PATH30190 & PATH30260 CTIII 11-12 DM Manifestations Quiz

Dermatomyositis (DM)

• Characterized by mechanic's hand, which is a rough and cracked skin on the lateral and palmar areas of the fingers
• Telangiectasia and vasculopathic changes, including dilated capillary loops in the nailfolds and gum
• Systemic symptoms include fever, malaise, weight loss, arthralgia, and Raynaud's phenomenon
• Other manifestations include:
  • Arthralgia, synovitis, or deforming arthropathy with subluxation in the interphalangeal joints
  • Oesophagus: dysphagia and gastrointestinal symptoms
  • Lung: pulmonary dysfunction due to weakness of the thoracic muscles
  • Subcutaneous calcifications and joint contractures, especially in children
  • Cardiac disturbances and malignancy in adults

Pathogenesis of DM

• Involves CD4+ T-cells and B-cells in the perimysial connective tissue and around blood vessels
• Deposition of C5b-9 (MAC) in capillary vessels
• Autoantibodies, including:
  • ANA (40-60% of patients)
  • Anti-Mi2 antibodies (25% of patients)
  • Anti-helicase antibodies (implicated in nucleosome remodelling)
  • Anti-Jo1 antibodies (associated with interstitial lung disease, arthritis, and "mechanic's hands")
  • Anti-P155/P140 antibodies (associated with paraneoplastic and juvenile cases of DM)

Polymyositis (PM)

• Characterized by bilateral proximal muscle weakness, similar to DM but without a rash
• May also have gastrointestinal, skin, cardiac, and peripheral neuropathy symptoms
• Microscopic pathology: granulomatous vasculitis and p-ANCA (MPO-ANCA) positive
• Treatment: supportive therapy and glucocorticoids

Henoch-Schonlein Purpura

• Characterized by IgA vasculitis and immune complex-mediated vasculitis, often following upper respiratory tract infection in young children
• Presentation: skin lesions on the buttocks and legs, progressing from blanching macules to petechiae to palpable purpura
• Other symptoms: oedema, polyarthritis, colicky abdominal pain, and haematuria
• May have associated IgA nephropathy
• Diagnosis: clinical, as lab results are often normal
• Treatment: supportive therapy and corticosteroids for gastrointestinal symptoms

Vasculitides

• p-ANCA (MPO-ANCA) and c-ANCA (PR3-ANCA) associated with different types of vasculitides
• General symptoms: fever, fatigue, weight loss, and specific symptoms depending on the affected organ
• Endothelial cells are attacked by immune cells, leading to direct damage and organ symptoms
• Immune cells accidentally target endothelial cells due to antigen mimicry (e.g., MPO, PR3)

Giant Cell Arteritis (GCA)

• Formerly known as temporal arteritis
• Granulomatous arteritis of large to small-sized arteries, mainly arteries in the head (extracranial branches of carotids)
• Commonest primary systemic vasculitis in individuals over 50 years old
• Symptoms: fever, fatigue, weight loss, headaches, visual disturbances, facial pain, and scalp tenderness
• Complication: 25% of untreated patients go blind
• Therapy: steroids

Polymyalgia Rheumatica (PMR)

• An inflammatory disorder that causes sudden bilateral neck, shoulder, and low back muscle pain and stiffness
• May be associated with malaise, tiredness, weight loss, depression, and fever
• Elevated ESR and CRP
• Marked improvement with steroids
• Prevalence: 1:133 in individuals over 50 years old
• Often seen with giant cell arteritis

Takayasu Arteritis

• Granulomatous vasculitis that mainly affects the aorta and its branches
• Symptoms: weak or no pulse in the upper extremities, visual and neurologic symptoms, and marked weakening of the pulses in the upper extremities
• Segmental and patchy granulomatous inflammation
• Asian women are more commonly affected
• Symptoms are vague, varied, and perplexing
• Low-grade fever, ischemia, and infarction of affected tissues and organs
• Treatment: steroids

Polyarteritis Nodosa (PAN)

• Segmental transmural necrotizing inflammation of small- to medium-sized arteries
• Every layer of the artery is affected
• Transmural inflammation of the arterial wall with a mixed infiltrate of neutrophils, eosinophils, and mononuclear cells
• Fibrinoid necrosis and thrombotic occlusion of the lumen
• Later, fibrous (occasionally nodular) thickening of the vessel wall that can extend into the adventitia

Kawasaki Disease

• Acute febrile, usually self-limited illness of infants and children (boys more commonly affected)
• Mucocutaneous symptoms and cervical lymph node enlargement
• Large, medium, and small arteries are affected, mostly coronary arteries
• Without treatment, there is a 25% risk of heart complications
• Classic symptoms: conjunctivitis, rash, adenopathy, strawberry tongue, and fever
• Anti-endothelial and smooth muscle antibodies
• Treatment: IVIG

Buerger's Disease / Thromboangiitis Obliterans

• Affects medium and small vessels
• Epidemiology: heavy smokers, males, 20-40 years old
• Pathogenesis: clots in vessels supplying fingers and toes
• Patients develop ulcers on fingers and toes
• Often co-exists with Raynaud's phenomenon
• Intermittent claudication may lead to gangrene and digit auto-amputation
• Superficial nodular phlebitis
• Histology: segmental thrombosing vasculitis
• Treatment: smoking cessation

Small Vessel Vasculitides

• ANCA-associated:
  • Microscopic polyangiitis
  • Granulomatosis with polyangiitis (Wegener's granulomatosis)
  • Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)
• Mediated by immune complexes:
  • IgA vasculitis (Henoch-Schonlein purpura)

Microscopic Polyangiitis (MPA)

• Leukocytoclastic or hypersensitivity vasculitis
• Transmural, necrotizing vasculitis of small vessels
• Organs involved: skin, mucous membranes, lungs, GI, kidneys, heart, and brain
• Is (MPO-ANCA) perinuclear ANCA / anti-myeloperoxidase
• Treatment: glucocorticoids and cyclophosphamide

Granulomatosis with Polyangiitis (Wegener's Granulomatosis)

• Classical clinical triad: kidney, nasopharynx, and lungs
• Kidney: focal necrotizing glomerulonephritis
• Nasopharynx: chronic pain from sinusitis, bloody mucus from ulcers
• Lungs: pneumonitis, haemoptysis, cough, and dyspnea
• D Biopsy: focal necrotizing vasculitis, granulomatous change, and PR3-ANCA (anti-proteinase 3/c-ANCA) positive
• Rapidly fatal if left untreated
• Treatment: glucocorticoids and cyclophosphamide

Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss Syndrome)

• Small vessel necrotizing vasculitis
• Typically affects vessels of the respiratory tract
• Strongly associated with asthma, eosinophilia, and pulmonary infiltrates