Dermatomyositis: its relationship with immunity and the advancement of clinical analysis

Dermatomyositis is an inflammatory disease of unknown cause characterized by muscle weakness, which causes characteristic skin manifestations such as red spots. This chronic disease can be associated with histocompatibility antigens, viruses, drugs and autoimmunity.

 

What is dermatomyositis?

Dermatomyositis (DM) is a rare idiopathic inflammatory myopathy that affects adults and children, mainly females, considered a heterogeneous disorder with several phenotypes, including myositis (inflammation of the muscles), dermatitis (inflammation of the skin) and interstitial lung disease (respiratory diseases characterized by inflammation and/or scarring of the lung tissue resulting in respiratory failure). With a prevalence of 10 to 60 cases per million inhabitants/year.

Typical skin symptoms may appear from six months to two years before muscle involvement (amyopathic dermatomyositis) in a slow and progressive manner, and include:

  • Red spots on the body (mainly on the face)
  • Heliotrope rash (swelling and purple or reddish spot around the eyelids)
  • Gottron papules (red spots on the elbows, knees, ankles, and joints of the fingers and toes)
  • Cuticular changes including periungual telangiectasia 
  • Photodistributed erythema or poikiloderma 
  • Scaly alopecia
  • Calcinosis on bony prominences

These skin lesions can usually appear or become more evident after exposure to sunlight.

The main muscles affected are those located in the thighs and in the proximal part of the arms. Muscle symptoms include:

  • Fatigue
  • Muscle weakness
  • Change in the respiratory musculature
  • Difficulty climbing stairs
  • Difficulty raising the arms

Less commonly, individuals with dermatomyositis may also experience systemic symptoms such as arthritis, esophageal disease, shortness of breath and difficulty in swallowing or speaking, and involvement of other organs such as the heart, lungs, and intestine. Some studies suggest that individuals over 60 years of age may be at higher risk of developing cancer, especially ovarian cancer.

Eventually the disease can present only with muscle manifestations (polymyositis), more frequent in adults compared to children (which delays the diagnosis and makes it more difficult), and more rarely, only with cutaneous manifestations (amyopathic dermatomyositis).

 

Difference between adult and juvenile dermatomyositis

We call it juvenile dermatomyositis when the disease starts before the age of 16. Being a very rare disease with an overall incidence of approximately 2 to 4 per million individuals, heterogeneous with variable clinical evolution, organ involvement and, being frequently complicated by the development of calcinosis, a condition characterized by the deposition of calcium salts under the skin and in soft tissues like muscles, tendons, and fat.

In dermatomyositis, it is common for children to report pain in the body and muscles, fever, dysphagia, difficulty raising the arms (such as combing the hair), climbing stairs, rising from the floor. Joint pain or swelling, difficulty swallowing, regurgitation or vomiting, coughing, difficulty breathing, and frequent falls may also occur.

 

What causes dermatomyositis? 

So far there is no definite cause. It is known that the development of the disease is related to an immunological disorder and associated with a genetic predisposition, which result in inflammation of the blood vessels (vasculitis). Virus or bacterial infections can precede the onset of symptoms. However, the role of these agents in triggering the disease is still uncertain.

 

What is the relationship between dermatomyositis and genetic predisposition?

The cause of autoimmune myositis appears to be an autoimmune reaction to muscle tissue in people with genetic susceptibility. In which, the human leukocyte antigen (HLA) subtypes DR3, DR52, and DR6 appear to be genetic predisposing. 

The association of the disease with the subtypes of human leukocyte antigens (HLA) is so important that the subclassification of dermatomyositis (DM) has been proposed in two large immunogenetic groups: HLA DRw52 (more severe myositis and worse prognosis) and HLA DRw53 (less severe myositis with better prognosis). Familial DM is rare, some cases have been described, mainly in juvenile dermatomyositis.

 

What are the viral factors that can trigger dermatomyositis? 

Viral infections can trigger DM. Influenza A, hepatitis B, Coxsackie, Echovirus, HIV, HTLV, and Picornavirus infections have been found in muscle cells, however their importance is not known, and viruses can trigger similar disorders in animals. 

 

– Other factors that can trigger dermatomyositis 

Other possible triggering factors include neoplasms and drugs. The association of cancer with dermatomyositis (except with polymyositis) suggests that a tumor can be triggered by an immune response against a common antigen present in muscle cells. Its association occurs in up to 30% of cases. The association with drug products has been reported in cases after the use of sulfonamides, penicillin, progesterone, isoniazid, and D-penicillamine.

 

Autoantibodies and Dermatomyositis

The clinical picture and the evolution of the disease are associated with the production of specific antibodies. There are two groups of autoantibodies: myositis-specific autoantibodies (MSAs) and myositis-associated autoantibodies (MAAs). By definition, myositis-specific autoantibodies (MSAs) are found only in patients with idiopathic inflammatory myopathies (dermatomyositis, polymyositis, inclusion-body myositis and necrotizing myopathies) and are associated with clinical characteristics of the dermatomyositis spectrum, aiding in the diagnosis and subclassification of patients for increasingly specific clinical care. While the myositis-associated antibodies are generally found in mixed connective tissue diseases with myositis. 

Specific antibodies against tRNA synthetase (anti Jo-1, anti-PL7, anti-PL12, anti-EJ, anti-0J) and antinuclear antibodies (ANA) are seen in up to 80% of patients and are important for identifying other overlap syndromes.

Recent studies have shown that autoantibodies can be identified in 60–95% of patients with juvenile dermatomyositis and provide an additional degree of phenotypic refinement, in addition to histopathological correlation, as they are associated with characteristic combinations of systemic and cutaneous phenotypes and, even in the absence of a common autoantibody testing platform, the recognition of these patterns and combinations can help in the diagnosis of dermatomyositis.

 

How is the diagnosis of dermatomyositis made?

The diagnosis of dermatomyositis is based on clinical manifestations and alterations in laboratory tests. Muscle enzymes such as creatine phosphokinase (CK), lactate dehydrogenase (LDH), aldolase, and transaminases (AST and ALT) are usually elevated. Muscle biopsy, skin biopsy and electroneuromyography (ENMG) are usually performed in cases of atypical presentation or when the diagnosis is not clear. Imaging tests such as ultrasound and nuclear magnetic resonance can also be performed to locate the best muscle group for biopsy.

The inconsistent clinical presentation creates a diagnostic challenge. In 2017, significant heterogeneity among patients with dermatomyositis led the European League against Rheumatism and the American College of Rheumatology to publish new classification criteria for adult and juvenile idiopathic inflammatory myopathies and their main subgroups.

Strategies to better define homogeneous subgroups of patients with dermatomyositis are essential to facilitate the diagnosis, inform the prognosis and allow new and existing therapies. In addition, myositis-specific autoantibodies are important auxiliary tools for the diagnosis and subclassification of patients that will guide increasingly specific clinical care in the future.

 

How to treat dermatomyositis

The treatment of dermatomyositis is performed according to the manifestation of the clinical symptoms presented by the patients, but generally includes the use of:

  • Corticoids to help reduce inflammation;
  • Immunosuppressants to decrease the immune system’s response;
  • Other medications to treat dermatological symptoms

These medications, in most cases, are used for extended periods (for one or more years) and are intended to reduce the inflammatory process and control the symptoms of the disease.

Physiotherapy helps to relieve symptoms and avoid possible contractures and retractions. The use of sunscreens (photoprotection) is also recommended to avoid worsening skin lesions.

The treatment of calcinosis can be carried out with the use of calcium-chelating agents such as diphosphonates, aluminum hydroxide and a low calcium diet. Epidemiological data show that the disease prognosis in children is better than in adults.

 

What test does SYNLAB offer for Dermatomyositis?

Since the analysis of myositis-specific antibodies is considered an important auxiliary tool for the diagnosis and subclassification of patients, and it can also contribute with key additional information on the prognosis of the disease, SYBLAB offers a panel of antibodies that analyzes the main antibodies related to dermatomyositis in the patient’s serum, namely: MDA5, TIF1, NXP2, SAE1, KU, MI2a, MI2b, PL12, PL7, SRP, PM-Scl100, PM- Scl75, JO1, EJ, OJ, RO52.

Detection is performed using an immunoblot technique, and the kits used to characterize the presence of these specific antibodies contain reagents with antigenic epitopes that allow the binding of only specific antibodies that may be present in the patient’s blood. 

The exam is available on our extranet, click here.

 

About the SYNLAB Group

The SYNLAB Group is a leader in providing medical diagnostic services in Europe, providing a full range of clinical laboratory analysis services to patients, healthcare professionals, clinics and the pharmaceutical industry. Resulting from the Labco and Synlab merger, the new SYNLAB Group is the undisputed European leader in medical laboratory services.

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