Understanding Dermatomyositis: From Genetic Predisposition to Diagnosis and Treatment

Dermatomyositis is a rare inflammatory disease that affects the skin and muscles, causing progressive muscle weakness and characteristic skin lesions. Although its exact origin is not yet fully understood, genetic, autoimmune, and environmental factors are believed to play a significant role in its development. Additionally, viral infections may act as triggers for the disease in predisposed individuals. 

In this article, we will explore what dermatomyositis is, its possible causes, symptoms, as well as the methods of diagnosis and treatment. We will also discuss the differences between the adult and juvenile forms of the disease. 

What is Dermatomyositis? 

Dermatomyositis (DM) is a rare autoimmune inflammatory myopathy, predominantly affecting women, that can occur in both adults and children. It is a heterogeneous disease with different phenotypes, including myositis (muscle inflammation), dermatitis, and interstitial lung disease (inflammation or scarring of lung tissue that can lead to respiratory failure) (1, 2). Its incidence ranges from 1.0 to 15 cases per million people per year (3). 

The condition is characterized by progressive muscle weakness and typical skin lesions, such as red or purple patches, especially on the face, hands, and sun-exposed areas, primarily affecting the skin and skeletal muscles. 

What Causes Dermatomyositis? 

The exact cause of dermatomyositis is still not fully understood. However, the disease is believed to develop due to a combination of genetic, immunological, and environmental factors, including viral infections, which can lead to inflammation of blood vessels (vasculitis) (4). 

The main factors that may contribute to the development of dermatomyositis include: 

• Genetic predisposition: The presence of specific genetic variants, such as certain HLA genes, may make some individuals more susceptible to developing the disease.

• Environmental factors: External factors, such as viral infections (e.g., enteroviruses or Epstein-Barr virus), can trigger an abnormal immune response leading to disease onset in genetically predisposed individuals.

• Autoimmune factors: The immune system mistakenly attacks the body’s own cells, leading to inflammation in the muscles and skin. This autoimmune response may be triggered by environmental factors or infections.

• Association with malignancies: In some cases, dermatomyositis may be a paraneoplastic syndrome, meaning it is triggered by an underlying cancer, particularly in older adults, such as lung, pancreatic, stomach, and ovarian cancers.

How is Dermatomyositis Related to Genetic Predisposition? 

Dermatomyositis (DM) is considered an autoimmune disease in which the immune system attacks muscle tissue, especially in genetically susceptible individuals. Evidence suggests that certain human leukocyte antigen (HLA) subtypes, such as HLA-DR3, HLA-DR52, and HLA-DR6, are associated with a genetic predisposition to developing the disease (4). 

The association between dermatomyositis and HLA subtypes is so significant that the disease has been classified into two major immunogenetic groups: the HLA-DRw52 group, associated with a more severe form of myositis and poorer prognosis, and the HLA-DRw53 group, linked to a milder form of myositis with a better prognosis (5). 

In addition to HLA subtypes, studies suggest that other genetic factors, such as variants in genes related to inflammatory response, may also influence the manifestation of dermatomyositis. The interaction between these genes and environmental factors, such as viral infections and sun exposure, may trigger the disease in genetically predisposed individuals. 

Although familial dermatomyositis is rare, there have been reports of cases, particularly in juvenile dermatomyositis, suggesting a possible genetic component (6). Identifying specific genetic variants may, in the future, help improve prognosis prediction and treatment personalization for patients with dermatomyositis. 

Which Viral Factors Can Trigger Dermatomyositis? 

Several viruses have been implicated in activating the immune system and developing inflammatory responses in muscles, which characterize the disease. 

Among the viruses frequently associated with DM are: 

• Influenza A
• Hepatitis B
• Coxsackie virus
• Echovirus
• HIV (Human Immunodeficiency Virus)
• HTLV (Human T-lymphotropic Virus)
• Picornaviruses

These viruses have been detected in muscle cells of dermatomyositis patients. Studies show that, although viruses are often found in the muscle cells of DM patients, the exact mechanism by which they contribute to disease development has not been fully elucidated (7). 

Some of these viruses, such as HIV and HTLV, have a well-established relationship with muscle disorders, and infection with these agents can trigger immune responses that overlap with dermatomyositis symptoms (8). 

Beyond direct viral infection, these viruses may act as triggers for autoimmune responses in genetically susceptible individuals (9). The immune system, in attempting to fight the viral infection, may start mistakenly attacking muscle tissue, leading to the characteristic inflammation of dermatomyositis (10, 11). 

Although evidence suggests that viruses may play a crucial role in the development of DM, the interaction between genetic, viral, and environmental factors remains an area of intense research. Understanding these mechanisms could help in deciphering the disease’s pathogenesis and developing more effective, personalized treatments. 

What Other Factors Can Trigger Dermatomyositis? 

Malignancies and certain medications are other potential triggers for dermatomyositis. 

The association between cancer and dermatomyositis is particularly strong, with studies indicating that up to 30% of DM patients may have a concomitant cancer diagnosis. This link may be explained by an immune response against a common antigen present in both muscle and tumor cells, leading to immune system activation and the characteristic muscle inflammation of the disease (9, 12). 

Additionally, the use of medications has been identified as a triggering factor in some cases (13). Substances such as sulfonamides, penicillin, progesterone, isoniazid, and D-penicillamine have been associated with the development of DM symptoms (14). 

The immune system’s response to these drugs can cause muscle inflammation similar to that seen in dermatomyositis, although the precise mechanism underlying this relationship remains to be fully understood. 

Autoantibodies and Dermatomyositis 

The clinical presentation and progression of dermatomyositis are strongly associated with the presence of specific antibodies. These antibodies are divided into two groups: myositis-specific autoantibodies (MSAs) and myositis-associated autoantibodies (MAAs). 

MSAs, by definition, are found exclusively in patients with idiopathic inflammatory myopathies, such as dermatomyositis, polymyositis, inclusion body myositis, and necrotizing myopathies (15). 

These antibodies are associated with clinical features within the spectrum of dermatomyositis, aiding in both diagnosis and patient subclassification, allowing for more targeted and specific clinical care. MAAs, on the other hand, are generally detected in mixed connective tissue diseases with myositis (16). 

Specific antibodies against tRNA synthetase, such as anti-Jo-1, anti-PL7, anti-PL12, anti-EJ, and anti-OJ, along with antinuclear antibodies (ANA), are found in up to 80% of patients with dermatomyositis. Identifying these antibodies is crucial for diagnosing overlap syndromes, as they help recognize additional phenotypic characteristics. 

Studies have shown that autoantibodies can be detected in 60 to 95% of juvenile dermatomyositis cases (17). These antibodies provide additional refinement in disease phenotype and have a strong histopathological correlation. 

Moreover, these antibodies are often associated with characteristic combinations of systemic and cutaneous phenotypes. Even in the absence of a common platform for autoantibody testing, recognizing specific patterns and combinations can be highly useful in diagnosing dermatomyositis (18). 

What Are the Signs and Symptoms of Dermatomyositis? 

Dermatomyositis symptoms can develop gradually or appear suddenly, varying in intensity. In many cases, skin manifestations emerge before muscle weakness, serving as one of the first signs of the disease. However, there are instances where muscular and cutaneous symptoms appear simultaneously. 

Symptoms can be divided into the following categories: 

Cutaneous Manifestations 

Typical skin symptoms may appear six months to two years before muscle involvement (amyopathic dermatomyositis), progressing slowly. These manifestations may arise or worsen after sun exposure and include (1): 

• Red patches on the body (mainly on the face);
• Heliotrope rash (swelling and purplish or reddish discoloration around the eyelids);
• Gottron’s papules (red patches on the elbows, knees, ankles, and joints of the fingers and toes);
• Cuticular abnormalities, including periungual telangiectasia;
• Photodistributed erythema or poikiloderma;
• Scaly alopecia;
• Calcinosis over bony prominences.

Muscular Manifestations 

Proximal muscles, such as those in the shoulders and hips, are most affected, making activities like climbing stairs or lifting arms difficult. Muscle symptoms include (19): 

• Fatigue;
• Muscle pain;
• Muscle weakness;
• Respiratory muscle impairment;
• Difficulty climbing stairs;
• Difficulty swallowing (dysphagia);
• Difficulty lifting the arms.

Other Systemic Manifestations 

Less commonly, individuals with dermatomyositis may also present systemic symptoms such as (20): 

• Arthritis;
• Esophageal disease;
• Shortness of breath;
• Difficulty swallowing (dysphagia) or speaking;
• Involvement of other organs, such as the heart, lungs, and intestines.

Studies suggest that individuals over 60 years of age may have an increased risk of developing cancer, particularly ovarian cancer (21). 

In some cases, the disease may present solely with muscular manifestations (polymyositis), which is more common in adults than in children—leading to diagnostic challenges and delays. More rarely, the condition may present only with skin symptoms (amyopathic dermatomyositis). 

How Is Dermatomyositis Diagnosed? 

The diagnosis of dermatomyositis is based on the presence of clinical manifestations, complemented by laboratory investigations (22, 23), including: 

• Laboratory tests: Muscle enzyme levels, such as creatine phosphokinase (CK), lactate dehydrogenase (LDH), aldolase, and transaminases (AST and ALT), are usually elevated. The assessment of myositis-specific autoantibodies is also employed.

• Imaging tests: Ultrasound and magnetic resonance imaging (MRI) can help locate the best muscle group for biopsy.

• Biopsy: Muscle biopsy, skin biopsy, and electromyography (EMG) are generally performed in cases with atypical presentation or when the diagnosis is uncertain.

The variability in dermatomyositis clinical presentation poses a significant diagnostic challenge. Due to the considerable heterogeneity among patients, the European League Against Rheumatism and the American College of Rheumatology established new classification criteria in 2017 for idiopathic inflammatory myopathies in both adults and children, including their major subgroups (24). 

Defining homogeneous patient subgroups is essential for improving diagnosis, predicting prognosis, and guiding the use of both novel and established personalized therapies. Additionally, assessing myositis-specific autoantibodies plays a fundamental role as a complementary tool, aiding in patient subclassification and enabling a more targeted clinical approach (25). 

How Is Dermatomyositis Treated? 

The treatment of dermatomyositis is multidisciplinary and aims to control inflammation, relieve symptoms, and prevent complications. The approach includes medications, rehabilitation therapies, and specific skin care to minimize the disease’s impact on the patient’s daily life. 

• Pharmacological Therapies 

The treatment of dermatomyositis is personalized according to each patient’s clinical manifestations. However, it generally involves the use of corticosteroids to reduce inflammation, immunosuppressants to modulate the immune system response, and other specific medications to manage skin symptoms. These medications are typically administered for prolonged periods, often for a year or more, to control inflammation and minimize symptoms. 

• Physical Therapy and Rehabilitation 

Physical therapy plays a fundamental role in managing dermatomyositis, helping to relieve symptoms, preserve and restore muscle strength, improve mobility, and prevent complications such as contractures and muscle atrophy. 

Supervised and personalized exercises, adapted to the stage of the disease, can reduce fatigue, optimize functionality, and improve the patient’s quality of life. Early rehabilitation is essential to minimize strength loss and maintain independence in daily activities. 

• Skin Care 

Since dermatomyositis often causes skin lesions, strict sun protection is essential to prevent worsening of skin manifestations. Daily use of broad-spectrum sunscreen, protective clothing, and avoiding prolonged sun exposure are fundamental measures. 

What Is the Difference Between Adult and Juvenile Dermatomyositis? 

Dermatomyositis can appear at any age and is classified into two main types: juvenile dermatomyositis, which occurs before the age of 16, and adult dermatomyositis, more common in individuals between 40 and 60 years old. 

Juvenile Dermatomyositis (JDM) 

Juvenile dermatomyositis is a rare systemic immune-mediated disease, with a global incidence of 2 to 4 cases per million people (26). It is increasingly recognized as a group of distinct phenotypes, with variable presentations and outcomes. 

JDM is a heterogeneous condition, with variable clinical evolution and potential involvement of multiple organs. One of the most common complications is calcinosis, characterized by the accumulation of calcium salts in the skin and soft tissues, such as muscles, tendons, and fat (25). 

JDM is often associated with a prolonged disease course, a higher risk of vasculopathic complications, and dystrophic calcifications. It also has a significant impact on children’s growth and development. 

The initial symptoms in childhood typically include muscle pain and weakness, fever, progressive difficulty in performing daily activities, such as combing hair, climbing stairs, or getting up from the floor. In addition, symptoms such as joint pain or swelling, dysphagia, reflux, coughing, respiratory difficulties and frequent falls may occur. 

Adult Dermatomyositis (ADM) 

ADM is frequently associated with underlying malignancies, such as lung, ovarian, and gastrointestinal cancers, particularly in patients over 50 years old. Additionally, it presents a distinct pattern of autoantibodies, such as anti-TIF1-γ and anti-NXP2, which help in oncological risk stratification (25). 

Clinically, proximal muscle weakness may have a slower progression, while skin manifestations tend to be persistent. Complications, such as interstitial lung disease and myocarditis, are more common and can impact overall survival. 

The response to treatment varies, and refractory cases may require immunosuppressants or biological therapies. 

What Test Does SYNLAB Offer for Dermatomyositis? 

Since the detection of myositis-specific autoantibodies is considered an important auxiliary tool for diagnosing and subclassifying patients, it can also provide valuable prognostic information. 

SYNLAB offers an autoantibody panel that analyzes key autoantibodies associated with dermatomyositis in the patient’s serum, including: MDA5, TIF1, NXP2, SAE1, KU, MI2a, MI2b, PL12, PL7, SRP, PM-Scl100, PM-Scl75, JO1, EJ, OJ, and RO52. 

The detection is performed using immunoblot technology. The kits used for characterizing the presence of these specific antibodies contain antigenic epitopes, allowing for the binding of only specific antibodies that may be present in the patient’s blood.

Get to know SYNLAB – A Leader in Medical Diagnostic Services! 

Accurate and up-to-date testing is essential for precise diagnoses and better treatment guidance. SYNLAB is here to help. 

We offer diagnostic solutions with rigorous quality control to the companies, patients, and healthcare providers we serve. Present in Brazil for over 10 years, we operate in 36 countries across three continents and are leaders in diagnostic services in Europe. 

Contact the SYNLAB team to learn about our available tests. 

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27. Sociedade Brasileira de Reumatologia. Disponível em: Dermatomiosite Juvenil – Sociedade Brasileira de Reumatologia