Vasculitis - General Issues and Classification

🧠 Summary

💡 Key Concept: Vasculitis refers to inflammation of blood vessel walls leading to damage, narrowing, thrombosis, or aneurysm formation. 🧾 The following classification follows the 2012 International Chapel Hill Consensus Conference (CHCC) — the modern gold standard for nomenclature.

📘 About

• Represents a heterogeneous group of autoimmune diseases affecting any vessel size.
• Common pathway: immune-mediated inflammation → vessel wall damage → ischaemia or haemorrhage.
• Manifestations depend on the calibre and distribution of affected vessels.

🧩 Pathophysiology & Aetiology

• 🧫 Immune complex deposition — e.g. Hepatitis B in PAN, Cryoglobulinaemia, SLE.
• 🦠 Endothelial infection — HIV, syphilis, hepatitis viruses.
• ⚡ ANCA-mediated cytotoxicity — PR3/MPO antibodies cause neutrophil activation and vessel injury.
• 🧬 T-cell–mediated inflammation — as in Giant Cell Arteritis and Takayasu Arteritis.
• 🩸 Autoantibodies to endothelium — seen in Behçet and Kawasaki disease.

🧑‍⚕️ Clinical Features

• 🩻 Systemic: Fever, weight loss, fatigue, myalgia, arthralgia.
• 🧠 Neurological: Mononeuritis multiplex, stroke, headache, seizures.
• 🫁 Respiratory: Alveolitis, haemoptysis, sinusitis, nasal crusting (esp. GPA).
• 💧 Renal: Glomerulonephritis → haematuria, proteinuria, renal impairment.
• 🫀 Cardiac: Coronary arteritis (Kawasaki), myocarditis.
• 🩹 Skin: Palpable purpura, urticaria, livedo reticularis, ulcers.
• 🦵 Musculoskeletal: Arthralgia, myositis.
• 👁️ GCA-specific: Jaw claudication, scalp tenderness, visual loss (ischaemic optic neuropathy).

🔬 Investigations

• 📈 Inflammatory markers: ESR and CRP often very high.
• 🩸 Autoantibodies: ANCA (PR3/MPO), ANA, dsDNA, RF, ENA.
• 🧬 Complement: C3/C4 (↓ in immune complex vasculitis).
• 🧫 Infective screens: Hepatitis B/C, HIV, syphilis.
• 🧪 Cryoglobulins and anticardiolipin antibodies where relevant.
• 🫀 Imaging: Angiography showing ‘beading’—segments of stenosis and aneurysm (classically in PAN).
• 🧫 Histology: Biopsy (skin, kidney, temporal artery, nerve) is diagnostic and essential before immunosuppression.

📚 Classification (Chapel Hill 2012)

• 🩸 Large vessel: GCA, Takayasu, isolated aortitis, primary CNS vasculitis.
• 🫀 Medium vessel: PAN, Kawasaki disease.
• 🧫 Small vessel: ANCA-associated (GPA, MPA, EGPA) or immune complex (IgAV, cryoglobulinaemia, anti-GBM, HUV).
• 🌈 Variable vessel: Behçet disease, Cogan syndrome.
• 🦠 Secondary vasculitis: Associated with SLE, RA, sarcoid, infections (HBV/HCV), or drugs (e.g. hydralazine, propylthiouracil).

💊 Management Principles

• 🎯 Diagnosis first: Always biopsy before starting high-dose immunosuppression if feasible.
• 💉 Induction: High-dose corticosteroids ± Cyclophosphamide or Rituximab for organ-threatening disease.
• 🩺 Maintenance: Azathioprine, Methotrexate, or Mycophenolate to prevent relapse.
• ⚖️ Adjunctive: Control infection risk (Pneumocystis prophylaxis), bone protection, and cardiovascular risk factors.
• ⛔ Monitor toxicity: Immunosuppressants cause cytopenias, infection, infertility.

💡 Teaching Tip

• Vasculitis represents an interface between autoimmunity, immunology, and vascular biology.
• Teach by “vessel size first, cause second” — it helps pattern recognition and diagnostic reasoning.
• Encourage pattern linkage: GCA → elderly + headache; PAN → HBV + neuropathy; GPA → nose + kidneys + lungs; EGPA → asthma + eosinophilia.
• Always distinguish primary vs secondary vasculitis — treating the trigger (e.g. hepatitis) can cure the disease.

📖 References

• BNF: Immunosuppressive Drugs Overview
• Jennette JC et al. Arthritis & Rheum 2013;65(1):1–11. The 2012 Chapel Hill Consensus Conference.
• NICE NG95 (2017): Fever and vasculitis in adults
• EMA Pharmacovigilance Updates on Rituximab and Cyclophosphamide (2023)