHON – Groupe d’intérêt GIMI
Anne-Elisabeth LAUNAY – aelaunay(at)afm-telethon.fr 

Additional ERN ReCONNET publications are available for consultation.