Inflammatory myopathy and skin manifestations.

Estimated incidents of one for 100,000 persons.

An autoimmune disease characterized by an erythematous rash and symmetrical proximal muscle weakness.

Skin manifestations of the face and metacarprophalangeal joints are characteristic.

Characteristic cutaneous findings include heliotrope erruption and Gottron papules and proximal symmetric skeletal muscle weakness.

Skin papules that form are often painful and ulcerated, and they are usually located on the palmar surface of the metacarpophalangeal and inter-phalangeal joint.

Skin findings suggestive of dermatomyositis include periorbital erythema and Edema, erythema on the upper chest consistent with a V-sign, and erythema involving the upper back, the shawl sign.

Characteristic skin findings include scalp erythema, mid facial erythema involving the nasal labial folds.

Additional findings include non-scarring alopecia, scalp erythema, and pruritus.

Gottron’s Papules are pink to iolations lichen oof papules on the metacarpalphalangeal for inter-phalangeal joints and or pathognomonic for dermatomyositis.

Bohan and Peter’s criteria-an inflammatory myositis with dermatologic features including Gottron’s papules, heliotrope rash over the eyelids, scaly erythematous rash over the dorsum of the hands or involvement of the knees, elbows, and medial malleoli, face, neck, and upper torso.

Proximal nailfold can be erythematous and edematous, and cuticles can be ragged and hypertrophied.

On Dermoscopy dilated capillary loops, capillary-loop drop out, and microhemorrhages can be seen.

Muscle biopsies revealed a mononuclear, inflammatory cell exudate in a perivascular and perifascicular distribution with degenerating and regenerating muscle fibers and perifascicular atrophy.

Muscle inflammation leads to rapid and long-standing muscle necrosis, reflected by a rise and circulating muscle enzymes such is creatine phosphokinase.

Patients classically have symmetric, proximal muscle weakness, which limits their ability to stand from a seated position, to climb stairs, or reach overhead.

The accumulation of immune cells in muscle, supported by circulating auto antibodies directed against nuclear components and constituents of muscle cells has led to the classification of this process as an autoimmune disease.

Anti-MDA ( anti-TIF-ly) melanoma differentiation associated gene 5) is an elevated autoantibody seen in the severe form of the disease compounded by lung involvement.

MDA-5 is a receptor of the innate immune system.

MDA-5 identifies viral dsRNA within the cytosol, and prompts the manufacture of type one interferons, which ultimately provokes a apoptosis of infected cells.

The precise roles MDA-5 and the anti-MDA-5 autoantibodies play in dermatomyositis are not completely understood.

Dermatomyositis was thought to be caused by a complement mediated microangiopathy but a microvascularopathy in skin and muscle damage are felt to be associated with dermatomyositis due primarily to toxicity from pathways mediated by type 1 interferon, most likely beta.

Production of anti-MDA-5 auto antibodies occurs during viral infections of the skin and lung epithelium and their formation is triggered by the release of fragments of MDA-5 after its proteolysis within infected cells.

Approximately 50-100% of patients positive for Anti-MDA-5 have a diagnosis clinically of amyopathic dermatomyositis.

Antibodies against MDA5 are associated to amyopathic dermatomyositis with rapidly progressive interstitial lung disease.

Melanoma differentiation–associated gene 5 (MDA5) is a autoantigen target in a subset of patients with dermatomyositis. 

Anti-MDA5 dermatomyositis is characterized by a unique mucocutaneous and systemic phenotype that includes cutaneous and oral ulceration, painful palmar papules, alopecia, panniculitis, arthritis, a lower incidence of myositis, and, an elevated risk of interstitial lung disease with a potentially fatal course. 

The clinical features can differ substantially from those typically observed in cutaneous dermatomyositis: the diagnosis is often overlooked, which might negatively affect patient outcomes. 

Amyopathic dermatomyositis is a subtype of dermatomyositis in which the characteristic skin findings are present in the absence of muscle involvement.

Amyopathic dermatomyositis is a diagnosis made after six months of the absence of muscle involvement and is confirmed diagnosis if muscle involvement remains absent two years after the onset of skin symptoms.

Amyopathic dermatomyositis represents approximately 20% of dermatomyositis cases.

Anti-MDA-5 is more commonly found in the Asian population.

The exact risk in incidence in association with cancer is unclear.

All patients should be screened for cancer.

Cancer is reported in 15–27% of patients and may precede, occur concurrently with, or follow the diagnosis.

Highest risk of cancer occurs in the first year after symptom onset but remains elevated through 3-5 years.

Cancer diagnoses associated with dermatomyositis include: lung, breast, ovarian, pancreatic, and colorectal cancers, among others.

Creatine kinase and aldolase levels should be measured in all patients with skin findings consistent with dermatomyositis, including those without muscle involvement.

It occurs in women twice as often as men and has bimodal peaks in childhood and the 4th-6 decades of life.

Patient with myositis specific autoantibodies TIF-1gamma have a higher risk of cancer.

Malignant disease may occur before the onset, concurrently or as a later paraneoplastic syndrome manifestation.

Adult patients with tomato myositis should be screened for associated interstitial lung disease and cancer.

It may follow a course that independent of the treated malignant disease.

There is an increased incidence of cancer in the first 3-5 years following the diagnosis of myositis.

Prevalence of this entity with cancer is associated in patients over the age of 50 and suggests a poor prognosis (Yazici Y).

Associated with cancers of the ovaries, lung, stomach, and colorectum.

Most often the diagnosis is a harbinger of a malignancy.

The relationship between myositis and cancer is hypothesized to be one of a compromised immune function.

In patients with cancer disappearance of skin and muscular signs after treatment of the malignant lesion indicates low probable paraneoplastic nature of the process.

All patients with the diagnosis should be evaluated for the presence of a malignancy.

Modern treatment has reduced mortality to less than 10%.

Risk of malignancy 6.5 fold increase.

Most common malignancies associated are ovarian, gastric and lymphoma.

Poor prognostic indicators include recalcitrant disease, delay in diagnosis, older age, malignancy, fever, asthenia, anorexia, pulmonary interstitial fibrosis, dysphagia and leucocytosis.

Interstitial lung disease is present in up to 40% of patients with dermatomyositis, and the risk is higher among patients with auto antibodies to RNA synthetase enzymes and melanoma differentiation-associated protein five ( MDA5) among whom as many as 80% will have interstitial lung disease.

Malignancy, cardiac and pulmonary dysfunction are the most common causes of death.

Agents used to control inflammation were initially steroids, often at high dose.

Diagnosis of classic dermatomyositis can be made by clinical and laboratory  criteria alone in patients with symmetric proximal muscle weakness, characteristic skin findings and elevated muscle enzyme, creatine kinase levels.

Skin and muscle biopsyies are not required for diagnosis, but they may provide useful information in a typical presentations.

Myositis specific auto-antibodies are found in approximately 60% of patients with the  dermatomyositis.

Anti-MDA ia an autoantibody in Dermatomyositis that is a marker of the severe form of the disease compounded by lung involvement.

Patients with MDA5 associated dermatomyositis may have a typical cutaneous findings of dermatomyositis but have a distinctive phenotype that includes cutaneous and oral ulcerations and painful palmar papules, non-scarring alopecia, calcinosis, arthritis, and mechanic’s hands.

Patient with MDA5 associated dermatomyositis  often do not experience proximal muscle weakness and may have normal creative kinase levels on blood testing.

Patients with MDA5 associated dermatomyositis have an elevated risk of interstitial lung disease with a prevalence ranging from 5 to 65%.

Patients with MDA 5 associated dermatomyositis should be evaluated with a CT of the chest.

MDA5 associated dermatomyositis  can be treated with a combination of immunosuppressive therapies including steroids, calcneurin antagonists, methotrexate, aziothioprine, Rituximab, cyclophosphamide, mycophenolate, and intravenous immunoglobulin for lung involvement.

Steroids are active but have many side effects including steroid induced myopathy and other agents have been added including: azathioprine, methotrexate, and cyclosporine.

A response of at least minimum improvement on a composite score of disease activity was significantly greater among patients who receive the IVI G than among those who receive placebo (Aggarwal).



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