Page 832 - Clinical Immunology_ Principles and Practice ( PDFDrive )

804 Part SIX Systemic Immune Diseases

for several years, and it is the standard of care for KD, but its steroid doses remain high after 6 months. Interstitial lung disease
use in AAV has been limited. An initial study suggested benefit, (nonspecific interstitial pneumonia) is reported in around 20%
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but the likelihood is relatively short-term control. Plasmapheresis of Japanese patients, especially those with MPA. This is a higher
has been available for several decades. It is not entirely clear how prevalence than that seen in other populations and may reflect
it works; there are many theories suggesting the removal of genetic and environmental differences unique to Japan. Chronic
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circulating immune mediators is effective in reducing inflam- neuropathy occurs in 15% of patients with AAV and can be
mation. It has been successful for rescue therapy in patients with very distressing for patients. Upper airway disease generally
very aggressive AAV or anti-GBM disease. The MEPEX trial continues to cause long-term problems in 65% of patients with
demonstrated that it was able to reduce renal dysfunction in GPA because of chronic mucosal damage causing symptoms of
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patients with severe AAV. However, the long-term follow-up chronic nasal congestion, discharge, and discomfort. Symptom
of the MEPEX trial demonstrated that the difference between relief is only partially successful in alleviating these problems.
patients treated with plasma exchange and those given methyl- The risk of cardiovascular disease among patients with small-
prednisolone pulses (both as adjunct treatment alongside vessel vasculitis is probably around four times greater in patients
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cyclophosphamide and steroid) did not last. It has been suggested with AAV compared with the general population. The risk of
this is accounted for by the fact that many patients with severe cardiovascular events is around 14% within 5 years of diagnosis,
renal disease had already developed irreversible changes to their especially in older patients who have baseline hypertension and
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kidneys and that renal dysfunction would have been secondary MPO antibodies. Cancer is associated with the presence of
to damage rather than active disease. A new study is underway small-vessel vasculitis. It may predate as well as occur at the same
to test the role of plasma exchange in patients with less severe time as diagnosis or develop subsequently, but it is recognized
renal disease, but results are not yet available. Plasmapheresis is as a risk among patients treated with immunosuppressive and
effective in conjunction with antiviral therapy and steroids in cytotoxic agents. Cancer of the bladder particularly has been an
the management of hepatitis B–related PAN. established risk arising from treatment with cyclophosphamide
for many years; the original data from the 1970s suggested up to
OUTCOMES 33-fold increased risk of bladder cancer among patients treated
with cyclophosphamide for vasculitis compared with background
The majority of patients have a successful initial outcome. Either controls. However, this risk has been reduced with the use of more
the condition is self-limiting in the case of more isolated forms limited courses of cyclophosphamide (typically 3–6 months dura-
of skin vasculitis or the initial immunosuppressive therapy is tion) and particularly with use of intermittent cyclophosphamide
successful. Over 94% of patients with generalized AAV would delivery. In a recent large series from the European Vasculitis
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expect to survive the first 18 months, whereas patients with Study Group (EUVAS), the only increased risk of cancer was for
more severe disease, especially with significant renal impairment, nonmelanoma skin cancer, and this may also have reflected the
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have a mortality of around 25% after 2 years. This contrasts use of azathioprine as well as use of cyclophosphamide. Shang
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with >80% likelihood of dying without adequate treatment. et al. showed that in a meta-analysis of over 2500 patients,
However, with current therapy, 5-year survival figures suggest the standardized incidence rate of late-occurring malignancies,
around 25–30% mortality among AAV-affected patients. 84 particularly nonmelanoma skin cancer, leukemia, and bladder
The bigger problem, however, is morbidity. The quality of cancer, was 1.74 (95% CI = 1.37–2.21). We advise all of our
survival for most patients with multiorgan disease is compli- patients to wear sun protection.
cated by episodes of relapse in 50–70% of cases and low-grade The ability to work is significantly affected by AAV; among
grumbling disease, which never quite goes into full remission 410 patients interviewed, 26% of those of working age were
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in up to a third of cases. This is added to the comorbidity classified as work disabled. The strongest influences on this
experienced by older patients, usually a combination of vasculitis- outcome were fatigue, depression, high levels of damage (measured
related damage, steroid-induced side effects, and the long-term using the VDI), and being overweight. Patients’ functional
consequences of immunosuppressive agents. In the first year of outcome can be variably affected by vasculitis and its treatment.
diagnosis, the most likely cause of mortality is active vasculitis Patients report impairment of function as measured by using
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or infection, the latter being a surrogate measure of the severity generic tools, such as EQ-5D or the short form 36. The impair-
in immunosuppressant therapy required to control the disease. ment is similar to that found in other chronic diseases. Physical
Long-term adverse outcomes in vasculitis can be measured functions tend to be more affected than mental functions,
using a structured VDI (see Assessment section above). One of especially in older patients with evidence of neurological involve-
the most important outcomes is the development of end-stage ment, usually peripheral neuropathy. Functional outcome is not
renal failure and the requirement for dialysis. It is likely that this directly correlated to disease activity, although in a Japanese
is significantly reduced as a result of effective therapy given within cohort, 18 months after initiation of therapy, many aspects of
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the first 4 months of diagnosis. Transplantation is successful function had started to improve. One of the problems of
in patients with AAV, and these patients should be offered this determining long-term outcomes in patients with vasculitis is
treatment. Ten-year survival rates (32.5%) are similar to those the compounding effect of the very intensive immunosuppressive
reported for other patients without diabetes receiving a kidney therapy required to control disease. Over the last 3 decades, we
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transplant. The immunosuppressive regimens used for maintain- have seen dramatic shift away from long course cyclophosphamide
ing the transplant (Chapter 81) are often sufficient to keep the toward short courses of intermittent dose therapy, but we are
vasculitis in remission, but there is a need for ongoing review. now witnessing an era when targeted biological therapies are
Infection is a significant concern, especially in the early course able to take the place of cyclophosphamide. Therefore eliminating
of disease when potent treatment being commenced, especially the use of cyclophosphamide altogether in some patients may
high doses of steroids. The risk of serious infection requiring reset potential future outcomes. If this is coupled with a reduced
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hospitalization is very high in the first year, especially if the use of glucocorticoid therapies and maintaining better disease