HY from vasculitis lecture Flashcards
definition of vasculitis
Inflammation of blood vessels with necrosis of blood vessels walls, narrowing, and occlusion. In some types of vasculitis, aneurysms may be present
how is vasculitis classified?
Classification is by size of blood vessels involved, current knowledge of the pathophysiology and pattern of organ involvement
what are the large vessel vasculitis? (4)
takayasu arteritis
giant cell arteritis
cogan’s syndrome
Bechet’s disease
what are the predom medium vessel vasculitidies?
polyarteritis nodosa
cutaneous polyarteritis nodosa
Buerger’s disease
kawasaki disease
primary angiitis of the central nervous system
what are the predominantly small vessel vasculitidies that are immune complex mediated
medium vessel: PAN
small vessel
good pasture’s
cutaneous leukoctoclastic angiitiis(hypersensitivity angiitis) henoch-schonlein purpura
hypocomplementemeic urticarial vasculitis
essential cyroglobulnemia
erthema elevatum diutinum
what are anca associated small vessel vasculitis?
Wegener’s (granulomatosis with polyangiitis) microscopic polyangiitis churg-strauss syndrome renal-limited vasculitis
what are some connective tissue disorders associated with medium vessel vasculitides?
SLE, rheumatoid, inflammatory bowel disease, paraneoplasitc, infection, Drug-induced vasculitis
what are 8 vasculitis associated with granulomatous inflammation?
giant cell arteritis
takayasu areteritis
cogan’s syndrome
Wegener’s
churg-strauss syndrome
primary angiitis of the CNS
buerger disease
rheumatoid vasculitis
skin manifestations of PAN often include:
As noted above, skin manifestations of PAN may include livedo reticularis, skin ulcers, and a bullous or vesicular eruption.
which organ MC involved in PAN?
_ kidneys_ are the most commonly involved organ. Renal involvement frequently leads to variable degrees of renal insufficiency and hypertension. Renal ischemia, leading to activation of the renin-angiotensin system, is thought to be the primary mechanism for the development of hypertension.
is PAN anca associated?
PAN are typically ANCA-negative; a positive test suggests either microscopic polyarteritis or Wegener’s granulomatosis.
describe cutaneous PAN
The term cutaneous PAN usually implies a separate entity from PAN that is limited to the skin
which virus is involved w/cutaneous PAN?
Hepatits C viral infection has been associated with cutaneous PAN
how to do you treat polyarteritis nodosa?
If HBV present, need to treat this with antiviral agents and use plasma exchange Corticosteroids/cytotoxic agents Prognosis is variable, but often high morbidity, mortality
thromboangiits obliterans =
buergers disease
define buerger’s disease
is an inflammatory vaso-occlusive disease that predominantly affects the vascular supply to the lower limbs
buerger’s MC in ______
young adult male tobacco smokers, although women and older adults can also be affected
how does Buerger’s begin?
Buerger’s disease typically begins with bilateral pain and ischemia in the lower extremities although the upper extremities may be the site of initial symptoms with pain on exposure to cold.
how does Buerger’s progress?
Most cases evolve rapidly, however, with increasing ischemic (claudicant) limb pain, digital cyanosis, splinter hemorrhages, and skin vesicles and digital ulcers often occur, especially after minor trauma.
what does the tx of Buerger’s include?
Treatment includes stop smoking; and anecdotal use of calcium channel blockers and pentoxifylline has improved some cases.
what are MC types of immune complex mediated vasculitis?
The most common types of IC-mediated vasculitis are hypersensitivity vasculitis, Henoch-Schönlein purpura (HSP), and mixed cryoglobulinemia. Rarer forms of this condition include hypocomplementemic urticarial vasculitis and erythema elevatum diutinum.
which systemic diseases associated with immune complexes?
Connective tissue disorders such as systemic lupus erythematosus, Sjögren’s syndrome, and rheumatoid arthritis can be associated with IC-mediated vasculitis.
most prominent features of immune complex vasculitis
The classic cutaneous finding in small vessel vasculitis is palpable purpura, but a variety of other skin lesions may be found including pustules, vesicles, urticaria, and small ulcerations.
what do immunoflourescent studies find in immune complex vasculitis?
Direct immunofluorescence studies of involved blood vessels demonstrate characteristic types and patterns of immunoglobulin (Ig) and complement deposition.
what causes hypersensitivity vasculitis?
reaction to a medication or an infection.
the following describes associated with purpura, arthritis, glomerulonephritis, and colicky abdominal pain. IgA deposition is found within blood vessel walls.
HSP, remeber this has tetrad of A GAP (palpable purpura, arthritis, abdominal pain, and glomerulonephritis)
which virus is mixed cryoglobulinemia associated with?
Cryoglobulinemic vasculitis is most often associated with long-standing hepatitis C virus infection. The term mixed cryoglobulinemia is sometimes used for this disorder because the immunoreactants involved in the disease include both IgG and IgM.
The term ____________ refers to an immune complex (IC)-mediated small vessel vasculitis of the skin that spares internal organs and usually following _______ and ______
what characterizes this disease?
just know: A similar illness-serum sickness- is a systemic illness that includes rash and prominent arthralgia or arthritis occurring 1-2 wks. after exposure to a drug or foreign antigen
what is another name for this disease?
The term hypersensitivity vasculitis refers to an immune complex (IC)-mediated small vessel vasculitis of the skin that spares internal organs and usually following drug exposures or infections.
The disease is characterized by IC deposition in capillaries, postcapillary venules and arterioles.
Cutaneous Leukocytoclastic Angiitis
Henoch schonlein purpura:
what is mostly affected?
granulomas?
what does it follow?
common in whom?
which antibody present?
Necrotizing vasculitis of small vessels, primarily postcapillary
venules
1. NOT associated with granulomas
2. Often follows a specific exposure (drug, infection)
3. More common in children, and less severe in children, than
adults
IgA is characteristically present, both in biopsy of involved tissue
and is elevated in the serum (IgA1)
what is the classic tetrad of HSP?
Classic tetrad of purpura(buttocks/extremeities), arthritis, abdominal pain(and hemorrhage), Glomerulonephritis
labs for HSP
Anemia, thrombocytosis, increased ESR, CRP
Hematuria, elevated creatinine, and RBC casts if renal involvement
Diagnosis is by presentation and biopsy of skin or kidney
Pathology reveals a leukocytoclastic vasculits consisting of PMN’s with nuclear debris, RBC extravasation. IgA characteristically present
how do you tx HSP?
Self limited, usually with good prognosis
If renal disease, steroids may be used
When plasma is refrigerated at 4°C for up to 72 hours, proteins may precipitate (cryoprecipitate). If paired serum from the same patient also forms a precipitate, then the precipitated proteins are referred to as _____________. If, however, precipitation develops after refrigeration of plasma but does not occur in cold serum, the plasma precipitate is referred to as _____________________
When plasma is refrigerated at 4°C for up to 72 hours, proteins may precipitate (cryoprecipitate). If paired serum from the same patient also forms a precipitate, then the precipitated proteins are referred to as cryoglobulins (CGs). If, however, precipitation develops after refrigeration of plasma but does not occur in cold serum, the plasma precipitate is referred to as cryofibrinogen (CF).
components of Cryofibrinogen?
compoenet of cyroglobulin?
cyroglobulin = immonglobulin + complement components
CF = may contain immunoglobulins they characteristically are composed of fibrinogen, fibrin, fibronectin and/or fibrin split products. By definition, CF are undetectable in serum.
A person whose serum, but not plasma, cryoprecipitates is referred to as having__________. T
A person whose serum, but not plasma, cryoprecipitates is referred to as having cryoglobulinemia.
type 1 cyroglobulinemia:
monoclonal or polyclonal?
which two diseases?
Type I cryoglobulinemia, in which there is a monoclonal immunoglobulin that is most often due to underlying multiple myeloma or Waldenstrom’s macroglobulinemia
type II cryoglobulinemia = _________
What is polyclonal?
what is monoclonal?
Type II cryoglobulinemia = essential mixed cryoglobulinemia
cryoglobulin contains both a polyclonal lgG (which may either act as an antigen or be directed against an antigen) and a monoclonal IgM rheumatoid factor directed against the lgG.
Type III cryoglobulinemia.
is it mixed?
what is polyclonal here?
Type III cryoglobulinemia, in which there is also a mixed cryoglobulin, but both the IgG and the rheumatoid factor lgM are polyclonal.
the accuracy of CF assays depends on _________
The accuracy of CF assays is critically dependent upon the method of collection
t/f. If heparin is used as an anticoagulant in blood collection tubes, it can lead to falsely negative results for cryofibrinogen.
true
what are cyroglobulins?
Cryoglobulins are antibodies that precipitate from serum under
conditions of cold and resolubilize upon warming.
describe type I cyroglobulins. what do they cause? (two conditions in particular)
-
Type I CG are monoclonal, RF negative, and are associated
with malignancies. Cause hyperviscosity syndromes, not
vasculitis.
describe Type II and III CG. what do they result in?
Type II and III CG are polyclonal (IgG and IgM antibodies,
have RF activity, and result in an immune complex
mediated vasculitis
diseases: Hep C, other infection, Sjogren’s syndrome, and SLE
which viruse are all CRYOGLOBULINEMIC VASCULITIS associated with?
Associated with Hepatitis C
Most common manifestation is palpable purpura with ulcers
Systemic symptoms(fever, weight loss, fatudue)
Neurological involvement with peripheral neuropathy
Raynaud’s
Digital ischemia (often secondary to cold exposure)
Secondary Sjogren’s
describes what?
CLINICAL MANIFESTATIONS OF CRYOGLOBULINEMIC VASCULITIS
which complement level is low in CRYOGLOBULINEMIC VASCULITIS? which complement factor is deposited?
Anemia, thrombocytosis, increased ESR, low C4 levels, RF positive
Diagnosis is by biopsy of clinically involved site (usually skin)
Pathology reveals a leukocytoclastic vasculitis with IgM and C3 deposits in and around small and medium sized vessels
confluent purpura usually seen in _________
mixed cryoglobulinemia
TREATMENT OF CRYOGLOBULINEMIC VASCULITIS?
Corticosteroids and cytotoxic agents
After control of inflammation, if hepatitis C positive, antiviral
____________occurs in systemic lupus erythematosus, mixed connective tissue disease, Sjogren’s syndrome, and overlap connective tissue disease.
1) Vasculitis occurs in systemic lupus erythematosus, mixed connective tissue disease, Sjogren’s syndrome, and overlap connective tissue disease.
In connective tissue disease associated vasculitis, what do levels of complement look like? how about levels of antinuclear antibodies?
Hypocomplementemia and high titers of antinuclear antibodies (ANAs), and biopsy shows IgG and C3 deposition in and around dermal blood vessels, with or without IgM, reflecting the contribution of immune complexes to the disease process.
2) _________is a potentially devastating complication that may involve both medium and small blood vessels and require most aggressive therapeutic interventions.
2) Rheumatoid vasculitis is a potentially devastating complication that may involve both medium and small blood vessels and require most aggressive therapeutic interventions.
3) Many clinical manifestations of RV are indistinguishable from _________, although microaneurysms are less common in RV.
3) Many clinical manifestations of RV are indistinguishable from polyarteritis nodosa, although microaneurysms are less common in RV.
rheumatoid vasculitis typically occurs in whom?
4) RV classically occurs in RA patients with nodular, rheumatoid factor positive, joint-destructive disease who have few clinical indications of active synovitis at the time vasculitis begins.
what is the hallmark of rheumatoid vasculitis?
what are some of the common presentations?
5) Most common presentation includes purpuric lesions with or without evidence of concomitant medium vessel vasculitis, and deep cutaneous ulcer over the malleoli are a hallmark of RV.
what would biopsy of a skin lesion in a pt with rheumatoid vasculitis show?
6) Biopsy of skin lesions show granular IgM and C3 deposition in vessels, consistent with an IC-mediated pathophysiology in which rheumatoid factor, complement, and cryoglobulins may all participate.
be aware: ANCA-positivity may be seen in patients with inflammatory bowel disease.
Antineutrophil cytoplasmic antibodies (ANCA) are autoantibodies directed against neutrophil cytoplasmic antigens. What is c-anca directed against? p-anca?
cANCA are usually directed against a serine protease called proteinase 3 (PR3). In patients with vasculitis, _pANCA are usually directed against myeloperoxidase (MPO). _
A prominent association exists between ________ and ulcerative colitis, primary sclerosing cholangitis, and to a lesser extent Crohn’s disease.
A prominent association exists between pANCA and ulcerative colitis, primary sclerosing cholangitis, and to a lesser extent Crohn’s disease.
KNOW: which three conditions are not ANCA associated?
, giant cell arteritis, Takayasu’s arteritis, and Behcet’s disease are not ANCA-associated.
Anti-glomerular basement membrane disease can have similar clinical renal and pulmonary manifestations to___________________ Although this disease is characterized by the presence of anti-glomerular basement membrane antibodies
Anti-glomerular basement membrane disease can have similar clinical renal and pulmonary manifestations to Wegener’s granulomatosis. Although this disease is characterized by the presence of anti-glomerular basement membrane antibodies
ANCA titer levels and disease
The use of sequential ANCA studies in clinical care remains unclear. Persistent high titers or rising titers of ANCA are often associated with relapse in patients with Wegener’s granulomatosis. However, in one study, 44 percent of patients with a rise in ANCA titer had no associated disease relapse. Elevation of ANCA should not be used as the sole criterion for justifying a change in therapy.
describes which condition?
Necrotizing vasculitis
- Affects small vessels (capillaries, venules, arterioles) and may also affect medium sized vessels
- Is associated with a glomerulonephritis
- Is NOT associated with granulomas
- Associated with pANCA more than cANCA
More common than PAN
MICROSCOPIC POLYANGIITIS: DEFINITIO
what are the clinical manifestations of microscopic polyangiitis?
systemic sympoms:
kidney:
lung:
CNS:
skin:
Systemic symptoms (fever, weight loss, fatigue)
75% have kidney involvement with glomerulonephritis
Lung involvement with pulmonary hemorrhage
Neuropathy
Any type of skin involvement
labs of microcopsic polyangiitis: be aware
Anemia, thrombocytosis, increased ESR, CRP, RBC casts in urine, elevated creatinine, ANCA positive (usually p-ANCA)
Diagnosis is by biopsy of an involved nerve, muscle or involved organ (usually kidney) or by arteriography (aneurysms May be present)
Pathology reveals a necrotizing vasculitis of small and medium sized muscular arteries. Granulomas are NOT present.
what is the triad of wegeners?
what are the URG manifestations?
tx of GPA?
Classic Triad of ENT, respiratory tract and kidney involvement
Upper respiratory manifestations:** chronic sinusitis, nasal
ulcerations, serious otitis media, saddle nose deformity, proptos**is
tx: Corticosteroids/cytotoxic agents (Cyclophosphamide, MTX, MMF, Retuximab) Pneumocystitis prophylaxis recommended
Prognosis is variable, but often high morbidity, mortality
His history of asthma and allergic rhinitis with nasal polyps, along with his peripheral eosinophilia, and a biopsy demonstrating necrotizing granulomatous vasculitis with extravascular eosinophilia most strongly support the diagnosis of ___________
churg-strauss
Most deaths in patients with AGPA result from complications of the vasculitic phase of the disease, and are most commonly due to: (5)
_Cardiac failure and/or myocardial infarction (heart, brain, kidney, GI, asthma) _
Cerebral hemorrhage
Renal failure
Gastrointestinal bleeding
Status asthmaticus
which condition?
Systemic symptoms (fever, weight loss, fatigue)
Lungs involvement with dypsnea, cough
Neurological involvement with peripheral neuropathy
Genitourinary involvement with eosinophilic granulomas of the urinary tract and/or prostate
Anemia, thrombocytosis, increased ESR, eosinophilia, eosinophiluria, RBC casts, proteinuria
Diagnosis is by biopsy of clinically involved site
Pathology reveals inflammation with necrotizing granulomas
tx:
Churg-strauss = ALLERGIC GRANULOMATOSIS WITH POLYANGIITIS [AGPA]
Corticosteroids (Rituximab) and cytotoxic agents (cyclophosphamide)
Prognosis is generally good
describes which condition?
Necrotizing inflammation of large sized arteries originating from the arch of the aorta
Is associated with granulomas
Is not associated with a glomerulonephritis
Polymyalgia rheumatica is a clinical syndrome (not a vasculitis) characterized by AM stiffness, pain in pelvic girdle and shoulders.
GIANT CELL/ TEMPORAL ARTERITIS
what is a complication of giant cell arteritis that warrants monitoring?
The development of thoracic aortic aneurysms is a potentially serious complication of GCA that warrants ongoing monitoring
note:
Although easy bruising is frequently seen in patients with GCA who have been treated with corticosteroids, there is no association between bleeding into the skin and untreated GCA
after no response to prednisone at 30mg/day what is your next step in diagnosing polymyalgia rheumatica without giant cell arteritis
reject diagnosis of polymyalgia rehumatica; search for alt diagnosis
which condition?
Systemic symptoms (fever, weight loss, fatigue)
Temporal headaches
Visual disturbances (can progress to sudden blindness)
Jaw or tongue claudication
Arthralgias
Physical examination may reveal tender, swollen, temporal artery
TEMPORAL ARTERITIS
which condition?
Necrotizing inflammation of large sized arteries with involvement of the aortic arch and its branches (also coronary and pulmonary arteries)
- Is associated with granulomas
- Is not associated with a glomerulonephritis
Primarily affects adolescent girls and young women of Asian descent
TAKAYSU’S ARTERITIS:DEFINITION
how to do you tx temporal arteritis?
Corticosteroids in high doses (1mg/kg/day of prednisone or equivalent)
It is critical to begin treatment with steroids as soon as diagnosis is suspected otherwise your patient may go blind permanently. One should treat and make arrangements for the temporal artery biopsy but do not wait for the biopsy to be done or results to be back before starting treatment
Prognosis is good with treatment. However, blindness is irreversible.
which condition?
Necrotizing vasculitis of small and medium-sized muscular arteries, especially the coronary arteries
Immune activation and cytokine alterations play pivotal role
Most common cause of acquired heart disease in US and Japan
KAWASAKI SYNDROME: DEFINITION = mucocutaneous lymph node syndrome
what are the diagnosis requirements for kawasakis?
Diagnosis requires fever for 5 or more days plus 4/5:
- *Polymorphous rash**
- *Bilateral conjunctival injection**
- *Cervical lymphadenopathy**
- *Extremity changes**
1. Erythema of palms/soles
2. Indurative edema of hands/feet
3. Membranous desquamation of fingertips
4. Beau’s lines (transverse grooves of the nails)
Mucous membrane changes
Diffuse injection of oral and pharyngeal mucosa
Erythema or fissuring of tongue
Strawberry tongue
cardiac findings for Kawasaki’s disease?
Cardiac findings with pericardial effusion, myocarditis, aneurysms, MI (coronary lesions responsible for most mortality)
which disease?
Anemia, thrombocytosis, increased ESR
Profound lymphocytosis in second week of disease
Diagnosis is by characteristic features of disease
EKG and echocardiogram (to monitor for aneurysms) are recommended
what is the Tx for this disease?
LABORATORY AND PATHOLOGY IN KAWASAKI’S SYNDROME
_aspirin + IVIG: _Prognosis is related to presence or absence of coronary aneurysms and extent of coronary disease
what is the definition of PRIMARY ANGIITIS OF THE CENTRAL NERVOUS SYSTEM (PACNS)?
Primary angiitis of the central nervous system (PACNS) is defined as vasculitis that is confined only to the brain, meninges, or spinal cord.
how does one diagnose primary angiitis of the CNS? what does one have to rule out?
The diagnosis of PACNS is based on compatible clinical features together with evidence from spinal fluid, brain and vascular imaging, and often brain biopsy.
Ruling out mimics that have a similar clinical or angiographic appearance is central to the diagnosis of PACNS.
how do you treat primary angiitis of the CNS?
Initial treatment of PACNS includes glucocorticoids either alone or in combination with cyclophosphamide based on the subset and severity of neurologic disease.
Outcome of PACNS is variable, with the highest rate of disability and mortality being seen in GACNS.(granulomatous angiitis of the CNS)
key features of bechet’s?
tx of bechet’s?
prognosis of bechet’s?
- oral and genital ulcers
- Treatment is based on the degree of systemic involvement and ranges from topical corticosteroids to thalidomide to systemic immunosuppressive agents and tumor necrosis factor inhibitors.
- Prognosis is variable, and patients typically have periods of exacerbations and remissions.
epidemiology of Bechet’s disease?
BD is more common in persons in their 20’s and 30’s and has a similar occurrence in males and females; more common in turkey and mediterranean
clinical features of Bechet’s
what are aphthae?
Aphthae: Painful and shallow aphthae or canker sores, occurring individually or in crops are often the initial features of BD and constitutes a requisite diagnostic feature. Genital aphthae frequently occur.
what are the MC cutaneous lesions of Bechets? ophthalmic? how about the type of arthritis involved?
cutaneous: pyoderma gangrenousum-like lesions, pathergy lesions (induced by trauma)
ophthalmic features: variety of ocular manifestations
Arthritis: The arthritis of BD occurs in 40-60% is typically a nonerosive, inflammatory, symmetric or asymmetric oligoarthritis, although, monoarticular and polyarticular forms occur; most common joints involved are knees, wrists, ankles and elbows.
