Kinder Vasculitis Flashcards
Common Presentations of Vasculitis
Constitutional
- Fever, weight loss, fatigue, and weakness
Musculoskeletal
- Arthralgias, arthritis, and myalgias
Cutaneous
- Palpable purpura, nodules, urticaria, livedo reticularis, phlebitis, and ischemia
Pulmonary
- Hemorrhage, nodules, infiltration, and cavities
Renal
- Nephritis, infarction, and hypertension
Neurologic
- Cephalgia, mononeuritis multiplex, and stroke
Lab
- Anemia, increased ESR, abnormal LFT, and hematuria
clinical manifestations of large vessel vaculitis
limb claudication asymmetric blood pressure absence of pulses bruits aortic dilation
clinical manifestations of medium vessel vasculitis
cutaneous nodules ulcers arthritis livedo reticularis digital gangrene mononeuritis multiplex microanerysms
clinical manifestations of small vessel vasculitis
purpura vesiculobullous lesions urticaria glomerulonephritis alveolar hemorrhage arthritis cutaneous extravascular necrotizing granulomas splinter hemorrhages uveitis, episcleritis, or scleritis
Giant Cell Arteritis and Polymyalgia Rheumatica
Almost all patients with Giant Cell Arteritis (temporal arteritis) are older than 50 years with average age of 72 years
Women are twice as likely as men to develop the disorder
Most common in whites or Americans of Scandinavian origin
Patients with PMR only are not at risk of losing vision and require low doses of prednisone (under 20 mg/day)
Patients with GCA are at risk for losing vision and require higher doses of prednisone (≥ 40 mg/day) to prevent blindness
Giant Cell Arteritis Presenting Manifestations- in order of frequency
ESR anemia headache jaw claudication constitutional symptoms polymyalgia rheumatica visual loss abnormal temporal artery arthritis
Giant Cell Arteritis Physical Examination
Temporal artery may be enlarged, difficult to compress, nodular, or pulseless
15-20% have axillary or subclavian disease
- Diminished pulses
- Unequal arm blood pressures
- Bruits above or below the clavicle
Aortic regurgitation
Giant Cell Arteritis main symptoms
Headache
- Dull, aching, and localized over the temporal area
- New or different headache
- Tenderness of the scalp, when combing or brushing hair
Jaw Claudication
- Pain in masseter muscle when chewing
- Most specific symptom
Polymyalgia Rheumatica
- Pain and stiffness in the neck, shoulders, and hip-girdle that are much worse in the morning
Pollymyalgia Rheumatica
Shoulders (70-95%) Hips (50-70%) Morning stiffness Pain is in the muscles Difficulty getting out of bed, rising, brushing hair or teeth Swelling, erythema, and heat are absent
goes with GIant Cell Arteritis
Diagnostic Criteria for Polymyalgia Rheumatica
Criteria of Healey
Pain persisting for at least 1 month and involving 2 of the following areas
Neck, shoulders, and pelvic girdle
Morning stiffness lasting > 1 hour
Rapid response to prednisone (20 mg/day or less)
Absence of other diseases causing musculoskeletal symptoms
Age older than 50 years
ESR > 40 mm/hr
Giant Cell Arteritis Visual Symptoms
1/3 of Giant Cell Arteritis Patients
Diplopia or visual loss
Visual loss can be monocular, binocular, transient, or permanent
Can occur abruptly
Often proceeded by episodes of blurred vision, or amaurosis fugax
On average develops 5 months after onset of GCA
Visual loss usually secondary to occlusion of the posterior ciliary artery, a branch of the ophthalmic artery
Giant Cell Arteritis Atypical Manifestations
Fever of unknown origin
Cough
Mononeuritis multiplex
- Shoulder
Large Artery Disease
- Aorta, vertebral, carotid, subclavian, and axillary arteries
- Symptoms
- – TIA, stroke, hand ischemia, arm or leg claudication
- Thoracic aortic aneurysm
- – Aortic regurgitation
- – MI
- – Dissection
Giant Cell Arteritis labs
Elevated ESR, often around 100 mm/h in Giant Cell Arteritis
Mild anemia
Giant Cell Arteritis Treatment
Prednisone 40-60 mg po q day
- Start tapering after first month by 10% every 1-2 weeks until down to 15 mg po q day, then decrease by 1 mg every 2 weeks Most patients need to be on steroids for 1-2 years
Methylprednisolone 1000 mg IV/day for 3-5 days if experiencing visual loss
Temporal Artery Biopsy – don’t delay treatment to obtain biopsy
Takayasu Arteritis
Large Vessel Arteritis
- Aorta and its major branches
Affects women during reproductive years (8:1 Women)
Presents with absent pulse, bruit, claudication, hypertension, or fever of unknown origin
ESR is usually elevated
Responds to Prednisone
Granulomatous inflammation affecting all levels of the vessel
Takayasu Arteritis Clinical Findings: Vascular Manifestations
Bruits - Carotids, supraclavicular, infraclavicular, arms, and abdomen Claudication – upper extremity Hypertension Light-headedness Unequal Blood pressures in extremeties Carotidynia Aortic Regurgitation – 20% of patients Loss of pulse
Takayasu Arteritis Clincal Findings: Constitutional and Musculoskeletal Symptoms
50% of patients Asthenia Weight loss Fever Myalgia Arthralgia Thoracic back pain – inflammation of the aorta
how to distinguish Takayasu from Giant Cell?
age. Young- takayaus
old- Giant Cell
Takayasu Arteritis labs and imaging
Laboratory
Elevated ESR and CRP in 80% of patients
Anemia 50% of patients
Thrombocytosis 33% of patients
Imaging: MRI CT Ultrasound Angiography
Takayasu Arteritis Diagnosis
Onset at age under 40 years Limb Claudication Decreased brachial artery pulse Unequal arm blood pressures (> 10 mm Hg) Subclavian or aortic bruit Angiographic evidence of narrowing or occlusion of the aorta or its primary branches, or large limb arteritis
Three of six criteria is 91% sensitive and 98% specific for Takayasu Arteritis
Takayasu Arteritis Treatment
Prednisone
Granulomatosis with Polyangiitis
Pathology with granulomatous inflammation, vasculitis, and necrosis
Clinical Features: - Fatigue, myalgias, weight loss, and fevers * Persistent upper respiratory tract and ear “infections” that do not respond to antibiotics - Orbital pseudotumors - Migratory arthritis - Nodular or cavitary lung lesions - Rapidly progressive glomerulonephritis ANCA
Granulomatosis with Polyangiitis- who and what affected
Small to medium sized blood vessels
Arterial and venous circulations
Male and female equally affected
Mean age of onset is 50 years
Granulomatosis with Polyangiitis Clinical Findings
Nose, Sinuses, and Ears
- 90% have nasal involvement
- Rhinorrhea, nasal obstruction, epistaxis
- Cartilagenous inflammation leads to septal perforation and “saddle-nose” deformity
- Conductive and sensorineural hearing loss
Eyes
- Orbital pseudotumors
- Scleritis, episcleritis, and conjunctivitis
Mouth
- “Strawberry gums” and Mouth Ulcers – both are painful
Trachea
- Subglottic stenosis
Lungs
- Pulmonary Lesions in 80% of patients
- Cough, hemoptysis, dyspnea, and pleuritic chest pain
- Pulmonary infiltrates and nodules on chest x-ray
- Cavitary lesions
Renal
- Up to 80% of patients
- Rapidly progressive glomerulonephritis
- Hematuria, red cell casts, and proteinuria
- Pauci-immune
Joints
- Migratory Arthritis
Biopsy – granulomatous inflammation, vasculitis, and necrosis
- Lung
- Kidney
- Upper Respiratory Tract
C-ANCA/PR3-ANCA
Granulomatosis with Polyangiitis Treatment
Severe Disease
Rituximab or Cyclophosphamide + Glucocorticoids
Limited Disease
Methotrexate + Glucocorticoids
Microscopic Polyangiitis
Most common cause of pulmonary-renal syndrome of alveolar hemorrhage and glomerulonephritis
Combination of two or more of the following
- Fatigue, myalgias, weight loss, and fevers
- Migratory arthralgias or arthritis, either pauciarticular or polyarticular
- Palpable purpura, sometimes with skin ulcerations
- Sensorimotor mononeuritis multiplex
- Alveolar hemorrhage associated with hemoptysis and respiratory compromise
- Glomerulonephritis – pauci-immune
ANCA (MPO-ANCA)
Microscopic Polyangiitis- who and what?
Necrotizing vasculitis Small blood vessels (capillaries, arterioles, or venules) Tropism for kidneys and lungs Mean age of diagnosis 60 years Male/Female 1:1
Microscopic Polyangiitis major symptoms
Glomerulonephritis 80% - Pauci-immune Weight loss 70% Mononeuritis multiplex 60% Fevers 55% Cutaneous vasculitis 60 % Alveolar Hemorrhage 12%
Microscopic Polyangiitis- organs
No upper respiratory manifestations like Granulomatous Polyangiitis
Lungs
- Capillaritis with alveolar hemorrhage
Kidneys
- 80% of patients have renal involvment
- Proteinuria, microscopic hematuria, and red cell casts
Nervous System
- Distal, asymmetric, axonal polyneuropathy (mononeuritis multiplex)
Microscopic Polyangiitis- skin
Small Vessel:
Palpable purpura
Vesiculobullous lesions
Splinter hemorrhages
Medium Vessel: Nodules Ulcers Livedo reticularis Digital gangrene
Microscopic Polyangiitis Treatment
Rituximab + Glucocorticoids
Cyclophosphamide + Glucocorticoids
Eosinophilic Granulomatosis with Polyangiitis
Asthma, eosinophilia, and systemic vasculitis
Clinical Features
- Allergic rhinitis and nasal polyposis
- Reactive airway disease
- Peripheral eosinophilia (10-60% of Leukocytes)
- Fleeting pulmonary infiltrates and occasional pulmonary hemorrhage
- Vasculitis neuropathy
- Congestive Heart Failure
P-ANCA in 50%
Eosinophilic Granulomatosis with Polyangiitis phases
Prodrome Phase
- Asthma and allergic rhinitis often lasts for several years
Eosinophilia/Tissue Infiltration Phase
- Peripheral eosinophilia
- Tissue infiltration of heart, lung, gastrointestinal tract, and other tissues
Vasculitis Phase
- Heart, lungs, peripheral nerves, and skin
Eosinophilic Granulomatosis with Polyangiitis Clinical Findings
Lungs
- Asthma in 90% of patients
- Eosinophilic infiltration in early disease
- Necrotizing vasculitis
- Granuloma
Peripheral Nerves
- Vasculitis neuropathy in 77% of patients
- Foot drop or wrist drop
Heart
- CHF
Kidneys
- Less likely to cause end-stage renal disease
Skin: Palpable purpura, Papules, Ulcers, Vesiculobullous lesions, Nodular skin lesions –, “Churg-Strauss granuloma”, Splinter hemorrhage, Digital ischemia, Gangrene of digits
Eosinophilic Granulomatosis with Polyangiitis labs
Eosinophilia up to 60% or white blood cell count
Elevated serum IgE
Elevated ESR and CRP
P-ANCA elevated in 50%
Eosinophilic Granulomatosis with Polyangiitis Treatment
Glucocorticoids Cyclophosphamide Azathioprine Mycophenolate mofetil Methotrexate
Polyarteritis Nodosa
Subacute onset
- Fever, weight loss, malaise, and arthralgias
- Lower extremity nodules and ulcerations
- Mononeuritis multiplex
- Intestinal angina
- – Postprandial pain secondary to mesenteric vessel disease
Cutaneous polyarteritis nodosa
-Variant in which vasculitis is limited to the skin presents as nodules that break down to ulcers
Polyarteritis Nodosa dx
Angiogram or biopsy of an involved organ required for diagnosis
- May reveal microaneurysms in the kidneys or GI tract
- Biopsies of the skin and peripheral nerves (with sampling of adjacent muscle) are the least invasive way of confirming the diagnosis
Necrotizing inflammation of muscular arterioles and medium-sized arteries
- Spares capillaries and no venous involvement
- No glomerulonephritis
Renovascular Hypertension and Renal infarctions
- Spares lungs
-No granuloma formation
- Men and women equally affected
Polyarteritis Nodosa Clinical Manifestations
Pain
- Myalgias, arthritis, peripheral nerve infarction, testicular ischemia, or mesenteric vasculitis
Skin and Joints
- Livedo racemosa
- Nodules, papules, and ulcerations
- Digital ischemia leading to gangrene
- Arthralgias of knees, ankles, elbows, and wrists occur in 50% of patients
Mononeuritis multiplex
- 60% of patients
- Most commonly in sural, peroneal, radial, and ulnar nerves
- First symptoms may be a foot or wrist drop
Gastrointestinal Tract
- Postprandial abdominal pain (”intestinal angina”)
- Mesenteric infarction
- Aneurysmal rupture
- Mesenteric angiography demonstrates multiple microaneurysms
Intraparenchymal Renal Inflammation
- 40% of patients
- Renal and interlobar arteries
- Microaneurysms in the kidney or wedge shaped infarctions
- Renin mediated hypertension
Polyarteritis Nodosa labs
Biopsy
- Skin, symptomatic nerve, or muscles
- Nodules, papules, and edges of ulcers
Angiography
- Segmental necrosis leads to aneurysm formation
- Microaneurysms in mesenteric and renal vasculature
Labs
- Hepatitis B associated with minority of cases
Polyarteritis Nodosa Treatment
Glucocorticoids
Cyclophosphamide
HBV Associated Disease
- Prednisone for two weeks followed by antiviral treatment
Mixed Cryoglobulinemia
Small and medium sized vessel involvement
Cryoglobulins
- Immunoglobulins that precipitate from the serum at low temperatures
Affected Organs
- Skin – most common
- Joints, peripheral nerves, and kidneys
Rheumatoid Factor Positive in most patients
90% of cases associated with Hepatitis C
33% of patients with Sjögren Syndrome
Mixed Cryoglobulinemia Diagnosis
Compatible clinical syndrome accompanied by cutaneous vasculitis
Isolation of cryoglobulins from the serum
Antibodies to Hepatitis C
Biopsies as necessary to exclude other diagnoses
Mixed Cryoglobulinemia Clinical Findings
Skin
- Small vessel disease
- Leukocytoclastic vasculitis
- Palpable purpura
- Predilection for lower extremities
Rheumatologic
- Arthralgias
- Raynaud phenomenon
- Acrocyanosis
Peripheral Nerve
- Sensory neuropathy prior to motor mononeuritis multiplex
Mixed Cryoglobulinemia Labs
Cryglobulins
Cryocrit
- Centrifugation of serum at 4℃.
Hypocomplementemia
Rheumatoid Factor Positive
Anti-HCV Antibodies and Quantification of HCV RNA
Hypersensitivity Vasculitis
Small-vessel vasculitis of the skin
Leukocytoclastic angiitis
Etiologies
- Medications
- Infections
- 40% unknown
Must rule out other known causes of vasculitis
Most cases are self-limited, but glucocorticoids are required in some cases
Hypersensitivity Vasculitis Diagnosis
Age at onset > 16 years Medication at disease onset Palpable purpura Maculopapular rash Biopsy including arteriole and venule, showing granulocytes in a perivascular or extravascular location
Hypersensitivity Vasculitis Clinical Manifestations
Skin
- Purpura, papules, urticaria/angioedema, erythema multiforme, vesicles, pustules, ulcers, and necrosis
- Lower extremity and buttocks most common
Joints
- Arthralgias
Labs
- Elevated ESR or CRP in less than 50% of patients
- Normal Tests
CBC, Electrolytes, LFTs, UA, ANA, RF, ANCA, C3, C4, Hep B, Hep C, Cryoglobulins, and chest x-ray
Hypersensitivity Vasculitis Treatment
Mild
- Leg elevation, NSAIDs, and antihistamines
Persistent Disease
- Colchicine
- Hydroxychloroquine
- Dapsone
Refractory
- Glucocorticoids
- May need addition of immunosuppressive such as azathioprine
Behçet Disease
Recurrent attack of painful oral apthous ulcers, painful genital ulcers, uveitis, and skin lesions
Young adults, aged 25-35 years
Prevalent in parts of Asia and Europe
Blindness, central nervous system disease, and large-vessel events are the most serious complications
Treatment
Glucocorticoids, immunosuppressive drugs, or both
Behçet Disease Clinical Manifestations
Oral ulcers- 100% genital ulcers skin lesions arthritis GI disease thrombophlebitis CNS disease epididymitis
Behçet Disease- skin, eyes, GI
Skin Lesions
- Erythema nodosum
- Pathergy
- – Phenomenon of developing an aseptic nodule or ulcer 24-48 hours following a sterile needle prick to the forearm
Ocular Inflammation
- Panuveitis
- Hallmark, appears early in course
- Leads to visual loss
GI
- Ulcers of the bowel can lead to pain, anorexia, rectal bleeding, vomiting, and diarrhea
Behçet Disease other findings
Arthritis
CNS
- Meningitis and meningoencephalitis
Large Vessel Vasculitis
- Pulmonary, carotid, aortic, iliac, femoral, and popliteal arteries
- – Occlusion, aneurysm, swelling, or rupture
- Peripheral thrombophlebitis
Labs
No specific lab findings
Behçet Disease diagnosis
recurrent oral ulceration- 3x over 12 months
Plus TWO of the following:
Recurrent genital ulceration
ocular lesions (uveitis/ retinal vasculitis)
Skin lesions (
Positive pathergy test
Behçet Disease Treatment
Recurrent oral ulcers
- Topical steroids or dapsone
Vision threatening uveitis or meningoencephalitis
- High dose systemic steroids and anti-TNF inhibitor
Henoch-Schönlein Purpura
Nonthrombocytopenic purpura, caused by inflammation of blood vessels in the superficial dermis
Leukocytoclastic vasculitis and deposition of IgA in the walls of the involved vessels
Tetrad – not all 4 required for diagnosis
- Purpura
- Arthritis
- Glomerulonephritis
- Abdominal pain
90% in children
Henoch-Schönlein Purpura presentation/ path
Disease follows an upper respiratory infection by 10 days in 2/3 patients
Skin pathology shows a leukocytoclastic vasculitis of small blood vessels in the superficial dermis
- Necrosis is often present
- No granulomas
- Immunofluorescent staining shows coarse, granular IgA deposition
Henoch-Schönlein Purpura Classic presentation and dx confirmation
Classic presentation
- Acute onset of fever
- Palpable purpura on the lower extremities and buttocks
- Abdominal pain, GI bleeding in 33%
- Arthritis
- Hematuria
Diagnosis confirmed by
- Direct immunofluorescence as well as conventional staining of biopsy specimens
- In children, treatment can be based on clinical presentation alone
Henoch-Schönlein Purpura Treatment
Dapsone
High Dose IV steroids + Azathioprine or Cyclophosphamide for severe nephritis
Most cases self-limited and resolve in 6-8 weeks, especially in children
Primary Angiitis of the CNS
Common presentation
- Headaches
- Encephalopathy
- Multiple Strokes
Angiographic abnormalities are suggestive, but not specific
Diagnosis requires brain biopsy
Treatment
- glucocorticoids
Secondary Vasculitis of the CNS
HIV Herpes zoster Hepatitis CBehçet Disease Polyarteritis nodosa Cocaine ANCA Vasculitis
Buerger Disease (Thromboangiitis Obliterans)
Typically young male smokers – mean age 40 years
Moderate to heavy tobacco use
Severe digital ischemia
Angiography with segmental involvement of medium-sized arteries with abrupt vascular cut-offs and corkscrew collaterals
Major vessel involvement occurs at the ankles and wrist
Buerger Disease Clinical Findings and treatment
Extremities
- Predilection for the feet and toes
- 60% of patients have an abnormal Allen Test
- Painful digits with gangrene, tissue loss, and autoamputation
Skin
- Superficial thrombophlebitis
- Splinter hemorrhages
- Gangrene of distal tissues (toes and fingers)
Treatment
- Smoking cessation
