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9474
What is Granulomatosis with Polyangiits (GPA)?
GPA is systemic, meaning that the efect of infam-maton
can be present in the entre body. It afects the upper
(sinuses and nose), and lower (lungs), respiratory system
and frequently involves the kidneys, lungs, eyes, ears,
throat, skin and other body organs. For unclear reasons,
blood vessels in afected areas may become infamed, and
clusters of certain cells (granulomas) may occur. Patents
who do not have involvement of the kidney, brain or gut
are said to have Limited GPA. However, using the term
limited has become unpopular because certain forms
of the illness may stll be very serious even though these
other organs are not involved.
As awareness of GPA grows, more patents are diagnosed
in the early stages of the disease when efectve treatment
can result in early remission and prevent organ failure.
Who gets GPA?
GPA is not a common disease, and can occur at any age.
It most ofen occurs in the 4th and 5th decade of life.
Patents are divided equally between males and females.
It appears that Caucasians are far more commonly
afected than other racial groups.
Symptoms
The onset of GPA may be slow moving with few
symptoms, or rapid and severe.
About 90% of patents have symptoms of a cold,
runny nose or sinusits that fail to respond to the usual
therapeutc measures and last considerably longer than
normal upper respiratory tract infectons.
Not all patents with GPA experience all symptoms,
and the severity of the disease is also diferent for each
patent. If any of the symptoms below persist, consider a
possible diagnosis of GPA and arrange to have a complete
evaluaton, including health history, physical exam,
laboratory studies, including a urinalysis and an ANCA test.
arthritc joint pain
blood in urine (which may or may not be indicated by
a change in urine color)
cough (with or without the presence of blood)
fever
infammaton of the ear with hearing problems
infammaton of the eye with vision problems
lack of energy
loss of appette
nasal membrane ulceratons and crustng
night sweats
numbness of limbs
pleurits (infammaton of the lining of the lung)
rash and/or skin sores
saddle-nose deformity
weakness, fatgue
weight loss
Diagnosis
The diagnosis of GPA is established by clinical and
laboratory fndings such as the ANCA blood test, other
blood and urine tests, x-rays, and tssue biopsy, if needed.
Antneutrophil Cytoplasmic Antbody (ANCA) is an
abnormal protein. ANCA is part of a large family of
molecules called immunoglobulins, (including antbodies),
that are made by all animals and are normally intended
to protect you. There are two types of ANCA: c
(cytoplasmic), and p (perinuclear). The great majority
of patents with GPA test positve for c-ANCA while a
small percentage of patents test positve for both p-and
c- ANCA. C-ANCA reacts with a normal human enzyme
contained in white blood cells (called proteinase 3 or
PR3), and has a yellow-green patern in the cell fuid called
the cytoplasm, hence the term c-ANCA. The quantty
of c-ANCA roughly correlates with disease actvity. Very
rarely, C-ANCA can be found in other diseases and even in
some normal individuals.
The c-ANCA/PR3 antbody test is a helpful diagnostc tool
that is used most efectvely when patents are thought
to possibly have GPA. A positve test is suppor-tve of
the diagnosis. However, occasionally the test is negatve
but GPA is present. Some physicians use the ANCA test
to monitor treatment and disease status. Test results
by themselves do not always indicate that the disease is
actve, so physicians cannot use them as the primary guide
to decision making about treatment. Decisions to change
treatment should be based on convincing features of GPA
disease actvity or remission, and appropriate laboratory
tests including urinalysis.
Granulomatosis with Polyangiits (Wegeners)
The immune system disease known as granulomatosis with polyangiits (GPA, formerly known as Wegeners
granulomatosis) is an uncommon disease that afects about 1 in 20,000 to 1 in 30,000 people. Symptoms are
due to infammaton that can afect many tssues in the body, including blood vessels (vasculits).
The cause of GPA is unknown. It is not contagious, and there is no evidence it is hereditary. GPA is considered
a disease of abnormal immune functon and likely is an autoimmune disease, meaning the bodys immune
system atacks its own body tssues.
contnued on reverse
Treatment
The treatment of GPA can be divided into two stages:
frstly, the inducton of disease remission, and secondly,
the maintenance of disease remission. Medicaton usually
consists of cytotoxic agents (a form of chemotherapy),
using cyclophosphamide (Cytoxan), and/or methotrexate
and/or azathioprine (Imuran), mycophenolate mofetl
(CellCept), and glucocortcoids (prednisone).
Treatment will vary based on patent symptoms, disease
actvity, organ involvement and lab test results. Patents
with kidney involvement and more severe GPA are
commonly prescribed cyclophosphamide and prednisone
as inital treatment. Ideally, the use of cyclophosphamide
will be limited to a three to six month period and then
replaced, based on kidney functon, by methotrexate
or azathioprine or mycophenolate mofetl. Recently,
rituximab (Rituxan) was approved for treatng GPA.
Patents with milder forms of GPA are commonly pre-
scribed methotrexate and prednisone. These medicatons
will be reduced over tme, and even eliminated, if the
patent remains in a stable remission. Patents with GPA
may also be prescribed calcium supplements and other
medicatons to prevent osteoporosis from extended
prednisone use. Many patents will also be prescribed
the antbiotc trime-thoprim/sulfamethoxazole (Bactrim,
Septra, others) to help prevent lung infectons caused by a
dangerous bug called pneumocysts jiroveci pneumonia
(also known as PCP). In additon, there is some evidence
that this antbiotc, used cautously, can have the benefcial
efect of reducing relapses and upper airway infectons.
Efectve treatment should include a team approach
with medical specialists according to the patents organ
involvement. It is common for a patent with GPA to
regularly see the following kinds of specialist doctors:
Nephrologist (Kidney), Otolaryngologist (Ear, Nose/Sinus,
Throat), Ophthalmologist (Eye), Pulmonologist (Lung),
and almost always a Rheumatologist or Immunologist.
Other specialists are involved as needed.
To help manage their disease, patents with GPA must
maintain a good relatonship with their doctors and
understand and follow instructons carefully. Many
patents fnd it useful to maintain a diary listng medica-
tons, test results and notes on any symptoms they are
experiencing. These notes should be reviewed during a
patent/doctor appointment. It is imperatve to have a
close, contnuous and long-term doctor follow-up, even
when in remission and of therapy, as relapses or fare-
ups are common and occur in over 50% of patents as tme
goes on.
Remission
There is no cure for GPA, but early diagnosis and proper
treatment is efectve in reducing the symptoms of
the disease and improving the quality of life and life
expectancy of patents who sufer from it. The disease can
be brought into remission with complete absence of all
signs of disease.
Long-term remission can be induced and maintained with
medicatons, close management and regular lab tests
to help monitor the disease. Treatment can produce
symptom-free intervals of 5 to 20 years or more. Some
patents will achieve a drug-free remission. However,
relapses are common but can be caught at their earliest
and most treatable stage, for most patents, by paying
atenton to patent symptoms and lab tests. Patents with
GPA who are in remission must not hesitate to see a doctor
if any GPA symptoms return or if they are not feeling well.
The past, present and future
We believe GPA is not so rare, but rarely diagnosed. In
areas where doctors are aware of the disease, more
patents are diagnosed and treated. Early diagnosis and
treatment are essental to improve patent outcomes and
prevent organ failure.
GPA treatment has come a long way. In 1958, patents
with GPA had an 82% mortality rate at one year, with an
average patent survival of fve months. During the early
1970s, innovatons in treatment pioneered by the Natonal
Insttutes of Health in Bethesda, Maryland changed the
course of GPA treatment remarkably by introducing the use
of cyclophosphamide and prednisone in combinaton. This
new approach improved survival rates dramatcally to over
90%. However, treatment side efects and drug toxicity
presented new challenges. The availability of rituximab
is a further advance in the treatment of GPA. Today,
drug toxicity is managed more carefully and long-term
remissions are possible. Some patents are able to lead
relatvely normal lives and have been in remission for 20+
years afer treatment!
Research into new medicatons, treatment optons and
the cause of GPA are being conducted at leading medical
centers throughout the world. Of course, more needs to
be done and with your help quicker GPA diagnosis and
even beter, and less toxic, treatments will become a
reality.
The Vasculits Foundaton gratefully acknowledges
Dr. Eric L. Mateson from the Mayo Clinic, Rochester, MN, for
his expertse and contributon in compiling this informaton.
This brochure was made possible by an educatonal grant
from Genentech, Inc., and Biogen Idec.
Granulomatosis with Polyangiits (Wegeners) contnued
www.VasculitisFoundation.org 800.277.9474