Page 49 - The Vasculitides, Volume 1: General Considerations and Systemic Vasculitis

Overview of Primary and Secondary Vasculitides 25

Immune Complex Vasculitis

The foundations for IC-mediated or hypersensitivity vasculitis were conceptualized by
Zeek [73, 74] between 1948 and 1952, as an immunologic response to antigenic material
associated with clinically evident purpura, and small vessel inflammation affecting arterioles,
capillaries, and post-capillary venules. It was likened by Zeek [75] to the anaphylactoid
Arthus reaction produced by the experimental injection of horse serum into rabbits [76].

IgA Vasculitis (Henoch-Schönlein Purpura)
Children with HSP were described by Gairdner [77] with anaphylactoid purpura

including one who developed rash, colic, melanotic stools, intussusception, and hematuria
following by a typical exanthema and fatal convulsion. Postmortem examination showed
scattered cortical hemorrhages associated with cerebral necrotizing arteriolitis. Levitt and
Burbank [78] described the clinicopathological findings in two previously non-allergic
patients with recurrent fatal attacks of HSP after injection of penicillin and ingestion of
strawberries respectively that included glomerulonephritis alone or with systemic arteriolitis.
The findings of IgA deposits in cutaneous blood vessel walls and in glomerular mesangial
biopsies of patients with HSP and IgA nephropathy (IgAN) [79, 80] were circumstantially
convincing enough to substitute the term IgAV for HSP. IgAV/HSP is the commonest
vasculitis in children. The 1990 ACR criteria [81] for the identification of HSP included age
less than or equal to 20 years at disease onset, palpable purpura, acute abdominal pain, and
tissue biopsy showing granulocytes in the walls of small arteries or venules. The presence of
any two or more of these criteria distinguished 85 patients who were diagnosed as having
HSP by physicians who submitted cases for the vasculitis criteria compared to 722 patients
diagnosed with other forms of vasculitis, arriving at sensitivity of 87.1% and specificity of
87.7%. The addition of gastrointestinal bleeding in a classification tree format respectively
increased sensitivity to 89.4% and specificity to 88.1%. The EULAR/PRINTO/PReS
classification criteria [3] which recognizes the contribution of IgA deposits, differs in the
mandatory finding of purpura with predominance in the legs, and the presence of one of the
four following features: diffuse abdominal pain, arthralgia or arthritis; a biopsy showing
predominant IgA deposits, and renal involvement including proteinuria and hematuria
Derived from the analysis of 827 patients in the database, the calculated sensitivity,
specificity for the clinical and laboratory findings in between the consensus panel and specific
definition were respectively 100% and 87%. Peru and colleagues [82] studied 254 children
with IgAV/HSP between 2003 and 2006 with a distribution of skin, joint, GI and renal
manifestations respectively of 100%, 66%, 56% and 30%. The disorder commences with
fever and palpable purpura, although early lesions can be urticarial. Arthralgia and abdominal
pain precede, accompany or follow the rash. Melena is common as are signs of peritonitis.
Proteinuria and hematuria are of variably severity and renal pathology may be of a mild
glomerulitis to necrotizing or proliferative glomerulonephritis. Ozen and coworkers [3] noted
palpable purpura, commonly in crops with lower limb predominance in 89% of patients,
arthritis or arthralgia in 78%, diffuse abdominal pain in 60%, proteinuria and hematuria
combined in 33%; and IgA deposition in 10% of children. The treatment of IgAV/HSP
remains empiric and largely supportive, with conflicting conclusions in retrospective and
uncontrolled case series of immune suppression in severe HSP nephritis [46]. Extrarenal
manifestations can be managed by symptomatic treatment.

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