An 8-year-old girl presented with sevreal months history for facial rash. Physical examinations revealed also scaly papules on the knuckles and knees. ANA was negative... What is your diagnosis? 

Diagnosis: Juvenile Dermatomyositis

By: Mehrdad Mehravaran, M.D.,  Szeged-Hungary

Dermatomyositis-Ploymyositis (DM-PM) are inflmmatory myopathies, which have prominent cutaneous findings. They may be primary or may be associated with connective tissue diseases, they have not been conclusively shown to have an association with malignacy. Childhood DM-PM are distinct entity from adulds DM-PM. Children or juvenile DM-PM are more likely than adults to have extensive calconosis and vasculitis. 

DM_PM are inflammatory diseases primarly affecting striated muscles, estimated incidence about 1/200,000 per year, females are affected more than males and are more frequent in black women. 

Porposed classification by Bohan et al 1 as follows:

• group 1 primary idiopathic polymysitis (the most common type)
• group 2 primary idiopathic dermatomysitis
• group 3 dermatomysitis or polymysitis associated with neoplasia
• group 4 childhood dermatitis or polymysitis
• group 5 polymysitis or dermatomysitis with associated connective tissue disease (overlap syndromes)

Diagnosis:

The five major diagnostic criteria:

1. progressive symmetrical proximal muscle weakness
2.  abnormal muscle biopsy consistent with polymysitis
3. elevation of muscle enzymes in the serum (e.g., creatine phosphokinase and aldolase
4. abnormal electromygram, consistent with polymysitis
5. characterisctic rash od dermatomysitis

The diagnosis of PM is established if patients have all four noncutaneous criteria; it is probable if three criteria are present and possible if two are present. The diagnosis of DM is established if four criteria (including the cutaneous criterion) are present and probable if three are present.

Pathologic and labratory features:

The cardinal pathologic features of DM-PM are abnormal muscle enzymes and abnormal findings on muscle biopsy and on electromyography.

Muscle enzymes are the most common sensitive indicators of disease activity, and cratinine phosphokinase (CPK) and aldolase are more sensitive and informative than transaminases or lactic dehydrogenase. Although none of these enzymes is specific for striated muscle injury, CPK isoenzyme levels may be used to distinguish stirated from smooth muscle injury and CPK levels can be useful in monitoring the course of the disease and the response to therapy.  Serum enzymes levels are elvated in over 95% of patients with active DM-PM but may be normal in those who have inactive disease or extensive loss of the muscle mass.

Muscle biopsy is abnormal in about 90% of patients. Since findings may be focal, abnormalities can be missed on a single biopsy. Biopsies may show a segmental necrosis of muscle fibers, an inflammatory infiltrate, and focal areas of muscle regeneration. The inflammatory infiltrate consists of variable amounts of macrophages, with phagocytosis of degenerating muscle fibers and a patchy infiltrate of lymphocytes and a few plasma cells. In children vascular injury isprominent.

Electromyography (EMG) shows abnormalites in about 80% of patient. It is useful in confirming the diagnosis of myopathy and in providing evidence against neuropathy. Abnormalites include low-amlitude, short-duration, and polyphasic potentials; spontaneous fibrillation; increased irritability on insertion of electrodes; and positiv sharp waves.

Skin histopathology is nondiagnostic; often, findings are only those of nonspecific inflammation.

DM-PM constitute a group of autoimmune diseases in which autoantibodies are often apparently absent, with 60% or fewer patients reported to have abnormal test for antinuclear antibodies (ANA). Several autoantibodies described in DM-PM are apparently specific for these diseases but are not detected in the majority of patients. These include antibodies to histidyl tRNA synthetase (Jo-1), which are found in about 25% of PM patients, and  antibodies to threonyl tRNA synthetase (PL-7) and alanyl tRNA synthetase (PL-12), which are found in a small fraction of patients.

Anti-Jo-1 antibodies are found more often in PM than in DM patients and appear to be most common in patients with PM who have interstitial lung disease. Antibodies to the Mi-2 antigen appear to be relatively specific for DM but are found in a minority of patients.  Antibodies to a complex of proteins called PM-Scl are found in patients with PM-scleroderma overlap syndrome.

Cutaneous lesions

The classic eruption of DM is erythema involving the face, a reddish purple color being prominent of eyelids. The rash in DM can precede clinical indications of muscle weakness, generally by a few weeks or months, but typical cutaneous lesions can appear as much as 4 years prior to clinically evident myopathy, and there are rare patients who never develope demostrable muscle diseases. The eruption of the eyelids is often called a helitrope rash.

The facial erythema in DM is most apparent on the malar areas and eyelids and may be indistinguishable from the lesions of acute cutaneous lupus erythematosus.  Scaly, erythematous lesions can involve not only in face but also in the neck, upper trunk, and extensor exterimites (eg, elbows and knees). Photosensitivity is common in DM.

Characteristic lesions occur on the hands and may be very helpful in distinguishing DM from LE. Erythema in DM occurs over the knuckles rather than over the phalanges as in lupus.  Violaceous erythema, with or without scale, over the knuckles, elbows, knees, and medial malleoli is known as Gottron’s sign. In addition to erythema, raised violaceous, flat topped lesions, called Gottron’s papules, may be present on the knunckles.

Othe skin signs are periungual erythema, telangiectasias, fragmentation of the cutiles, nail fold capillary abnormalities, poikilodermatous skin changes (the affcted area consists of widespread, mottled hyper- and hypopigmentation, withtelangiectasias and atrophoy and sometimes with ulcerations), cutaneous calcification (are typical in childhood DM), Raynaud’s phenomenon and sclerodactly.

Internal Oragan Involvement

Systemic findings:

The onset of systemic problems is usually insidious, beginning with fever, malaise and diffuz weakness. Proximal muscle weakness is present in virtually all patients. Patients often experiance diffliculty in climbing stairs or rising from the floor or from a low chair. Weakness may progress to involve the shoulder gridle, and patients may have difficulty in raising the arms above the head, as when combing their hair. Neck muscles, facial muscles, and pharyngeal muscles may be affected, and muscle pain and tenderness may occur. Involvement of the appropriate muscles can lead to dysphagia, dyspnea or dysphonia. Reflexes usually present but reduced, sensory disturbances do not occur.

Cardiac involvement consiting of myocarditis and/or conduction system abnormality is seen in most patients with adult DM-PM. Lung disease is also very common and can be a result of interstitial fibrosis, aspiration penumonia due to weakened pharyngeal muscles, or hyperventilation due to involvement of the respiratory muscles. Esophageal dysmotility is a frequent finding. Cervical dysphagia and nasopharyngeal reflux are seen in DM-PM. Arthritis is seen occationally in patients with the primary disorders and often in those with an overlap syndrome.

Marked muscle destruction can lead to myoglobinurea and acute renal failure. Dysphagia can complicate the pulmonary picture and causing aspiration penumonia.

In children acute gasterointestinal problems may develop secondary to necrotizing arteritis with ulcerations and infarctions. Other difficulties include ocular muscle weakness, carpal tunnel syndrome, osteoprosis secondary to corticosteroids.

In fulminant cases, such as tumor associated dermatomyositis is adult the patient may wind up virtually helpless. In children such dramatic courses are uncommon.

Whiles arthiritis or Raynoaud phenomenon suggest an overlap syndrome, arthralgias and morning stiffness are often present. Arthritis may also associated with pulmonary fibrosis and anti-Joi antibodies (in children pulmonary involvement is uncommon).

Childhood (Juvenile) DM-PM, vasculitis is much more common than it is in the adult forms. The gastrointestinal tract is often affected, with resultant ulceration, bleeding, and perforation. Calcinosis is more common in children and can involve muscle and tendon as well as skin.

Malignancies of various internal organs have been reported to be associated with DM-PM, but it is still nor clear if this is a true relationship is a subgroup of adult patients. Juvenile DM is not associated with malignancy.

Juvenile DM

Both childhood and adult forms of DM and PM adhere to same diagnostic criteria, but childhood disease have unique features of vasculitis and calcinosis. Juvenile DM have two presentations. Approximately one half of the patients have rapidly progressive diseases with a high mortalityrate characterized by fever, anorexia, and clinical and histologic vasculitis in addition to classic cutanepus and muscle abnormalities. Vasculitis can result in GI hemorrhage and even bowel perforation. Therapeutic response and prognosis are poor. The remainder of children have a more subacute presentation with gradual progression of muscle weakness and subsequent calcinosis. Clacinosis can be superficial; subcutaneous near joints (knee, elbows, fingers); in the fascial planes within muscle; or rarely as a diffuse exoskeleton.

Managment and treatment:

• The mainstay of therapy is sytemic steroids with relatively high dose (1mg/kg/day) until improvement is seen and then tapered very slowly, often by no more than 10% per month.
• In refractory cases if the response to steroids is insufficient, cytostatic drugs may be added. Mehtotrexate, cyclophasphamide, chlorambucil, azathioprine, plasmapheresis, and more recently Intravenous Immunoglobin (IVIgs) are advocated.
• Cutaneous lesions can be treated with topical corticosteroids and antimalatial agents.

References:

1. Bohan A, peter JB: polymysitis and dermatomysitis. N Engl J Med 1975;292:344-347, 403-407.