Question

Discuss myositis, the pathophysiology, causes, risk factors, clinical manifestations and the prognosis

Answer 1

MYOSITIS

Myosistis is a general term referring to inflammation of the muscles.

The basic classification includes:

• Polymyositis

• Dermatomyositis

• Necrotizing immune-mediated myopathies

• Inclusion body myositis

PATHOPHYSIOLOGY

Myositis is a complex disease since multiple etiologies and pathogenic pathways simultaneously contribute to muscle damage and weakness. Among these, the most important are the innate and adaptive immune pathways and variations occur based on the type of myositis

For example, pathogenesis of dermatomyositis includes binding of immune complexes to endothelial cells with subsequent activation of the complement system and cell lysis, mediated by the membrane-attack complex (MAC),thereby causing necrosis of these cells, and a reduced number of capillaries .As a result,the blood supply reduces,which can cause perifascicular atrophy.

The pathogenesis of polymyositis is characterized by local activation of immune cells in skeletal muscle. The proinflammatory cascade includes expression of cytokines such as IFN-γ, IL-6, IL-1β, tumour necrosis factor (TNF)-α , as well as chemokines such as IL-8, CCL-2, etc contributing to the local inflammation, and are the attracting stimulus for immune cells.

The cellular components of the immune system involved in inflammation are T cells, B cells, macrophages and plasmacytoid dendritic cells are found in perimysial and perivascular areas.

So the basic idea is that dermatomyositis is characterized by immune complex deposition in the vessels and is considered a complement-mediated vasculopathy while in polymyositis, direct T cell–mediated muscle injury contributes to the pathophysiology.

Pathologic changes induced by these mediators include cellular damage and atrophy, with variable degrees of inflammation in the muscles.

CAUSES

Myositis is caused by any condition that leads to muscle inflammation.These include:

• Inflammatory conditions:These include autoimmune conditions, in which the body attacks its own tissues like dermatomyositis,polymyositis and inclusion body myositis

Other conditions causing milder forms of myositis, includes lupus,scleroderma and arthritis.

• Infections:Viral infections are the most common.Rarely, bacteria, fungi, or other organisms can also cause myositis. Examples include cold and flu viruses, as well as HIV
• Drugs:The different medications that can cause temporary muscle damage include:

1. Statins
2. Colchicine
3. hydroxychloroquine
4. Alpha-interferon

Myositis may occur right after starting a medication, or may occur after taking a drug for months or years.

• Injury. Vigorous exercise results in muscle pain, swelling, and weakness for hours or days after a workout. This always resolve completely with rest and recovery.
• Rhabdomyolysis:Rhabdomyolysis is a condition characterized by quick break down of muscles.

RISK FACTORS

• Environmental risk factors include viruses, bacteria,ultraviolet radiation,smoking, occupational and perinatal exposures and exposure to drugs(including biologic agents)
• Juvenile myositis generally affects children from 5 to 15 years old.
• Though dermatomyositis can affect all ethnic groups and both genders;women are twice as likely to develop the disease.
• The risk of developing polymyositis increases with age and highest rates of incidence is between the ages of 35 to 44 and 55 to 64. Women are also twice as likely as men to develop polymyositis
• The risk of developing IBM increases with age and usually appears in patients over the age of 50; however, patients may develop symptoms as early as their 30s and is twice as likely to develop in men as in women.
• Genetic predisposition:Example ,HLA subtypes are associated with increased risk of myositis

CLINICAL MANIFESTATIONS

The main symptom of myositis is muscle weakness which may be noticeable or may only be found with testing. Muscle pain (myalgias) may or may not be present.

• Dermatomyositis, polymyositis, and other inflammatory myositis conditions causes weakness that gets worse slowly over weeks or months. Also, it mostly affects large muscle groups, including the neck, shoulders, hips, and back.Bilaterally affected

Other symptoms that may be present along with inflammatory conditions include:

• Rash
• Fatigue
• Thickening of the skin on the hands
• Swallowing difficulty
• Breathing difficulty

Myositis caused by a virus usually have symptoms of a viral infection, such as runny nose, fever, cough and sore throat, or nausea and diarrhea which may subside days or weeks before myositis symptoms begin.

PROGNOSIS

The long-term outlook for patients affected by myositis varies.

• In most affected people,treatment produces good response and helps to regain muscle strength, although a certain degree of muscle weakness may persist in some cases.
• In most cases,myositis is not life-threatening, and patients recover completely or partially from the disease.They can be at an increased risk of recurrence of symptoms.
• In case of ineffective treatment, individuals may develop significant disability.
• In rare cases, people with severe and progressive muscle weakness may develop complications like respiratory failure or pneumonia. Difficulty swallowing may cause weight loss and malnutrition.
• Those with polymyositis are more likely to develop other autoimmune diseases, cancer, or osteoporosis.