Pathophysiology and clinical manifestations of immune complex vasculitides

Abstract

Immune complex (IC) vasculitides present inflammations of vessel walls associated with perivascular deposition of immunoglobulins (Igs), mostly ICs. They encompass systemic and skin-limited variants of IgA vasculitis (IgAV), cryoglobulinemic vasculitis (CV), rheumatoid, lupus, and hypocomplementemic vasculitides, serum sickness cutaneous IgM/IgG (non-IgA) vasculitis, and recurrent macular (hypergammaglobulinemic or exertion-induced) vasculitis. Serum sickness and CV fulfill the criteria of a type III hypersensitivity immune reaction as large lattices of the IC precipitate at vessel walls and activate polymorphonuclear neutrophils (PMNs). Immunoglobulin-A vasculitis differs with regard to the causes of perivascular deposition of ICs since here many IgA1 molecules are hypoglycosylated (Gd-IgA1), which appears to facilitate their perivascular deposition in skin and mesangium (via e.g. CD71). The reasons for increased generation of immunoglobulins or formation of IC and their perivascular deposition in either skin or systemic organs are different and not fully explored. A common denominator of OC vasculitides is the activation of PMNs near the vessel wall via Fcy or Fcα receptors. Acute episodes of IgAV additionally require PMNs to become preactivated by IgA1 or by IC already in circulation. This intravascular priming results in increased adherence and subsequently vessel-destructive NETosis when they encounter IgA deposited at the vessel walls. Binding of IgA1 to PMNs in blood stream is associated with increased serum levels of hypogalactosidated IgA1. The characteristic clinical picture of IgAV (and also of so-called IgG/IgM vasculitis) comprises palpable or retiform purpura with a clear predilection for lower legs, probably due to stasis-related reduction in blood velocity, while in other IC vasculitides, additional factors influence the sites of vasculitides. Our knowledge of distinct forms and different pathophysiological pathways of IC vasculitides may lead to in efficacious or targeted therapies. Antibodies to complement components or intestinal budesonide for IgAV are promising agents (the latter suppresses the pathophysiologically related IgA nephropathy by reducing the generation of mucosal IgA.

Kutane Vaskulitiden: Relevant für den dermatologischen Alltag

“…Als seltenes Krankheitsbild beläuft sich die geschätzte jährliche Inzidenz auf etwa 48 Fällen pro 1 Million. Eine Prädominanz des weiblichen Geschlechts sowie eine vorwiegende Lokalisation auf die Unterschenkel wurde in einer retrospektiven Analyse von 41 Patienten beobachtet [12].…”

“…Bei anhaltenden Beschwerden könnten topische Glukokortikosteroide oder NSAID in Betracht gezogen werden [14]. ähnlich den Behandlungsansätzen bei der IgA-Vaskulitis [12].…”

“…3). Des Weiteren fällt auf, dass Patienten im Allgemeinen nicht über sig-nifikante Beschwerden wie starke Schmerzen oder erhebliche Beeinträchtigungen des allgemeinen Gesundheitszustands berichten[12].DiagnostikDurch eine ausführliche Anamnese, körperliche Untersuchung unter Berücksichtigung der Ausbreitung der Hautveränderungen oberhalb der Gürtellinie sowie möglicher Bauch-oder Gelenkschmerzen, Probebiopsien für die Histologie inklusive direkter Immunfluoreszenz sowie eine Laboruntersuchung, die i. d. R. ein Blutbild mit Nieren-und Leberparametern, LDH, CRP sowie eine Urinanalyse beinhaltet, soll eine mögliche Systembeteiligung sowie das Vorliegen einer IgA-Vaskulitis ausgeschlossen werden[12].HistologieDas feingewebliche Bild unterscheidet sich nicht von der IgA-Vaskulitis. Therapie Die Hautveränderungen einer Non-IgA-Vaskulitis heilen überwiegend spontan innerhalb von 3-4 Wochen ab, wobei gelegentlich Hämosiderin-Hyperpigmentierungen verbleiben können.…”

Complement

“…Low circulating C4 and/or C3 is seen in a minority of patients with small vessel vasculitis. However, in most cases other than AAV, the underlying cause is still thought to be immune complex deposition featuring predominantly IgG or IgA (17,23), for which local complement activation may not be essential to initiate inflammation but is highly likely to contribute. Although IgA does not activate the classical pathway through C1q, the prominent glomerular deposition of C3 and sometimes reduction in serum C3 in patients with IgA nephropathy (24) suggest that complement plays a role in IgA vasculitis as well.…”

The Role of Neutrophils in ANCA-Associated Vasculitis: The Pathogenic Role and Diagnostic Utility of Autoantibodies

“…2. Vasculitis associated with immunologic complexes-anti-glomerular-basementmembrane-(anti-GBM) disease, cryoglobulinemic vasculitis (CV), IgA vasculitis, and hypocomplementemic-urticarial vasculitis (HUV) [26]. The current AAV classification is presented in Table 2.…”