NOTES NOTES VASCULITIS GENERALLY, WHAT IS IT? PATHOLOGY & CAUSES ▪ Inﬂammation of blood vessels ▪ Vasculitides categorized by blood vessel size: small, medium, large CAUSES Damaged endothelium ▪ Damaged endothelium → exposed collagen, tissue → increased blood coagulation → weakened, damaged blood vessel walls → aneurysms → vessel wall heals, stiffens as ﬁbrin deposits Autoimmune disease ▪ Direct method: body mistakes endothelial layer of blood vessel for foreign pathogen → attacks ▫ Molecular mimicry: immune system white blood cells (WBCs) mistake normal antigens of endothelial cells for foreign invaders (e.g. bacteria) ▫ Medium, large-vessel vasculitides ▪ Indirect method: immune system attacks healthy cells near vascular endothelium → damages endothelial cells ▫ Small-vessel vasculitides (exception: Henoch-Schönlein purpura) SIGNS & SYMPTOMS ▪ Inﬂammatory response symptoms: fever, weight loss, malaise, fatigue ▪ Ischemia ▫ Blood cells clump to exposed collagen inside blood vessels → blood clots → restricted blood ﬂow ▫ Fibrin deposits in vessel wall → wall thickens, bulges into vessel → stenosis → restricted blood ﬂow 162 OSMOSIS.ORG DIAGNOSIS LAB RESULTS ▪ C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), complete blood count (CBC), various autoantibodies ▪ Biopsy vessel segment TREATMENT MEDICATIONS Reduce inﬂammatory response ▪ Corticosteroids/immunosuppressive drugs
Chapter 25 Vasculitis OSMOSIS.ORG 163
BEHCET'S DISEASE osms.it/behcets-disease PATHOLOGY & CAUSES ▪ Autoimmune multisystem vasculitis affecting any sized vessel, arterial/venous RISK FACTORS ▪ Individuals who are 20–30 years old, of Middle Eastern/Asian descent, biologically male COMPLICATIONS TREATMENT MEDICATIONS ▪ Skin creams, mouth rinses, eye drops ▪ Corticosteroids: (e.g. prednisone) control inﬂammation ▪ Medications: (e.g. azathioprine, cyclosporine, or cyclophosphamide) suppress immune system ▪ Medications: (e.g. interferon alfa-2b) alter immune system response ▪ Blindness from untreated uveitis (inﬂammation in eyes) SIGNS & SYMPTOMS ▪ Recurrent, painful, sterile oral/genital ulcers (pathergy) ▪ Skin papules indistinguishable from acne ▪ Uveitis, optic neuritis, conjunctivitis iritis ▪ Neurologic involvement (meningoencephalitis, intracranial HTN, stroke, headache) ▪ Arthritis (knees, ankles) ▪ Fever, weight loss DIAGNOSIS OTHER DIAGNOSTICS Clinical presentation ▪ Recurrent oral ulcers (three in one year) + two of following ▪ Recurrent genital ulcers ▪ Eye lesions, uveitis ▪ Skin lesions ▪ Positive pathergy test ▪ ≥ 2mm papule 24–48 hours after oblique insertion 5mm into skin with 20-gauge needle, often performed on forearm 164 OSMOSIS.ORG Figure 25.1 Mucosal ulcer in an individual with Behcet’s disease.
Chapter 25 Vasculitis BUERGER'S DISEASE osms.it/buergers PATHOLOGY & CAUSES ▪ Nonatherosclerotic, segmental, inﬂammatory disease affecting small-, medium-sized veins, arteries of extremities → inﬂammatory occlusive thrombus → distal extremity ischemia, digit ulcers/ gangrene → autoamputation ▪ AKA thromboangiitis obliterans ▪ Associated with use of tobacco products RISK FACTORS LAB RESULTS Biopsy ▪ Deﬁnitive; rarely (healing a concern) ▪ Histopathologically, acute-phase lesions show highly cellular, inﬂammatory thrombus with minimal inﬂammation of blood vessel TREATMENT ▪ Immediate smoking cessation ▪ Individuals < 45 years old, who are biologically male, use tobacco ▪ Chronic anaerobic periodontal infection (⅔ of people with Buerger disease) SIGNS & SYMPTOMS ▪ Ulceration of digits ▪ Ischemic claudication: cold, painful, cyanotic distal extremities ▪ Subcutaneous nodules, superﬁcial thrombophlebitis ▪ Paresthesias of extremities ▪ Raynaud phenomenon DIAGNOSIS DIAGNOSTIC IMAGING Figure 25.2 A volume rendered CT angiogram demonstrating obliteration of the right femoral artery secondary to thromboangiitis obliterans. There is also stenosis of the femoral artery on the left. Angiogram ▪ Lack of atherosclerosis ▪ Collateralization, segments of diseased vessel interspersed: smoking → atherosclerosis + Buerger disease simultaneously OSMOSIS.ORG 165
CHURG–STRAUSS SYNDROME osms.it/churg-strauss-syndrome PATHOLOGY & CAUSES ▪ Small, medium vessel granulomatous vasculitis involving many organ systems (cardiac, gastrointestinal, respiratory, skin, renal, neurologic) in individuals with allergy-related respiratory conditions (esp. asthma) ▪ AKA eosinophilic granulomatosis with polyangiitis (EGPA), allergic granulomatosis ▪ P-ANCA reacting with neutrophilic myeloperoxidase ▪ Etiology unknown RISK FACTORS ▪ Age 30–50; asthma/nasal issues SIGNS & SYMPTOMS ▪ Allergies ▫ Asthma, chronic rhinosinusitis, usually precedes vasculitic phase by 8–10 years ▪ Neurological ▫ Peripheral neuropathy (usually mononeuritis multiplex) ▫ Subarachnoid, cerebral hemorrhage, cerebral infarction, cranial nerve palsies ▪ Skin ▫ Palpable purpura, subcutaneous nodules ▪ Cardiac ▫ Damage → heart failure, arrhythmias ▫ Accounts ½ deaths ▪ Other organ systems (renal, gastrointestinal) → symptoms similar to medium-vessel vasculitides 166 OSMOSIS.ORG DIAGNOSIS DIAGNOSTIC IMAGING Chest X-ray ▪ Transient, patchy, symmetrical opacities, often in hilar/peripheral distribution ▪ Pulmonary hemorrhage ▪ Bilateral nodular disease without cavitation High-resolution CT scan ▪ Peribronchial, septal thickening ▪ Widely scattered indistinct opacities Pulmonary function test ▪ Obstructive pattern consistent with asthma Bronchoalveolar lavage ▪ High % of eosinophils LAB RESULTS ▪ Eosinophilia > 1500/microL, > 10% on differential leukocyte count ▪ P-ANCA/MPO-ANCA antibodies ▪ Acute phase reactants: ↑ ESR, CRP Lung/skin biopsy ▪ Deﬁnitive TREATMENT ▪ Prognosis poor (ﬁve year survival, 25% without treatment; 50% with treatment) MEDICATIONS ▪ Corticosteroids, immunosuppressive drugs
Chapter 25 Vasculitis Figure 25.3 Histological appearance of vasculitis in Churg-Strauss syndrome. The background is composed almost entirely of eosinophils. GIANT CELL ARTERITIS osms.it/giant-cell-arteritis PATHOLOGY & CAUSES ▪ Chronic vasculitis of large-, medium-sized vessels ▪ AKA temporal arteritis ▪ Cranial branches of arteries originating from aortic arch ▫ Temporal branch of carotid artery ▪ Aorta, carotids also affected ▪ Most common systemic vasculitis CAUSES ▪ Unknown: possibly genetic, environmental, autoimmune-related RISK FACTORS ▪ Almost always in individuals ≥ 50 ▪ More common in individuals who are biologically female ▪ Strong association with polymyalgia rheumatica (40–50% of GCA individuals) COMPLICATIONS ▪ Irreversible blindness (if untreated) SIGNS & SYMPTOMS ▪ New-onset headache (most common): temporal branch of carotid artery ▪ Jaw claudication (pain when chewing) ▪ Transient unilateral vision loss (amaurosis fugax): ophthalmic artery ▪ Carotid bruits, decreased pulses in arms, aortic regurgitation ▪ Tender, palpable nodules, absent temporal pulse ▪ Increased risk of aortic dissection, aortic aneurysm MNEMONIC: TEMPORAL Characteristics of Temporal (Giant cell) arteritis Temporal artery tenderness ESR >100 Multinucleated giant cells Pain Onset >50 years old polymyalgia Rheumatica association Amaurosis fugax Lost vision OSMOSIS.ORG 167
DIAGNOSIS LAB RESULTS ▪ Extremely elevated ESR (> 100mm/hr), ↑ IL-6 associated with active disease Temporal artery biopsy ▪ Tightly packed monocytes/macrophages, as if one giant cell, in internal elastic lamina; segmental pattern; 90% sensitivity TREATMENT ▪ Corticosteroids Figure 25.4 A histology photomicrograph demonstrating giant cell arteritis. The external elastic lamina to the right has been completely destroyed by granulomatous inﬂammation. GRANULOMATOSIS WITH POLYANGIITIS osms.it/granulomatosis-with-polyangiitis PATHOLOGY & CAUSES ▪ Small-vessel vasculitis involving nasopharynx, lungs, kidneys ▪ AKA Wegener’s granulomatosis ▪ Granulomatous disease of respiratory tract → systemic necrotizing vasculitis ▪ B-cells release cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCA) → binds to proteinase 3 (neutrophil granule) in neutrophils → neutrophils release free radicals → free radicals damage neighboring endothelial cells → vasculitis ▪ Triad ▫ Focal, necrotizing vasculitis ▫ Necrotizing granulomas in upper airway, lungs ▫ Necrotizing glomerulonephritis (renal vasculitis) RISK FACTORS ▪ Middle aged individuals who are biologically male 168 OSMOSIS.ORG MNEMONIC: 3Cs “C” drawn from upper respiratory tract to lungs, kidneys (all involved) C-anca Corticosteroids/ cyclophosphamide (treatment) SIGNS & SYMPTOMS ▪ Chronic pain: oral ulcers, bloody nasal mucus, chronic sinusitis, saddle nose (nose caves in/curls) ▪ Hemoptysis, dyspnea, cough, pleuritic chest pain (inﬂammation of lung vessels) ▪ Decreased urine production, hypertension, hematuria, red cell casts, proteinuria (glomerular inﬂammation)
Chapter 25 Vasculitis DIAGNOSIS DIAGNOSTIC IMAGING Abnormal chest X-ray ▪ Nodules, ﬁxed inﬁltrates, cavities, bronchial stenosis TREATMENT ▪ Relapse common if c-ANCA still present MEDICATIONS ▪ Corticosteroids, cyclophosphamide/ rituximab LAB RESULTS ▪ c-ANCA in 90%, thrombocytopenia ▪ Abnormal urinary sediment; microscopic hematuria (with/without red cell casts) Open lung biopsy ▪ Conﬁrm diagnosis; granulomatous inﬂammation of artery/perivascular area OTHER DIAGNOSTICS Nasal/oral inﬂammation ▪ Oral ulcers; painful/painless ▪ Purulent bloody nasal discharge ▪ Chronic sinusitis, saddle nose/destructive sinonasal disease Figure 25.5 Illustration demonstrating the effects of granulomatosis with polyangiitis. OSMOSIS.ORG 169
HENOCH–SCHÖNLEIN PURPURA osms.it/henoch-schonlein-purpura PATHOLOGY & CAUSES ▪ Small vessel vasculitis secondary to IgA immune complex deposition. ▪ Elevated IgA in blood targets selfendothelial cells: molecular mimicry ▪ Most common systemic vasculitis of childhood ▪ Frequently follows upper respiratory infection ▪ Associated with Berger disease (IgA nephropathy) ▪ Unknown cause; immune-mediated vasculitis triggered by infections/ immunizations ▪ Self-limited disease ▪ Tetrad ▫ Palpable purpura, without coagulopathy/ thrombocytopenia; mainly lower extremities ▫ Arthritis/arthralgias ▫ Renal disease ▫ Abdominal pain TREATMENT ▪ Self-resolving, may reoccur MEDICATIONS ▪ Steroids, only if severe SIGNS & SYMPTOMS ▪ Palpable purpura of buttocks, legs (skin discolouration, as if blood collected under skin surface); abdominal pain; arthritis/ arthralgias; hematuria, decreased kidney function (associated with IgA nephropathy) DIAGNOSIS LAB RESULTS Biopsy ▪ Deﬁnitive, not necessary 170 OSMOSIS.ORG Figure 25.6 The clinical appearance of Henoch-Schönlein purpura.
Chapter 25 Vasculitis KAWASAKI DISEASE osms.it/kawasaki-disease PATHOLOGY & CAUSES ▪ Coronary arteries: inﬂammation → aneurysms ▪ AKA mucocutaneous lymph node syndrome ▪ Most common type of vasculitis in children ▪ Usually self-limited RISK FACTORS ▪ Infants, children < ﬁve years old, Asian descent, biologically male COMPLICATIONS ▪ Coronary artery aneurysm ▪ Decreased myocardial contractility → heart failure ▪ Myocardial infarction (MI) ▪ Arrhythmias ▪ Peripheral artery occlusion DIAGNOSIS DIAGNOSTIC IMAGING Chest X-ray ▪ Cardiomegaly Echocardiography ▪ Coronary artery aneurysms, pericardial effusions, decreased contractility LAB RESULTS ▪ ↑ CRP, ESR, platelet count (reactive thrombocytosis) OTHER DIAGNOSTICS ▪ Four of ﬁve CRASH symptoms, high fever lasting ﬁve days ECG ▪ Arrhythmias, abnormal Q waves, prolonged PR, QT intervals SIGNS & SYMPTOMS MNEMONIC: CRASH & BURN Signs & Symptoms Conjunctivitis: bilateral, nonexudative Polymorphous Rash: desquamating Cervical lymphAdenopathy Strawberry tongue: cracked red lips, oral mucositis Hand-foot erythema/ desquamation: edema, erythema Fever: “burn” Figure 25.7 A coronary angiogram demonstrating a massive right coronary artery aneurysm. OSMOSIS.ORG 171
TREATMENT MEDICATIONS ▪ Intravenous immunoglobulin (IVIG) ▪ Aspirin MICROSCOPIC POLYANGIITIS osms.it/microscopic-polyangiitis PATHOLOGY & CAUSES ▪ Necrotizing vasculitis: kidney, lung vessels ▪ No granulomas present ▪ Associated with perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA)/MPOANCA ▪ Pauci-immune glomerulonephritis (minimal immunoﬂuorescent staining for IgG) ▪ Older adults SIGNS & SYMPTOMS ▪ Similar to granulomatosis with polyangiitis, without nasopharyngeal involvement ▪ Fever, weight loss, fatigue, myalgia, arthralgias ▪ Cough, dyspnea, hemoptysis, pleuritic chest pain ▪ Decreased urine output, hematuria, red cell casts, proteinuria ▪ Skin lesions (especially lower extremities): purpura → focal necrosis → ulceration 172 OSMOSIS.ORG DIAGNOSIS LAB RESULTS ▪ p-ANCA/MPO-ANCA levels; elevated ESR, CRP, anemia, increased creatinine ▪ Protein, red blood cells (RBCs) TREATMENT ▪ Relapse common MEDICATIONS ▪ Corticosteroids, cyclophosphamide
Chapter 25 Vasculitis POLYARTERITIS NODOSA osms.it/polyarteritis-nodosa PATHOLOGY & CAUSES ▪ Immune system forms antibody antigen complex (sometimes associated with hepatitis B) → deposits in vessel wall → immune reaction → invasion of polymorphonuclear leukocytes → segmental, transmural inﬂammation of muscular arteries → necrosis of three artery layers (tunica intima, media, adventitia) → ﬁbrosis as walls heal (ﬁbrinoid necrosis) → ﬁbrosed vessel wall weakens, prone to aneurysms → ﬁbrotic aneurysms (hard bulges) develop ▪ Different stages of inﬂammation in different vessels RISK FACTORS ▪ Individuals > 40 years old, biologically male ▪ Active hepatitis B (HBV)/hepatitis C (HCV) infection ▪ HIV ▪ Prescription/illicit drug exposure, amphetamines SIGNS & SYMPTOMS DIAGNOSIS DIAGNOSTIC IMAGING Mesenteric angiogram ▪ “String of beads” pattern along artery, spasms LAB RESULTS ▪ HBV, HCV serologies, Cr, muscle enzymes, urinalysis Biopsy OTHER DIAGNOSTICS Physical exam ▪ Vascular lesions, motor weakness (due to ischemia) TREATMENT MEDICATIONS ▪ Corticosteroids ▪ Cyclophosphamide: supplement corticosteroids in moderate to severe cases ▪ Systemic: fever, fatigue, weight loss, arthralgia ▪ End organ ischemic damage ▪ Renal arteries: HTN ▪ Mesenteric artery: mesenteric ischemia, severe abdominal pain, gastrointestinal bleeding ▪ Mononeuropathy multiplex: motor, sensory deﬁcits occur in > one nerve throughout body ▪ Skin arteries: skin lesions (e.g. ulcers, erythematous nodules resembling erythema nodosum, purpura, livedo reticularis) OSMOSIS.ORG 173
Figure 25.8 Illustration showing polyarteritis nodosa’s characteristic “string of beads” pattern running along the artery. TAKAYASU ARTERITIS osms.it/takayasus-arteritis PATHOLOGY & CAUSES ▪ Segmental, patchy granulomatous vasculitis of aortic arch, major branches ▪ Stenosis, thrombosis, aneurysm CAUSES ▪ Unknown; possibly bacterial (e.g. spirochetes, Mycobacterium tuberculosis, streptococcal) ▪ Genetic RISK FACTORS ▪ Individuals of Asian descent, < 40 years old, biologically female COMPLICATIONS ▪ Limb ischemia; aortic aneurysm; aortic regurgitation; stroke; secondary hypertension (HTN) due to renal artery stenosis 174 OSMOSIS.ORG SIGNS & SYMPTOMS ▪ Inﬂammation ▫ Aortic branches, upper extremities: weak/absent pulse ▫ Aortic branch, head: neurological symptoms (e.g. headaches, syncope, stroke) ▫ Coronary arteries: angina ▫ Renal arteries: HTN ▪ Visual disturbances: ocular vessels/retinal hemorrhage ▪ Constitutional symptoms: fever, night sweats, arthralgias, malaise, fatigue ▪ Ischemia in areas of stenosis DIAGNOSIS DIAGNOSTIC IMAGING CT angiography (CTA), magnetic resonance angiography (MRA) ▪ Luminal narrowing/occlusion of major aortic branches ▪ Vessel wall thickening ▪ Aortic valve disease (e.g. regurgitation,
Chapter 25 Vasculitis stenosis) ▪ Aneurysmal dilation/pseudoaneurysm formation Ultrasound ▪ Homogeneous and circumferential thickening of arterial wall (contrast to atherosclerotic plaque: non-homogeneous, calciﬁed, irregular walls) ▪ Vascular occlusion due to intimal thickening/secondary thrombus formation ▪ Loss of pulsatility of vessel LAB RESULTS ▪ ↑ ESR TREATMENT MEDICATIONS ▪ Corticosteroids ▪ Treat HTN SURGERY ▪ Angioplasty (when no acute inﬂammation); bypass grafting if severe Figure 25.9 An angiogram demonstrating multiple stenosis of the aortic arch vessels, a feature of Takayasu arteritis. OSMOSIS.ORG 175