Juvenile Dermatomyositis

A 5-year-old boy presented with a runny nose, cough, and fever that was diagnosed as an upper respiratory tract infection (URI). The child was treated symptomatically. Four days later, his mother noticed that he was having difficulty in walking up stairs; he complained of pain and weakness in both legs and asked her to carry him short distances.

Clinical examination revealed that the patient had tender calf muscles, with normal tone and reflexes. His creatine phosphokinase (CPK) level was elevated to 1252 U/L (normal, less than 130 U/L). Viral myositis was diagnosed-the most common myositis in the setting of URI-although results of viral studies were negative. The patient’s mother was advised to treat him with acetaminophen and to schedule a follow-up appointment 2 weeks later.

At follow-up, pain and weakness in the boy’s lower limbs had worsened. His CPK level had risen to 1400 U/L. The complete blood cell count was normal. He was referred for a neurology consult.

The patient was well nourished, with no dysmorphic features. He took short steps, walked on his toes, and had a slightly prominent lumbar lordosis with a positive Gower sign. His mother reported that her uncle had muscle weakness during his childhood and had passed away when he was roughly 9 years old. This history prompted a workup for Duchenne muscular dystrophy: however, results of genetic testing were negative. 

Therapy with prednisone was initiated because of worsening muscle weakness. This yielded slight improvement in his muscle weakness.

Two months later, the patient returned to the clinic with erythematous papules over his proximal and distal [[{"type":"media","view_mode":"media_crop","fid":"25569","attributes":{"alt":"","class":"media-image media-image-right","id":"media_crop_1388838802679","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"2341","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"float: right;","title":" ","typeof":"foaf:Image"}}]]interphalangeal and metacarpophalangeal joints and an erythematous rash around the eyelids. These suggested Gottron papules and heliotrope rash, respectively. Electromyography showed high-frequency repetitive discharges, spontaneous fibrillations, and positive sharp waves, consistent with a diagnosis of juvenile dermatomyositis (JDM).

At this point, the patient’s CPK level had risen to 1750 U/L and aldolase, to 60 U/L. Therapy with a combination of methotrexate and prednisone was initiated; this significantly diminished the muscle weakness and the skin lesions disappeared in 3 months.

The patient now makes regular follow-up visits to a rheumatology clinic: his CPK and aldolase levels continue to trend downward.

Juvenile Dermatomyositis
JDM is the most common idiopathic inflammatory myopathy of childhood: it accounts for approximately 85% of cases. It has an annual incidence of 2 to 4 cases per 1 million children in the United States.¹ Early diagnosis is key to preventing calcinosis and joint contractures.

The diagnosis of JDM can be challenging when proximal muscle weakness develops without the characteristic skin manifestations. This is the unique finding in our case: The rash appeared 2 months after the onset of muscle weakness. As a result, the initial diagnosis was viral myositis. The misdiagnosis resulted in delayed treatment.

JDM is primarily a capillary vasculopathy of unclear etiology.² It belongs to a group of inflammatory myopathies. In the absence of cutaneous manifestations, JDM is often very difficult to differentiate from a noninflammatory myopathy, including Duchenne (as we suspected in our patient) and Becker muscular dystrophy, which are hereditary disorders of the muscular protein dystrophin, as well as from a myopathy from a metabolic cause, such as a deficiency of carnitine or fatty oxidation. Inflammatory forms of myositis include viral myositis from influenza or Coxsackie virus (these are usually acute and transient); polymyositis; and myositis from rheumatologic conditions, such as juvenile rheumatoid arthritis and systemic lupus erythematosus. Disorders due to denervation from lesions in the brain, spinal cord, and nerves may also produce symptoms indicative of myositis. EMG is a very helpful diagnostic tool in differentiating myositis from disorders of denervation.

Specific genetic testing and immunohistochemistry will differentiate inflammatory from noninflammatory myopathies. MRI is increasingly used in the diagnosis of childhood inflammatory myopathy to avoid the morbidity associated with muscle biopsy and EMG. However, muscle biopsy remains the gold standard diagnostic tool in the absence of skin manifestations. 

In 1975, Bohan and Peter^3,4 proposed diagnostic criteria for the various forms of myositis, including JDM. These were progressive symmetrical proximal muscle weakness and pathognomonic heliotropic rash (reddish purple rash on the upper eyelids with periorbital edema), Gottron papules (erythematous, papulosquamous eruption over the dorsal surfaces of the knuckles), elevated muscle enzyme levels (CPK, aldolase), EMG findings of myopathy, and muscle biopsy showing necrosis and inflammation. 

As per the JDM Research registry and single tertiary Canadian center, the most common initial presentation of JDM is Gottron papules (in 91% of cases) followed by a heliotrope rash (in 75% of cases). Muscle weakness is present in only 24% of cases. Thus, JDM needs to be kept in the differential when a patient presents with muscle weakness. Early diagnosis and treatment are associated with a better prognosis and decreased morbidity.⁵
 
Mortality associated with JDM has decreased to less than 3% since the advent of corticosteroids.⁶ Monocyclic disease with muscle weakness and rash occurs in roughly 1 of 3 patients with JDM; this form of the disease is associated with a good prognosis and a good response to standard therapy, as in our patient’s case. Chronic continuous or polycyclic disease occurs in two-thirds of patients with JDM; this form predicts a poorer outcome and increased risk of persistent pain, calcinosis, and disability.⁷ Vascular, skin, and muscle symptoms respond well to therapy. However, up to one-third of affected patients require long-term medication.

Take-Home Points
• Dermatomyositis can manifest in several forms. In only about half of cases is the characteristic rash initially present. In about 25% of cases, the rash appears concomitantly with muscle weakness.
• Keep dermatomyositis in mind when a child presents with progressive muscle weakness. Viral myositis is usually acute and transient.
• In case of worsening muscle weakness, EMG and muscle biopsy can help in the diagnosis of inflammatory myositis-especially in the absence of skin manifestations-and provide the opportunity to start early aggressive treatment, which can forestall further complications associated with the disease.

References
1.US incidence of juvenile dermatomyositis, 1995-1998: results from the National Institute of Arthritis and Musculoskeletal and Skin Diseases Registry .
2. Pachman LM, Abbott K, Sinacore JM, et al. Duration of illness is an important variable for untreated children with juvenile dermatomyositis. J Pediatr. 2006;148:247-253.
3. Bohan A, Peter JB. Polymyositis and dermatomyositis-I. N Engl J Med. 1975;292:344-347.
4. Bohan A, Peter JB. Polymyositis and dermatomyositis-II. N Engl J Med. 1975;292:403-407.
5. Ramanan AV, Feldman BM. Clinical features and outcomes of juvenile dermatomyositis and other childhood onset myositis syndromes. Rheum Dis Clin North Am. 2002;28:833-857.
6. Huber A, Feldman BM. Long-term outcomes in juvenile dermatomyositis: how did we get here and where are we going? Curr Rheumatol Rep.2005;7:441-446.
7. Fisler RE, Liang MG, Fuhlbrigge RC, et al. Aggressive management of juvenile dermatomyositis results in improved outcome and decreased incidence of calcinosis. J Am Acad Dermatol. 2002;47:505-511.