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The epidemiology of Wegener's granulomatosis. Estimates of the five-year period prevalence annual mortality and geographic disease distribution from population-based data sources

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ARTHRITIS & RHEUMATISM
Vol. 39. No. 1, January 1996, pp 87-92
Q 1596, American College of Rheumatology
87
THE EPIDEMIOLOGY OF WEGENER’S GRANULOMATOSIS
Estimates of the Five-Year Period Prevalence, Annual Mortality, and
Geographic Disease Distribution from Population-Based Data Sources
MARY FRANCES COTCH, GARY S. HOFFMAN, DIANE E. YERG, GERALD I. KAUFMAN,
PAUL TARGONSKI, and RICHARD A. KASLOW
Objective. To estimate the prevalence, annual
mortality, and geographic distribution of Wegener’s
granulomatosis.
Methods. Analysis of national vital statistics data
and hospitalization data from a national survey and
from all New York State inpatient facilities.
Results. Between 1979 and 1988, 1,784 death
certificates in the United States listed Wegener’s granulomatosis as a cause of death. Nationally, an estimated
10,771 hospitalizations included Wegener’s granulomatosis among the discharge diagnoses. In New York State,
there were 978 hospitalizations among 571 individuals
with Wegener’s granulomatosis.
Conclusion. The prevalence of Wegener’s granulomatosis in the United States is approximately 3.0 per
100,OOO persons. Clear differences in the geographic
distribution of Wegener’s granulomatosis are apparent
when analyses consider rates of disease in individual
counties. Contrary to previous reports, associations
between disease exacerbations and season were not
apparent.
Presented in part at the 58th National Meeting of the
American College of Rheumatology, Minneapolis, MN, October
1994.
Supported in part by the Edward A. Lozick Foundation,
Cleveland, Ohio.
Mary Frances Cotch, PhD, Diane E. Yerg, MA, MSPH,
Richard A. Kaslow, MD, MPH: National Institute of Allergy and
Infectious Diseases, National Institutes of Health, Bethesda, Maryland; Gary S. Hoffman, MD: Cleveland Clinic Foundation, Cleveland, Ohio; Gerald I. Kaufman, PhD: New York State Department
of Health, Albany; Paul Targonski, MPH: University of Illinois
School of Public Health, Chicago.
Address reprint requests to Gary S. Hoffman, MD, Chairman, Department of Rheumatic and Immunologic Diseases, Cleveland Clinic Foundation, 9500 Euclid Avenue, A50, Cleveland, OH
44195.
Submitted for publication January 4, 1995; accepted in
revised form July 26, 1995.
Wegener’s granulomatosis is an idiopathic systemic disease that is characterized by sterile inflammatory injury to the upper and lower airways and, in
most instances, includes glomerulonephritis. The inflammatory changes typically include necrosis, granuloma formation, and vasculitis of small to mediumsized vessels. Patients in whom the disease is
unrecognized and those who are inadequately treated
often die within 1 year. Although treatment strategies
for this serious disease have been developed, little is
known about its pathogenesis or epidemiology. Epidemiologic information has been limited to reports of
isolated cases (1-4) and selected case series (5,6).
To better describe the epidemiology of this
disease in the United States, national mortality data
from 1979 through 1988 and hospitalization data from a
national sample of hospitals and from all nonfederal,
nonpsychiatric hospitals in the State of New York for
the period 1986-1990 were examined. The findings are
presented here.
MATERIALS AND METHODS
For all 3 data sources, instances of Wegener’s granulomatosis were identified using the International Classification of Diseases Ninth Revision (ICD-9-CM) code (ICD
446.4) (7).
Vital statistics data on deaths occurring in the United
States during the 10-year period from 1979 to 1988 were
obtained from all death certificates listing Wegener’s granulomatosis as the underlying or contributing cause of death.
The computerized multiple causes of mortality data tapes,
which are created and released annually by the National
Center for Health Statistics (NCHS), were used. A national
average annual mortality rate was estimated by dividing the
average number of Wegener’s granulomatosis deaths yearly
during the 10-year study period by the 1983 US population
estimate of persons ages 3 and older.
COTCH ET AL
Table 1. Statistics on individuals whose death certificate listed
Wegener’s granulomatosis, 1979-1988
Number of deaths
Year of death, no.
1979
1980
1981
1982
1983
1984
1985
I986
1987
1988
Sex, %
Males
Females
Age group, %
<20 years
20-44 years
45-64 years
65+ years
Age at death, mean years k SD
Males
Females
Ethnicity, %
White
Black
Other
Season of death, %
Spring (March-May)
Summer (June-August)
Fall (September-November)
Winter (December-February)
Autopsy performed, %*
Annual mortality rate, per million person-years
1,784
135
129
132
157
I74
I97
20 1
200
217
242
53.1
46.9
1.2
7.7
34.9
56.1
61.7
66.2
* 14.1
?
13.4
95.3
3.5
1.1
24.7
26.0
23.7
25.6
34.3
0.79
* Value represents 553 of 1,611 persons: autopsy status was not
stated on 173 death certificates.
The National Hospital Discharge Survey (NHDS) is
an annual survey of hospital discharges from nonfederal
short-stay hospitals in the United States that is conducted by
the NCHS. The survey design, sampling method, and general estimation procedures are described in detail elsewhere
(10,ll). Sampling weights incorporating survey design effects were provided by NCHS for computation of national
estimates. We report data from NCHS estimates of all
hospitalizations for the 5-year period 1986-1990 for which
Wegener’s granulomatosis was listed as a discharge diagnosis. Prevalence estimates were calculated for a 5-year period
by dividing the total estimated number of hospitalizations by
1.7 (based on estimates from the Statewide Planning and
Research Cooperative System [SPARCS] that patients with
Wegener’s granulomatosis average 1.7 hospitalizations in 5
years) and further dividing by the size of the 1990 US
population.
SPARCS of New York State routinely collects discharge and uniform billing data from all hospitalizations in
nonfederal, nonpsychiatric facilities within the state.
SPARCS was able to link these individual hospital discharge
records from 1986 to 1990, according to sex, date of birth,
medical record number, residence, and insurance information, using a previously reported and validated methodology
(8). For the present study, data on the first hospitalization
during the 5-year study period in which an individual had
Wegener’s granulomatosis listed as a discharge diagnosis
were analyzed. Period prevalence rates of Wegener’s granulomatosis were estimated as the number of first hospitalizations (1 per person) over the 5-year study period divided
by the size of the 1990 population for the entire state and,
separately, for each county of residence. The geographic
distribution of individuals with Wegener’s granulomatosis in
New York State was mapped by county using Epi Map (9).
Variations in seasonal proportions of hospitalizations were examined, defining December-February as winter, March-May as spring, June-August as summer, and
September-November as fall.
RESULTS
There were 1,784 persons in the United States
whose death certificates listed Wegener’s granulomatosis as a cause of death in the 10-year period from
1979 to 1988. Twenty-two deaths occurred in children
under age 15. The national average annual mortality
rate from Wegener’s granulomatosis for the 10-year
study period was 0.8 deaths per million persons. The
actual mortality rate increased from 0.6 deaths per
million persons in 1978 to 1 death per million persons
in 1990. Ofthe approximately 2 million deaths per year
in the United States, approximately 1 in 10,000 occurred in individuals with Wegener’s granulomatosis.
Table 1 contains the distribution of these deaths by
age, race, and sex.
Wegener’s granulomatosis deaths were significantly more likely to occur in males (P < 0.01). The
vast majority of the deaths (95%) occurred in Caucasians, who are disproportionately overrepresented
among the ethnic groups affected by Wegener’s granulomatosis. Of the 571 individuals with Wegener’s
granulomatosis hospitalized in New York State over
the 5-year period, 11% (63 persons) died prior to
discharge, which is comparable to 10% mortality in
hospitalizations of Wegener’s granulomatosis patients
in the US.
SPARCS reported 978 hospitalizationsfor Wegener’s granulomatosis occumng in 571 persons in New
York State, and NHDS reported 10,771 hospitalizations for Wegener’s granulomatosis in the US for the
5-year period between 1986 and 1990 (Table 2). The
5-year period prevalence of Wegener’s granulomatosis
in New York State was 3.2 per 100,OOO persons.
Assuming an average of 1.7 hospitalizations for Wegener’s granulomatosis per individual over a 5-year
THE EPIDEMIOLOGY OF WEGENER’S GRANULOMATOSIS
89
Summary of hospitalization data for Wegener’s granulomatosis: National Hospital Discharge Survey, 1986-1990, and New York’s Statewide Planning and Research Cooperative System,
19861990
Table 2.
National Hospital
Discharge Survey*
New York’s Statewide
Planning and Research
Cooperative System
10,771
978
Total hospitalizations
involving Wegener’s
granulomatosis
Number of individuals
Sex, %
Males
Females
Age group, %
<20
20-44
465 +
Age, mean years f SD
Males
Females
Race, %
White
Black
Other
Not stated
Season of admission, %
Spring (March-May)
Summer (JunsAugust)
Fall (September-November)
Winter (December-February)
Average length of stay, days
Disposition at discharge, %
Dead
Alive
Not stated
Five-year period prevalence
per 100,OOO personst
571
48.6
51.4
48.2
51.8
0.1
30.0
40.2
29.7
3.3
22.6
35.6
38.5
50.9 2 16.2
59.1 f 14.8
54.5 2 17.2
57.4 t 17.6
80.9
2.3
0.9
15.8
83.3
7.9
8.8
0
22.8
18.3
33.5
25.4
12
25.6
25.2
22.1
27.1
17
10.4
83.4
6.2
2.6 (0.35)
11
89
0
3.2
* National estimates based on survey hospitals.
t Estimated using the 1990 population as a reference, assuming 1.7 hospitalizations for Wegener’s
granulomatosis per person over 5 years (248 million in the US; 18 million in New York). Standard error
in parentheses.
period (as was found in the SPARCS data), the period
prevalence extrapolated from the NHDS data was 2.6
per 100,000 persons (99% confidence limit 1.7-3.5).
Males and females were about equally represented among patients hospitalized for Wegener’s
granulomatosis in both data sources. Compared with
the age-specificdistribution of NHDS hospitalizations,
a larger proportion of the SPARCS cases were either
under the age of 20 (3.3% versus 0.1%) or over the age
of 64 (38.5% versus 29.7%). The mean ages were in the
sixth decade for males and females. There were
marked racial differences in the SPARCS data compared with the NHDS findings, in that 8% of the
SPARCS cases versus 2.3% of the NHDS cases were
black, 8.8% of the SPARCS cases versus 0.9% of the
NHDS cases were other nonwhites, and the remainder
of the cases were white. By comparison, 16% of the
New York population and 12% of the national population was black, while nonwhites constituted 10% and
12% of these respective populations in 1990. Clear,
significant differences in seasons of hospitalization
were not observed. The average length of stay in New
York was 17 days, compared with 12 days nationwide.
To examine the geographic distribution of Wegener’s granulomatosis cases in the SPARCS data, the
cases were mapped by county of residence (Figure 1).
Twenty-one of the 62 counties in New York State had
no cases hospitalized in the 5-year period between
1986 and 1990. Several counties appeared to have
clusters of cases; however, after adjusting for popula-
90
COTCH ET AL
F
w 1. Number of individuals with Wegener’s granulomatosis,
by county, in New York State from 1986 to 1990.
tion density, a different pattern emerged (Figure 2).
Differences in the prevalence of Wegener’s granulomatosis across counties were observed; the frequency
was at least 7 per 100,OOO persons in Onondaga,
Otsego, Schenectady, Warren, and Columbia counties,
as depicted geographically from west to east in Figure 2.
Prevalence was also elevated in New York City.
DISCUSSION
Based on surveys of hospitalizations, we estimated the prevalence of Wegener’s granulomatosis in
the US to be at least 3.0 per 100,OOO persons. We
suspect that individuals with mild features of the
disease who were not hospitalized may not have been
identified. In the only published population-based
prevalence estimate known to us, Andrews and colleagues (12) reported 17 incident cases of Wegener’s
granulomatosis between 1985 and 1989, among approximately 1.3 million people in the Leicester, England region. This corresponds to an approximate
5-year incidence rate of 1.3 per 100,OOOpersons. Given
this estimate of incidence and the range in 5-year
survival of patients with Wegener’s granulomatosis, it
is not improbable that the period prevalence in Leicester approached or exceeded 2.0 per 100,000 persons.
Despite the potential for discrepant findings for
a condition as uncommon as Wegener’s granulomatosis, the consistency of estimates obtained from the
vital statistics data, the NHDS data, and the SPARCS
data is encouraging. Our ability to utilize hospitaliza-
tion data to estimate the prevalence of Wegener’s
granulomatosis depends on the assumption that virtually all individuals with fully expressed forms of Wegener’s granulomatosis are either diagnosed while inpatients or are hospitalized at least once as a result of
complications of the disease or its treatment. For
example, of the 571 persons hospitalized for Wegener’s granulomatosis in New York State, 383 individuals had either respiratory tract biopsies or renal
complications recorded in their SPARCS hospitalization records.
The potential for underdiagnosis and miscoding
of this rare disease increases the likelihood that both
the number of deaths and the prevalence of Wegener’s
granulomatosis may be underestimated in this study. If
we calculate the number of deaths nationally using the
estimated number of hospitalizations ending in death
(from the NHDS), 2,240 Wegener’s granulomatosisrelated deaths would be expected during a 10-year period. Alternatively, by extrapolating from the SPARCS
data to national estimates, we estimate that 1,736 people in the US would have Wegener’s granulomatosisrelated deaths over a 10-year period. This underestimate may be due to an undetermined number of deaths
from Wegener’s granulomatosis that occur out of the
hospital. The actual number of deaths as recorded on
all death certificates in the US for a 10-year period was
1,784.
Similarly, extrapolating from a period prevalence of 3.2 per 100,OOO persons, as calculated from
the SPARCS data, we estimate that 7,936 individuals
in the US would have Wegener’s granulomatosis in a
5-year period. The NHDS prevalence estimate of 2.6
Figure 2. Estimated rate of Wegener’s granulomatosis, by county,
in New York State from 1986 to 1990.
THE EPIDEMIOLOGY OF WEGENER’S GRANULOMATOSIS
per 100,000 persons (based on an average of 1.7
hospitalizations for Wegener’s granulomatosis over a
5-year period) corresponds to an estimate of 6,448
persons. Because the sampling method of the survey
requires consideration of the standard error of the
estimate, the number of individuals identified with
Wegener’s granulomatosis in the US over a 5-year
period would range from 5,580 to 7,316 (using a
confidence limit of 99%).
We considered the SPARCS data to be the most
reliable source of data we analyzed. The collection of
discharge data and uniform billing data from all hospitalizations in nonfederal, nonpsychiatric facilities in
the State of New York is mandated by law. Since the
records of all Wegener’s granulomatosis-related hospitalizations were already linked to specific individuals
by SPARCS, and because we were not privy to
personal identifiers, we were not able to assess the
accuracy of linkage; however, a previous attempt to
examine this issue found the linkages to be highly
accurate and reasonably complete (10).
Individuals with Wegener’s granulomatosis
identified in the SPARCS data differed in some respects from a case series of 158 patients seen at the
National Institutes of Health (NIH) (5). The most
notable differences were in the mean ages and racial
composition of the populations. The mean age was 41
years (range 9-78 years) for patients with Wegener’s
granulomatosis seen at the NIH, compared with 56
years (range 6-92 years) for those seen in New York
State hospitals. Only 2% of the patients followed up at
the NIH were black (1% were other nonwhites), while
8% of those with Wegener’s granulomatosis in New
York State were black (9% were other nonwhites).
Demographically in 1990, whites, blacks, and other
nonwhites comprised 76%, 12%, and 12%, respectively, of the US population and 74%, 16%, and lo%,
respectively, of the population of New York State.
Since the NIH serves as a referral center, these
differences likely reflect biases in referral patterns. In
both populations, males and females were rather
equally represented.
Raynauld and colleagues (13) recently reported
seasonal variations in the onset of symptoms in 84
Wegener’s granulomatosis patients diagnosed during
an unspecified 5-year period. They found spring (particularly April) to be the period in which the largest
proportion experienced symptom onset (34.5%), followed by winter (29.8%), fall (21.4%), and summer
(14.3%). The seasonal pattern of hospitalizations reported in our study is different (Table 2). The reasons
91
for these apparent discrepancies may be several. First,
the SPARCS data do not necessarily reflect only
incident (new) cases, while those reported in the
Raynauld study are said to be incident cases. If,
however, the trigger responsible for the initial diagnosis and hospitalization for Wegener’s granulomatosis
is also responsible for subsequent hospitalizations, for
our purposes, it should not matter whether or not
cases are incident. Second, if the agent that triggers
symptoms is infectious in nature, perhaps viral as has
been postulated (14-16), the month in which this
trigger is reintroduced into the population may vary
annually. Given the rarity of this disease, a thorough
examination of seasonality would require detailed examination of cases by month over a number of years.
Another possibility is that some of the hospitalizations
were elective and may not have been uniformly distributed throughout the year. Last, there may not be
seasonal variations in the onset of Wegener’s granulomatosis symptoms.
Since the etiology of Wegener’s granulomatosis
is unknown and a few small communities with seemingly excessive numbers of cases have come to our
attention, we were eager to produce prevalence estimates for reference purposes (Figures 1 and 2). The
distribution of cases shown in Figure 1 is informative,
in that it displays the pattern of Wegener’s granulomatosis cases by county of residence and reflects the
anecdotal accounts of clusters of cases. However, the
depiction of prevalence rates (Figure 2) is more helpful
in identifying specific counties with elevated occurrence, i.e., an excess in Wegener’s granulomatosis
cases per population. With the exception of New York
City, the counties with the highest prevalence rates
were not those containing large metropolitan areas.
In the absence of a Wegener’s granulomatosis
registry, requiring carefully defined diagnostic criteria,
we believe the data reported herein represent the best
population-based source of information available on
this rare disease. More intensive epidemiologic investigations, especially in areas of high prevalence, may
accelerate progress toward establishing the etiology of
Wegener’s granulomatosis.
ACKNOWLEDGMENTS
The authors would like to thank Mr. Gene D. Therriault and the New York Statewide Planning and Research
Cooperative System for kindly allowing us to use their data.
COTCH ET AL
92
REFERENCES
1. Hay EM, Beaman M, Ralston AJ, Ackrill P, Bernstein RM,
2.
3.
4.
5.
Holt PJL: Wegener’s granulomatosis occumng in siblings: a
case report. Br J Rheumatol 30:144-145, 1991
Muniain MA, Moreno JC, Campora RG: Wegener’s granulomatosis in two sisters. Ann Rheum Dis 4k417-421, 1986
Sewell RF, Hamilton DV: Time-associated Wegener’s granulomatosis in two members of a family (letter). Nephrol Dial
Transplant 7:882, 1992
Singer J, Suchet I, Horwitz T: Paediatric Wegener’s granulomatosis: two case histories and a review of the literature. Clin
Radio1 4250-51, 1990
Hoffman GS, Kerr GS, Leavitt RY, Hallahan CW, Lebovics
RS, Travis WD, Rottem M. Fauci AS: Wegener’s granulomatosis: an analysis of 158 patients. Ann Intern Med 116:488498,
10.
11.
12.
13.
1992
6. Murty GE, Mains BT, Middleton D, Maxwell AP, Savage DA:
HLA antigen frequencies and Wegener’s granulomatosis. Clin
Otolaryngol 16:448451, 1991
7. Public Health Service and Health Care Financing Administration: International Classification of Diseases, Ninth Revision:
Clinical Modification. Washington, DC, Public Health Service,
14.
15.
1989
8. National Center for Health Statistics: Development of the
Design of the NCHS Hospital Discharge Survey. Vital and
Health Statistics. PHS Publication No. IOOO, Series 2, No. 39.
Washington, DC, United States Government Printing Office,
1970
9. National Center for Health Statistics: Development and Main-
16.
tenance of a National Inventory of Hospitals and Institutions.
Vital and Health Statistics. PHS Publication No. 1000, Series I ,
No. 3. Washington, DC, United States Government Printing
Oflice, 1%5
Kaufman GI, Grabau JC, Schmidt EM, Han Y: HIV-infected
hospital patients in New York State: the development of longitudinal information from a hospital discharge data system. N Y
State J Med 90:238-242, 1990
Dean JA, Burton AH, Dean AG, Brendel KA: Epi Map: A
Mapping Program for IBM-Compatible Microcomputers. Atlanta, GA, Centers for Disease Control and Prevention, 1993
Andrews M, Edmunds M, Campbell A, Walls J, Feehally J:
Systemic vasculitis in the 1980s: is there an increasing incidence
of Wegener’s granulomatosis and microscopic polyarteritis? J R
Coll Physicians 24284-288, 1990
Raynauld JP, Bloch DA, Fries JF: Seasonal variation in the
onset of Wegener’s granulomatosis, polyarteritis nodosa and
giant cell arteritis. J Rheumatol 20:15241526, 1993
Falk JR, Hogan S , Carey TS, Jennette JC: The clinical course
of patients with anti-neutrophil cytoplasmic autoantibodyassociated glomerulonephritis and systemic vasculitis. Ann Intern Med 113:656-663, 1990
Jennette JC, Falk RJ: Anti-neutrophil cytoplasmic autoantibodies and associated diseases: a review. Am J Kidney Dis 15517529, 1990
Finkel TH, Torok TJ, Ferguson PJ, Durigon EL, Zaki SR,
Leung DYM. Harbeck RJ, Gelfand EW, Saulsbury FT,Hollister JR, Anderson LJ: Chronic parvovirus B19 infection and
systemic necrotising vasculitis: opportunistic infection or aetiological agent? Lancet 343:1255-1258, 1994
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