Page 828 - Clinical Immunology_ Principles and Practice ( PDFDrive )

800 Part SIX Systemic Immune Diseases

Immunosuppressants given to patients can significantly improve point each); with 15–19 major items and 19–23 minor items,
disease control but may increase the risk of malignancy. The the range of sores is 0–76. The PVAS was developed as a pediatric
continued use of high doses of glucocorticoid therapy contrib- version of the BVAS, but validated in children with vasculitis
utes to hypertension, diabetes, heart diseases, osteoporosis, and and demonstrated to be effective at discriminating different
infection. disease states and is increasingly used as a research tool in pediatric
It is therefore obvious that careful evaluation of a patient’s vasculitis.
status is required throughout the course of disease. Constant
vigilance is required to detect and manage any flare-up of disease
because the consequences of untreated inflammation of vessels
to vital organs can be severe. Although for most patients, initial KEY CONCEPtS
therapy is very successful and improvements in disease status is
obvious to the patient, the subsequent disease course can be Assessment of Disease Activity in Vasculitis
much more complicated because of comorbidities, the evolution
of disease-related damage, and morbidity caused by treatment • For small- and medium-vessel vasculitis in adults, version 3 and a
specific version of the BVAS for granulomatosis with polyangiitis (GPA)
as well as disease flare-ups. There are no suitable biomarkers are used.
that can be universally applied in small- and medium-vessel • BVAS version 3 is the most generic and applicable across different
vasculitides to determine the patient’s disease state to provide forms of vasculitis; BVAS for GPA has been specifically designed for
an evidence-based rationale for adjustment of therapy. ANCA use in GPA and contains very specific items related to that
titers fluctuate during the course of disease, and although ANCA condition.
remains a very useful diagnostic test, its value in managing • During sequential monitoring, a time frame of 3 months is recommended
so that disease activity is considered to be of most relevance during
variations in disease activity is very limited. Up to 40% of patients this time. The time frame is based on pragmatic clinical experience
have an elevation of ANCA without any new deterioration in that this is the usual time taken during which immunosuppressive
clinical state, but a recent study has shown that patients with therapy is likely to have a significant effect on active disease
renal involvement as part of their presentation are likely to have manifestations.
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relapses associated with ANCA rises. Among 166 patients with
AAV, all were positive for ANCA and 104 had renal involvement
(a mixture of PR3-ANCA and MPO-ANCA). The hazard ratio
for ANCA rises predicting subsequent relapse was 11.09 (CI
5.01–24.55), suggesting that this test may be of value in detection Damage Assessment in Vasculitis
of future relapse in this subset of patients. However, for the The concept of damage in patients with vasculitis is about the
majority of patients with systemic vasculitis, careful clinical permanent consequences of having vasculitis. It is an attempt
evaluation remains a cornerstone of effective disease management to measure disease burden regardless of cause. The Vasculitis
as recommended by the EULAR guidelines on management of Damage Index (VDI) is the most widely used and validated
systemic vasculitis. 78 measure for assessment of damage in vasculitis (reviewed in
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In simple terms, at the onset of the condition, disease activity Ponte et al., 2014). The VDI captures the long-term consequences
is the dominant problem, and treatment should be directed of a diagnosis of vasculitis and its treatment and associated
toward it; but over the course of time, with the development of comorbidities. Damage is defined as lasting at least 3 months
consequences of vasculitis or its treatment, there is an increasing or occurring at least 3 months ago for single time point events
component of damage or scarring and also side effects of drug (e.g., stroke or myocardial infarction) and should be recorded
therapy. Similarly, different patients function at different levels as a permanent change to the patient’s damage status. A VDI of
with the same amount of disease, or damage, and therefore the >5 points recorded within 6 months of disease carries a significant
ability to perform normal tasks is an important component of increased risk of subsequent mortality compared with a lower
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their overall condition to consider (Table 58.3). damage index at 6 months (reviewed in Ponte et al., 2014).
The primary tool used is the Birmingham Vasculitis Activity VDI is a useful index of future harm. A further development of
Score (BVAS) in adults and the Paediatric Vasculitis Activity the damage index has been the combined damage assessment
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Score (PVAS) in children (reviewed in Ponte et al., 2014). (CDA). In a comparative study with the VDI, CDA was shown
Training is recommended for assessment in the Birmingham to be inferior to it (reviewed in Ponte et al., 2014). 79
Vasculitis Activity Score (BVAS). BVAS provides a quantitative
score based on individual items, providing an effective means TREATMENT
to define the patient’s status with regards to response to therapy.
Many recent studies of different immunosuppressive agents have Once a diagnosis of small- and medium-vessel vasculitis has
made use of the BVAS either to define improvement in terms been established, treatment should be focused on patients and
of a fall in BVAS score or to define a cut-off representing active their problems rather than the specific diagnosis. Treatment for
disease, or inactive disease, or flare-up, depending on the number different forms of vasculitis may look very different, but many
of items present. Although it is subject to observer variability, aspects of different forms of vasculitis require the same therapeutic
it provides an effective means by which groups of patients can approach. Without a clear understanding of the underlying
be compared against each other and allows individual patients pathogenesis of disease, we are inevitably led by the need to
to be followed up over the course of their condition. The score suppress inflammation and reduce damage to prevent mortality
is weighted according to the organ system and the individual and improve survival. However, as well as modifying immune
manifestation, to reflect the severity of the disease. The range dysregulation, it is important to consider other aspects of the
of scores for BVAS and PVAS are 0–63. For BVAS GPA, items patient’s condition, such as comorbidities and the prevention
are divided into major (scoring 3 points) and minor (scoring 1 of future comorbidities.