Vasculitis Flashcards
What are the 4 vessel size classifications of vasculitis?
Small, mixed small and medium vessel, medium vessel and large vessel
What are the primary clinical features of small vessel vasculitis?
Palpable purpura, petechiae, vesicles, pustules
What are the hallmark clinical features of mixed medium and small-vessel vasculitis?
Mixture of features from small/medium vasculitis
-palpable purpura, petechiae, vesicles, pustules, livido reticularis, retiform purpura, ulcers, subcutaneous nodules
What are the hallmark clinical features of medium vessel vasculitis?
Livido reticularis, Subcutaneous nodules, retiform purpura, ulcers
What are the hallmark clinical features of large vessel vasculitis?
Specific to dz
Temporal arteritis: erythematous tender nodules or ulceration on the frontotemporal scalp
Takayasu’s arteritis: erythematous, subcutaneous nodules, PG-like lesions on the lower extremity (more so than upper)
What are the 6 main groups of small vessel vasculitis?
Henoch-schonlein purpura, Acute hemorrhagic edema of infancy, urticarial vasculitis, erythema elevatum diutinum, granuloma faciale, secondary vasculitis (drug, infection, malignancy, autoimmune)
What are the main groups of mixed small and medium-sized vessel vasculitis?
Mixed cryoglobulinemia types II and III, ANCA-associated vasculitis: Microscopic polyangitis, Wegener’s granulomatosis, Chrug-Strauss syndrome
What are the hallmark dz’s of medium vessel vasculitis?
Polyarteritis nodosa and Kawasaki dz
What are the two main large-vessel vasculitides?
Temporal arteritis, Takayasu’s arteritis
What are the 5 main triggers of small vessel vasculitis?
infection (15-20%), inflammatory disorders (15-20%), Drug (10-15%), Neoplasm (<5%), other (thrombotic, embolic, cryoglobulinemia
Who gets cutaneous small vessel vasculitis most commonly?
Adults> children
What is the pathophysiology of cutaneous small vessel vasculitis?
Immune complex deposition in post-capillary venules which activates complement leading to a neutrophilic inflammatory response
- This causes vessel damage, hemorrhage, and tissue ischemia
- Fibrinoid necrosis of blood vessels arises via lysosomal enzymes (collagenases and elastases) and reactive oxidative species
This is why lower extremity is the most common, these deposits follow gravity, settle into lower extremity vessels
What are the most common infections associated with small-vessel vasculitis?
Bacterial: group A β-hemolytic Streptococci, Staphylococcus aureus, Chlamydia, Neisseria, Mycobacterium
Viral: hepatitis C > B ≫ A, HIV Fungal/yeast: Candida
What are the most common connective tissue diseases to cause small vessel vasculitis?
SLE, Sjogren’s, RA >>DM, scleroderma, polychondritis
IBD
Behcet’s
What are the most common drugs to cause small-vessel vasculitis?
Antibiotics: β-lactams (penicillin, cephalosporins), sulfonamides, minocycline, quinolones
Antiinflammatory: NSAIDS, COX-2 inhibitors
Most common neoplasms to be a/w small vessel vasculitis?
Hematologic malignancy (MM, monoclonal gammopathies) T-cell leukemia, MF, AML, CML, diffuse large cell leukemia, hairy cell leukemia
Solid-organ ca are much less commonly associated
What is the presentation of small vessel vasculitis?
Crops of partially blanchable, symmetric, palpable purpura on the lower extremities, dependent areas, and under tight clothing
Other manifestations: erythematous papules, urticaria,
vesicles, pustules, and livedo reticularis
Rarely happens on the face, palms, soles, or mucous membranes
What is the timing usually from exposure to onset of small vessel vasculitis lesions?
7-10 days
How long does small vessel vasculitis usually take to resolve?
3-4 weeks w/ some hyperpigmentation or atrophy
What kind of symptoms may be a/w small vessel vasculitis?
Skin: Asymptomatic, pruritus, or burning/pain
Systemic: fever, malaise, arthralgias, myalgias, and GI/GU sx’s.
If you note systemic sx’s need to consider a systemic vasculitis
In what percentage of patients is the small vessel vasculitis chronic and follows a relapsing course?
10%
What is the timing of the DIF and H&E biopsies to maximize diagnostic yield?
H&E: within 18-48 hrs
DIF: 8-24 hrs
What will be the DIF findings in small vessel vasculitis?
80% w/ perivascular C3 and IgM
What is the histology of small vessel vasculitis?
Perivascular neutrophilic infiltrate (w/ leukocytoclasis) centered around post-capillary venules w/ fibrinoid necrosis of vessel walls and endothelial swelling, and RBC extravasation
Concomitant involvement of the deeper larger vessels would suggests systemic vasculitis
What lab values would be suggestive of more systemic disease?
Elevated ESR and significant complement consumption
What should be done if there is suspicion of systemic involvement?
CBC (eosinophilia in CSS), BMP (looking for creatine), ESR (>40?), LFTs, UA, serial UA’s, hepatitis panel, ASO titer, CXR, ANA, RF, C3,C4, CH50, C1q, ANCA, anti-phospholipid antibodies, SPEP/UPEP, blood smear, cryoglobulins
What is the treatment approach to mild cases of small vessel vasculitis?
Supportive measures: 90% will have a spontaneous resolution, 10% will have a chronic course
Remove suspected meds
Leg elevation and compression stockings NSAIDS for arthralgias is controversial H1 blockers, H2 blockers
Topical steroids
What is the treatment approach to chronic or moderate cases of small vessel vasculitis?
Colchicine (0.6 mg, 2–3x/day)
Dapsone (100–200 mg/day)
Combination of colchicine + dapsone or
colchicine + pentoxifylline is more efficacious than monotherapy
What is the treatment for severe small vessel vasculitis w/ ulceration?
Oral prednisone (0.5–1 mg/kg with a 4–6 wk taper)
Can add immunosuppressive agents including: Azathioprine (1–2 mg/kg a day) Mycophenolate mofetil (up to 2g daily) Cyclophosphamide (1–2 mg/kg a day) Cyclosporine (2.5–5 mg/kg a day)
IVIG (in an immunodeficient patient) Plasmapheresis (in refractory cases)
What is the epidemiology of Henoch-Schonlein purpura (IgA vasculitis)
M/c pediatric vasculitis
- 90% of cases occur in children, often <10 y/o w/ male’s getting more often
- Tends to occur in the winter
What is the pathophysiology of Henoch-Schonlein purpura?
IgA vascular deposition in small blood vessels results in:
- Activation of several cytokines
- Neutrophil activation of nitric oxide and ROS
What are the most common triggers of Henoch-schonlein purpura?
- Occurs 1–2 weeks after a URI or Streptococcus infection
- Other infections: Bartonella henselae, Parvovirus B19, S. aureus, H. pylori, and Coxsackievirus
- Drug exposure reported in a minority of patients
What is the tetrad of the clinical presentation of Henoch-Sconlein Purpura?
Palpable purpura on the Buttocks and lower extremities (100)
Musculoskeletal: arthralgias (75%), arthritis of the knees and ankles
GI: Colicky abdominal pain (65%), diarrhea, hematochezia
Renal (40-50%): hematuria w/ risk of nephritis –> end-stage renal failure seen in 1-3%
How many of those with Henoch-Scholein Purpura get end-stage renal failure?
1-3%
What is the difference in prognosis for HSP in adults?
More likely to have an aggressive course w/ diarrhea and chronic renal insufficiency
What are two important predictors of IgA glomerulonephritis in adult pts w/ HSP?
Elevated ESR, fever, and purpura above the waist
What types of neoplasms are more a/w HSP in adults?
More commonly a/w solid organ tumors (especially lung cancer) over hematologic ones
What percent of adult HSP recurs?
40%
What percent of children with HSP get severe renal dz?
40%
What is a significant predictor of nephritis in children w/ HSP?
Abdominal pain
When should prednisone and or cyclosporine be added to HSP?
If there is abdominal pain, arthritis, or severe nephritis
These are largely symptomatic, it is controversial if prednisone is preventative of renal dz (Cochrane review did not find enough evidence to support benefit)
What is the role of ranitidine in the tx of HSP?
If there is abdominal pain it can decrease duration and severity
When should IVIG be considered in HSP?
In the setting of rapidly progressive glomerulonephritis
What is the DIF findings in HSP?
IgA in blood vessel walss
What type of follow-up is needed in HSP?
Long term f/u w/ serial UA’s required (hematuria, proteinuria, and abnormal creatine)
What is seen in the histology of HSP?
LCV
DIF = IgA deposits, C3, and fibrin in dermal small blood vessels
rate of renal dz is higher if no eos are seen on skin bx
What is the epidemiology of acute hemorrhagic edema of infancy?
Children <3 y/o
70% are boys
what is the pathophysiology of acute hemorrhagic edema of infancy?
Immune complex deposition in small blood vessels (similar to HSP but no systemic)
Clinical presentation of acute hemorrhagic edema of infancy?
Large annular or targetoid/cockade, edematous, hemorrhagic plaques on the head (cheeks and ears) and upper extremities
*spares trunk
Tender non-pitting acrofacial edema
Not ill appearing
What is the prognosis of acute hemorrhagic edema of infancy?
Resolves in 1-3 weeks
What is the histology of acute hemorrhagic edema of infancy?
LCV, DIF can show IgA
Treatment for acute hemorrhagic edema of infancy?
Can give histamines for sx’s but largely supportive
What are the two major types of urticarial vasculitis?
Normocomplemetemic (70-80%) and hypocomplementemic (20-30%)
What is the difference in prognosis between normocomplementemic and hypocomplementemic urticarial vasculitis?
The normocomplementemic version is skin-limited and idiopathic, the hypocomplementemic version is highly a/w systemic dz
What is the epidemiology of urticarial vasculitis?
Females > 50 y/o are the most common people to get this especially the hypocomplementemic variety
What is the pathophysiology of urticarial vasculitis?
Complement and immune complex deposition in blood vessel wall and activation of the complement cascade
Hypocomplementemic form: IgG antibodies bind C1q leading to reduced serum levels of C1q
What autoimmune dz are most often a/w urticarial vasculitis and what subtype are they most commonly associated with?
SLE (hypocomplementemic) and Sjogren’s (both)
What infections are associated with urticarial vasculitis?
Hepatitis B/C, EBV
What medications are most often a/w urticarial vasculitis?
NSAIDs, MTX, TNF-α inhibitors, Cimetidine, Fluoxetine, Potassium iodide
What malignancies are most often a/w urticarial vasculitis?
Leukemia/lymphoma and gammopathies (IgM and IgG)
What is the clinical presentation of urticarial vasculitis?
Painful/burning urticarial lesions lasting >24 hrs (vs < 24 hrs for normal urticaria) on trunk and LE; resolves w/ hyperpigmentation or purpura; may have concomitant angioedema
Recurrent episodes lasting months to years
What are the most common systemic symptoms/findings in urticarial vasculitis?
Most commonly seen in the hypocomplementemic version
MSK (50%): Arthralgias, myalgias
GI (15-30%): recurrent abdominal pain, diarrhea, N/V
Pulm (20%): SOB, severe COPD, laryngeal edema
Renal (20-30%): glomerulonephritis or interstitial nephritis
Ocular (10%): Uveitis, conjunctivitis, episcleritis
Constitutional sxs: fever, malaise, arthralgias, myalgias
What lab findings help distinguish the hypocomplementemic version from the normocomplementemic version?
Decreased CH50, C3 and C4; anti-C1Q Ab (~100% of HUV patients) and elevated ESR
-Should check ANA given strong association of HUV with SLE
(up to 50%)
What is Schnitzler’s syndrome?
urticarial vasculitis + IgM gammopathy + two of the following: fever, arthralgia, bone pain, elevated ESR, or elevated WBC
What is the treatment of primary urticarial vasculitis?
Antihistamines, oral steroids, indomethacin
alternatives: Dapsone, Colchicine, hydroxychloroquine
What is the treatment of severe urticarial vasculitis?
Prednisone + MMF
Rituximab
IVIG
What is the most common association with erythema elevatum diutinum?
HIV
What is the epidemiology of erythema elevatum diutinum?
Rare
Chronic condition of middle-aged and older pts
A/w HIV
Clinical presentation of erythema elevatum diutinum?
Early lesions: red-brown violaceous papulonodules and plaques on extensor surfaces and near joints
- Later lesions: firm nodules and masses at previously inflamed sites
- Systemic associations: ocular (scleritis/uveitis) and arthralgias
What is the histology of erythema elevatum diutinum?
Early: LCV w/ interstitial neuts resembling neutrophilic dermatoses
Late: perivascular storiform fibrosis (onion skin fibrosis) around dermal vessels and neutrophils
Treatments for erythema elevatum diutinum?
Dapsone is treatment of choice
can consider NSAIDS, tetracyclines and cochicine
What is the epidemiology of granuloma faciale?
Adults, caucasian>African American, and M>F
What is the clinical presentation of granuloma faciale?
Single or multiple discrete red-brown papules, plaques, and nodules on the face, especially the nose, malar prominence, forehead, and ear
- Some consider granuloma faciale and EED to be the same entity with different anatomic predilections
- May have follicular prominence, telangiectasias, or a “peau d’orange” appearance
What is the histology of granuloma faciale?
LCV (findings may be difficult to identify)
Grenz zone
Dense mixed dermal infiltrate consisting of eosinophils, neutrophils, lymphocytes and plasma cells
Treatment for granuloma faciale?
Intralesional triamcinolone (2.5–5 mg/mL)
Cryotherapy + intralesional triamcinolone
Topical steroids
Topical tacrolimus
If unresponsive, consider dapsone (50–100 mg/day), colchicine, or plaquenil
PDL
What is the pathophysiology of ANCA + vasculitis?
The ANCA-mediated vascular injury is caused by neutrophils and monocytes that produce toxic oxygen metabolites
What ist he main c-ANCA associated vasculitis?
Wegners >>MPA
What is more specific, p-ANCA or c-ANCA?
c-ANCA is much more specific (p-ANCA is a/w most of the ANCA vasculitis entities)
What are the main p-ANCA associated vasculitides?
Levamisole-induced vasculitis, Churg-Strauss syndrome, MIcroscopic polyangiitis, and minocycline-induced lupus erythematosus
What is the pathophysiology of Wegener’s granulomatosis/granulomatosis w/ polyangiitis?
c-ANCA mediated (anti-PR3) Th1 immune response leading to granuloma formation
Unknown triggers
What is the specific antibody associated with granulomatosis w/ polyangiitis?
anti-PR3
What is the clinical triad seen in granulomatosis w/ polyangiitis?
- Necrotizing granulomas of the upper and lower respiratory tract: cough hemoptysis, SOB,
- Nasal/sinus inflammation: rhinorrhea, sinusitis, and purulent or bloody nasal discharge
- Systemic vasculitis
- Musculoskeletal: arthralgias
- Ocular: conjunctivitis, proptosis, and keratitis
- CNS: peripheral neuropathy and CVA
- Glomerulonephritis
- Death from renal disease if left untreated (>80% 1
year mortality)
Most common cause of death in untreated granulomatosis w/ polyangiitis?
Renal dz (80% 1 year mortality if untreated)
How common are cutaneous findings in granulomatosis w/ polyangiitis?
10-21% at initial presentation but 15-46% throughout the course of dz
What are the most common skin findings in granulomatosis w/ polyangiitis?
Palpable purpura in dependant areas
- Oral ulcers common, gingival hyperplasia w/ strawberry gums is less common but near pathognomonic
- Can have “pyoderma-like” nodules or necrotic ulcers
- Cutaneous dz can be a/w wearlier onset and more widespread dz
What are the limited forms of granulomatosis w/ polyangiitis?
Can have limited cutaneous or limited pulmonary
What is the histology of granulomatosis w/ polyangiitis?
LCV + extravascular necrotizing palisading granulomas w/ basophilic debris
What laboratory abnormalities can be seen in patients w/ granulomatosis with polyangiitis?
Can see an increase in ESR and WBC, can also see c-ANCA (sensitivity up to 90% and specificity 80-100%)
- Abnormal UA: microscopi hematuria or RBC casts
- Abnormal CXR: nodules, infiltrates, and cavities often found
- Sinus involvement: abnormal sinus X-ray, CT sinus or nasal bx
What ist he treatment for granulomatosis with polyangiitis?
Prednisone (1mg/kg/day) + cyclosphosphamide (2mg/kg/day)
Maintence: MTX (20-25mg/kg) and or oral steroids, azothioprine (2mg/kg/day)
What is the prognosis of granulomatosis w/ polyangiitis?
50% relapse within 5 years
What conditions is microscopic polyangiitis associated with?
Endocarditis, medications, and malignancies
What is the clinical presentation of microscopic polyangiitis?
Cutaneous palpable purpura, petechiae > livedo reticularis, retiform purpura, ulcers, and splinter hemorrhages
Constitutional symptoms may be present for months to years
- Most common cause of pulmonary-renal syndrome
What are the most common systemic sx’s seen with microscopic polyangiitis?
Renal (70-90%): focal segmental necrotizing glomerulonephritis
Pulmonary (25-50%): pulmonary capillaritis, pulmonary hemorrhage
Neurological (up to 33%): Mononeuritis multiplex, peripheral neuropathy
What are some key differences between microscopic polyangiitis vs polyarteritis nodosa?
Renal glomerulonephritis not seen as often as are pulmonary sx’s and ANCA is left often present in microscopic polyangiitis.
Tends to have HTN and microaneurysms as well as a hepatitis Bor C association (PAN)
What is the histology of microscopic polyangiitis?
LCV w/ segmental small > medium vessel vasclulitis
No granuloma formation, unlike WG or Churg-Strauss syndrome
What is the specific antibody seen in microscopic polyangiitis most commonly?
+ANCA –> specific antibody will be Anti-MPO most commonly (60%)
What other lab/workup abnormalities can be seen in microscopic polyangiitis /
p-ANCA + (MPO)
- abnormal UA (proteinuria/hematuria)
- Abnormal CXR or CT chest
- Abnormal EMG or lung/nerve/kidney biopsy
Treatment for microscopic polyangiitis?
Induction:
Cyclophosphamide (2 mg/kg per day) + oral steroids
(1 mg/kg per day)
Rituximab + cyclophosphamide
Remission:
-MTX or azathioprine, similar to WG
- Localized
- TMP-SMX + oral steroids
What are the possible triggers of Churg-Strauss syndrome?
Rapid steroid taper, vaccination, leukotriene inhibitors, and anti-IgE ab (omalizumab)
What are the 3 classic clinical states of Churg-Strauss syndrome?
- Adult-onset asthma, nasal polyps, and allergic rhinitis
- Eosinophilia, pneumonia, GI: N/V, abdominal pain
- Systemic: necrotizing vasculitis, neurologic: mononeurtiis multiplex, symmetric polyneuropathy, cardiac: pericarditis, valvular disease, endocardiomyopathy
What is the primary cause of death in Churg-Strauss syndrome?
Endocardiomyopathy
How often does Churg-Strauss present with cutaneous lesions?
14% as an initial presentation, but the vast majority will develop lesions through the course of the disease
What are the clinical presentations of Churg-Strauss Syndrome?
Palpable purpura on the lower extremities, painful symmetric subcutaneous nodules of the extremities and scalp
What is the histology of Churg-Strauss Syndrome?
- LCV w/ mixed infiltrate of eosinophils, neutrophils, lymphocytes, and macrophages
- Palisading neutrophilic and eosinophilic extravascular granulomas with degenerated collagen fibers (“red granulomas”)
What laboratory findings can be seen in Churgg-Strauss Syndrome?
+ ANCA (linked to neurologic and renal dz)
- ANCA (more linked to cardiac dz)
- p-ANCA > C-ANCA in leukotriene-associated dz
- Eosinophilia (eos > 1500)
- Leukocytosis
- Increased IgE
- CXR: patchy infiltrates, interstitial dz, and nodular masses
Treatment for Churg-Strauss syndrome?
Oral steroids (1 mg/kg a day)
Internal organ involvement:
- Cyclophosphamide (2 mg/kg a day) + oral steroids
What are the possible triggers of polyarteritis nodosa?
Possible triggers: meds, infections, inflammatory disease (IBD, SLE), and hairy cell leukemia; may be immune complex-mediated
a/w hepatitis B (5%–7%) and hepatitis C
Cutaneous form:
a/w streptococcal infection in children
Has been a/w minocycline
What is the most common specific antibody associated with p-ANCA?
Anti-myeloperoxidase
What is the staining pattern for p-ANCA?
Perinuclear staining (Churg-Stauss syndrome, MPA>PAN, chronic infection, other autoimmune dz
What is the staining pattern of c-ANCA?
Granular cytoplasmic staining (Wegener’s>>MPA)
What test must be also drawn with an ANCA?
ANA, can obscure the p-ANCA especially (the staining can overlap). If you see a + ANA need to discuss w/ lab, need to be really careful w/ procedure
What are the two forms of PAN?
Classic: systemic dz w/ multi-system vasculitis
Cutaneous: subtype w/ limited systemic involvement
What clinical features do you see w/ PAN?
- Palpable purpura on the lower extremities, painful single/multiple subcutaneous nodules on lower extremities which can ulcerate, Nodules may follow the course of superficial blood vessels, Livedo reticularis, rarely can have digital or penile infarction
- The cutaneous subtype: pink to purple-red nodules on LE near the malleoli and may extend proximally
- Atrophie blanche; atrophic ivory, stellate scars, livedo reticularis, digital gangrene
What systemic findings can be seen in PAN?
Constitutional sx’s: fever, weight loss, arthralgias, malaise
Renal: HTN and renal failure (most common cause of death)
Cardiac: cardiomyopathy, MI, arrhythmias
Neuro: paresthesias, motor or polyneuropathies
GI: N/V, bowel infarction, hemorrhage, mesenteric ischemia
GU: orchitis
What is the histology of PAN?
LCV
Necrotizing arteritis of medium-sized arteries
- In skin, these vessels are located in subcutis and at the dermopannicular junction
- Microaneurysms leading to thrombosis, ischemia, and necrosis
- Microaneurysms seen on angiography of medium-
sized vessels (coronary, renal, celiac, and mesenteric arteries)
Later course defined by fibrosis
DIF: IgM and/or C3 in the walls of cutaneous blood
vessels
What is DIF finding of PAN?
IgM and/or C3 in the walls of cutaneous blood vessels
Laboratory findings of PAN?
CBC: anemia and leukocytosis
- UA for hematuria and RBC casts
- Hepatitis B and C
- ANCA (p-ANCA <20% positive)
- Consider angiography if suspect microaneurysm or stenosis
- In children, consider anti-streptolysin O
What is the treatment for PAN?
-Interferon-α +/− vidarabine/lamivudine + plasma exchange
Cutaneous subtype:
Intralesional steroids, NSAIDS, and oral steroids for 3
to 6 months if severe skin involvement
Children: consider penicillin, given the association
with streptococcal infection • Severe systemic disease:
Cyclophosphamide (2 mg/kg a day) + oral steroids for 12 months
MTX (7.5–20 mg/week)
IVIG
-Hepatitis B (+): Interferon-α +/− vidarabine/lamivudine + plasma exchange
What is the epidemiology of Kawasaki dz?
80% cases in kids <5 y/o; M>F
Increased incidence in Japanese
What is the pathophysiology of Kawasaki dz?
Unclear etiology, likely 2/2 infection by unknown agent
Inflammation, scarring, stenosis, and aneurys formation in the small, medium, and large musculoelastic arteries including the coronary artery
What is required for the dx of Kawasaki dz?
Needs fever >= 5 days, + 4/5 of the below findings:
Conjunctival injection (usually non-exudative)
Mucous membrane: lip/oral mucosa erythema, fissured lips, strawberry tongue, and injected oral and pharyngeal mucosa
Cutaneous: polymorphous eruption including psoriasiform, morbilliform, scarlatiniform (particularly perineal with desquamation), and EM-like lesions on hands/feet
Cervical lymphadenopathy
Extremity changes: peripheral edema/erythema of hands/feet, or periungual desquamation
What nail findings may occur in Kawasaki disease?
Orange-brown or white transverse nail discoloration
What systemic complications can be seen Kawasaki dz?
Cardiac: coronary artery aneurysms/ectasia (secondary to vasculitis) and myocarditis
Musculoskeletal: arthritis/arthralgias
Pulmonary: pneumonitis
CNS: aseptic meningitis and facial nerve palsies
Ophtho: anterior uveitis
GI: gastroenteritis, hepatomegaly, bile duct
inflammation/hepatitis, jaundice, and pancreatitis
Laboratory findings in Kawasaki dz?
Increased CRP and ESR, LFT’s, and GGT
CBC (anemia, leukocytosis, increased neutrophil/eosinophils, and thrombocytosis)
Decreased albumin, sodium, potassium, and HDL
Check echocardiogram at diagnosis, 2, 6, and 8 weeks
What must be serially checked in Kawasaki’s dz?
Check echocardiogram at diagnosis, 2, 6, and 8 weeks
Treatment of Kawasaki’s dz?
High-dose Aspirin (80–100 mg/kg a day) + IVIG (2 g/kg)
-If given within first 10 days leads to a decreased rate of coronary artery issues
Resistant cases: IVIG + steroids, cyclophosphamide, cyclosporine/CIs, plasma exchange, TNF-α inhibitors, MTX, rituximab, and anakinra
Maintenance: aspirin
What is the #1 cause of acquired pediatric heart dz in the US?
Kawasaki’s dz
What is the difference in the prognosis of children w/ Kawasaki’s dz who are <12 months old?
They do not tend to respond to treatment as well
Epidemiology of temporal arteritis?
More common in Caucasians, females
->50 yo
Pathophysiology of temporal arteritis?
Vessel involved: any medium to large vessel (especially temporal artery)
Granulomatous vasculitis leading to ischemia, occlusion, infarction, and aneurysm
What are the clinical findings in large vessel vasculitis?
Early: tenderness and erythema along scalp and temples with possible cord-like nodule along the temporal scalp
Other cutaneous symptoms: erythema, purpura,
alopecia of overlying skin, and scalp necrosis
Unilateral temporal headache
Loss of temporal pulse
Jaw claudication
Glossitis, necrosis of anterior tongue (lingual artery)
Late: ulceration or gangrene
Systemic findings in large vessel vasculitis?
Systemic findings:
Polymyalgia rheumatica (40%–60%) with limb and girdle muscle pain, stiffness, and weakness
Fever and weight loss
Neurologic: vision loss (14%), stroke, subarachnoid
hemorrhage, and altered mental status
What is the histology of large vessel vasculitis?
- Segmental granulomatous large vessel arteritis with giant cells
- Disruption of media with fragmentation of the internal elastic lamina
What is the laboratory workup for large vessel vasculitis?
Increased ESR and CRP
- Anticardiolipin antibody (may be increased)
- MRA and Temporal artery biopsy helpful for w/u
What is the treatment of large-vessel vasculitis?
Aspirin 81 mg/day + oral steroids (40–60 mg/day)
Consider methylprednisolone (1 g/day for 3–5 days) if acute visual loss
What is the pathophysiology of Takayasu’s arteritis?
The vessel involved: aorta and its main branches
Granulomatous vasculitis leading to stenosis, occlusion, and aneurysms
What is the clinical findings in Takayasu’s arteritis?
Cutaneous symptoms seen in 50% of individuals, including: Purpura, Erythematous subcutaneous nodules, EN-like lesions, PG-like lesions, Raynaud’s phenomenon and digital gangrene
Systemic symptoms: Constitutional symptoms: fever, fatigue, malaise, night sweats, and weight loss, HTN, Loss of carotid or radial pulse
What are the workup findings in Takayasu’s arteritis?
Increased esr and MRA w/ visualization of all branches of the aortic arch needed
Treatment of Takayasu’s arteritis?
Oral prednisone (1 mg/kg) for 1 to 3 months with a 6 to 12-month taper
MTX 15–25 mg/week + prednisone
Cyclophosphamide
Trials with infliximab or etanercept are promising
Surgical intervention for cerebral hypoperfusion, valvular
insufficiency, and aneurysms
What disease is cryoglobulinemias a/w?
Likely related to HCV
What are cryoglobulins?
Immunoglobulins that precipitate at colder temps
Which type of cryoglobulinemia has a monoclonal cryoglobulinemia?
Type I (IgM>>IgG, IgA, light chains)
What is the histology of type I cryoglobulinemia?
Complete occlusion of vessel lumens w/ hyaline material
-Lacks LCV
What are the two types of mixed cryoglobulinemia?
Type II and III
Which types of cryoglobulinemia lack LCV?
Type I
Which cryoglobulinemia have LCV?
Type II and III
What are the clinical findings in cryoglobulinemia type I?
Raynaud’s phenomenon
-Purpura, livedo reticularis, and ulceration
-Cold-induced acrocyanosis of helices
Cryoglobulinemia types II and III have what typical cutaneous findings?
Palpable purpura and urticarial lesions
-Systemic findings common
What are the histological findings of cryoglobulinemia?
Type I: occlusive vasculopathy with vessels completely filled by homogenous hyaline material; lacks LCV
Types II and III: characteristic features of LCV
What labs are found in cryoglobulinemia?
Increased cryoglobulins
-Complement (hypocomplementemia in 90%; decreased C4)
- RF(+) (Types 2 and 3)
- Hepatitis B/C
- LFTs
What are the types of cryoglobulinemia associated with + RF?
Types 2/3
What are the immunoglobulins involved in type II cryoglobulinemia and are they polyclonal or monoclonal?
IgG=polyclonal and IgM=Monoclonal
What are the immunoglobulins involved in type III cryoglobulinemia and are they polyclonal or monoclonal?
IgG=polyclonal and IgM = polyclonal
What is the treatment of cryoglobulinemia?
HCV-related:
Interferon-α +/− ribavirin to prevent relapse
Low dose oral steroids (0.1–0.3 mg/kg per day if
arthralgia/weakness present)
High dose (0.5–1.5 mg/kg per day) for renal or
nervous system involvement
HCV-unrelated disease (connective tissue or malignancy
related) is less clear
