Page 67 - The Vasculitides, Volume 1: General Considerations and Systemic Vasculitis

Overview of Primary and Secondary Vasculitides 43

serum IgG4 levels with progression to autoimmune pancreatitis, and Stone and coworkers
[206] described IgG4-related thoracic aortitis with a media-predominant pattern of aortic wall
infiltration and marked elevation of serum IgG4 levels, unequivocally linking IgG4-RD with
thoracic lymphoplasmacytic aortitis.

Color-Doppler sonography, MR combined with MRA and CTA, which adequately
visualize the aortic wall and lumen, combined with FDG PET to detect increased uptake by
metabolically active cells including inflammatory cells infiltrating the vessel wall, are
essential in the assessment of the extent and severity of the various forms of aortitis including
IgG4 types. The histopathologic analysis of biopsy specimens has been the cornerstone of the
diagnosis of IgG4-RD.

A 2012 consensus statement on the pathology of IgG4-RD by Deshpande and colleagues
[207] proposed a terminology scheme for the diagnosis of IgG4-RD based upon the
morphological appearance and tissue IgG4+ plasma cell counts in biopsy tissue. Three
histopathological features associated with IgG4-RD included a dense lymphoplasmacytic
infiltrate, fibrosis arranged at least focally in a storiform pattern, and obliterative phlebitis in
morphological specimens. The majority of cells were T-cell with scattered B-cells, and an
essential component of plasma cells with occasional eosinophils and macrophages. The level
IgG4 antibody, which represents less than 5% of the total IgG in healthy individuals is tightly
regulated and has a unique structure and functional property. It undergoes half antibody
exchange in vivo resulting in recombined antibodies composed of two different binding
specificities. Their production is driven in part by Th2 cytokines that mediate allergic
reactions and IgE production. It does not activate complement pathways and has reduced
effector function relative to other IgG subtypes. It remains unclear as to whether IgG4
directly mediates the disease process or reflects a protective response induced by
anti-inflammatory cytokines, making it simply a valuable biological marker of IgG4-RD.

A Japanese consensus management guideline [208] suggested the initiation of oral
prednisolone for induction of remission at a dose of 0.6 mg per kilogram per day for 2 to 4
weeks, with tapering by 5 mg every 1 to 2 weeks based on clinical manifestations,
biochemical blood tests, and repeated imaging, to a maintenance dose of 2.5 to 5 mg per day
for up to 3 months. Re-administration of corticosteroids is advised for treating relapses.
Treatment with azathioprine, mycophenolate mofetil and methotrexate can be used as
corticosteroid sparing agents or as remission-maintenance drugs after corticosteroid-induced
remissions. Patients with recurrent or refractory disease and B-cell depletion may be
considered for rituximab [209].

Nonsystemic Peripheral Nerve Vasculitis

Vasculitic neuropathy is a heterogeneous disorder that presents in the setting of systemic
vasculitis, but in some patients, necrotizing vasculitis may remain clinically and
pathologically restricted to the PNS, affecting peripheral nerve and muscle tissue, analogous
to primary CNS vasculitis, which is recognized by the 2012 Revised CHCC [1] as a SOV and
not just a limited expression of one of the systemic vasculitides. The Peripheral Nerve Society
[210] established guidelines for the classification, diagnosis, investigation, and
immunosuppressant treatment of NSPNV. There have only been a few postmortem studied
patients with NSPNV to justify the entity. Kernohan and Woltman [19] reported a 54-year-old

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