Pocket Medicine: The Massachusetts General Hospital Handbook of Internal Medicine (114 page)

biopsy → microgranulomas, fibrinoid necrosis and thrombosis of small arteries and

veins with eosinophilic infiltrates

• Treatment: high-dose
corticosteroids
+ cyclophosphamide if severe
Renal-limited vasculitis

• Small vessel pauci-immune vasculitis causing RPGN w/o other organ involvement • Dx studies: 80%
ANCA (MPO > PR3); biopsy with pauci-immune GN ± granulomas • Treatment identical to that for GPA/MPA

IMMUNE COMPLEX–ASSOCIATED SMALL-VESSEL VASCULITIS

Henoch-Schönlein purpura (HSP)

•
IgA-mediated
vasculitis w/ predilection for
skin
,
GI tract
and
kidneys
• Epidemiology:
>
, children > adults, onset in winter > summer • May develop after upper respiratory tract infection (esp. strep) or drug exposure • Clinical manifestations

palpable purpura
on extensor surfaces (lower extremity first) & buttocks

polyarthralgias
(nondeforming) esp. involving hips, knees, & ankles

colicky
abdominal pain
± GIB or intussusception

nephritis ranging from
microscopic hematuria
& proteinuria to ESRD

• Dx studies:
skin bx w/ immunofluorescence
→
leukocytoclastic vasculitis
w/
IgA

and
C3
deposition in vessel wall; renal bx → mesangial IgA deposition

• Treatment: often self-limiting over 4 wk; steroids ± DMARDs for renal or severe disease
Cryoglobulinemic vasculitis (see “Cryoglobulinemia”)

Connective tissue disease–associated vasculitis

• Small vessel vasculitis a/w
RA
,
SLE
or
Sjögren’s syndrome
• Clinical manifestations

distal arteritis: digital ischemia, livedo reticularis, palpable purpura, cutaneous ulceration

visceral arteritis: pericarditis and mesenteric ischemia

peripheral neuropathy

• Dx studies: skin/sural nerve bx, angiography, EMG; ↓ C′ in SLE;
RF or anti-CCP in RA • Treatment: steroids, cyclophosphamide, MTX (other DMARDs)
Cutaneous leukocytoclastic angiitis

• Heterogeneous group of clinical syndromes due to
immune complex deposition
in capillaries, venules and arterioles; includes
hypersensitivity vasculitis

• Overall the most common type of vasculitis • Etiologies

drugs: PCN, ASA, amphetamines, levamisole, thiazides, chemicals, immunizations

infections: Strep, Staph, endocarditis, TB, hepatitis

malignancy (paraneoplastic)

• Clinical manifestations: abrupt onset of
palpable purpura
and
transient arthralgias
after exposure to the offending agent; visceral involvement rare but can be severe • Dx studies: ↑ ESR, ↓ complement levels, eosinophilia; ✓ U/A;
skin biopsy
→ leukocytoclastic vasculitis
w/o
IgA deposition
in skin (to distinguish from HSP); if etiology not clear, consider ANCA, cryoglobulins, hepatitis serologies, ANA, RF

• Treatment: withdrawal of offending agent ± rapid prednisone taper
Behçet’s syndrome
(
Curr Rheum Opin
2010;12:429)
•
Systemic vasculitis
affecting all vessel sizes, a/w
oral and/or genital ulcers
• Epidemiology: usually young adults (25–35 y); a/w HLA-B51 in areas of highest prevalence on the old Silk Road (Turkey, Middle East and other Asian countries) • Classification criteria (#1 + ≥2 others is 91% Se & 96% Sp; Lancet 1990;335:1078) 1. recurrent
oral aphthous ulceration
(≥3× in 1 y, usually 1st manifestation) 2. recurrent
genital ulceration
(labia in females, scrotum in males) 3.
eye
lesions: uveitis, scleritis, retinal vasculitis, optic neuritis (may threaten vision) 4.
skin
lesions: pustules, papules, folliculitis, erythema nodosum (scarring) 5.
pathergy test (prick forearm w/sterile needle → pustule) (not sensitive in Caucasians) • Other clinical manifestations: most recur but are not chronic

arthritis: mild, ± symmetric, nondestructive, involving knees and ankles

neurologic: usually involvement of midbrain parenchyma; peripheral neuropathy rare

vascular: superficial or deep vein thrombosis (25%); arterial stenosis, occlusion and aneurysm can also occur; low incidence of thromboembolism

• Dx studies: ↑ ESR/CRP; ulcer swab to r/o HSV; ulcer bx nonspecific; ophtho eval if sx • Treatment (Rheumatology 2007;46:736; Ann Rheum Dis 2008;67:1656 & 2009;68:1528)

mucocutaneous

mild:
topical steroids
,
colchicine
(esp. for erythema nodosum), dapsone

severe: oral steroids, steroid-sparing agents

arthritis: NSAIDs, colchicine, steroids, steroid-sparing agents

ocular:
topical and/or systemic steroids
± steroid-sparing agents

steroid-sparing: AZA, anti-TNF, CYC (large vessel and CNS ds), CsA, MTX, IFNɑ-2A

venous thrombosis: steroids and anticoagulation (careful if aneurysm present)

IGG4-RELATED DISEASE

Definition & etiology
(
NEJM 2012;366:539)

• Responsible for
tumor-like inflammatory lesions
of nearly every organ/tissue • Etiology unclear: ? autoimmune; unclear role of IgG4 Ab; may have h/o atopy
Clinical manifestations

• Commonly pancreatitis, aortitis, cholangitis, sialadenitis, orbital structures, retroperitoneal fibrosis • Multiple lesions may be present synchronously or metachronously
Diagnosis
(Mod Pathol 2012;25:1181)
•
Biopsy
w/ specific histopathology & immunohistochemistry findings: lymphoplasmacytic infiltrate w/ significant IgG4+ plasma cell infiltrate, fibrosis, obliterative phlebitis • ↑ serum IgG4 in 40%; not specific seen in GPA, bronchiectasis, etc (Modern Rheum 2012;22:419)
Treatment

•
Prednisone
vs. rituximab (Medicine 2012;91:57)

CRYOGLOBULINEMIA

Definition & types
(Lancet 2012;379:348)
•
Proteins that precipitate on exposure to the cold and redissolve on rewarming
, characterized by their composition •
Cryoglobulins
=proteins that precipitate from serum and plasma when cooled • Distinguish from cryo
fibrinogenemia
=proteins (eg, fibrin, fibrinogen) that precipitate only from plasma; found in autoimmune dis, malignancies, infxns; unclear clinical significance