Juvenile Dermatomyositis

Etiology

Dermatomyositis is an inflammatory myopathy distinguished by a mononuclear inflammatory infiltrate of the striated muscle. Genetic susceptibility is no longer in doubt since predisposing human leukocyte antigen (HLA) systems have been identified. There is an activation of the complement leading to the deposition of the membrane attack complex in the wall of blood vessels, which causes microangiopathy and an inflammatory reaction. Because the disorder appears to have seasonal clustering, it is believed that some infectious organisms may be playing a role in self-tolerance and generation of the autoimmune response. Infections implicated include:

• Parvovirus B19
• Coxsackievirus
• Streptococcus
• Enteroviruses

Non-infectious agents implicated include silica exposure, silicone implants, and medications that decrease lipids. There is a strong association of JDM with HLA-DR3.

Epidemiology

The mean age at onset of the disease is around 7 years, with earlier onset in girls. The mean time between the onset of the first symptoms and confirming the diagnosis is 6 months, ranging from 5 weeks to 2 years. The disorder is more common in females than males; in addition, JDM is more frequent in children of the White population than in other races.

Pathophysiology

It is believed that autoantibodies are directed against an unknown endothelial antigen that is responsible for vascular injury. Both T and B cells appear to play a dominant role in the disease pathophysiology with the generation of numerous cytokines, including interleukin 6 and 17. It appears that type 1 interferon-inducible genes may play a critical role in the pathogenesis of dermatomyositis.

History and Physical

In JDM, the clinical features are usually insidious. Muscle weakness is the main reason for consultation, usually accompanied by systemic signs like asthenia, anorexia, irritability, pain, fever, and deterioration of one's general condition. The dermatological manifestations are like those of adults and are highly characteristic. Their recognition is essential because they can precede muscular signs. The periorbital violaceous patches like frames of glasses are almost pathognomonic as well as Gottron papules.[2][3] These latter are found in 30% to 70% of cases and are easy to recognize.

Violaceous papules are usually seen over the metacarpophalangeal area, the proximal and distal interphalangeal joints of hands, and less commonly, in the extensor surfaces of elbows and knees. One can also observe painful periungual erythema with telangiectasia, cuticular hypertrophy, facial edema, erythematous patches involving the "V-neck," shoulders anterior chest wall, and Raynaud phenomenon. More rarely, there are skin lesions of cutaneous vasculitis and photosensitivity. The muscular deficit is usually progressive, symmetric, bilateral, proximal, and non-selective, involving striated muscles of the pelvis and shoulders. The muscle weakness intensity varies from one patient to another, ranging from simple myalgia to a severe muscle deficit.

Children may report difficulties in dressing, combing hair, and climbing stairs. During evolution, calcinosis may occur more commonly in children than in adults. These calcifications arise from subcutaneous tissues or deeper locations such as musculoaponeurotic structures. The commonest sites of calcinosis include elbows, knees, buttocks, and trauma areas. Its evolution is unpredictable. It can regress spontaneously, and ulcerate with a risk of secondary infections causing major aesthetic and functional sequelae. It can mimic cold abscesses.[4] No standardized approach to the management of calcinosis associated with JDM has been established. Its incidence may decrease with early treatment by systemic corticosteroid therapy at high doses. Experienced physicians are more likely to use bisphosphonates as first-line treatment.[5][6] The involvement of the pharyngeal and esophageal muscles is responsible for dysphonia, dysphagia, and dyspnea, affecting the vital prognosis. Transferring the patient for admission to the intensive care unit is necessary to initiate appropriate treatment.[7] Amyopathic forms of JDM are rare.[8] They are characterized by typical skin manifestations without muscle involvement. Serum muscle enzymes, electromyographic examination, and muscle biopsy are normal. There is usually no calcinosis or vasculopathy. The prognosis is excellent.

Myocardial involvement may cause ventricular arrhythmias. Lipodystrophy usually occurs after a long evolution. The fat loss is slow and progressive, typically affecting the upper part of the trunk. It can be associated with hirsutism, hepatomegaly, and acanthosis nigricans lesions. JDM is associated with a high risk of cardiovascular and cerebrovascular comorbidities.[9] Pulmonary manifestations include interstitial lung disease and respiratory muscle involvement.[10]

Evaluation

An abnormal elevation of serum activities of muscle enzymes is the most common biological finding in JDM.  Elevation of creatine kinase is expected in 75% to 85% of cases with average values around 2000 U/L plus or minus 1000. A normal rate can be observed at the beginning of the disease and in amyopathic forms. Regular creatine phosphokinase monitoring is recommended during the evolution under treatment to evaluate its effectiveness. Other laboratory workups include erythrocyte sedimentation rate, lupus profile, and myositis-specific antibodies.

The electromyogram shows a myogenic pattern. A muscle biopsy confirms the diagnosis. Some histological abnormalities are common to other myositides: myofiber degeneration and an inflammatory mononuclear infiltrate. Other findings are more specific, for example, a highly characteristic perifascicular atrophy, perivascular inflammatory infiltrate, and sometimes intravascular microthrombi. Magnetic resonance imaging is a non-invasive tool used to guide the muscle biopsy site to optimize its sensitivity. Muscle edema is the major abnormality observed on MRI, particularly in the T2 sequence with fat suppression or short tau inversion recovery sequence. This edema is usually proximal and symmetrical but might be focal and distal. The signal intensity seems to be correlated with an aggressive, chronic disease course.[11]

Treatment / Management

Systemic corticosteroids are the established primary treatment for the management of JDM. As yet, there is no consensus regarding the dose regimen and the therapeutic modalities. It is recommended to initiate the treatment with 1 milligram per kilogram of daily equivalent prednisone. Intravenous treatment is preferable in the case of gastrointestinal involvement. This late is known to be associated with vasculitis causing malabsorption. Long-term steroid treatment is usually required to achieve complete remission. It should be gradually decreased. Adjunctive hygienic-dietary measures, as well as daily supplementation with calcium and vitamin D,  must be systematic. However, these children are at high risk of osteoporosis.

In cases of therapeutic failure or significant side effects under steroid therapy, the use of subcutaneous methotrexate should be considered. Combining corticosteroids and methotrexate is a good alternative to control disease activity without significant adverse reactions.[12] Using hydroxychloroquine may be a new therapeutic approach. Targeted biotherapies (infliximab, rituximab) may be indicated in refractory forms of JDM. Only controlled and randomized clinical trials will be able to validate their safety in children.[13] Therapeutic abstention in amyopathic JDM is the rule. In this case, patients generally remain asymptomatic even after several years of evolution. Physical therapy is an important part of the treatment. It should be started as soon as symptoms are under control. It aims to rebuild muscle strength and prevent joint contraction.[14] For those who have dysphagia, occupational and speech therapy is necessary to educate the patient/family regarding food consistency and proper positioning of the chin, head, and tongue.(B2)

Differential Diagnosis

The differential diagnosis for JDM includes the following:

• Myositis
• Lupus
• Raynaud phenomenon
• Scleroderma
• Eczema
• Psoriasis
• Tinea
• Muscular dystrophy

Prognosis

The condition's evolution is unpredictable. The disease may have a monocyclic, polycyclic, or chronic course. The prognosis has significantly improved over recent years with the emergence of new therapeutic options. Early treatment and close monitoring may lead to better control of the disease. However, developing countries still have a high mortality rate.[15] The major causes of death are usually severe muscle weakness, super-added infection, gastrointestinal vasculitis with a risk of bowel perforation, myocardial failure, and respiratory distress. Calcinosis cutis occurs in 30% of patients and is associated with high morbidity. Besides poor cosmesis, it causes pain and limits function. Calcinosis cutis may also lead to contractures, ulcerations, and nerve entrapment. Before the advent of corticosteroids, one-third of patients spontaneously improved, one-third had a chronic, lingering course, and one-third died from the disease. JDM is usually not associated with the development of malignancies, unlike the adult form.[16]

Complications

Potential complications accompanying dermatomyositis include:

• Dysphagia can occur when esophageal muscles are affected, leading to weight loss and malnourishment.
• Aspiration pneumonia; issues affecting swallowing can also lead to the inspiration of food particles, liquids, or saliva.
• Problems breathing; if there is the involvement of the chest or thorax muscles, it can result in dyspnea.
• Calcium deposits; as the disease progresses, can present in the muscles, connective tissues, and skin.