02-27 Vasculitis

Question 1

General definition of vasculitis

Answer 1

Inflammatory destruction of the vessels (usually arteries: can effect any arterial bed from caps. to aorta.) —causing sx of: ischemia, dysfunction or embolism through vessel narrowing or aneurysm

Question 2

1. Skin Clues to Vasculitis?

Answer 2

• Palpable purpura
• Ulcers - esp/ stellate (star-shaped) [see image here]
• Nodules
• Ischemic digits (become gangrenous)
• Livedo reticularis, or reticulated purpura

Use diascopy (pushing on skin w/ your finger) to differentiate extravasated blood (non-blanching) from dilation and stasis (blanching)

Question 3

Systemic clues that suggest vasculitis

Answer 3

• Skin lesions suggestive
  
  • esp. palpable purpura, stellate or punched out ulcers
• Glomerulonephritis
• Mononeuritis multiplex
• Diseases of the old in the young (e.g. 20 y/o who has a stroke)
• Systemic diseases (e.g. fever, chills, looks “toxic”) in the absence of infection or malignancy
• Someone who just shows up w/ multisystem illness (i.e. not someone already really sick in the ICU)

Question 4

1° vs. 2° Vasculitis?

Answer 4

Primary

• idiopathic (etiologic agent unknown)
• Only have theories on pathogenesis

Secondary

• Associated w/ another C.T. dz
• Infection related
  
  • hep C, hep B, parvovirus, herpes zoster, SBE
• Drug induced (loads of drugs can do it; usu. small vessels)
• Malignancy (all tumors can cause)
• Cardiac myxoma
• Cryoglobulins (cold-preciptating proteins that occur for a variety of reasons)

Question 5

Etiology of Idiopathic (Primary) Vasculitis

Answer 5

• IC deposition or in situ formation of IC in the vascular wall (serum sickness, Arthus reaction)
• Inflammation following deposition
• Likely influenced by adhesion molecules in vascular bed, turbulent blood flow, & hydrostatic pressure
• Possibly provoked by infections, exposures WITH a prior genetic predisposition
  
  • e.g. not everyone w/ Hep B gets polyarteritis nodosum

Question 6

SMALL VESSEL VASCULITIS

DZ: HSP

• Etiology
• S/Sx
• Biopsy findings
• A.K.A.?

Answer 6

Henoch Schoenlein Purprua

• Small vessel vasculitis
• S/Sx: Associated with dependent* skin rash, bloody diarrhea due to vasculitis of the bowel lining, glomerulonephritis and arthralgias.
  
  • *dependent b/c we think immune complexes deposit in a gravity-dependently
• Biopsy: neutrophilic, leukocytoclastic process with IgA present in the vessels
• A.K.A.: Sometimes referred to as “hypersensitivity vasculitis” or “leukocytoclastic vasculitis”

[A similar skin picture is found in vasculitis caused by drug reactions, other infections and in connective tissue diseases]

Question 7

Name this skin sign?

Answer 7

livido reticularis

usually more violet than red

on legs, arms, phlanks

Question 8

How could you tell if this ulcer were vasculitic or not?

Answer 8

Hard to tell when this big

biopsy from the middle of the ulcer

Question 9

Patient presents with this pulsatile, red bump under the skin. Dx?

Answer 9

Erythema nodosum

Question 10

50 yo man visits Thailand. On returning to NH he develops malaise, fever, anorexia followed by jaundice and elevated LFTs.

• He is diagnosed with Hep B infection.
• He appears to be getting better, only to loss his appetite, develop hypertension and a large painful ulcer on this calf after minor trauma (bumping it on coffee table, e.g.).

1. What process unites this man’s complaints?
2. Etiology
3. Other Presentating S/Sx
4. Dx
5. Biopsy Findings?

Answer 10

MEDIUM-VESSEL VASCULITIS

1. Polyarteritis nodosum
2. neutrophilic vasculitis of med. size muscular arteries causing aneuryms.
   
   • Almost universally 2° to Hep B
     
     • very similar histo process is seen in RA, lupus, Kawasaki’s dz (which is also called pediatric polyarteritis) in kids.
3. In addition to the loss his appetite, HTN and ulcers after minor trauma,
   
   • gut ischemia, coronary aneurysms, renal artery involvement casing hypertension, large ulcers, mononeuritis
4. Bx, angiogram
5. Biopsy shows nodular aneurysm at one end of artery [see image here]

Question 11

Name the queen:

Answer 11

Sharon Needles

America’s Season 4 Drag Super Star

Question 12

Cryoglobulinema is caused by?

Answer 12

• Hep C, MM, others
• Cryoglobulinemic vasculitis = cold precipitating antibodies causing a small vessel vasculitis including GN most strongly associated with hepatitis C.

Question 13

35 yo man is seen with eye inflammation [see image here], sinusitis, lung lesions, hemoproteinuria and gangrene of the fingers.

• Chest x-ray shows nodules (in upper lungs)

1. Dx
2. Classic triad of sx?
3. Biopsy of lung shows?
4. Related to other dzs (name them) w/ this same lab finding (name it!).
   
   • These ANCA (+) vasculities are fairly common
   • have common pulmonary-renal presentation

Answer 13

SMALL VESSEL VASCULITIS

1. GPA (Granulomatosis w/ Poly-Angitis)
   
   • formerly Wegener’s granulomatosis (re-named b/c he was a Nazi)
2. Triad
   
   • Vasculitis
   • extravascular granulomas in the upper & lower respiratory tract
   • pauci-immune glomerulonephritis
3. See biopsy image here w/ giant cells, cell necrosis and maybe (squint your eyes) granuloma signs
4. Similar presentation in microscopic angiitis (MPA) and Churg-Strauss disease
   
   • All assoc’d w/ (+) ANCA (anti-neutrophilic cytoplasmic Ab’s)
   • GPA is a C-ANCA

Question 14

ANCA

1. What is it testing for?
2. What four pieces of info do you get?
3. Which is pANCA and which is cANCA on this image?
4. Difficulties

Answer 14

1. Tests for: Auto-Ab’s to enzymes & proteins in granules of neutrophils
   
   • pattern & specificity of prot. it’s directed to help dx vasculitis.
   • one of the more “specific” lab tests in dx of vasculitis
     
     • (but really not that specific or sensitive)
   • most other lab tests are really non-specific
   • NOT specific for mPAN or Wegener’s
2. Four patterns
   
   • Positive or negative?
   • Staining pattern (cANCA or pANCA)
   • PR3 (serine proteinase 3, most common Ag for cANCA)
   • MPO (myeloperoxidase, most common Ag for pANCA)
3. cANCA is on the left, pANCA is on right
4. Operator-dependent (DHMC doesn’t do them in house!);
   
   • depend on Ag-purity
   • many false positive

Question 15

A 70 yo man is seen because of new headaches located where his hat rubs on his temples. He finds his scalp painful when he combs his hair, his vision has momentarily gone black and his jaws hurt to chew steak. He has lost 10 pounds and he has a low grade fever of 100 on a daily basis.

1. What can this illness be?
2. Classic presentation
3. Etiology
4. How can we make a diagnosis of vasculitis?

Answer 15

LARGE VESSEL VASCULITIS

1. GCA (Giant-cell arteritis, or “Temporal Arteritis”)
2. Classic presentation
   
   • Age > 50
   • Arteries tend to be tender and non-pulsatile
     
     • (i.e. not all swollen temporal aa. = GCA! may be collateral flow → expect puslatile)
   • classically effects extra-cranial arteries causing:
     
     • headache
     • scalp pain
     • sore throat
     • visual loss (amaurosis fugax)
     • cough
     • hearing loss
     • vertigo
   • but can also effect the aorta and its branches.
3. Etiology = mononuclear cell infiltrate destroys the elastic lamina of muscular arteries
4. Biopsy is best (see image here); could do angio, MRA, or lab tests but all those are non-specific
   
   • choose symptomatic tissue (i.e. kidney only if renal involvement)
   • get big chunk cause this isn’t continuous (e.g. 4cm of temporal a.)
   • loss of elastic lamina

Question 16

DZ: What is Takayasus aortitis?

Answer 16

LARGE VESSEL VASCULITIS

Very similar pathology at GCA

• see in young patients
• more global sx
  
  • constitutional symptoms
  • extremity claudication
    
    • check BP in both arms and both legs
  • HTN (from renal a stenosis)
  • visual ∆s
  • vertebrobasilar sx of dizziness and imbalance.
• More prevalent in Asians.
• Women predominate.

Question 17

A 65 yo woman is seen with necrotic skin lesions on the thighs and calves, severe pain associated with the skin lesions and weight loss.

• Has skin findings shown here
• Biopsy showns non-inflammatory vessel obstruction/narrowing

Answer 17

Think vasculopathy - processes that cause vessel obstruction or narrowing that is non-inflammatory.

• Cholesterol emboli
• SBE (Subacute bacterial endocarditis) giving off emboli
• Antiphospholipid antibodies
• Disseminated intravascular coagulation
• Ergot and sympathomimetic drugs
• Vasospasm, seen especially in the CNS.
• Calciphylaxis
• Amyloid
• Fibromuscular dysplasia

Question 18

TX: How do you tx vasculitis?

Answer 18

Generally same treatment for most of these

• Remove precipitants

Ask, is this still active inflammation or sequlae from past inflamm?

• Treat inflammation (steroids, immunosuppressives)
• Treat damaged endothelium and complications like hypertension

Continue with:

• Monitor for active inflammation vs ischemic sequella
• Move to lowest dose of immunosuppression that controls inflammation

Question 19

Summary

Answer 19

1. Know WHEN to consider the diagnosis of vasculitis.
2. Know HOW to substantiate the diagnosis.
   
   • Biopsy is always best!
3. Know WHAT ELSE looks like vasculitis.
   
   1. e.g. vasculopathy
4. Consider if the process is primary or secondary.
5. Consider the vessel size and organ distribution.
6. THEN give it a label.
7. These frequently relapse, especially in adults so f/u every year once stable.

Question 20

Thumbnail sketch: Churg-Strauss Syndrome

Answer 20

SMALL VESSEL VASCULITIS

• Another Wegener’s-like disease in patients with a history of asthma or atropy.
• Classically, pulmonary infiltrates, cardiac and neurologic features with blood eosinophilia are the hallmark of the disease.

Question 21

Thumbnail sketch: Kawasaki’s Disease

Answer 21

MEDIUM VESSEL VASCULITIS

A febrile illness in children under the age of 6 includes inflammation of the oral mucous membranes, lymphadenopathy, rash and irritability. Coronary arteritis is the vasculitic complication in this otherwise limited disease.

Question 22

Thumbnail sketch: Behcet’s disease

Answer 22

Behcet’s – peculiar in involving veins as well as arteries. Associated with intensely painful oral and genital ulcers, thrombophlebitis, retinal vasculitis and anterior eye disease, encephalitis and rash.

Question 23

Thumbnail sketch: Buerger’s disease

Answer 23

thromboangiitis obliterans.

• obliterative arterial and venous disease of the hand and feet
• felt by some to be a vasculopathy (not true vasculitis)
• Causes digit loss
• closely related to cigarette smoking.