Dermatomyositis

Dermatomyositis/Polymyositis

In 1863, Wagner first recognized dermatomyositis/polymyositis. In 1891, Unverricht provided the first description of dermatomyositis. Dermatomyositis and polymyositis have been classified into the following clinical groups, as Walton and Adams originally proposed:

Primary polymyositis (idiopathic, adult)

Dermatomyositis (idiopathic, adult)

Childhood dermatomyositis or myositis with necrotizing vasculitis

Polymyositis associated with connective tissue disorder (ie, overlap syndrome)

Polymyositis or dermatomyositis associated with neoplasia

Inflammatory myopathies are acquired muscle diseases characterized by primary muscle weakness, endomysial inflammation, and elevated levels of serum muscle enzymes. Polymyositis and dermatomyositis, along with inclusion-body myositis, are the most common diseases of the striated muscle, skin, and surrounding connective tissue that clinicians observe. Each has unique clinical and histologic features. The pathology of both polymyositis and dermatomyositis have an underlying autoimmune basis, but the mechanisms for the 2 conditions differ.

Pathophysiology

Polymyositis

Polymyositis is presumed to be an autoimmune-mediated disease secondary to defective cellular immunity, which may be due to diverse causes that may occur alone or in association with viral infections, malignancies, or connective-tissue disorders. Evidence suggests that a T cell–mediated cytotoxic process is directed against unidentified muscle antigens. Supporting this conclusion are CD8 T cells, which, along with macrophages, initially surround healthy nonnecrotic muscle fibers and eventually invade and destroy them.

Dermatomyositis

Dermatomyositis is likely the result of a humoral attack on the muscle capillaries and small arterioles. Complement c5b-9 membrane-attack complex is deposited and is needed in preparing the cell for destruction in antibody-mediated disease. B cells and CD4 (helper) cells are also present in abundance in the inflammatory reaction associated with the blood vessels. As the disease progresses, the capillaries are destroyed, and the muscles undergo microinfarction. Perifascicular atrophy occurs in the beginning; however, as the disease advances, necrotic and degenerative fibers are present throughout the muscle

Mortality/Morbidity

The active period of the disease is approximately 2-3 years in both children and adults. The duration is greater for patients with cardiac or pulmonary complications than for others; approximately 20% of the patients recover completely. The mortality rate after several years of the disease is approximately 15%; the rate is increased in patients with dermatomyositis with connective tissue diseases and malignancy.

Race

No racial predilection is observed.

Sex

A female preponderance has been reported in all age groups, with a female-to-male ratio of 2:1.

Age

Most patients present with polymyositis when aged 30-60 years, with a small peak in people aged 15 years.

Dermatomyositis affects children and adults equally. The peak incidence is observed in individuals aged 45-64 years, with a small peak in children aged 5-14 years

Polymyositis

Polymyositis is a disease of exclusion with acute or subacute onset. It is best defined as an inflammatory myopathy of subacute onset (ie, weeks to months) and steady progression occurring in adults who develop diffuse weakness, which is more severe proximally than distally.

The weakness is painless in two thirds of the patients. A rash is not present.

Eye muscles are not involved, and facial muscles are involved only with severe disease.

Family history of neuromuscular disease, endocrinopathy, or exposure to myotoxic drugs or toxins is absent.

The disease may exist for several months before the patient seeks medical advice, and all the muscles of the thighs, trunk, shoulders, hips, and upper arms are usually involved.

Symptoms include difficulty getting up from a chair, climbing steps, stepping onto a curb, lifting objects, and combing hair. Fatigue, myalgias, and muscle cramps may also be present.

In contrast, fine motor movements that depend on the strength of distal muscles, such as buttoning a shirt, sewing, knitting, or writing are affected only late in the disease.

Dermatomyositis

Dermatomyositis occurs in children as well as adults. It is characterized by the muscle weakness.

Extramuscular manifestations of the disease may include the following:

General systemic disturbances, fever, arthralgia, malaise, weight loss, Raynaud phenomenon

Dysphagia, similar to that of scleroderma

Atrioventricular defects, tachyarrhythmias, dilated cardiomyopathies

Gastrointestinal (GI) ulcers and infections

Contracture of joints

Pulmonary involvement due to weakness of thoracic muscles, interstitial lung disease

Subcutaneous calcifications

Dermatomyositis in children resembles the adult form. Children commonly develop a tiptoe gait secondary to flexion contracture of the ankles in early childhood.

Children tend to have extramuscular manifestations, especially GI ulcers and infections, more frequently than adults do.

Physical

Polymyositis

Nothing is characteristic about the muscle weakness. It is not painful, although a minority of patients report aches or cramps.

The weakness may fluctuate from week to week and from month to month.

Ocular muscles remain normal even in advanced untreated cases.

Facial muscles remain normal except in rare advanced cases.

The pharyngeal and neck flexor muscles are often involved, causing dysphagia and difficulty in holding up the head.

In advanced cases and rarely in acute cases, respiratory muscles are affected. Severe weakness is almost always associated with muscular wasting.

Sensation remains normal.

On occasion, the muscle may be sore to palpation and may have a nodular and grainy feel.

The tendon reflexes are preserved, but they may be absent in severely weakened or atrophied muscles.

Primary cardiac abnormalities due to myocarditis may be present in a few patients. These abnormalities mainly manifest as atrioventricular conduction defects, tachyarrhythmias, low ejection fraction, dilated cardiomyopathy, or congestive heart failure.

General systemic disturbances, such as fever, malaise, weight loss, arthralgia, and Raynaud phenomenon, may occur when polymyositis is associated with a connective-tissue disorder.

Dermatomyositis

The rash consists of a heliotrope (ie, blue-purple) discoloration on the upper eyelids; a flat, red rash involving the face and upper trunk; and a raised, violaceous, scaly eruption on the knuckles (ie, Gottron rash).

The erythematous lesions may result in scaling, pigmentation, and depigmentation of the skin, producing a shiny appearance.

The rash may involve other body surfaces, including knees, elbows, neck, anterior chest (ie, V sign), or back and shoulders (ie, shawl sign); sun exposure can exacerbate the rash.

Dilated capillary loops at the base of the fingernail are characteristic of dermatomyositis. The cuticles may be irregular and thickened, and the palmar and lateral surfaces of the fingers may become rough and cracked.

Myopathy in dermatomyositis is more proximal than distal.

The degree of weakness may range from mild to moderate to severe. Sometimes, quadriparesis are observed.

Muscle pain and tenderness are observed early in the course of the disease.

Sensation is normal, and tendon reflexes are preserved unless the muscle is severely weak and atrophic.

Causes

The causes of idiopathic polymyositis and dermatomyositis are not known. An autoimmune process is implicated (as discussed above) because these conditions may be associated with other autoimmune diseases, such as myasthenia gravis, Hashimoto thyroiditis, scleroderma, Waldenstrِm macroglobulinemia, and others and because they respond to immunosuppressive medication.

Groups of diseases that should be excluded

Familial neuromuscular diseases
Systemic metabolic muscle diseases, eg, endocrinopathies and mitochondriopathies
Systemic medical illness, eg, malabsorption syndromes, alcoholism, cancer, vasculitis, granulomatous disease, sarcoidosis, or treatment with various known myotoxic drugs or toxins
Biochemical muscle diseases (eg, enzyme deficiencies)
Inclusion-body myositis (excluded by histologic findings

                                                            Lab Studies

• Polymyositis

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• The diagnosis of polymyositis is established by using serum enzyme levels and electromyography (EMG) studies and confirmed by means of diagnostic muscle biopsy.
• The most sensitive enzyme is creatine kinase (CK). In the presence of disease, levels can be elevated as much as 50 times the reference level. The CK level usually parallels disease activity. In active polymyositis, it is rarely in the reference range. The level may also be in the reference range in some patients with polymyositis associated with connective-tissue disease.
• Anti-Jo-1 antibodies are present in one fifth of patients.

Along with CK, levels of aldolase, serum aspartate aminotransferase (AST, or glutamic-oxaloacetic transaminase [SGOT]), serum alanine aminotransferase (ALT, or glutamic-pyruvic transaminase [SGPT]), and lactate dehydrogenase (LDH) may also be elevated. If AST levels are higher than ALT levels, a myogenic cause should be suspected.

Dermatomyositis

Levels of serum CK are usually, though not always, elevated. Levels may be as high as several 100s to 1000 U/mL.

AST, ALT, LDH, and aldolase levels may also be elevated.

Cancer antigen 125 (CA125) and cancer antigen 19-9 (CA19-9) may be useful markers of the risk of tumors in patients with dermatomyositis and polymyositis. Therefore, tests of these markers should be included in the search for cancer in patients with dermatomyositis/polymyositis, especially those without interstitial lung disease

Imaging Studies

MRI may show increased signal intensity in the affected muscles and surrounding tissues.

Because of the lack of sensitivity and specificity, MRI is not helpful in diagnosing the disease; however, it can help in monitoring its progress, and it may be used to guide decisions regarding muscle biopsy.

Procedures

EMG may be helpful in diagnosis, though findings can be normal in 15% of patients. It shows a typical myopathic pattern with irritability, although it is not specific for the condition. These findings are most consistently observed in weak proximal muscles. EMG also is helpful in selecting a muscle for biopsy.

Specific findings are as follows:

In polymyositis, needle EMG shows myopathic potentials characterized by short-duration, low-amplitude polyphasic units on voluntary activation and increased spontaneous activity with fibrillations, complex and repetitive discharges, and positive and sharp waves, along with early recruitment.

In dermatomyositis, needle EMG shows myopathic features with indications of muscle irritability. The myopathic potentials are characterized by short-duration, low-amplitude, polyphasic units and increased spontaneous activity with fibrillations, complex repetitive discharges, and positive sharp waves. Recruitment pattern shows early recruitment.

Single-fiber EMG (SFEMG)

In 1 study, SFEMG were recorded from the extensor digitorum communis of 34 patients with polymyositis or dermatomyositis and compared with findings on routine EMG, serum CK determination, and muscle biopsy.

SFEMG recordings were abnormal in all 34 patients. The prominent feature was markedly increased fiber density with normally or mildly increased jitter.

SFEMG is of great value in diagnosis and in evaluating the disease process to understand inflammatory myopathies in patients with clinically suspected disease but normal findings on routine EMG, CK determination, and muscle biopsy.

Histologic Findings

Polymyositis

Muscle biopsy is the definitive test not only for establishing the diagnosis of polymyositis but also for excluding other neuromuscular diseases. In polymyositis, inflammation is the histologic hallmark of the disease. The endomysial infiltrates are mostly in foci in the fascicles, initially surrounding healthy muscle fibers and finally invading these cells and resulting in phagocytosis and necrosis. Because the inflammatory infiltrates can be small and multifocal, they can be missed in a small muscle-biopsy specimen. Perifascicular atrophy or prominent perivascular infiltrates are not present, and the blood vessels are normal. When the disease becomes chronic, the connective tissue increases. The diagnosis of polymyositis is definite when a patient has subacute elevated levels of serum CK and findings on muscle biopsy consistent with the histologic features of polymyositis

Dermatomyositis

Findings on muscle biopsy can be diagnostic. Although inflammation is the histologic hallmark of dermatomyositis, polymyositis, and inclusion-body myositis, dermatomyositis is the only disease that shows perifascicular atrophy. In addition, many fibers undergo degeneration and necrosis that cause them to lose their staining ability; therefore, they are termed ghost fibers. When these changes are associated with collections of inflammatory cells around the blood vessels, the diagnosis of dermatomyositis is certain

Medical Care

The goal of therapy is to improve muscle strength to improve function in activities of daily living. Improvement in strength is usually accompanied by a decrease in the serum CK level, a change that must be interpreted with caution because most immunosuppressive therapies decrease levels of serum muscle enzymes without necessarily improving muscle strength.

Consultations

Consultation with an occupational and rehabilitation therapist may help patients with ambulation by providing necessary equipment.

A swallowing evaluation for dysphagia is recommended.

Proper emotional support is also important.

Diet

Advise patients who are receiving steroid therapy to follow a strict low-salt, low-carbohydrate, and high-protein diet to avoid weight gain and hypertension.

Activity

Physical therapy helps to preserve muscle function and prevents disuse atrophy of the weak muscles or joint contractures; therefore, consider it in the initial stage of the disease

Of all the treatments that are available, prednisone remains the drug of choice. If treatment with steroids is not successful, other lines of treatment are considered, such as intravenous immunoglobulins (IVIG), antineoplastic agents, and antimetabolites

Corticosteroids act as anti-inflammatory and immunosuppressive agents and are the first-line drug for treating both polymyositis and dermatomyositis.1-2 mg per kg for 4-6 weeks with waiting for remission or add another drug

Other immunosuppressants. If your body doesn t respond adequately to corticosteroids, your doctor may recommend other immunosuppressive drugs, such as azathioprine (Imuran) or methotrexate (Rheumatrex). Your doctor may prescribe these alone or in combination with corticosteroids.

When in combination, these additional immunosuppressants can be used to lessen the dose and potential side effects of the corticosteroid. Immunosuppressants, such as cyclophosphamide (Cytoxan) and cyclosporine (Neoral, Sandimmune), may improve symptoms of polymyositis and interstitial lung disease.

Physical therapy. A physical therapist can show you various exercises to maintain and improve your strength and flexibility and advise an appropriate level of activity. Your exercise program is likely to change during the course of the disease and treatment period. Staying active will help maintain muscle strength.

Polymyositis treatments that are still under investigation include:

Plasmapheresis. This treatment, also called plasma exchange, is a type of blood cleansing in which damaging antibodies are removed from your blood.

Radiation therapy. This involves irradiation of the lymph nodes to suppress your immune system.

Intravenous immunoglobulin (IVIg). This involves receiving intravenous infusions of antibodies from a group of donors over two to five days. This treatment is usually expensive. It may be an option for you if your dermatomyositis is severe or resistant to other forms of therapy.

Fludarabine (Fludara). This agent prevents the development and growth of malignant cells.

Tacrolimus (Prograf). This transplant-rejection drug may work to inhibit the immune system. Tacrolimus is often used topically to treat dermatomyositis and other skin problems.

Monoclonal antibodies. These man-made antibodies are designed to target and destroy specific types of cells. Clinical trials are studying the effects of infliximab (Remicade) and rituximab (Rituxan) on both polymyositis and dermatomyositis

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Mycophenolate Mofetil (CellCept),

 The use of a nonsteroidal immunosuppressive drug is determined by the need for a steroid-sparing effect when (1) serious complications have developed with steroid use, (2) repeated relapses have occurred each time an attempt was made to lower a high steroid dosage, (3) prednisone did not improve strength, or (4) the patient has a rapidly progressive disease accompanied by severe weakness and respiratory failure.

Biological agent : they to use in the treatment specially in children group of disease

Prognosis

The natural history of polymyositis and dermatomyositis is unknown because patients are now almost always treated with steroids.

Patients with interstitial lung disease may have a high mortality rate.

A number of patients still do not respond adequately to therapies and remain disabled.

Acute fulminating disease seems to be difficult to treat and resistant to therapies.

Patients in whom treatment is initiated soon after the onset of the symptoms have the best prognosis.

When treatment is unsuccessful, the patient should be reevaluated and the muscle biopsy specimen reexamined.

A second biopsy may be considered to ensure that the diagnosis is correct.

The disorders most commonly mistaken for polymyositis are inclusion-body myositis and sporadic limb-girdle muscular dystrophy, which is suspected when the disease has a slow onset and progression and when the muscle-biopsy specimen does not show primary inflammatory features.