Term
Name the primary vasculitides by vessel size:
Large
Medium
Small |
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Definition
Large: Takayasu's, Giant cell (aka Termporal)
Medium: Kawasaki, Polyarteritis nodosa
Small: Wegener's granulomatosis, Microscopic polyangiitis, Churg-Strauss syndrome, HSP, Cryoglobulinemic vasculitis, isolated cutaneous vasculitis |
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Term
Giant cell arteritis
1. Symptoms
2. Signs
3. Complications |
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Definition
1. Fever, fatique, headache, scalp tenderness, jaw/tongue claudication, polymyalgia rheumatica (up to 50%)
2. nodular, tender temporal artery with reduced/absent pulsation
3. visual loss from optic nerve ischemia, delayed mortality from thoracic aortic aneurysm. death from stroke, MI is uncommon. |
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Term
| Giant cell arteritis: DX and TX |
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Definition
Dx: biopsy (panmural mononuclear infiltration0, disruption internal elastic lamina, giant cells
TX:
1. Prednisone 40-60mg qd (initiate immediately, while bx is being arranged). Can prevent vision loss
2. ASA 81mg qd
NOTE: relapse is common |
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Term
Kawasaki Disease
1. Epidemiology
2. Symptoms
3. Signs
4. Complications |
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Definition
1. 80% of cases occur prior to age 5.
2. Acute febrile illness
3. 1-3 days afer fever onset, kids get rash, conjunctival injection, cervical LAN, extremity changes, oral mucosal changes
4. Coronary artery aneurysms: 1-4 wks after fever onset. 1-2% acute mortality. Relapses are uncommon. |
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Term
| Kawasaki Disease: DX and TX |
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Definition
DX: clinical, based on fever + 5 features (rash, conjunctival injection, cervical LAN, extremity changes, oral mucosal changes)
2. ASA
TX:
1. IVIG: 2 g/kg as single dose (reduces risk of aneurysms) |
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Term
Polyarteritis Nodosa: disease of medium vessels
1. Associated with hepatitis B?
2. Lung involvement?
3. Glomerular involvement?
4. Associated with ANCA?
5. Relapses common? |
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Definition
1. Yes
2. No
3. No
4. No
5. No (relapses are uncommon). 80% 5 yr survival |
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Term
| PAN: clinical manifestations |
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Definition
Constitutional: fever, wt loss, arthralgias, night sweats
Nerve: mononeuritis multplex (foot/wrist drop), CNS disease
Kidney: hypertension, infarction (NOT Glomerulonephritis)
GI: pain, infarction, perf, bleed
Heart: angina, MI
Digits: infarction, ishemia |
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Term
| PAN: DX and TX (consider role of associated Hepatitis B) |
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Definition
Dx: Biopsy (necrotizing inflammation of medium or small arteries, lots of PMNs, fibinoid changes. Arteriogram: microaneurysms, stenoses, beading
TX: If no hepatitis B, then immunosuppress with prednisone +/- cyclophosphamide (add cyclophos for life-threatening disease).
If hepatitis B, use anti-viral tx. Immunosuppressive tx only as needed to control vasculitis. |
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Term
| Describe the acute and chronic toxicities of cyclophosphamide and how to prevent them |
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Definition
Acute: infxn, cytopenias, bladder injury
Chronic: infertility, Cancer (bladder, blood, skin)
Prevention: morning admin with lots of fluid; CBC q1-2 wks, U/A with cystoscopy for non-glomerular hematuria, urine cytology q6 mos |
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Term
| Wegener's granulomatosis epidemiology |
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Definition
Adults 40-60, but can occur at any age
Women = Men
Uncommon: 3 in 100,000 |
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Term
Wegener's granulomatosis: clinical manifestations.
Name the organ triad. |
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Definition
Affects:
1. Resp tract (granulomatous inflam): sinuses involved in 95% of pts and lungs (pulm nodules/infitrates/cavitary lesions/hemorrhage) in 85% of pts
2. Kidneys: 80% of pts. U/A: Proteinuria, hematuria, RBC casts. Often asymptomatic but can be rapidly progressive and severe (renal failure)
3. Can also affect joints, eyes, skin, nerve |
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Term
cANCA vs pANCA
1. Staining pattern
2. Target antigens
3. Test methods for 1 and 2 |
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Definition
1. c=cytoplasmic and p=perinuclear
2. cANCA: proteinase-3 and pANCA: myeloperoxidase (remember that p's do not go together, pANCA doesn' go w/proteinase)
3. Test methods: cANCA and pANCA by indirect immunofluorescence. Target antigens by ELISA. A positive c/pANCA should be conrimed by Pr-3 or MPO ELISA |
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Term
1. Which diseases have +cANCA and +Pr-3 ELISA?
2. Which diseases have +pANCA and +MPO by ELISA? |
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Definition
1. Wegener's (70-95%), microscopic polyangiitis, Churg-Strauss (5-20%)
2. Churg-Strauss (20-70%), Microscopic polyangiitis, Wegener's (5-20%) |
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Term
Key issues regarding ANCA
1. Can ANCA be used to diagnose Wegener's?
2. Do high ANCA levels indicate active vasculitis? |
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Definition
1. Usually not, biopsy is required in most pts
2. Levels are higher overall in people with active disease but are NOT reliable in assessing disease activity in a given individual |
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Term
Wegener's DX and TX
1. What do biopsies show?
2. Tx of mild vs severe disease
3. Relapse rate |
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Definition
Resp tract bx: necrosis, granulomas, small vessel vasculitis.
Kidney bx: focal, segmental, crescentic, necrotizing glomerulonephritis, few to no immune complexes (pauci-immune GN)
2. If mild, use prednisone + methotrexate. If severe, use prednisone + cyclophosphamide. If treated, 80% survival; if untreated, median survival time is 5 months.
3. Relapse rate: 50% |
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Term
Microscopic Polyangiitis: affects small vessels
1. Associated with hepatitis?
2. Lung involvement?
3. Glomerular involvement?
4. ANCA associated?
5. Relapses common? |
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Definition
1. No
2. Yes
3. Yes
4. Yes
5. Yes |
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Term
Microscopic Polyangiitis and Wegener's:
How are they similar?
How are they different? |
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Definition
Small vessel diseases
ANCA-associated
pulmonary hemorrhage and glomerulonephritis
Differences: no granulomas in microscopic polyangiitis |
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Term
| Microscopic Polyangiitis: clinical manifestations |
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Definition
Frequently affects the capillaries
Lungs: alveolar hemorrhage
Kidney: glomerulonephritis
Can also affect nerves and skin |
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Term
Microscopic Polyangiitis: DX and TX
What is the role of ANCA testing? |
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Definition
DX: BX.
In lung: small vessel vasculitis.
In kidney: focal, segmental, crescentic, necrotizing GN; few to no immune complexes (pauci-immune GN)
Should not use ANCA testing for DX.
TX: as for Wegener's.
If mild, prednisone + methotrexate
If severe, prednisone + cyclophosphamide
Like Wegener's, 75% survival w/Tx but poor outcome if untreated. |
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Term
| Churg-Strauss Syndrome: epidemiology |
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Definition
Men = women
Uncommon: affects 3 per million |
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Term
Churg-Strauss: clinical manifestations
Name the 3 phases of this disease |
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Definition
Podromal phase: asthma, allergic rhinitis
Eosinophilic phase: peripheral and tissue eosinophilia
Vasculitis: nerve, skin, lung, gut, heart |
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Term
Churg-Strauss: DX and TX
What is the main cause of mortality? |
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Definition
DX: based upon clinical features of asthma, hypereosinophilia, vasculitic signs/symptoms.
ANCA associated in up to 50% of cases. pANCA is positive more often than cANCA
Bx: features include eosinophilic tissue inflitrates, extravascular allergic granuloma, small vessel vasculitis but are often hard to demonstrate.
TX: Usually prednisone is sufficient. If severe, use prednisone + cyclophosphamide.
Main cause of death: cardiac involvement |
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Term
| Henoch-Schonlein Purpura: epidemiology |
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Definition
Mostly in kids (75% of cases occur before age 8)
2/3 of pts have antecedent resp infxn |
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Term
| What are the 4 cardinal manifestations of Henoch-Schonlein Purpura? |
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Definition
Palpable purpura
Arthritis
Glomerulonephritis
GI: intussusception |
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Term
| Henoch-Schonlein Purpura: DX and TX |
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Definition
DX: Pattern of clinical manifestations. BX is usually not needed.
Skin BX shows leukocytoclastic vasculitis,IgA deposits.
Kidney BX shows mesangial proliferation and segmental, crescentic glomerulonephritis and
+IgA, IgG, C3
Prognostic utility
TX: usually not needed (self-limited disease).
Prednisone may reduce arthritis, GI sx, risk of intussusception
Use prednisone + cyclophosphamide for glomerulonephritis with renal dysfunction
Relapses: in 40% of cases, usually in first 3 mos |
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Term
Cryoglobulinemic Vasculitis: Epidemiology
Occurs in conjunction with which diseases? |
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Definition
HCV (most cases)
Myeloma (plasma cell or lymphoid cancers)
Chronic infection
Connective tissue diseases |
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Term
| Cryoglobulinemic Vasculitis: clinical manifestations |
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Definition
Palpable purpura
Arthritis
Neuropathy
Glomerulonephritis (usually not rapidly progressive) |
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Term
| Cryoglobulinemic Vasculitis: DX and TX |
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Definition
DX: combo of clinical features + lab tests suggestive of cryoglobulinemia
Labs:
Cryoglobulins (hard to measure)
Rheumatoid factor
Hepatitis C (if neg, search for other causes)
Hypocomplementemia
BX: may be useful in selected cases.
Skin, kidney. membranoproliferative glomerulonephritis, positive immunofluorescence, acellular intraluminal protein (cryoglobulins)
TX: treat underlying process.
Hep C: per-interferon + ribavirin
Improvement in vasculitis correlates with reduction in viremia. Relapse occurs with return of viremia. |
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Term
Cutaneous Vasculitis
Manifestations
Causes
TX |
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Definition
Manifestations: palpable purpura
Causes (>70% occur in setting of an underlying process): medication, infxn, cancer, conn tissue disease, heralding feature of primary systemic vasculitis) If no cause found, then idiopathic.
TX: Treat/remove underlying process. For idiopathic, use least toxic yet effective regimen |
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Term
Urticarial Vasculitis
What are the 2 key elements?
Age and gender most commonly affected? |
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Definition
Clinical: wheals have central darkness or redness, last > 24 hrs, leave residual hyperpigmentation or purpura, are painful/burning or stinging, less pruritic than true urticaria. Angioedema is present in many cases.
Also, can be assoc with systemic features: musculoskeletal/arthralgias, arthritis, pulm/COPD, kidney and GI
Histology: leukocytoclastic vasculitis (>80% have immunofluorescence with immunoglobulin, complement or fibrin around blood vessels and at basement membrane zone of dermal-epidermal junction (this can also be seen in SLE). Leukocytoclasis and Vessel wall damage occurs. Histopathology can be indistinguishable from palpable purpura.
Peak incidence 4th decade.
Women > Men |
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Term
Name common causes of normocomplementemic (NUV) vs hypocomplementemic urticarila vasculitis (HUV).
How do you establish normal complement levels? |
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Definition
NUV: usually idiopathic. Can be due to monoclonal gammopathy, cancer, UV light sensitivity, repeated cold exposure
HUV: most are due to SLE, Sjogren's, serum sickness rxn, cancer
CH50, C3, C4, C1q values should be normal on 2-3 occasions over several months during both disease activity and quiescence. |
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Term
| What is the lab investigation of urticarial vasculitis? |
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Definition
CH50, C3, C4, C1q (all are decreased in HUV and HUVS and anti-C1q antibodies are present in 100% of HUV)
CBC with diff
ESR (increased)
U/A
Chemistries
Hepatitis B and C serologies
ANA (50% are +), anti-DNA (negative), ENA
ANCA
RF and anti-CCP
SPEP
Cryoglobulins
Consider shest imaging, PFTs (COPD), xrays (joint pain) |
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Term
| What is Hypocomplementemic Urticarial Vasculitis Syndrome (HUVS)? |
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Definition
More than 6 mos of urticaria with hypocomplementemia in the presence of systemic findings.
Clinical features: urticarial vasculitis, angioedema (50% of cases), COPD (50% of cases), uveitis/episcleritis (30%), mild glomerulonephritis may occur; sometimes looks like SLE. Also may have recurrent abd pain.
Lab:
low/undetectable C3, C4
C1q low in all when disease is active
Anit-C1q antibodies (C1q precipitins) in all. Anti-DNA and anti-Sm are uncommon. |
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Term
| Diagnostic criteria for Hypocomplementemic Urticarial Vasculitis Syndrome (HUVS) |
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Definition
2 major criteria (need both):
urticaria for more than 6 mos and hypocomplementemia
Minor criteria (need 2 or more):
Dermal venulitis, arthralgia or arthritis, glomerulonephritis, uveitis or episcleritis, recurrent abdominal pain, positive C1q preciptin test with a suppressed C1q level |
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Term
| Urticarial Vasculitis: TX and Prognosis |
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Definition
Treat underlying disease if present
prednisone, hydroxychoroquine, dapsone or colchicine; also indomethacin, azathioprine, methotrexate, cyclophosphamide, mycophenolate.
Use systemic immunosuppression for severe disease.
For HUVS: TX as above; consider cyclosporin. COPD often presents major challenges.
Prognosis: mean duration is 3-4 yrs
UV typically benign. HUVS has a worse prognosis (due to COPD assoc morbidity and mortality) |
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Term
Name 3 subtypes of Urticarial Vasculitis.
Which type is most severe? |
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Definition
Normocomplmentemic
Hypocomplementemic UV
Hypocomplementemic UV Syndrome (HUVS)
HUVS is most severe |
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