After completing this note you will be able to construct a systematic clinical approach to a patient with suspected vasculitis, recognise the key tropical and infectious triggers relevant in Kenya, and outline the immediate and definitive investigations and management while knowing to verify drug doses and local protocols against the Kenya MoH guideline and your hospital formulary.
Definition
Vasculitis is a heterogeneous group of disorders characterised by inflammation of blood vessel walls, leading to vessel wall damage, luminal narrowing or occlusion, aneurysm formation and downstream tissue ischaemia or necrosis. The classification is usually based on the size of vessels involved (large, medium, small) and on the presence of systemic features or organ‑specific disease.
Anatomy and physiology you need
| Vessel size | Typical examples | Key functions |
|---|---|---|
| Large | Aorta, carotid, renal arteries | High‑flow conduit, pressure regulation |
| Medium | Mesenteric, hepatic, coronary arteries | Distribution to organs, pulsatile flow |
| Small | Arterioles, capillaries, venules | Exchange of gases, nutrients, immune cells |
| Endothelium | Lining of all vessels | Barrier, anticoagulant surface, cytokine release |
| Media | Smooth muscle layer | Vascular tone, structural integrity |
| Adventitia | Connective tissue, nerves | Support, vasa vasorum supply |
Understanding that inflammation can begin in any layer but most clinically relevant damage occurs when the media and adventitia are breached, causing aneurysm or rupture, or when the intima thickens, causing stenosis.
Causes and risk factors
| Category | Relevant agents in Kenya | Reason for relevance |
|---|---|---|
| Infectious | HIV, Mycobacterium tuberculosis, Plasmodium falciparum, hepatitis B & C, streptococcal infections | Chronic immune activation, molecular mimicry, direct endothelial invasion |
| Autoimmune / rheumatic | Systemic lupus erythematosus, rheumatoid arthritis, Sjögren’s, mixed connective tissue disease | Auto‑antibody mediated vessel injury |
| Hematologic | Sickle cell disease, antiphospholipid syndrome | Vaso‑occlusion, thrombosis, endothelial activation |
| Drug‑induced | Minocycline, allopurinol, anti‑TNF agents, certain herbal preparations | Hypersensitivity vasculitis, immune complex deposition |
| Malignancy | Lymphoma, leukemia, solid tumours | Paraneoplastic immune complexes |
| Genetic / primary | ANCA‑associated vasculitides, Takayasu arteritis, polyarteritis nodosa | Auto‑immune dysregulation, HLA associations |
| Environmental | Dust, silica exposure, smoking | Chronic irritation, immune priming |
Pathophysiology
- Trigger (infection, auto‑antibody, drug) →
- Immune activation (innate & adaptive) →
- Formation of immune complexes or ANCA antibodies →
- Deposition in vessel wall →
- Complement activation & neutrophil recruitment →
- Release of proteases & reactive oxygen species →
- Endothelial injury →
- Vessel wall necrosis, fibrinoid change →
- Luminal narrowing or aneurysm formation →
- Tissue ischaemia, infarction or hemorrhage → clinical syndrome.
Clinical features
| History element | Why it matters |
|---|---|
| Onset and tempo – sudden vs insidious | Acute onset suggests infection‑related or drug‑induced vasculitis; a gradual course fits primary systemic vasculitides. |
| Pattern of organ involvement – skin lesions, neuropathy, renal symptoms, respiratory complaints, gastrointestinal pain, fever, weight loss | Vasculitis is a multisystem disease; the distribution of symptoms helps to map the size of vessels involved (large‑vessel – limb claudication, aortic pain; medium‑vessel – nodular skin lesions, mononeuritis multiplex; small‑vessel – palpable purpura, glomerulonephritis). |
| Skin findings – palpable purpura, livedo reticularis, ulcerations, necrotic nodules, urticarial rash | Small‑vessel disease typically gives palpable purpura; livedo reticularis points to medium‑vessel involvement; necrotic ulcers suggest severe ischemia. |
| Neurologic symptoms – mononeuritis multiplex, peripheral neuropathy, stroke‑like events | Nerve ischemia is common in medium‑ and small‑vessel vasculitis; focal deficits raise suspicion for CNS vasculitis or embolic phenomena. |
| Renal complaints – hematuria, proteinuria, edema, hypertension | Glomerulonephritis is the hallmark of small‑vessel (ANCA‑associated) vasculitis; hypertension may reflect renal artery involvement. |
| Respiratory signs – cough, hemoptysis, dyspnoea, sinusitis, otitis media | Pulmonary capillaritis (hemoptysis) is typical of ANCA vasculitis; chronic sinusitis points to granulomatosis with polyangiitis. |
| Gastro‑intestinal symptoms – abdominal pain, melena, perforation | Mesenteric ischemia from medium‑vessel vasculitis or vasculitic ulceration. |
| Constitutional symptoms – fever, night sweats, weight loss, malaise | Systemic inflammation; also overlap with infections (TB, HIV) common in Kenya. |
| Drug exposure – recent antibiotics, anti‑TNF agents, cocaine, herbal remedies | Drug‑induced vasculitis often mimics primary forms but resolves with withdrawal. |
| Infectious history – HIV status, recent TB treatment, malaria episodes, chronic hepatitis B/C | Infections can trigger immune complex vasculitis (e.g., hepatitis B‑associated polyarteritis nodosa) or act as direct pathogens (e.g., HIV‑associated vasculitis). |
| Sickle cell disease – crises, transfusion history | Sickle cell vasculopathy can present with similar skin and renal findings; differentiating is essential. |
| Family history / autoimmune disease – SLE, rheumatoid arthritis, Sjögren’s | Overlap vasculitis may accompany systemic autoimmune disorders. |
Examination findings and rationale
| Finding | Pathophysiologic explanation |
|---|---|
| Palpable purpura (non‑blanching, raised) | Leukocytoclastic inflammation of post‑capillary venules causing extravasation of red cells. |
| Livedo reticularis / racemosa | Occlusion of medium‑size dermal arteries producing a net‑like mottling. |
| Necrotic or ulcerated nodules (especially on lower limbs) | Ischemic necrosis from vessel occlusion; common in polyarteritis nodosa. |
| Mononeuritis multiplex (asymmetric sensory loss, foot drop) | Segmental ischemia of peripheral nerves due to vasa nervorum involvement. |
| Blood pressure elevation | Renal artery stenosis or glomerular inflammation leading to sodium retention. |
| Renal bruit | Turbulent flow in stenotic renal arteries (large‑ or medium‑vessel disease). |
| Pulmonary crackles or haemorrhagic infiltrates | Alveolar hemorrhage from pulmonary capillaritis. |
| Joint swelling/tenderness without erosions | Immune complex deposition in synovium; often non‑destructive. |
| Abdominal tenderness, guarding | Mesenteric ischemia or bowel infarction from medium‑vessel vasculitis. |
| Peripheral pulses diminished (especially femoral/renal) | Large‑vessel stenosis or occlusion (e.g., Takayasu arteritis). |
| Mucosal ulcers (oral, nasal) | Small‑vessel inflammation of mucosal capillaries. |
Differential diagnosis
| Condition | Points toward it | Distinguishing feature |
|---|---|---|
| Primary ANCA‑associated vasculitis (GPA, MPA, EGPA) | Upper airway disease, pulmonary haemorrhage, rapidly progressive GN, ANCA positivity | Necrotising granulomas on biopsy; ANCA pattern (c‑ANCA vs p‑ANCA) |
| Polyarteritis nodosa | Medium‑vessel involvement, abdominal pain, hypertension, hepatitis B association | No glomerulonephritis; angiography shows microaneurysms |
| Cryoglobulinaemic vasculitis | Hepatitis C infection, low complement, palpable purpura, arthralgia | Cryoglobulins in serum; low C4 |
| Lupus vasculitis | Positive ANA, dsDNA, systemic lupus features | Immune‑complex deposition; low complement, other SLE criteria |
| Infective endocarditis‑related vasculitis | Fever, murmur, Janeway lesions, positive blood cultures | Vegetations on echo; embolic phenomena |
| Drug‑induced leukocytoclastic vasculitis | Recent drug exposure, abrupt skin rash, resolves on withdrawal | Temporal relation to drug, lack of systemic organ involvement |
| Sickle cell vaso‑occlusive disease | Known sickle cell, painful crises, hemolysis | Hemoglobin electrophoresis, sickled cells on smear |
| HIV‑associated vasculitis | Positive HIV, opportunistic infections, skin ulcerations | Low CD4 count, HIV viral load, response to ART |
Investigations
| Test | What it answers | Interpretation |
|---|---|---|
| CBC with differential | Anaemia, leukocytosis, eosinophilia | Eosinophilia suggests EGPA; anaemia of chronic disease common in systemic vasculitis |
| ESR/CRP | Inflammatory activity | Markedly raised in active vasculitis, but non‑specific |
| Urinalysis + microscopy | Hematuria, proteinuria, casts | RBC casts → glomerulonephritis; proteinuria quantifies renal involvement |
| Serum creatinine & eGFR | Renal function | Rising creatinine signals renal vasculitis |
| ANCA (c‑ANCA, p‑ANCA) | Presence of anti‑proteinase 3 or MPO antibodies | Positive in GPA (c‑ANCA) or MPA/EGPA (p‑ANCA); negative does not exclude vasculitis |
| Complement levels (C3, C4) | Immune‑complex activity | Low C4 suggests cryoglobulinaemia or lupus vasculitis |
| Hepatitis B & C serology | Infectious trigger | Positive HBV → polyarteritis nodosa; HCV → cryoglobulinaemic vasculitis |
| HIV test | Underlying immunosuppression | Positive HIV may indicate HIV‑associated vasculitis |
| Cryoglobulin assay | Cryoglobulinaemia | Detectable cryoglobulins support cryoglobulin vasculitis |
| Chest X‑ray / CT thorax | Pulmonary infiltrates, cavitation | Diffuse alveolar hemorrhage or nodules point to ANCA vasculitis |
| Angiography (CT/MR/Conventional) | Vessel lumen, aneurysms, stenoses | Microaneurysms in mesenteric/renal arteries → polyarteritis nodosa |
| Skin or renal biopsy with immunofluorescence | Histopathology, immune deposits | Leukocytoclastic vasculitis, necrotising granulomas, immune‑complex deposition pattern |
| Nerve conduction studies | Neuropathy type | Mononeuritis multiplex supports vasculitic neuropathy |
| Urine culture, blood cultures | Exclude infection | Negative cultures favour primary vasculitis over infective endocarditis |
Diagnosis and severity
- Establishing the diagnosis
Combine clinical pattern (size of vessels, organ systems), laboratory markers (ANCA, complement, serology), imaging (angiography, chest CT) and, when feasible, tissue biopsy.
- Definite primary vasculitis: compatible clinical picture + positive specific serology (e.g., ANCA) ± characteristic biopsy.
- Probable vasculitis: typical clinical features with supportive labs/imaging but no biopsy.
- Secondary vasculitis: identified trigger (infection, drug, underlying autoimmune disease) with vasculitic manifestations.
- Assessing severity
| Domain | Mild | Moderate | Severe / Life‑threatening |
|---|---|---|---|
| Renal | Creatinine <2 mg/dL, no dialysis | Creatinine 2–4 mg/dL, proteinuria >1 g/day | Creatinine >4 mg/dL, dialysis dependence, rapidly progressive GN |
| Pulmonary | Mild cough, no haemoptysis | Dyspnoea, limited haemoptysis | Massive haemoptysis, respiratory failure |
| Neurologic | Peripheral neuropathy without functional loss | Mononeuritis multiplex with disability | CNS involvement (stroke, seizures) |
| GI | Mild abdominal pain | Persistent pain, melena | Perforation, massive bleeding |
| Constitutional | Low‑grade fever, mild weight loss | Fever >38 °C, significant weight loss | Septic‑like picture, multi‑organ failure |
| Laboratory | Normal or mildly raised CRP/ESR | CRP/ESR markedly raised, anemia | Cytopenias, high CRP, organ‑specific labs deranged |
Patients with any severe domain are classified as high‑risk and require urgent immunosuppression and close monitoring.
- Classification for management
- Large‑vessel (e.g., Takayasu, giant‑cell arteritis) → focus on vascular imaging and high‑dose glucocorticoids plus steroid‑sparing agents.
- Medium‑vessel (polyarteritis nodosa) → treat with glucocorticoids and cyclophosphamide‑class agents; antiviral therapy if HBV positive.
- Small‑vessel ANCA‑associated → induction with glucocorticoids plus rituximab or cyclophosphamide‑class agents; maintenance with azathioprine, methotrexate or mycophenolate.
- Immune‑complex (cryoglobulinaemia, lupus) → address underlying infection/autoimmune disease, add glucocorticoids and disease‑specific agents (e.g., hydroxychloroquine for SLE).
Severity scoring guides intensity of induction therapy, need for plasma exchange (e.g., pulmonary haemorrhage with renal failure), and level of inpatient monitoring (ICU vs ward).
Management
1. Immediate stabilisation
| Situation | Action | Rationale |
|---|---|---|
| Severe renal impairment (eGFR < 30 ml/min) or rapidly rising creatinine | Initiate urgent plasma exchange (if ANCA‑associated) and start high‑dose intravenous glucocorticoid pulse | Removes pathogenic antibodies and controls inflammation while definitive therapy is arranged |
| Life‑threatening pulmonary haemorrhage or diffuse alveolar bleeding | Admit to high‑dependency/ICU, give IV methylprednisolone, consider plasma exchange, give supplemental O₂, monitor ABGs | Prevents respiratory failure; early aggressive immunosuppression improves survival |
| Acute neuropathy with motor weakness threatening airway or limb viability | Give IV glucocorticoids immediately; arrange nerve conduction studies once stable | Reduces inflammatory edema of nerves, limits permanent deficit |
| Uncontrolled hypertension in renal vasculitis | IV labetalol or nicardipine infusion, then oral antihypertensives | Protects kidney and prevents cerebrovascular complications |
2. Definitive treatment
| Vasculitis type (most common in Kenya) | First‑line immunosuppression | Adjunct/maintenance |
|---|---|---|
| ANCA‑associated (GPA, MPA, EGPA) | Intravenous glucocorticoid pulse → oral taper + cyclophosphamide (or rituximab if cyclophosphamide contraindicated) | Azathioprine or methotrexate for maintenance; low‑dose glucocorticoid taper |
| Immune‑complex small vessel (IgA vasculitis, cryoglobulinaemic) | Oral glucocorticoids; add mycophenolate mofetil if renal involvement is severe | Hydroxychloroquine for skin/joint disease; treat underlying infection (e.g., hepatitis C) |
| Large‑vessel (Takayasu, giant‑cell) | High‑dose oral glucocorticoids + tocilizumab (IL‑6 blocker) or methotrexate | Low‑dose glucocorticoid taper; aspirin for arterial protection |
| Medium‑vessel (polyarteritis nodosa) | Glucocorticoids + cyclophosphamide; if hepatitis B related, add antiviral therapy | Azathioprine for maintenance |
| Vasculitis secondary to HIV, TB, malaria or sickle cell | Treat underlying infection/disease first; use short‑course glucocorticoids only if organ‑threatening inflammation persists | Continue disease‑specific therapy (antiretrovirals, anti‑TB drugs, antimalarials) |
3. Monitoring & safety
- Clinical: Daily assessment of organ function (urine output, skin lesions, neuropathy, respiratory status).
- Laboratory: CBC, renal panel, liver enzymes, CRP/ESR, urinalysis, ANCA titres, hepatitis B/C serology, HIV viral load as indicated.
- Drug toxicity:
- Glucocorticoids – watch for hyperglycaemia, infection, hypertension, gastric ulcer.
- Cyclophosphamide – monitor blood counts, urine for haematuria, counsel on fertility.
- Rituximab – screen for hepatitis B reactivation, monitor Ig levels.
- Imaging: Repeat chest X‑ray or CT if pulmonary symptoms persist; renal ultrasound if obstructive component suspected.
- Follow‑up schedule: Initially weekly to fortnightly until remission, then every 3 months for the first year, then 6‑monthly.
Contra‑indications & safety notes
- Avoid cyclophosphamide in active infection, severe neutropenia, or pregnancy.
- Rituximab is contraindicated in uncontrolled hepatitis B infection; give prophylactic antivirals.
- High‑dose steroids are unsafe in uncontrolled diabetes, active peptic ulcer disease, or severe uncontrolled hypertension without appropriate prophylaxis.
- Plasma exchange is not indicated for isolated skin‑limited vasculitis; reserve for organ‑threatening disease.
Complications and prognosis
| Complication | Typical time‑frame | Clinical impact |
|---|---|---|
| Chronic kidney disease / end‑stage renal failure | Months to years if renal vasculitis untreated | Requires dialysis or transplant; major mortality driver |
| Permanent peripheral neuropathy | Weeks to months | Functional disability, may need physiotherapy or orthotics |
| Pulmonary fibrosis after alveolar haemorrhage | 6–12 months | Reduced exercise tolerance, risk of respiratory failure |
| Aneurysm formation (especially in polyarteritis nodosa) | Variable | Risk of rupture → life‑threatening hemorrhage |
| Opportunistic infection (TB, PCP, fungal) | During immunosuppression | Increases morbidity; prophylaxis (e.g., cotrimoxazole) often needed |
| Malignancy (especially bladder cancer with cyclophosphamide) | Years after exposure | Requires long‑term surveillance |
| Relapse of vasculitis | Any time, most common within first 2 years | Re‑initiation of induction therapy; close monitoring of ANCA titres helpful |
Prognosis depends on organ involvement, speed of diagnosis, and adequacy of immunosuppression. ANCA‑associated vasculitis has a 5‑year survival > 80 % with modern therapy, but renal or pulmonary involvement lowers survival markedly. Early treatment of infection‑related vasculitis improves outcomes dramatically.
High‑yield exam points
- Look‑alike conditions:
- Infective endocarditis can mimic small‑vessel vasculitis with palpable purpura and glomerulonephritis – always obtain blood cultures.
- Henoch‑Schönlein purpura (IgA vasculitis) in adults may be confused with ANCA vasculitis; IgA staining on skin biopsy and normal ANCA help differentiate.
- Commonest wrong first step: Jumping straight to high‑dose steroids without ruling out active infection (TB, HIV, hepatitis B) – can precipitate fulminant sepsis or viral reactivation.
- Typical bedside examiner question: “Explain why you would check ANCA titres before starting cyclophosphamide in this patient with rapidly progressive glomerulonephritis.” (Answer: to confirm ANCA‑associated disease, guide choice of cyclophosphamide vs. rituximab, and avoid unnecessary toxicity.)
- Key physical sign: “Palpable purpura on the lower limbs with livedo reticularis suggests medium‑vessel involvement; ask what organ systems you would screen next.”
- Management nuance: “When is plasma exchange indicated in ANCA vasculitis?” (Answer: severe renal impairment (creatinine > 5 mg/dL) or pulmonary haemorrhage.)
Clinical case
Case: A 28‑year‑old Kenyan woman, HIV‑positive (well‑controlled on ART), presents with a 2‑week history of fever, arthralgia, and a non‑blanching purpuric rash on both legs. She reports dark urine and reduced urine output. Examination shows palpable purpura, mild peripheral edema, and blood pressure 150/95 mmHg. Urinalysis reveals protein + and microscopic haematuria. ANCA is positive (c‑ANCA).
Questions
- What is the most likely diagnosis?
Answer: Granulomatosis with polyangiitis (c‑ANCA‑associated small‑vessel vasculitis) with renal involvement.
- What immediate management step should be taken?
Answer: Admit to a monitored bed, start intravenous glucocorticoid pulse and arrange plasma exchange because of rapidly progressive glomerulonephritis.
- Which long‑term therapy is appropriate after remission is achieved?
Answer: Switch to azathioprine (or methotrexate) for maintenance together with a slow oral glucocorticoid taper, while continuing ART and monitoring for drug interactions.
Practice questions
Question 1
A 45‑year‑old man with a 3‑day history of cough, haemoptysis, and rising creatinine is found to have diffuse alveolar infiltrates and a positive p‑ANCA. What is the next best step?
A. Start oral prednisone only
B. Initiate intravenous methylprednisolone pulse and arrange plasma exchange
C. Begin high‑dose cyclophosphamide without steroids
D. Observe and repeat labs in 48 h
Answer: B. Initiate intravenous methylprednisolone pulse and arrange plasma exchange
Explanation: Pulmonary‑renal syndrome requires rapid control of inflammation; plasma exchange improves outcomes in severe cases.
Question 2
A 60‑year‑old woman with known hepatitis B presents with fever, weight loss, livedo reticularis, and mesenteric aneurysms on CT. Which treatment is contraindicated?
A. Cyclophosphamide
B. Antiviral therapy for hepatitis B
C. Low‑dose aspirin
D. Glucocorticoids
Answer: A. Cyclophosphamide
Explanation: Cyclophosphamide can cause viral reactivation and hepatic toxicity; antiviral prophylaxis and steroids are preferred.
Question 3
A patient with sickle cell disease develops painful nodular lesions on the shins and microscopic haematuria. Which investigation will most help differentiate sickle‑cell vaso‑occlusive skin changes from true vasculitis?
A. Serum complement levels
B. Skin biopsy with immunofluorescence
C. Chest X‑ray
D. Peripheral blood smear
Answer: B. Skin biopsy with immunofluorescence
Explanation: Histology can demonstrate leukocytoclastic vasculitis versus sickle‑cell infarcts.
Question 4
A 32‑year‑old woman with newly diagnosed ANCA‑positive microscopic polyangiitis is started on cyclophosphamide. Which monitoring parameter is essential in the first month?
A. Serum calcium
B. Urine pregnancy test
C. Serum uric acid
D. Serum triglycerides
Answer: B. Urine pregnancy test
Explanation: Cyclophosphamide is teratogenic; pregnancy must be excluded before use.
Question 5
In a patient with renal‑limited ANCA vasculitis, which finding would prompt you to add rituximab instead of cyclophosphamide?
A. Age > 65 years
B. Presence of asthma
C. Positive anti‑GBM antibodies
D. Low complement levels
Answer: A. Age > 65 years
Explanation: Older patients tolerate rituximab better and have lower risk of cyclophosphamide‑related toxicity.
Drafted with AI assistance from standard references and reviewed for structure. Check details against your lecture notes and the Kenya MoH guideline.