Vasculitis and Vasculitides - Differential Diagnosis Framework



When to Consider Vasculitis:

 • Purpura, ischemic skin lesions

 • Mononeuritis multiplex

 • Hematuria, proteinuria, rapidly progressing GN

 • New pulmonary and renal abnormalities



SMALL VESSEL VASCULITIS:

ANCA Associated - ANCA specific for myeloperoxidase (MPO-ANCA) or proteinase 3 (PR3-ANCA):

 • Microscopic Polyangiitis:

	- No Granulomas 

	- ANCA is present in >90%, MPO > PR3

	- Necrotizing glomerulonephritis and/or pulmonary capillaritis

 • EGPA:

	- Eosinophilia, asthma, chronic rhinosinusitis, + Granulomas

	- MPO > PR3 60%

 • GPA:

	- +Granulomas

	- ANCA is present in >80% (80-90% have PR3-ANCA)

	- Necrotizing, pauci-immune glomerulonephritis

	- Granulomatous inflammation of the upper and lower respiratory tracts

Immune Complex Vasculitis 

 • Glomerulonephritis is often present

 • Henoch Schonlein Purpura (IgA vasculitis) - Affects the skin and gastrointestinal tract, and often causes arthritis. (± glomerulonephritis)

 • Anti-GBM - (10-40% ANCA +MPO)

 • Cryoglobulinemic Vasculitis - Skin, glomeruli, and peripheral nerves are often involved

 • Hypocomplementemic Urticarial Vasculitis (anti-C1q Vasculitis):

	- Urticaria and hypocomplementemia, Glomerulonephritis, arthritis, obstructive pulmonary disease, and ocular inflammation

Others:

 • Lupus Vasculitis

 • Drug Associated (Commonly MPO-ANCA)

 • Levamisole Associated: (± 100 % Commonly MPO-ANCA)

 • Hydralazine-Induced ANCA-Associated Vasculitis: + MPO-ANCA



MEDIUM VESSEL VASCULITIS:

 • Polyarteritis Nodosa:

	- Kidneys: glomerular ischemia

	- Skin: erythematous nodules, purpura, livedo reticularis, ulcers, and bullous or vesicular eruption

	- Joints: myalgia and muscle weakness

	- Nerves: neuropathy

	- GI tract: abdominal pain

 • Kawasaki Disease:

	- Mucocutaneous lymph node syndrome

	- Coronary arteries

	- Fever

	- Conjunctivitis, mucositis

	- Rash, arthritis



LARGE VESSEL VASCULITIS (Granulomatous disease):

 • Takayasu:

	- Age < 30 years

	- Aorta and branches

 • GCA:

	- Aorta and Superficial temporal artery

	- Age > 50 years



VARIABLE-VESSEL VASCULITIS:

 • Behçet Syndrome:

	- Recurrent oral and/or genital aphthous ulcers, cutaneous, ocular, articular, gastrointestinal, and/or central nervous system involvement. 

	- Thrombosis and arterial aneurysms can also occur.

 • Cogan Syndrome:

	- Ocular inflammatory lesions-interstitial keratitis, uveitis, and episcleritis as well as inner ear disease



Differential Diagnosis: 

Systemic rheumatic diseases, such as systemic lupus erythematosus, atherosclerotic disease, drug reactions, and vaso-occlusive processes. Among the most important diseases to exclude are infections and malignancies.



Presentation - Systemic Symptoms (Sx) in Vasculitis:

 • Fevers

 • Fatigue

 • Anorexia

 • Weight loss

 • Night sweats

 • Arthralgias

 • Eye inflammation, particularly scleritis

 • Palpable purpura: strong sign of cutaneous leukocytoclastic vasculitis

 • Sensory and/or motor neuropathy

 • Absent, diminished, or tender pulses, bruis, or blood pressure discrepancies



Findings by Vessel Size:

 • Large Vessel: Blood pressure difference in extremities, upper extremity claudication, aortitis, aortic aneurysm

 • Medium Vessels: Supply gut -> abdominal pain, testes -> pain, infarct

 • Small Vessels: Skin -> causing palpable purpura. Nerves -> mononeuritis multiplex/neuropathy. Kidneys -> glomerulonephritis. Eye -> retinopathy



Lab Tests:

 • CBC

 • LFT

 • ESR

 • ANA (Suggest CTD)

 • ANCA (Dx: GPA, EGPA, microscopic polyarteritis, drug-induced vasculitis)

   - 2 relevant target antigens are proteinase 3 (PR3) and myeloperoxidase (MPO)

   - (C-ANCA) pattern: antibodies directed against PR3

   - (P-ANCA) pattern: is usually directed against MPO

 • Complement (Low levels mixed cryoglobulinemia, urticarial vasculitis, and SLE)

 • Urinalysis (Renal involvement)

 • TSH

 • SPEP

Consider:

 • Serologies for Cryoglobulins

 • HIV

 • HBV HCV

 • ASO



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