POLYMYOSITIS AND DERMATOMYOSITIS (PM & DM)
· Polymyositis is an inflammatory process affecting skeletal muscle.
· Dermatomyositis is the same disease but with skin involvement.
Epidemiology
· They are rare diseases with an incidence of 2-10 cases per million /year.
· The onset is usually between 40 and 60 years of age.
· The cause is unknown, although there is evidence for a genetic contribution.
Classification of Polymyositis / Dermatomyositis
PolymyositisAdult
Pediatric
Inclusion-body myositis
Overlap (myositis associated with a connective tissue disease)
Dermatomyositis
With muscle weakness
Adult
Associated with cancer
Not associated with cancer
Pediatric
Without muscle weakness (amyopathic dermatomyositis or dermatomyositis sine myositis)
Clinical features of polymyositis
· Symmetrical proximal muscle weakness affecting the lower limbs more than the upper limbs.
· Gradual onset.
· Sometimes associated with muscle pain.
· Systemic features of fever, weight loss and fatigue are common.
· Respiratory or pharyngeal muscle involvement can lead to ventilator failure or aspiration.
· Interstitial lung disease occurs in 30% of patients.
Clinical features of dermatomyositis
· Presents similarly to PM but in combination with skin lesions.
· Gottron's papules (scaly erythematous or violaceous psoriaform plaques occurring over
the extensor surfaces of proximal and distal IPJ's, elbows & knees.
· Gottron's sign: symmetric, nonscaling, violaceous Erythematous macules or plaques, often
atrophic, in the same distribution as Gottron's papules.
· Heliotrope rash (violaceous discoloration of the eyelid in combination with periorbital
edema.
· Rash on the upper back, chest and shoulders (shawl distribution).
· There is about a three-fold increased risk of malignancy in patients with DM & PM.
Systemic Manifestations and Complications of Polymyositis and Dermatomyositis
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Systemic manifestationsCommon: proximal muscle weakness, dysphonia, dysphagia
Less common: respiratory muscle weakness, visual changes, abdominal pain
Systemic complications/associations
Cardiomyopathy
Cardiac conduction defects
Aspiration pneumonia secondary to respiratory muscle weakness
Diffuse interstitial pneumonitis/fibrosis
Large-bowel infarction secondary to vasculopathy has occurred in juvenile patients with myositis
Muscle atrophy
Muscle calcification
Ocular complications including iritis, nystagmus, cotton-wool spots, optic atrophy, conjunctival edema and pseudopolyposis
Internal malignancy
Investigations
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Muscle enzyme elevationSerum creatine phosphokinase (CPK), aldolase, ALT and LDH
Autoantibodies
ANA levels: elevated in 60 to 80 percent of patients with classic DM/PM
Antisynthetase antibodies
Jo-1: most common antisynthetase found; 20 percent of patients with DM may have positive result
ESR: elevated in approximately 50 percent of patients, does not correlate well with disease activity
Rheumatoid factor: elevated in 20 percent of patients, most often in those with overlap syndromes
EMG: myopathic pattern, 10 percent are false-negative
Muscle biopsy: fiber necrosis, regeneration and inflammatory cell infiltrate
Screening for underlying malignancy (chest / abdomen / pelvis CT, gastrointestinal tract imaging and mammography for women)
Treatment Modalities for Dermatomyositis
Treatment modality / Dosage / Side effects / Comments /Oral prednisone / 0.5 to 1.5 mg per kg daily until serum creatine kinase normalizes, then slowly taper over 12 months / Gastrointestinal symptoms, adrenal suppression, immunosuppression, avascular necrosis, osteoporosis / Initial pharmacologic agent; consider adjunctive therapy if no improvement in objective muscle strength after three months of therapy.
Methotrexate / Oral: 7.5 to 10 mg per week, increased by 2.5 mg per week to total of 25 mg per weekIntravenous: 10 mg per week, increased by 2.5 mg per week to total of 0.5 to 0.8 mg per kg Children: 1 mg per kg. As dosage increases, taper off steroid dose. Give 3 mg daily of folic acid to minimize side effects of methotrexate. / Stomatitis, hepatic fibrosis, cirrhosis, nausea, abdominal pain, neutropenia, thrombocytopenia, pruritus, fever, pneumonitis, and gastrointestinal symptoms / First-line adjuvant therapy in patients unresponsive to steroids.
Azathioprine / 2 to 3 mg per kg per day tapered to 1 mg per kg per day once steroid is tapered to 15 mg per day. Reduce dosage monthly by 25-mg intervals. Maintenance dosage is 50 mg per day. / Lymphoma, nausea, vomiting, hepatotoxicity, leukopenia, oral ulcers, thrombocytopenia
Cyclophosphamide / Oral: 1 to 3 mg per kg per dayIntravenous: 2 to 4 mg per kg per day, in conjunction with prednisone / Increased risk for malignancy, leukopenia, thrombocytopenia, hemorrhagic cystitis, anorexia, nausea, vomiting, alopecia, sterility, congestive heart failure and stomatitis / In refractory cases only
Mycophenolate
Mofetil
Cyclosporine / 2 g /day
2.5 to 10 mg per kg per day* / Bone marrow suppression, hepatotoxicity
Impairs T-cell proliferation; nephrotoxicity, lymphoma, hypertension, hypertrichosis, gingival hyperplasia, hepatotoxicity, paresthesias, fatigue, hyperesthesias, depression and seizures
Hydroxychloroquine / 200 mg twice daily in adults; 2 to 5 mg per kg per day in children / Myopathy, differentiated by biopsy; hematologic toxicity, hepatotoxicity, antimalarial retinopathy, dizziness, ataxia and weight loss / Adjunctive treatment to reduce rash
Intravenous immunoglobulin / 2 g per kg in divided doses once per month for three months / Pancytopenia, death, lymphoma / Showed improvement in 70 percent of patients; limited by high cost
Topical steroids / Class I (super-high potency) or class II (high potency) topical steroid is recommended / — / For further control of the erythematous and pruritic skin changes
Physical therapy / — / — / Directed at preventing atrophy andcontractures; technique should focus initially on passive stretching and splinting; more aggressive strength-building therapy once inflammation is controlled
Sun avoidance / — / — / Broad-spectrum sunscreen, protective clothing, avoiding ultraviolet light exposure
SJOGREN'S SYNDROME (SS)
Sjogren's syndrome is a chronic, slowly progressive, inflammatory autoimmune disorder characterized by the infiltration of lymphocytes (T-cells in the majority of cases), monocytes and plasma cells into the parotid (salivary) glands and lacrimal (tear) glands. This chronic lymphocytic infiltration interferes with the normal function of these glands and eventually results in a significant reduction or cessation in the production and secretion of saliva and tears. The condition is named after Henry Sjogren, an ophthalmologist, who first described the primary clinical features of this disorder in 1933.
In approximately 40% of patients, Sjogren's syndrome progresses beyond the exocrine glands and systemic (extraglandular) features develop.
Classification
Two distinct forms of Sjogren's syndrome have been recognized:
· Primary Sjogren's syndrome - defined as dry eye and dry mouth that occurs by itself and is not associated with another autoimmune disorder. Primary Sjogren's syndrome occurs in approximately 50% of cases
· Secondary Sjogren's syndrome - characterized by dry eye and dry mouth that occurs in the presence of a major underlying autoimmune disease such as rheumatoid arthritis, systemic lupus erythematosus, scleroderma, primary biliary cirrhosis, chronic active hepatitis, or myasthenia gravis.
Epidemiology
The overall prevalence of Sjogren's syndrome in the general population has been estimated to range from 0.5% to 3%. Sjogren's syndrome is a condition that affects primarily women with a female to male ratio of about 9:1. Symptoms of the disorder most often begin between the ages of 40-60.
Pathogenesis
The theories regarding the underlying causes of Sjogren's syndrome include:
o Chronic inflammation
o Cellular apoptosis (self-death of a cell)
o Autonomic nervous system dysfunction
o Neurotransmitter abnormality
o Genetic predisposition (HLA-B8/DR3 association)
Clinical features
· The classic signs and symptoms of Sjogren's syndrome affecting the oral cavity (dry mouth, patients need water to swallow food) and the eyes (dry eye, conjunctivitis, blepharitis and filamentary keratitis).
· The signs and symptoms of Sjogren's syndrome that affects other areas of the body, known as systemic or extraglandular features of Sjogren's, which may include:
o Salivary gland enlargement
o Non-erosive arthritis
o Raynaud's phenomenon
o Fatigue
o Low-grade fever
o Interstitial lung disease
o Cryoglobulinemia, Vasculitis
o Peripheral neuropathy
o Lymphadenopathy
o Lymphoreticular lymphoma
o Glomerulonephritis
o Renal tubular acidosis
Investigations
- Anemia, leucopenia, thrombocytopenia
- High ESR, hypergammaglobulinemia
- Patients typically have a positive ANA, RF, anti SS-A (anti-Ro) and anti SS-B (anti-La) antibodies.
- Special laboratory tests that are used to confirm the diagnosis of Sjogren's syndrome that are designed to measure abnormalities in the production of saliva and tears (Srmer tear test, Rose Bengal staining).
- Lip biopsy
Treatment
Currently there is no known cure for Sjogren's syndrome. The major goals of treatment are to control the symptoms and prevent or limit the involvement of other organs of the body.
The treatment options that are available to better manage the symptoms associated with dry mouth, including:
o Saliva substitutes
o Saliva stimulants (sugar-free chewing gum or lozenges)
o Good oral hygiene practices
o Lifestyle modifications
The treatment options that are available to better manage dry eye symptoms, including:
o Artificial tears
o Methylcellulose inserts
o Eye ointments
o Soft contact lenses
o Muscarinic agonist drugs
o Punctual occlusion surgery
The treatment options for the management of patients with Sjogren's syndrome who manifest systemic or extraglandular involvement of other body organs such as the skin, joints, lungs, kidney or nervous system.
· Steroids
· Immunosuppressive drugs