Dr. Israa

Vasculitis

Definition & Scope

Vasculitis is the inflammation of blood vessels.

• Can affect all blood vessels.
• Mainly affects arteries.
• Includes: Gland arteries, arterioles, capillaries, veins, and venules.

Pathogenesis

1. Large and Medium Blood Vessels (Direct Injury):

   • Molecular mimicry: Immune system activation of CD4+ T-cells leads to direct injury of blood vessels.
   • Occurs in Rheumatic Fever, Multiple Sclerosis, and Vasculitis.
   • Example: A virus enters the blood vessel wall; the immune system attacks it. Proteins in the endothelium resemble viral antigens, causing the immune system to attack the endothelium itself.

2. Indirect Injury (Neutrophil Interaction):

   • A conflict between immune components (plasma cells and neutrophils).
   • Antibodies against neutrophils are produced (e.g., immune cells recognize neutrophils as foreign and destroy them).
   • Content release: Proteases lead to damage of the blood vessel (primarily affects small vessels).

3. Immune Complex Deposition:

   • Antigen-Antibody complexes deposit in blood vessel walls (another disease; SLE as an example).
   • Example: In SLE, if complexes are in high amounts and cannot be excreted by the kidney, they deposit in walls, activating the complement system and damaging the vessel.

Healing and Consequences

• Damage to BV → Underlying collagen is exposed → Stimulates coagulation cascade → Activation of clotting factors.
• Thrombosis → Target organ damage.
• Healing by Fibrosis → Reduced diameter → Ischemia.

General Clinical Manifestations

Due to inflammation and the release of inflammatory cytokines (IL-1, TNF):

• Cytokines go to the hypothalamus and elevate body temperature.
• Fever, myalgia, arthralgia.
• Systemic: Reduced appetite, loss of weight, fatigability.
• Labs: High ESR and CRP.
• Symptoms of organ ischemia.

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Large Vessel Vasculitis (Elastic Arteries)

Temporal (Giant Cell) Arteritis

• Pathogenesis: Usually direct injury via CD4+ activation against blood vessel components (elastic fibers) due to molecular mimicry.
• Demographics: Elderly Caucasian females (Giant mother).
• Histology: Giant Cell Arteritis involves tunica media granuloma, elastic lamina destruction, and thickening of the tunica intima CC wrong?.
• Layers of BV:
  • Tunica intima
  • Tunica media
  • Tunica adventitia
• Anatomy: Affects branches of the Carotid Artery:
  • External Carotid branches: Lingual, superior thyroid, ascending pharyngeal, facial, buccal, occipital, posterior auricular, maxillary, and superficial temporal.
• Note: (e)

Clinical Manifestations

• General: Fever, malaise, myalgia.
• PMR: Often associated with Polymyalgia Rheumatica (generalized muscle pain).
• Specific Symptoms (if left untreated):
  • Blindness: Due to decreased blood supply to the Ophthalmic Artery (branch of internal carotid).
  • Temporal Headache: Can feel the thickened temporal artery.
  • Jaw Claudication: When eating, muscles of mastication will not find blood, leading to ischemia of the muscles (supplied by Trigeminal Mandibular V3).

Management

• Diagnosis: Biopsy. Take a 20mm sample because the involvement is patchy (Patory); a small sample might miss the lesion.
• Treatment: High-dose Glucocorticoids.
  • CRITICAL: Give immediately if suspected, even before biopsy confirmation, to prevent blindness.

Takayasu Arteritis

• Demographics: Young Japanese females.
• Anatomy: Affects the Aorta and its branches (e.g., Subclavian artery → axillary → brachial).
• Pathology: Transmural inflammation and granulomas in the subclavian artery that heal by fibrosis.
• Clinical Features:
  • Pulseless Disease: Absent pulse; can’t feel pulse in rabal.
  • Unequal Pulses: A cause of unequal pulse.
  • Differential for Unequal Pulse: Trauma (most common), poor technique, or injury to artery during ABG healing by fibrosis.
• Treatment: Corticosteroids.

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Medium Vessel Vasculitis (Muscular Arteries)

Kawasaki Disease

• Target: Coronary Artery.
• Demographics: Babies and children younger than 4 years.
• Clinical Manifestations:
  • Fever + Cervical Adenopathy.
  • Rash: Hands and feet (Hand-foot syndrome).
  • Mucocutaneous: Oral ulcers (Strawberry tongue), genital ulcers, erythema.
• Imaging: Beading of coronary artery noticed during catheterization (other).
• Cardiac Risk: Young patients presenting with chest pain or ST elevation on ECG without history of familial hyperlipidemia or CREM. Think of inflammation of coronaries caused by Kawasaki.

Management & Differential

• Management: High-dose Aspirin (given if suspicion is high).
• Risk: In the young, can cause Reye Syndrome.
• Differential Diagnosis (DD):
  • Mononucleosis + HIV.
  • Hand-Foot-Mouth Syndrome (caused by Coxsackie virus).

Buerger’s Disease (Thromboangiitis Obliterans)

• Demographics: Male smokers, usually above age 40.
• Pathogenesis: Smoking causes changes in the endothelium, making it look foreign to immune cells.
• Clinical Features:
  • Claudication, Raynaud phenomenon, and autoamputation of fingers (leads to if severe ischemia).
  • Note: Cessation of smoking decrease disease activity; delay deterioration of disease (about not stop it).
• Anatomy: Most affected vessels include the femoral, popliteal, anterior tibial, and posterior tibial arteries.

Management

• Primary: Smoking cessation.
• Medical: Prostaglandins, Calcium Channel Blockers (CCB) (to cause vasodilation).
• Endothelin Receptor Antagonists: Cause VD by inhibiting calcium entry to BV.
• Contraindications: Beta-blockers (BB) are contraindicated because small vessels have B2 receptors that cause VD; blocking them causes VC, leading to more ischemia.

Polyarteritis Nodosa (PAN)

• Pathology: Affects medium-sized muscular and elastic arteries.
• Imaging: “String of Pearls” appearance.
• Key Feature: Palpable purpura.
• Sparing: Does NOT affect pulmonary vessels.
• Associations: 30% of patients are positive for Hepatitis B.
• Organ Involvement:
  • Kidney: Antigen-antibody complex deposits lead to renal failure (elevated creatinine).
  • Nervous System: Peripheral neuropathy (wrist drop, foot drop) due to affection of bvs supplying nerve.
  • CNS/Eyes: Ptosis, ophthalmoplegia, acuminatorn affection.
• Necrosis: Can occur “everywhere” except the lungs.

Treatment

• Corticosteroids: Note that long-term use can cause Cushing Syndrome.
• Steroid-sparing agents: Methotrexate, Azathioprine, Cyclosporine.

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Small Vessel Vasculitis

Granulomatosis with Polyangiitis (Wegener’s)

• Antibody: C & C ANCA (antibody against PR3).
• Clinical Triad (L-U-K):
  • L (Lower Respiratory): Hemoptysis.
  • U (Upper Respiratory): Sinusitis, Saddle-shape nose deformity.
  • K (Kidney involvement): Nephritis/Nephritic syndrome (Hematuria, HTN).

Microscopic Polyangiitis

• Antibody: p-ANCA positive.
• Differences from Wegener’s:
  • No Upper Respiratory involvement (no sinusitis, no saddle nose).
  • No Granulomas.
• Similarities: Lower respiratory and Kidney involvement (Nephritic syndrome).

Churg-Strauss Syndrome (EGPA)

• Antibody: p-ANCA positive.
• Clinical Features (H-E-L-P):
  • H (Heart involvement): Pericarditis.
  • E (Eosinophilia).
  • L (Allergic): Asthma (leukotriene antagonist).
  • P (Peripheral Neuropathy).
• Treatment: Corticosteroid.
• Note: Rash is common with all small vessel diseases. (Handwritten note: “rash with all small vessel disease”).

Henoch-Schönlein Purpura (IgA Vasculitis)

• Pathogenesis: Abnormal form of IgA. Often follows an Upper Respiratory Tract Infection (URTI) or Gastroenteritis (within 1 week).
• Mechanism: IgA increases; IgG attacks the abnormal IgA (Antibody against Antibody). Deposits in blood vessels and kidneys.
• Clinical Features (G-A-P):
  • G (Glomerulonephritis): Berger’s Disease (immune complex deposits).
  • A (Arthralgia): Joint pain.
  • P pANCA negative (Palpable Purpura): Found on eczensor surface of leg, extensor surface of back, and buttocks.
  • Complications: Intussusception, intestinal valvulosis, honaturia/hematuria, glomerulonephritis.
• Antibody: p-ANCA negative.

Management & Differential

• Treatment: Corticosteroids, Plasmapheresis, and Immunoglobulins (to clear IgA).
• Differential (IgA in Kidney):
  • IgA Nephropathy: Disease only in kidney; presents 3-4 days after infection ((3 normal), deposit in mesangial cells).
  • Post-Streptococcal GN: Presents 2 weeks after infection; (3 low); humpY dumpy subepithelial deposits.

Gyoglobulinemia (Small BV Disease)

• Association: Bassociated with Hepatitis C.

Behçet’s Disease

• Scope: Affects all blood vessels (arteries and veins, capillaries). - presents with thromboosis
• Clinical Features:
  • Oral and Genital Ulcers.
  • Anterior Uveitis.
  • Erythema Nodosum (on legs).
  • Arthralgia.
  • Complications: Widespread thrombosis and embolism.

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