Page 70 - The Vasculitides, Volume 1: General Considerations and Systemic Vasculitis

46 David S. Younger

tomography and angiography; DNA and RNA, deoxyribonucleic and ribonucleic acid; ds, double-
stranded; DSA, digital subtraction angiography; ELISA, enzyme-linked immunosorbant assay;
ENF, epidermal nerve fiber; ESR, erythrocyte sedimentation rate; 18FDG body PET-CT,
Fluorodeoxyglucose positron emission tomography fused with CT; IC, HIV1, human
immunodeficiency virus type 1; HLA, human leukocyte antigen; Ig, immunoglobulin; immune
complexes; IFE, immunofixation electrophoresis; IIF, indirect immunofluorescence; dsDNA, MRI
and MRA, magnetic resonance imaging and angiography; MPO, myeloperoxidase; PCR,
polymerase chain reaction; PLP9.5, protein gene product 9.5; PR3, proteinase 3; RBC and WBC,
red and white blood cells; RF, rheumatoid factor; SPECT, single photon emission CT; T and B,
thymus and bone marrow derived cells; TB, tuberculosis; USG, ultrasonography; VDRL, Venereal
Disease Research Laboratory.

Treatment

Physicians treating vasculitides must choose the sequence and combination of available
immunosuppressant and immunomodulating therapies to induce and sustain remission and
treat relapses, recognizing the possible beneficial and adverse effects. The standard of care for
the treatment of vasculitides, notably AAV, has been evolving in response to several factors
[216]. One factor is the steady influx of multicenter, national and international randomized
clinical trials (RCT). A second factor has been large collaborative networks such as the
French (FVSG), European (EUVAS), and Italian (IVSG) Vasculitis Study Groups, and the
Vasculitis Clinical Research Consortium (VCRC) that share data. A third is the influence of
gene-wide association studies (GWAS) that have elucidated risk gene loci, single nucleotide
polymorphism (SNP) and human leukocyte antigens (HLA) in disease clusters and population
cohorts [217]. Such inherited and environmental factors, gene-gene interactions, epigenetic
factors, and other influences upon the immunopathogenesis of vasculitides have important
theoretical importance for the performance of an RCT in vasculitides subtypes, as well as the
relevance of screening studies and timing of therapy. Table 3 lists the available treatment
regimens for primary and nervous system vasculitides as reported in the literature.
The following section deals with the specific therapeutic agents employed in vasculitides.

The usefulness of corticosteroids in the treatment of systemic vasculitis has been
appreciated for over 50 years, however there has never been a randomized controlled trial
conducted to support their use. The beneficial effects of corticosteroids are attributed to a
multiplicity of effects on the cell and humoral immune system, including inhibition of
activated T-, and B-cells, APC, and leukocytes at sites of inflammation, IFN-?, induced main
histocompatibility class (MHC) class II expression, macrophage differentiation, pathogenic
cytokine expression, complement interactions, and immunomodulation of cell adhesion
molecules. Patients receiving long term corticosteroid therapy for vasculitis should be
monitored closely for hypertension, fluid retention, glucose intolerance, cataracts, myopathy,
avascular necrosis, osteoporosis, infection, gastric and duodenal ulcers, and psychosis, and
followed empirically for the need of short acting insulin coverage as needed, physiotherapy,
calcium supplementation, and bone densitometry.

The effectiveness of a daily oral regimen of 2 mg/kg/day or oral cyclophosphamide with
prednisone in GPA served as a template for the treatment of virtually all types of systemic
vasculitis for decades [49], and together they remained the standard treatment for inducing
remission in virtually all forms of potentially fatal systemic vasculitis until 2010 when Stone

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