Medical Archive

Definition

Classification

Pathophysiology and pathogenesis

Granulomatosis with polyangiitis (Wegener’s)

Necrotizing granulomatous vasculitis involving nasopharynx, lungs, and kidneys

Middle-aged male with sinusitis or nasopharyngeal ulceration, hemoptysis with bilateral nodular lung infiltrates, and hematuria due to rapidly progressive glomerulonephritis.

Organ	Clinical manifestations	Biopsy
Upper respiratory	Sinusitis/otitis, saddle-nose deformity	– (High rates of false negative)
Lower respiratory	Lung nodules/cavitation Tracheal narrowing with ulceration	Granulomatotus vasculitis
Renal	Rapidly progressive GN	Pauci-immune GN
Skin	Livedo reticularis, nonhealing ulcers	Leukocytoclastic vasculitis

Mild leukocytosis and anemia.

Serum ANCA positive
PR3(c): ~70%, MPO(p) ~20%
HIV can increase the chance of false-positive ANCA results and should be ruled out.

Treatment is cyclophosphamide and steroids; relapses are common.

Microscopic Polyangiitis

• Necrotizing vasculitis involving multiple organs, especially lung and kidney
• Presentation is similar to Wegener granulomatosis, but nasopharyngeal involvement and granulomas are absent.
• Serum p-ANCA levels correlate with disease activity.
• Associated with antibiotic use
• Treatment is corticosteroids and cyclophosphamide; relapses are common.

Eeosinophilic granulomatosis with polyangiitis (Churg-Strauss)

• Laboratory findings
  • Necrotizing granulomatous inflammation with eosinophils involving multiple organs, especially lungs and heart
  • Antibodies against neutrophil myeloperoxidase.
    • Most commonly have a pattern of perinuclear staining (p-ANCA)
    • Serum p-ANCA levels correlate with disease activity.
• Clinical presentation
  • Asthma and peripheral eosinophilia are often present
  • Mononeuritis multiplex
    • D/t involvement of the epineural vessels of peripheral nerves
    • Eg, wrist drop d/t radial nerve involvement
  • Skin nodules
  • Migraatory/transient pulmonary infiltrates
  • Paranasal sinus abnormalities.

Polyarteritis nodosa PAN

Pathophysiology

Necrotizing vasculitis involving multiple organs; lungs are spared.
Associated with serum HBsAg(~30%), HCV

• Patients with PAN tend to have very high levels of circulating inflammatory cytokines, which frequently causes:
  • Constitutional symptoms (eg, malaise, intermittent fever, weight loss)
  • Elevated inflammatory markers (eg, ESR)
  • Anemia of chronic disease

Clinical presentation

Classically presents in young adults.

• Constitutional symptoms
  • Fever, myalgia, joint pains, fatigue
• Skin
  • Nodules, ulcers, purpura
  • Livedo reticularis
• Nervous
  • Headache, seizures
  • Mononeuritis multiplex (>70%)
• Renal
  • Renal insufficiency d/t renal artery narrowing (almost all)
  • Hypertension
• Abdominal
  • Mesenteric ischemia
  • Mesenteric angiography – microaneurysms and distal abrupt cutoffs.
• Myocardial ischemia
• Retinal ischemia
• Orchitis

Giant cell arteritis and polymyalgia rheumatica

Clinical manifestations

• M/c vasculitis >50 yrs; usually affects females.
• Systemic: fever, fatigue, malaise
• Headache (temporal artery), visual disturbances (ophthalmic artery), and jaw claudication.
• Polymyalgia rheumatica
  • Flu-like symptoms with joint and muscle pain. 
  • Morning stiffness affecting the shoulders and hips.
  • Does not cause muscular weakness – b/c PMR is an inflammatory disorder of the proximal joints, bursae, and tendons; the muscle itself is unaffected.
  • ?ESR, ?CRP, normal CK
• Normochromic anemia
• Serios complications
  • Vision loss (~20%) – sudden, painless, and irreversible
  • Thoracic aortic aneurysm (10%-20%) – in 10 years median.

Pathology and pathogenesis

Temporal artery biopsy

• Inflamed vessel wall with giant cells and intimal fibrosis without distinct granulomas.
• Lesions are segmental; diagnosis requires biopsy of a long segment of vessel, and a negative biopsy does not exclude disease.
• Biopsy findings remain detectable up to 30 days after start of treatment.

Treatment

• Since GCA can rapidly progress to result in permanent vision loss, treatment should be initiated immediately and should not be delayed while awaiting biopsy
• PMR only
  • Low-dose glucocorticoids (eg, prednisone 10-20mg daily)
• GCA
  • Intermediate- to high-dose oral glucocorticoids (eg, prednisone 40-60mg daily)
• Active ocular involvement
  • eg, amaurosis fugax, vision blurring
  • Pulse-dose parenteral glucocorticoids (eg, methylprednisolone 500-1,000mg daily)

Takayasu Arteritis

Classically involves the aortic arch at branch points
Presents in adults < 50 years old (classically, young asian females)
Visual and neurologic symptoms with a weak~absent pulse in the upper extremity. ESR is elevated.
Treatment is corticosteroids.

Clinical features

• Fever, malaise, arthralgia, night sweats 
• Vascular symptoms
  • Decreased bilateral brachial and radial pulses (so-called pulseless disease)
  • Syncope, angina pectoris
  • Impaired vision
  • Movement-induced muscular pain in one or more limbs
  • Raynaud phenomenon
  • Bilateral carotid bruits
  • Hypertension 
• Skin manifestations
  • Erythema nodosum
  • Urticaria

IgA vasculitis (Henoch-Schönlein; HSP)

Epidemiology

• Vasculitis due to IgA immune complex deposition
• usually occurs following an URI
• M/c vasculitis in children (esp. in age 2~8)

Clinical manifestations

• Lower extremity
  • Palpable purpura
  • Arthralgia/arthritis
  • ?? scrotum, ??, but ??/trunk? X
• Gastrointestinal
  • Abdominal pain/intussusception
  • Hemorrhage
• Renal disease
  • Hematuria (IgA nephropathy) ? RBC casts
  • Mild proteinuria
  • Normal to ?Cr (unlike adults)

Treatment

• Disease is self-limited and resolves as the circulating immune complexes clear.
• But may recur
• Supportive
  • ????, ???? for most patients.
• If severe
  • Prednisone. ???, ? ???? ?? X ??? ?? ????.

Cryoglobulinemic vasculitis

• Cryoglobulins
  • Cold-precipitable monoclonal or polyclonal immunoglobulins (IgM) positive rheumatoid factor
  • Leading to endothelial injury and end-organ damage.
• 5% of patients with chronic hepatitis C will develop cryoglobulinemic vasculitis

	Type I	Mixed (type II & III)
Disease associations	Lymphoproliferative or hematologic (eg, multiple myeloma)	Chronic HCV, HIV, SLE
Clinical findings	Asymptomatic Hyperviscosity (eg, blurry vision) Thrombosis (eg, Raynaud phenomenon) Skin: livedo reticularis, purpura	Fatigue, arthralgias, HTN, renal/liver involvement Pulmonary (dyspnea, pleurisy) Skin (palpable purpura, LCV)
Complement levels	Normal	Low C4

Management

• Asymptomatic cryoglobulinemia does not require treatment
• NSAIDs
  • For arthralgia and fatigue
• Plasmapheresis and immunosuppression
  • For patients with rapidly progressive or life-threatening courses.
• Pegylated interferon-alpha (INFg) combined with ribavirin
  • In patients with cryoglobulinemia associated with HCV infection, CML

Single-organ vasculitis

Idiopathic cutaneous vasculitis

Triggered by infections, medications, inflammatory conditions, or malignancy.
Nonblanching violaceous ptechiae that can calesce into palpable purpura.

Primary central nervous system vasculitis

Beh?et?s disease

Cogan?s syndrome

Kawasaki?s disease

Classically affects Asian children < 4 years old

Presents with nonspecific signs including fever, conjunctivitis, erythematous rash of palms and soles, and enlarged cervical lymph nodes

Coronary artery involvement is common and leads to risk for (1) thrombosis with myocardial infarction and (2) aneurysm with rupture.

Treatment is aspirin and IVTG; disease is self-limited.

Polyangiitis overlap syndromes

Secondary vasculitis

Drug-induced vasculitis

Serum sickness, and serum sickness-like reactions

• Etiology
  • Heterologous proteins
    • Chimeric monoclonal antibodies
    • Nonhuman immunoglobulins
  • Nonprotein drugs ? serum sickness-like reactions
    • e.g., penicillin, cefaclor, and TMP-SMX.
• Pathophysiology
  • Type III hypersensitivity; immune complex? endothelium? ??. (2? vasculitis)
• Clinical manifestations
  • ?? self-limited.
  • Fever, urticaria, skin rash, polyarthralgias, and lymphadenopathy 7?10 days after primary exposure.
  • Most of the manifestations are not due to a vasculitis; however, occasional patients will have typical cutaneous venulitis that may progress rarely to a systemic vasculitis.
    • Low C3 and C5 complement levels.
  • ???
    • 1???? 7-10?
    • 2???? 2-4?
• Lab findings
  • Nonspecific hypocomplementemia
  • ?ESR, CRP
• Treatment
  • Remove/avoid offending agent
  • Supportive care
  • Steroids or plasmapheresis if severe.