L4 Anti-phospholipid syndrome

IDIOPATHIC INFLAMMATORY MYOPATHIES

ILOs (Intended Learning Outcomes)

  • Describe mechanisms of Systemic Sclerosis pathogenesis.

  • Diagnose Systemic Sclerosis (SSc).

  • Investigate internal organ involvement via lab and imaging.

  • Prescribe overall treatment and specific treatments for target organs in SSc.

  • Explain main complications of SSc.

Skeletal Muscle Disorders

  • I. Inflammatory muscle disorders

  • II. Non-inflammatory Disorders:

    1. Hereditary: Duchenne muscular dystrophy

    2. Endocrinal: Cushing's syndrome, hypothyroidism

    3. Metabolic: Storage diseases

    4. Electrolyte disturbances: Hypokalemia, hypocalcemia

    5. Others

Inflammatory Muscle Diseases

  • I. Idiopathic inflammatory myopathies:

    1. Polymyositis (PM)

    2. Dermatomyositis (DM)

    3. Juvenile DM-PM

    4. Myositis associated with other connective tissue/inflammatory disorders (e.g., lupus, rheumatoid arthritis, scleroderma)

    5. Myositis linked to malignancy

    6. Inclusion Body Myositis (IBM)

  • II. Myositis secondary to infectious agents

  • III. Drug- and toxin-induced myositis

Idiopathic Inflammatory Myopathies Characteristics

  • Heterogeneous disorders featuring:

    • Proximal muscle weakness

    • Non-suppurative inflammation of skeletal muscle with lymphocytic infiltrates

Epidemiology

  • Incidence: 2-8 cases per million per year

  • Gender Ratio: Female: male = 2:1

  • Bimodal Age Distribution:

    • 7-10 years

    • 45-60 years

  • Age of onset in myositis associated with another condition is similar to that of the underlying condition

  • IBM and myositis related to malignancy common after age 50

Pathogenesis

  • Etiology of Idiopathic Inflammatory Myopathies (IIM) is unknown.

  • Aberrations in the immune system result in increased infection susceptibility.

  • Modifications of cellular immunity lead to mononuclear cells that can damage muscle.

  • Complement may contribute to tissue injury in DM.

Clinical Features of Polymyositis (PM)

  • Proximal muscle weakness in 90-95% of cases, often insidious.

  • Affected muscles include:

    • Limb girdle muscles (shoulder, pelvic)

      • Challenges: hair combing, lifting, climbing stairs, transitioning from sitting

    • Neck muscles affecting head positioning due to exhaustion

    • Respiratory muscles (diaphragm, intercostals) affecting breathing and swallowing

    • Cardiac muscles: dilation and cardiomyopathy

    • Ocular muscles are unaffected.

Extra-Muscular Manifestations

  • Cardiac disturbances:

    • ECG changes, conduction disturbances, arrhythmias, cardiomyopathy, congestive heart failure

  • Respiratory manifestations:

    • Interstitial fibrosis, interstitial pneumonitis

  • Systemic symptoms:

    • Arthralgia, fever, malaise, Raynaud’s phenomenon.

Dermatomyositis

  • Rash is the primary symptom in 95% of cases.

  • Only 50-60% present with proximal muscle weakness initially.

  • Follow-up is crucial as many develop weakness later.

  • Other features include arthralgia, Raynaud’s phenomenon, dysphagia (10-25% of cases).

  • Rare complications: interstitial pneumonitis, cardiomyopathy, heart block.

Skin Manifestations in DM

  1. Heliotrope rash: Violaceous eyelid discoloration, often with periorbital edema.

  2. Gottron’s sign/papules: Scaly, violaceous eruptions over extensor joints.

  3. Mechanic's Hands: Dark lines on palms/fingers.

  4. Shawl sign: Erythema over shoulders and chest.

  5. V-sign: Erythema over neck and chest.

  6. Nailbed changes (periungual).

  7. Holster sign: Rash on thigh.

  8. Ulcers: May develop in various locations due to vascular changes.

  9. Calcinosis: Cutaneous calcium deposits, can become inflamed and ulcerated.

Diagnosis of PM & DM

  1. Symmetric, progressive proximal muscle weakness.

  2. Elevated serum muscle enzymes: CK, aldolase, LDH, AST.

  3. Electromyographic (EMG) triad characteristic of myositis.

  4. Chronic inflammation evidence on muscle biopsy.

  5. Typical rashes in dermatomyositis.

Essentials of Diagnosis

  • Progressive muscle weakness is key.

  • Dermatomyositis is noted for characteristic skin manifestations (Gottron papules, heliotrope rash) and increased malignancy risk.

  • High creatine kinase levels present, myositis-specific antibodies, muscle biopsy essential for diagnosis.

  • Distinction from infectious, metabolic, or drug-induced cases essential.

Investigations

  1. Acute phase reactants: ESR and CRP (normal in 50%).

  2. Antinuclear antibodies (ANA).

  3. Muscle enzyme levels.

  4. EMG findings.

  5. Myositis-specific autoantibodies.

Myositis Serologic Groups & Clinical Presentations

  • Anti-synthetase: Interstitial lung disease, arthritis, mechanic's hands, fever.

  • Anti-SRP: Significant cardiac involvement, acute muscle weakness.

  • Anti-Mi-2: Classic dermatomyositis features with good prognosis.

Muscle Biopsy Results

  • Dermatomyositis: B cells, macrophages, CD4 T cells, and decreased capillaries.

  • Polymyositis: CD8 T cells and endomysial infiltrate, myonecrosis present.

  • Inclusion Body Myositis: Rimmed vacuoles and eosinophilic cytoplasmic inclusions.

Childhood Myositis

  • Common presentation age: 7-10 years, slightly more in girls.

  • Characteristic DM rash at presentation in most cases.

  • 90% show proximal muscle weakness.

  • Myopathy features: Atrophy, contractures, calcifications, with higher visceral involvement.

  • Acute myositis may cause fever, malaise, abdominal pain, and gastrointestinal complications.

Myositis with Connective Tissue Diseases (CTD)

  • Overlap syndromes present with PM/DM and another CTD fulfilling diagnostic criteria.

  • Presenting features are indicative of the underlying CTD.

Myositis with Malignancy

  • Higher risk in elderly patients with PM-DM.

  • 10%-20% may have associated malignancy, with dermatomyositis more common.

  • Myositis commonly precedes cancer by an average of 1-2 years in 70% of cases.

Inclusion Body Myositis (IBM)

  • Primarily affects older men, insidious onset.

  • Differences from polymyositis include focal, distal weakness and minimal enzyme elevation.

  • Progression may be steady or plateau.

Treatment

  • Most IIM patients respond to corticosteroids.

  • Immunosuppressants reduce steroid use, address extra-muscular manifestations.

  • Early treatment critical to limit muscle damage and atrophy.

  • Methotrexate (MTX) is first-line after corticosteroids for refractory cases.

  • Azathioprine shows efficacy in myositis treatment.

  • Mycophenolate mofetil (1-1.5 g orally twice daily).

  • Hydroxychloroquine can benefit skin lesions in dermatomyositis, while sun exposure should be minimized.

  • Additional options: Cyclosporine, Tacrolimus (CNI), IVIG, and Rituximab for resistant cases.