DDx: Systemic Vasculitides Flashcards Preview

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Flashcards in DDx: Systemic Vasculitides Deck (20):

DDx: Systemic Vasculitides

Large vessel vasculitis:

Giant cell arteritis (GCA)/polymyalgia rheumatica (PMR)

Takayasu arteritis

Variable vessel vasculitis:

Behçet disease

Cogan syndrome

Medium vessel vasculitis:

Polyarteritis nodosa

Kawasaki disease

Small vessel vasculitis:

ANCA-associated vasculitis

Granulomatosis with polyangiitis (Wegener)

Eosinophilic granulomatosis with polyangiitis (Churg-Strauss)

Microscopic polyangiitis

Immune-complex mediated vasculitis:

Anti-glomerular basement membrane (Goodpasture) disease

IgA vasculitis (Henoch-Schönlein purpura)

Cryoglobulinemic vasculitis

Cutaneous leukocytoclastic angiitis (hypersensitivity vasculitis)

Hypocomplementemic urticarial vasculitis (anti-C1q vasculitis)


Ddx: Large Vessel Vasculitis

Giant cell arteritis (GCA)/polymyalgia rheumatica (PMR)


Giant cell arteritis (GCA)/polymyalgia rheumatica (PMR)

Takayasu arteritis


Giant cell arteritis (GCA) is the most common systemic vasculitis in adults, frequently affecting adults aged >50 years.

Polymyalgia rheumatica (PMR) is a condition closely related to GCA that presents with hip and shoulder girdle stiffness and pain and elevated inflammatory markers. Although PMR may occur independently from GCA and is not considered a vasculitis, it shares many features with GCA, including the same inflammatory cytokines and associations with age, ethnicity, and HLA class II alleles.

Hx: GCA: New-onset headache, with temporal artery tenderness or enlargement, jaw claudication, transient ischemic attacks or stroke and fever and malaise. scalp tenderness (GCA), and noncranial ischemia (such as arm claudication). 

Visual symptoms, including diplopia and loss of vision, may be irreversible and reflect occlusive arteritis of the posterior ciliary artery.

PMR: Arthralgias and myalgias involving the proximal limb and axial musculature and tendinous attachments; fever is uncommon and malaise and weight loss are frequent. Pain is worse with movement, but muscle strength is preserved.

Dx: GCA and PMR: Elevated erythrocyte sedimentation rate, seen in 96% of patients. A mild normocytic anemia may be seen.

GCA requires a temporal artery biopsy, which has a sensitivity of 90% to 95%. In some patients a contralateral second biopsy is necessary.  Inflammation with lymphocytic infiltration affects extracranial branches of the aorta in a segmental fashion, with the presence of multinucleated giant cells seen in half of biopsy specimens.

Tx: CGA: Given the risk of irreversible vision loss in patients with GCA, prompt initiation of glucocorticoid therapy (1 mg/kg/day of prednisone) is warranted. Up to 4 weeks of steroid therapy is needed until symptoms and laboratory abnormalities resolve, followed by a slow taper. 

PMR: In the absence of symptoms or clinical findings consistent with GCA, a trial of glucocorticoid therapy is indicated, as PMR typically responds dramatically to this therapy. Patients with PMR tend to respond to 10 to 20 mg/day of prednisone, with rapid improvement in musculoskeletal pain and stiffness.


Takayasu arteritis

Hx: Young Asian women

Px: Limb claudication, vascular bruits, aortic regurgitation,

Dx: Vascular stenosis/occlusion/aneurysm on CT angiography


Ddx: Variable vessel vasculitis:

Behçet disease

Cogan syndrome


Behçet disease

Behçet's is a chronic multisystem disease commonly found in Asians and people of Mediterranean origin. 

Painful oral and genital ulcerations, uveitis, skin lesions, gastrointestinal or CNS involvement, and oligoarthritis.

Cutaneous manifestations include erythema nodosum, pyoderma gangrenosum, Sweet syndrome-like lesions or pustules. Pathergy, the appearance of a pustule or papule 48 hours after the skin is pricked with a 20- to 21-gauge needle, is present in some patients.

Ocular involvement, including uveitis and hypopyon (purulent exudate in the anterior chamber), is common. Treatment includes topical, intraocular or systemic glucocorticoid, and addition of immunosuppressive agents when severe.

Px: Oral and genital ulcers, uveitis, pathergy, cutaneous lesions.


Cogan syndrome

Hx: Aortic aneurysm or regurgitation, interstitial keratitis, sensorineural hearing loss


Ddx: Medium-vessel vasculitis

Polyarteritis nodosa

Kawasaki disease


Polyarteritis nodosa

Hx: Abdominal pain, new onset hypertension. 

Dx: Renal insufficiency, mononeuritis multiplex, cutaneous lesions, aneurysms on angiography.


Kawasaki disease

Hx: Mostly in children, but also in HIV-infected adults; arthritis, acute coronary syndrome, aneurysms.

Px: Conjunctivitis, strawberry tongue, erythematous rash, cervical lymphadenopathy,


Ddx: Small-vessel vasculitis

ANCA-associated vasculitis: Antineutrophil cytoplasmic antibodies (ANCA) are defined by indirect immunofluorescence performed on neutrophils with 2 patterns of staining observed: cytoplasmic (c-ANCA) or perinuclear (p-ANCA). c-ANCA are targeted to serine proteinase-3 (PR3); whereas, p-ANCA positivity indicates antibodies mostly against myeloperoxidase (MPO). The ANCA-associated vasculitides affect small- to medium-sized vessels and do not involve immune complex deposition (“pauci-immune”). The diagnostic value of ANCA testing is well established, but antibody titers do not correlate with disease activity.

Granulomatosis with polyangiitis (Wegener)

Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)

Microscopic polyangiitis



Granulomatosis with polyangiitis (Wegener)

Hx: Upper respiratory (otitis media, nasal ulcers, saddle-nose deformity, sinusitis), lower respiratory tract (pulmonary infiltrates, cavitary lesions and nodules, hemoptysis).

Constitutional symptoms include fever and weight loss.

Upper airway involvement includes otitis media, nasal ulcers, saddle-nose deformity, sinusitis and subglottic stenosis.

Pulmonary manifestations include hemoptysis, cough, fleeting pulmonary infiltrates and bilateral, occasionally cavitary, pulmonary nodules. Limited GPA refers to the absence of renal involvement.

Renal: Glomerulonephritis occurs in up to 80% of patients and is suggested by the findings of urine red blood cell casts, hematuria, and proteinuria. Up to 40% of patients ultimately develop chronic renal insufficiency

Dx: Positive c-ANCA (95% specific); dx is best established by lung or kidney biopsy. 

Tx: Combination of glucocorticoids and daily oral cyclophosphamide.

Newer studies have shown efficacy of rituximab as an alternative to cyclophosphamide. Plasma exchange is used as adjunctive therapy with life-threatening disease. Although about 90% of patients achieve remission, up to 30% will relapse, requiring maintenance therapy with an immunosuppressant.


Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)

Eosinophilic granulomatosis with polyangiitis (EGPA) is a necrotizing small vessel vasculitis with eosinophilic infiltration.

Hx: Asthma, allergic rhinitis and sinusitis.

Dx: Migratory pulmonary infiltrates, mononeuritis multiplex, necrotizing crescentic glomerulonephritis, palpable purpura, cardiomyopathy and gastrointestinal disease.  Peripheral eosinophilia occurs in the prodromal stages. Also see crescentic glomerulonephritis, pulmonary infiltrates, mononeuritis multiplex. Only 40% of patients will be p-ANCA-positive; therefore, biopsy is frequently necessary.

Tx: Limited cases respond well to glucocorticoid therapy alone, but addition of cyclophosphamide is needed with kidney involvement (azotemia, proteinuria >1 g/day), cardiomyopathy, gastrointestinal disease, or neurologic manifestations. 


Microscopic polyangiitis

Microscopic polyangiitis (MPA) is a necrotizing vasculitis

Hx: Presents with rapidly progressive glomerulonephritis and pulmonary capillaritis. Similar to other ANCA-associated vasculitides, arthralgias, myalgias, and fever are common, along with palpable purpuric skin lesions. 

Pulmonary manifestations range from mild dyspnea and anemia to massive alveolar hemorrhage, with patchy to diffuse infiltrates noted on chest radiography.

Dx: Positive p-ANCA; dx best made by biopsy of skin, kidney, or lung lesions. 

Tx: Combined therapy with glucocorticoids and cyclophosphamide (or rituximab) is used to induce remission,


Ddx: Immune-complex mediated vasculitis

Development of antibody-antigen (immune) complexes (IC) is called the Arthus reaction; deposition of these complexes in blood vessel walls initiates complement activation, an influx of inflammatory cells, thrombus formation, and hemorrhagic infarction. In the skin, palpable purpura, the most common cutaneous finding in IC-mediated vasculitis, results from extravasation of erythrocytes through damaged vessel walls.  These nonblanching lesions are distributed symmetrically in dependent areas of the body, where tissue hydrostatic pressure is increased (eg, lower extremities, buttocks). On light microscopy, cellular infiltrates consisting predominantly of neutrophils within and around vessel walls are seen, along with endothelial swelling and proliferation and neutrophil degranulation; hence, the term leukocytoclastic vasculitis.

Anti-glomerular basement membrane (Goodpasture) disease

IgA vasculitis (Henoch-Schönlein purpura)

Cryoglobulinemic vasculitis

Cutaneous leukocytoclastic angiitis (hypersensitivity vasculitis)

Hypocomplementemic urticarial vasculitis (anti-C1q vasculitis)





Anti-glomerular basement membrane (Goodpasture) disease

Anti-glomerular basement membrane (GBM) disease is a vasculitis caused by the deposition of autoantibodies reactive against type IV collagen found in basement membranes of the glomerular and pulmonary capillaries. 

Hx: Necrotizing glomerulonephritis, pulmonary hemorrhage, anemia, rash.

Dx: Circulating anti-GBM antibodies in serum or detection of linear IgG deposits to GBM on kidney biopsy. 

Tx: Treatment involves plasma exchange and use of immunosuppressants.


IgA vasculitis (Henoch-Schönlein purpura)

Small-vessel vasculitis that most commonly occurs in children under 5; the syndrome may affect adults with greater severity. 

Hx: Presenting features include a purpuric rash predominantly affecting the distal lower extremities, arthritis, abdominal pain, and hematuria.

Antecedent (occuring before) upper respiratory infection, abdominal pain, palpable purpura, arthralgias, glomerulonephritis.

Dx: Biopsy shows a predominance of IgA deposition on immunofluorescence. 

Tx: The disease can be self-limited when mild.  When kidney involvement is present, aggressive immunosuppressive therapy including systemic glucocorticoids and cyclophosphamide is prescribed.


Cryoglobulinemic vasculitis

Cryoglobulins are immunoglobulins (IgG or IgM).  When plasma is refrigerated at 4ºC for up to 72 hours, proteins may precipitate (cryoprecipitate). If refrigerated serum and plasma both form 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).

Type I cryoglobulinemia is associated with an isolated monoclonal immunoglobulin most often due to an underlying B cell proliferative disorder such as Waldenström macroglobulinemia (IgM) or multiple myeloma (usually IgG).

Hx: Hyperviscosity and thrombosis, but vasculitic symptoms can occur. 

Type II cryoglobulinemia: Is associated with both a polyclonal IgG (which may either act as an antigen or be directed against an antigen) and a monoclonal IgM rheumatoid factor directed against the IgG.

About 90% are associated with hepatitis C infection. When type II cryoglobulinemia is not associated with hepatitis C, the disease is called essential mixed cryoglobulinemia. 

Essential mixed cryoglobulinemia can cause palpable purpura, nephritis, and neuropathy. Although 30% of patients with SLE have mildly elevated aminotransferase levels, these findings should lead to a search for hepatitis B or C in which this disorder frequently occurs.

Hx: Triad of arthralgias, myalgias, and palpable purpura.  Involvement of medium-sized vessels results in cutaneous ulcers, digital ischemia, and fixed livedo reticularis. 

Severe involvement leads to membranoproliferative glomerulonephritis and mononeuritis multiplex.

Tx: Based on suppression of viral replication

Type III cryoglobulinemia is characterized by the presence of polyclonal IgG and polyclonal IgM.

Hx: Frequently seen in patients with chronic infections, Sjögren syndrome, and systemic lupus erythematosus.

Triad of arthralgias, myalgias, and palpable purpura. 

Involvement of medium-sized vessels results in cutaneous ulcers, digital ischemia, and fixed livedo reticularis. 

Severe involvement leads to membranoproliferative glomerulonephritis and mononeuritis multiplex.

Hx: Arthralgias, myalgias, palpable purpura, common in hepatitis C infection.

Dx: Membranoproliferative glomerulonephritis, mononeuritis multiplex, low C3 and C4 levels, presence of serum cryoglobulins, positive rheumatoid factor

Laboratory abnormalities include high titers of rheumatoid factor, a low serum complement C4 level (out of proportion to the decreased C3 level), and the detection of serum cryoglobulins.

Tx: Patients with severe involvement, such as mononeuritis and glomerulonephritis, require immunosuppressive therapy (glucocorticoids and rituximab) and plasma exchange to reduce circulating cryoglobulins.


Cutaneous leukocytoclastic angiitis (hypersensitivity vasculitis)

This disease is defined by exposure to an offending agent, usually a medication or infectious agent.

Px: Palpable purpura and/or maculopapular rash. No systemic involvement

Dx: Biopsy shows neutrophilic infiltration around a blood vessel. 

Tx: Discontinuation of the medication, with systemic glucocorticoids used only when disease is extensive.


Hypocomplementemic urticarial vasculitis (anti-C1q vasculitis)

Hx: Painful urticarial lesions, glomerulonephritis, arthritis, COPD, uveitis.

Dx: Positive ANA, positive C1q precipitin, low C3 and C4 levels