Title: GZ / The Grenz Zone Season 2 / 28 Vasculitis I
Tags: GZ DermnetNZ

In the vascular reaction pattern, there are 8 subgroups: These include
1.     Erythema multiforme
2.     Toxic erythema – viral exanthems, drug eruptions, and toxin mediated eruptions (SSSS)
3.     Figurate erythema – EAC, erythema gyratum repens, erythema migrans, erythema marginatum
4.     Urticaria (hives)
5.     Vasculitis
6.     Vasculopathy
7.     Retiform purpura
8.     Vascular growths

Q: Vasculitis is caused by inflammation of the blood vessel wall and causes [palpable/nonpalpable] purpura on dependent areas (e.g. lower legs)
Vasculopathies refer to blood vessel damage with minimal or no inflammation of the vessel walls and typically causes [...] or [palpable/nonpalpable] purpura
A: palpable; macular; nonpalpable
Back Extra: Inflammation of vessels bring edema with it→ palpable

Purpura refers to visible hemorrhage into the skin or mucosa, and may further be classified by 6 types:
Petechiae - nonblanchable, pinpoint
red macules ≤ 4 mm, think platelets
Macular Purpura - nonpalpable and 5-
9 mmin size, think coagulation
Ecchymosis - aka a bruise, nonpalpable and is ≥1cm, think
coagulation
Palpable Purpura - can range in size
from a few mm’s to many cm’s, suggests vasculitis and inflammation
Non-inflammatory or Inflammatory Retiform Purpura - purpura with an angulated or branching pattern, BAD SIGN!!
Back Extra: Petechiae
Ecchymosis

Q: The pathogenesis of vasculitis typically involves a type [...] hypersensitivity reaction
A: 3
Back Extra: Antibodies to an antigen → Immune complexes form→ Deposit in vessel
walls→ Complement cascade activated→ Inflammation of blood vessel walls

Q: Small vessel only vasculitis damages the arterioles, capillaries, and postcapillary venules in the upper and mid dermis and presents as palpable purpura, petechiae, and urticarial papules
Some examples include [...], [...], [...], acute hemorrhagic edema of infancy, erythema elevatum diutinum (EED), and granuloma faciale
A: cutaneous small vessel vasculitis (CSVV); Henoch- Schonlein purpura (HSP); urticarial vasculitis
Back Extra: HSP
CSVV

Q: Small plus medium vessel vasculitides involve medium vessels include small arteries and veins in the deep dermis or sub-Q, and can be broken down into 2 groups
Group 1: [...]
Group 2: [...]
A: Mixed cryoglobulinemia types 2 and 3; ANCA-associated vasculitides
Back Extra: Can present as purpura, petechiae, urticarial papules, livedo reticularis, ulcers, sub-cutaneous nodules, and even retiform purpura
More visceral involvement than small vessel only (e.g. kidneys, liver, heart, and mesentery)

There are 3 ANCA-associated vasculitides, which may have both old and new names
1. Granulomatosis with polyangiitis (GPA), formerly known as Wegener’s granulomatosis
2. Microscopic polyangiitis
3. Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss syndrome

Q: Medium vessel only vasculitides mainly involve 2 entities:
1. [...]
2. [...]
A: Polyarteritis nodosa (PAN); Kawasaki disease

Q: Large vessel vasculitides mainly involve 2 entities:
1. [...]
2. [...]
A: Temporal arteritis (giant cell arteritis); Takayasu’s arteritis
Back Extra: Involve larger-named arteries like the aorta

Q: Buzz words for a certain vasculitis:
The most common vasculitis, often caused by drugs and bugs
[...]
A: Cutaneous Small Vessel Vasculitis (CSVV)
Back Extra: Mostly leukocytoclastic vasculitis (LCV) that is mostly confined to the skin
Pathogenesis: An antigen trigger is bound by antibodies and forms big immune complexes that deposit into post-capillary venules→ these lodged immune complexes then activate complement, which activates the immune system → causes inflammation that damages the vessels and allows red cells to leak out → petechiae and palpable purpura in dependent areas

Triggers for Cutaneous Small Vessel Vasculitis (CSVV) can be remembered with the mnemonic MANIC
Medications (e.g. beta lactam antibiotics, bactrim, thiazides, and oral contraceptives)
Autoimmune connective tissue diseases (e.g. lupus, RA or Sjogren’s)
NSAIDs
Infections (e.g. group A strep, hepatitis and HIV, and candida) or Inflammatory Bowel Disease (IBD)
Cancer (<5% of cases, e.g. leukemias and solid organ cancers)
Back Extra: Same triggers as urticarial vasculitis, EED, and Sweet’s syndrome
Petechiae and palpable purpura on lower legs that present ~ 1-2 weeks after a trigger of infection or medication or ~ 6 months for autoimmune diseases or cancer
May become bullous or pustular
May be more severe under areas of pressure like the
May be itchy or painful
May have systemic symptoms (e.g. fevers and arthralgia)
Typically resolve over several weeks

Q: With Cutaneous Small Vessel Vasculitis (CSVV), petechiae and palpable purpura on lower legs start ~ [...] after a trigger of infection or medication or ~ [...] if associated with autoimmune diseases or cancer
A: 1-3 weeks; 6 months
Back Extra: Remember your MANIC mnemonic!

Histology of cutaneous small vessel vasculitis, or leukocytoclastic vasculitis:
1. Vessels in the superficial dermis with fibrin deposition and expansion of the vessel walls
2. RBC extravasation
3. Perivascular infiltrate containing neutrophils and karyorrhexis
Back Extra: PEARL: When it comes to terminology for CSVV, some people refer to it as “Leukocytoclastic vasculitis”, but keep in mind that LCV is actually a histology finding and can also be seen in other systemic vasculitic disorders such as granulomatosis with polyangiitis

Q: Buzz words for a certain vasculitis:
Child, arthralgia, purpura, melena, hematuria
[...]
A: Henoch-Schonlein Purpura (HSP)
Back Extra: IgA vasculitis which is THE most common form of vasculitis in children
Strep of upper resp infection, followed by tetrad of arthralgia of knees and ankles, renal issues (including hematuria), palpable purpura on the legs and butt, GI issues with or without melena
Treatment: Supportive treatment with or without prednisone or dapsone
Monitor patients with serial UA’s and stool guaiac if they have GI symptoms

Q: In adults with Henoch-Schonlein purpura, there are 3 main risk factors that may indicate renal involvement
1. [...]
2. ↑ [...]
3. Purpura located [...]
A: Fever; ESR; ABOVE the waist (“closer to kidneys”)

Q: Histology of Henoch-Schonlein purpura
Leukocytoclastic vasculitis with DIF showing positive Ig-[...] in blood vessel walls
A: A

Q: Buzz words for a certain vasculitis:
Hives, pain, purpura, low complement level
[...]
A: Urticarial vasculitis
Back Extra: Urticaria clinically, LCV histopathologically
4 unique differences than regular urticaria:
1. Individual lesions last longer than 24 hours (vs. <24 hours)
2. More pain and burning than itching
3. May have purpura or systemic Symptoms

Q: Urticarial vasculitis has 4 unique differences than regular urticaria:
1. Individual lesions last [shorter/longer] than 24 hours
2. More [...] and [...], rather than itching seen in regular
3. May have purpura or 4. systemic symptoms
A: longer; pain; burning
Back Extra: ~3/4 of cases have normal complement levels and are skin-limited
~1/4 of cases are HYPOcomplementemic & associated with systemic changes (e.g. arthralgias; pulmonary, GI, renal, and ocular changes; decreased CH50, C3, and C4 levels; and anti-C1q antibodies)

Q: ~3/4 of cases of urticarial vasculitis have [↓/↑/normal] complement levels and are skin-limited
~1/4 of cases have  [↓/↑/normal] levels of complement & associated with systemic changes (e.g. arthralgias; pulmonary, GI, renal, and ocular changes
A: normal; ↓
Back Extra: Hypocomplementeric type: Decreased CH50, C3, and C4 levels; and anti-C1q antibodies

Q: A patient with urticarial vasculitis, IgM gammopathy, fevers, bone pain, and arthralgias has [...]
A: Schnitzler’s syndrome

Q: Buzz words for a certain vasculitis:
Cold-induced purpura
[...]
A: Cryoglobulinemia
Back Extra: Cryoglobulins are immunoglobulins that precipitate in the cold
Broken down into 3 types

Type 1 Cryoglobulinemia is caused by monoclonal IgM > monoclonal IgG and is associated with lymphoproliferative disorders
Type 2 exhibits monoclonal IgM or IgG directed at polyclonal IgG
Type 3 has polyclonal IgM with polyclonal IgG
Back Extra: Type 1
Sludging and occlusion of blood vessels→ vasculopathy NOT vasculitis (1 type of antibody, no antibody antigen complex)→no LCV on path
Presents with livedo reticularis, Raynaud’s phenomenon, acrocyanosis, and purpura
Types 2 and 3 - mixed cryoglobulinemias → cause leukocytoclastic vasculitis

Lab abnormalities associated with mixed cryoglobulinemia (Types 2 and 3)
↑ Cryoglobulins
↓ C4 complement levels due to consumption
Positive rheumatoid factor (70-90%)
May have positive hepatitis B or C test
Back Extra: To show cryoglobulins, sample must be maintained near 98.6◦F until it is spun down, otherwise you get a false- negative result
PEARL: Rheumatoid factor by definition is the presence of an antibody that is binding to the Fc portion of IgG. Remember that the Fc portion is the bottom of the antibody’s Y shape. Since types 2 and 3 mixed cryoglobulinemias have polyclonal IgG, it makes sense that you end up with antibodies binding to IgG and thus a positive rheumatoid factor