Chapter 25 - Cutaneous Vasculitis Flashcards
When referring to “small vessel vasculitis”, what type of vessels could be involved?
Arterioles, capillaries, and post-capillary venules which are found in the superficial and mid-dermis of the skin
Increased neutrophil and lymphocyte endothelial cell adhesion results from an increase in which two selectin molecules on the endothelial cells.
E-selectin and P-selectin
Increased neutrophil and lymphocyte endothelial cell adhesion results from an increase in which three members of the immunoglobin superfamily on the endothelial cells?
ICAM-1, VCAM-1, and PECAM-1
What does “ANCA” stand for?
Antineutrophil cytoplasmic antibodies (ANCA)
List the molecules found within the cytoplasm of neutrophils that are potential targets for ANCA antibodies.
Proteinase 3 (PR3) and myeloperoxidase (MPO)
Why do lesions of palpable purpura in small vessel vasculitides occur predominantly on dependent sites, as well as under tight-fitting clothing?
Because hydrostatic pressure and stasis are involved in the pathophysiology of small vessel vasculitis. The slow flow of blood in these areas allows for deposition of the immunoglobulins and complement
If you suspect a cutaneous vasculitis, should you biopsy a new or old lesion for H&E? What about for DIF?
New lesions should be biopsied for both H&E and DIF
In small vessel vasculitis, what will the DIF show?
C3, IgG, IgM and/or IgA in a granular pattern within the vessel wall
True or false: when a patient has constitutional (fevers, weight loss, arthralgias) or musculoskeletal symptoms, your diagnosis of small vessel vasculitis of the skin should likely be reassessed.
False; patients with small vessel vasculitis of the skin often present with constitutional symptoms and musculoskeletal symptoms
True or false: when a patient has gastrointestinal, genitourinary, or neurologic symptoms, your diagnosis of small vessel vasculitis of the skin should likely be reassessed.
True; these symptoms should raise the possibility of a systemic vasculitis
What percentage of patients with small vessel cutaneous vasculitis will have resolution of cutaneous lesions within several weeks?
90%; 10% will have chronic or recurrent disease
True or false: small vessel cutaneous vasculitis can occur in the context of an autoimmune connective tissue disease or neoplasm.
True; if so, this will affect the patient’s prognosis
List four small vessel cutaneous vasculitides.
HSP, acute hemorrhagic edema of infancy, urticarial vasculitis, and erythema elevatum diutinum
List two large vessel vasculitides.
Temporal arteritis and Takayasu’s arteritis
List the two classic medium-vessel vasculitides.
Classic (systemic) PAN and cutaneous PAN
List the three ANCA-associated small-medium vessel vasculitides.
Microscopic polyangiitis, Wegener’s granulomatosis, and Churg-Strauss
True or false: cryoglobulinemia can cause a small-medium vessel vasculitide.
True
List four causes of secondary small-medium sized vasculitides.
Infections, autoimmune connective tissue diseases, drugs, and neoplasms
Approximately what percentage of cutaneous small vessel vasculitides are idiopathic? What percentage are secondary to another cause (e.g. infection, autoimmune disorder, etc.)?
About 50% idiopathic; 50% secondary to another cause
What is the tetrad of clinical findings of HSP?
Palpable purpura, arthritis, abdominal pain, and hematuria
What size of vessel is involved in HSP? What type of immunoglobin is involved?
Small vessels become coated in IgA
What is the most common form of vasculitis in children?
HSP
Does HSP follow a seasonal pattern? If so, when is it most common?
Yes; peak incidence during winter
What type of infection typically precedes HSP?
Upper respiratory tract infection
Over what general time frame do skin lesions associated with HSP regress?
Weeks to months
True or false: children or young adults with a history of HSP have an increased risk of pregnancy-induced hypertension.
True
Although the treatment of HSP is usually supportive (because the skin lesions resolve in weeks to months), what drug has been shown to decrease the duration of skin lesions?
Systemic steroids and dapsone; systemic steroids also help with the arthritis and abdominal pain
What’s the rare form of cutaneous vasculitis that was once thought to be a benign form of HSP?
Acute hemorrhagic edema of infancy; it’s now known to be it’s own entity
What’s the most common eponymn associated with acute hemorrhagic edema of infancy?
Finkelstein’s disease
How old are children that are typically affected by Finkelstein’s disease?
Children with acute hemorrhagic edema of infancy (Finkelstein’s disease) are usually between 4 - 24 months old (i.e. less than 2 years old)
True or false: patients with acute hemorrhagic disease of infancy (Finkelstein’s disease) typically present with fever and appear toxic.
False; patients may present with fever, but otherwise they appear well
True or false: proteinuria often accompanies Finkelstein’s disease (acute hemorrhagic edema of infancy).
False; there is no extracutaneous involvement
True or false: acute hemorrhagic edema of infancy (Finkelstein’s disease) often occurs after a recent infection, drug exposure, or immunization.
True
What two types of urticarial vasculitis are classically described?
Hypocomplementic and normocomplementic
True or false: urticarial vasculitis is often associated with SLE.
True
Which type of urticarial vasculitis follows a more benign course? Hypocomplementic or normocomplementic?
Normocomplementic; it typically resolves within 3 years
Which patients with urticarial vasculitis, those with the hypo- or normocomplementic type, are more likely to have extra cutaneous involvement?
Those with the hypocomplementic form
Urticarial vasculitis associated with a monoclonal IgM gammopathy and two of a list of systemic findings is known as:
Schnitzler’s syndrome
True or false: histologically, urticarial vasculitis will show LCV.
True
Name the small vessel vasculitis that presents with symmetric red-violet to red-brown papules and plaques on the extensor surfaces. The skin lesions tend to be persistent.
Erythema elevatum diutinum
How long does it typically take for erythema elevatum diutinum to resolve?
The disease has a chronic course: between 5-10 years, although many cases lasting over 40 years have been described
What is the classic unique histologic feature of erythema elevatum diutinum that is seen in late-stage lesions?
Extracellular cholesterol
What drug has been reported to induce a dramatic improvement in erythema elevatum diutinum (although there’s often a relapse when the medication is discontinued)?
Dapsone
What are the three types of cryoglobulins?
Type I: monoclonal IgM or IgG
Type II: monoclonal IgM against polycloncal IgG
Type III: Polyclonal IgM against IgG
What type of vasculitis is seen with type I cryoglobulinemia?
None; vasculitis is only seen with types II and III
What three organ systems are most commonly affected by cryoglobulins?
Skin, kidneys, and peripheral nervous system
What two infectious diseases have cryoglobulinemic vasculitis been associated with?
HCV and HBV; 70-90% of patients with essential mixed cryoglobulinemia have HCV and 5% have HBV
True or false: mixed cryoglobulinemic disease has been associated with HCV, HBV, HIV, auto-immune disease, lymphoproliferative disorders, and certain carcinomas.
False; mixed cryoglobulinemic disease has been associated with HCV, HBV, HIV, auto-immune disease, and lymphoproliferative disorders, but not carcinomas.
True or false: the three main ANCA-associated vasculitides include Wegener’s, Churg-Strauss, and mixed essential cryoglobulinemia.
False; the three main ANCA-associated vasculitides include Wegener’s, Churg-Strauss, and microscopic polyangiits (not mixed essential cryoglobulinemia)
What is the target of the C-ANCA antibody? What about the P-ANCA antibody?
C-ANCA: proteinase 3 (PR3)
P-ANCA: myeloperoxidase (MPO)
What does the “C” and “P” stand for in C-ANCA and P-ANCA?
Cytoplasmic-ANCA
Perinuclear-ANCA
What type of ANCA is associated with microscopic polyangiitis?
Both C-ANCA and P-ANCA are associated with microscopic polyangiitis; 30% of the time with C-ANCA and 60% of the time with P-ANCA
What percentage of patients with Wegener’s will have a positive C-ANCA?
80%
What percentage of patients with Churg-Strauss will have a positive P-ANCA?
60%
True or false: ANCA-associated vasculitides are classically characterized by a lack of immune complex deposition in the renal vessels (“pauci-immune”; although this may not be true in the skin).
True
True or false: microscopic polyangiitis is not recognized as an entity in the American College of Rheumatology classification scheme.
True; most patients are instead given the diagnosis of PAN or Wegener’s
*Note: microscopic polyangiitis is considered a diagnosis under the Chapel Hill Consensus conference classification scheme
Why is microscopic polyangiitis named this way?
The name reflects the pathophysiology; it reflects the fact that capillaries, venules, and veins can be involved, in addition to arteries and arterioles (“POLYangiitis”)
True or false: like PAN, microscopic polyangiits is associated with HBV infection.
False; PAN is associated with HBV but microscopic polyangiits is NOT associated with HBV infection
What percentage of patients with microscopic polyangiitis will develop renal disease?
90%; classically a pauci-immune crescentic necrotizing glomerulonephritis
Will the necrotizing vasculitis seen in microscopic polyangiitis be continuous or discontinuous?
It will be discontinuous (segmental)
True or false: patients with microscopic polyangiits have a higher rate of relapse than patients with classic PAN.
True
What is the classic triad associated with Wegener’s granulomatosis?
Granulomatous inflammation of the upper and lower airways, systemic necrotizing small vessel vasculitis, and pauci-immune glomerulonephritis
True or false: nasal carriage of S. aureus is associated with relapse of Wegener’s granulomatosis.
True
True or false: ulcers often develop in patients with Wegener’s granulomatosis that are frequently misdiagnosed as pyoderma gangrenosum.
True
True of false: nodules, especially common on the elbows, can often occur in Wegener’s granulomatosis. However, unlike in rheumatoid nodules, they never ulcerate.
False; nodules on the elbows commonly DO occur in Wegener’s granulomatosis, however they COMMONLY ulcerate, while the nodules associated with rheumatoid arthritis virtually never ulcerate
What percentage of patients with Wegener’s granulomatosis will have a positive rheumatoid factor?
50%
What percentage of patients with Wegener’s granulomatosis will have a positive C-ANCA?
80%
Is the inflammation that’s seen histologically in Wegener’s granulomatosis granulomatous or non-granulomatous.
Granulomatous; hence the name Wegener’s granulomatosis
True or false: Churg-Strauss has a lower incidence of renal disease than Wegener’s and is usually associated with asthma and eosinophilia.
True
True or false: histologically, microscopic polyangiitis lacks granulomatous inflammation.
True
What is the neurologic complication that commonly occurs in patients with Churg-Strauss (70% of patients)?
Mononeuritis multiplex
True or false: granulomatous inflammation of the myocardium can occur in both Wegener’s and Churg-Strauss.
False; it only occurs in Churg-Strauss and it’s the leading cause of death
What is the unique hematologic abnormality associated with Churg-Strauss?
Eosinophilia
What percentage of patients with Churg-Strauss will have a positive P-ANCA?
60%
True or false: 10-15% of patients with Churg-Strauss will have a positive C-ANCA.
True
True or false: just like in eosinophilic fasciitis, in a biopsy of a papulonecrotic lesion of Churg-Strauss, the lesion itself will not have many eosinophils (even though there is typically dramatic peripheral eosinophilia).
False; in Churg-Strauss, biopsies typically have lots of eosinophils in addition to there being dramatic peripheral eosinophila; this is in contrast to eosinophilic fasciitis (a completely unrelated disorder) in which there is typically peripheral eosinophila, but few eosinophils in the biopsy specimen
True or false: asthma and allergic rhinitis are typically associated with Churg-Strauss.
True
What size of vessel does PAN affect?
Medium sized vessels
What percentage of cases of PAN are classic (systemic), and what percentage are cutaneous (limited to the skin)?
10% cutaneous and 90% classic (systemic)
True or false: cutaneous PAN follow a benign course.
True; although the course can be very chronic
What is the most common infectious trigger of classic (systemic) PAN?
HBV
What percentage of patients with classic (systemic) PAN have skin findings?
50%; the most common findings are livedo reticularis and “punched-out” ulcers
True or false: in male patients with classic (systemic) PAN, orchitis frequently occurs.
True; extracutaneous disease is the rule in classic (systemic) PAN
Which form of PAN is more common in children: classic (systemic) or cutaneous?
Cutaneous
What infectious disease is cutaneous PAN often associated with in children?
Streptococcal infections; in adults the association is with HBV
True of false: patients with cutaneous PAN may have systemic symptoms.
True, despite the fact that they have “disease limited to the skin”. The systemic symptoms are limited to fever, myalgias, arthralgias, and peripheral neuropathy
True or false: the histology of PAN involves segmental necrotizing vasculitis of medium-sized arteries.
True
True or false: digital necrosis can occur in PAN.
True; sometimes this improves with IV prostaglandins or calcium channel blockers
True or false: in a patient with a suspected vasculitis and hypertension, a medium vessel vasculitis, involving the intrarenal vessles, may be present.
True
What size of vessel is typically involved if palpable purpura, urticarial papules, pustules, vesicles, and petechiae are present?
Small vessel
What type of skin findings are associated with medium vessel vasculitides?
Subcutaneous nodules, livedo reticularis, ulcerations, and digital infarcts
True or false: biopsies taken from nodules tend to have a higher diagnostic yield for medium sized vessel vasculitides than those taken from an ulcer edge or livedo reticularis.
True
True or false: if a biopsy of livedo reticularis is planned, one should biopsy in the center of the circular livedo segment, not in the radiating peripheral erythema.
True; the peripheral erythema represents venous cyanosis or congestion
True or false: ulcers should be biopsied at their edge.
True; because incidental vasculitis can often be found underlying ulcers and is non-diagnostic
What is the classification for vasculitis of small vessels and its subclassifications?
Cutaneous small vessel vasculitis. Henoch Schonlein purpura, acute hemorrhagic edema of infancy, urticarial vasculitis, erythema elevatum diutinum.
What are the classifications for vasculitis of small-medium vessels and their subclassifications?
Secondary (infection, inflammatory disorders, drug, neoplasm). Cryoglobulinemia. ANCA associated (microscopic polyangiitis, Wegener’s granulomatosis, Churg Strauss syndrome).
What is the classfication for vasculitis of medium vessels and its subclassifications?
Polyarteritis nodasa/PAN. Classic/systemic PAN, cutaneous PAN.
What are the classifications for vasculitis of large vessels?
Temporal arteritis, Takayasu’s arteritis.
What depositions are most frequently seen on DIF of patient with cutaneous vasculitis?
C3, IgG, IgM, IgA
What is the classic tetrad of symptoms in HSP?
Palpable purpura, arthritis, abdominal pain, hematuria.
What increases the risk of long term renal impairment in HSP by 10x?
Nephritic or nephrotic syndrome
What are some of the differences between HSP and hemorrhagic edema of infancy?
AHEI, <2yo, affects only skin, short duration (1-3wks)
What other systemic disorders can urticarial vasculitis be associated with?
Autoimmune CTD (Sjogren’s syndrome, SLE), infections, drugs, malignancies, serum sickness
How does urticarial vasculitis differ from chronic urticaria (ie. both have urticarial lesions lasting >24hrs)?
Lesions associated with burning, pain (rather than pruritus), resolve with PIH, truncal and proximal extremities (rather than acral surfaces)
What infections are most commonly associated with erythema elevatum diutinum (EED)?
B-hemolytic strep, HBV, HIV
What is the histology of late lesions in EED?
Minimal inflammatory infiltrate, marked perivascular fibrous thickening, vertically oriented capillaries, extracellular cholesterol deposits
What infection is most commonly associated with cryoglobulinemic vasculitis?
HCV (50% with HCV have CV, but only 5% develop overt CV)
What are the 2 clnically relevant patterns of immunofluorescent staining with ANCA?
- cyptoplasmic ANCA directed against Ag proteinase 3 (c-ANCA, PR3); 2. perinuclear ANCA directed against Ag myeloperoxidase (p-ANCA, MPO)
What are some differences between PAN and microscopic polyangiitis?
MP has more association with small vessel vasculitic changes (eg. glomerulonephritis, pulmonary hemorrhage), is not associated with HBV infection, role of p-ANCA and is pauci-immune, more likely to relapse. They rarely present with HTN, aneurysms
What is the triad of Wegener’s granulomatosis?
granulomatous inflammation of resp tract, vasculitis (systemic, necrotizing, small vessel), pauci-immune glomerulonephritis
What are some of the symptoms affecting the resp tract in WG?
Recurrent epistaxis, mucosal ulcerations, nasal septal performation, saddle nose deformity, dyspnea, cough, hemoptysis, pleuritis
What are some of the key features of Churg Strauss syndrome?
Asthma, allergic rhinitis, eosinophilia, necrotizing granulomatous vasculitis
What are the 3 phases of CSS?
- allergic rhinitis, nasal polyps, asthma; 2. peripheral eosinophilia, URTI/LRTI, GI symptoms; 3. systemic vasculitis with granulomatous inflammation
How is cutaneous PAN different from classic PAN?
Skin limited, benign, but chronic, most common in children, 10% of all PAN, associated with strep, parvovirus B19, HIV
What is the leading cause of death in CSS?
Granulomatous inflammation of the myocardium
