Pemphigus in Hartford County, Connecticut,

From 1972 to 1977

David G. Simon, MS, MD; David Krutchkoff, MS, DDS; Richard A. Kaslow, MPH, MD; Richard Zarbo, DMD

\s=b\ An investigation of a possible cluster
of pemphigus cases that were diagnosed
in Hartford County, Connecticut, in 1977
provided data for estimating the incidence
of this disease in a defined population for
the years 1972 to 1977. The average
annual incidence (new cases per popula-
tion per year) estimated for the overall
adult population (over the age of 20 years)
was 0.42 cases per 100,000 people,
whereas that for Jewish adults was 3.2
cases per 100,000. Thus, the results of
this report both support the hypothesis
that Jewish people are at higher risk than
others for the development of pemphigus
and provide a basis for comparison with
the results of other studies of this dis-
ease.
(Arch Dermatol 116:1035-1037, 1980)
is a rare, probably
Pemphigus
autoimmune disease of unknown
causes. We have found no reports on
its rates and patterns of occurrence in
a defined population in the United
States; only one published study from
Israel1 deals with ascertaining the fre¬
quency of pemphigus. This report on
the incidence of pemphigus in Hart¬
ford County, Connecticut, was
Accepted for publication Jan 25, 1979.
From the Chronic Diseases Division, Bureau of
Epidemiology, Center for Disease Control, Atlan-
ta (Drs Simon and Kaslow), and the Department
of Oral Diagnosis/Pathology, School of Dental
Medicine, University of Connecticut, Farming-
ton, (Drs Krutchkoff and Zarbo).
Reprint requests to the Center for Disease
Control, Chronic Diseases Division, 1600 Clifton
Rd NE, Atlanta, GA 30333 (Dr Simon).
prompted when one of us (D.K.) had
five patients with pemphigus referred
for biopsy of oral lesions in the last
half of 1977 after seeing no other
cases in 5Vè years of practice there.
Four of these patients resided in the
greater Hartford area, and the fifth
visited the area frequently. We there¬
fore tried to determine whether the
cluster represented a truly unusual or
increasing occurrence of the disease in
Hartford County.
METHODS
We used several surveillance techniques
in an attempt to find all cases of pemphi¬
gus vulgaris, foliaceus, vegetans, or ery-
thematosus that occurred in Hartford
County between Jan 1, 1972, and Dec 31,

Fig 1 .—Representative photomicrograph of typical oral lesion in Fig 2.—High-power magnifications of suprabasilar region from
case of oral pemphigus vulgaris. Note obvious suprabasilar oral biopsy specimen in second case of oral pemphigus vulgaris.
cleavage with "tombstone" effect created by residual basal cells Note suprabasilar cleft with acantholytic cells floating within
(hematoxylin-eosin, x 220). vesicular space (hematoxylin-eosin, X440).

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 Fig 3.—Pemphigus cases, by year
ford County, Connecticut, 1972 to
1977. An oral pathologist (D.K.) evaluated
the condition of four such patients with
oral lesions and little or no cutaneous
involvement. Each case was examined by
at least one other pathologist, diagnosed
histopathologically as pemphigus vulgaris
on acantholysis and suprabasi¬
the basis of
lar cleavage (Fig 1 and 2), and confirmed
by direct or indirect immunofluorescence
microscopy. Details of the immunofluores¬
cence tests were not available, however.
Two dermatopathologists in Connecticut, a
large private laboratory with a surgical
pathology service, and the pathology
departments of ten hospitals in Hartford
County and the Yale-New Haven (Conn)
Medical Center were asked to search their
records for reports of pemphigus that
occurred in the six-year study period. We
examined medical records of patients dis¬
charged in the same period with a diagno¬
sis of pemphigus from any of the general
hospitals in Hartford County or from
Yale-New Haven Medical Center. Finally,
we canvassed all dermatologists listed in
the 1977 Directory of Medical Specialists or
the Hartford County telephone directory
as practicing dermatology in Hartford
County.
We selected the basis of the
cases on
following criteria: the patient
was a resi¬
dent of one of the 24 towns listed below,
the clinical diagnosis was confirmed histo¬
pathologically with light microscopy and/
or immunofluorescence microscopy, and
onset of symptoms was determined by
chart review or personal interview to have
occurred between Jan 1, 1972, and Dec 31,
1977.
Although we screened all of Hartford
County in the initial survey, our final study
population included residents of the follow¬
ing 24 (of 27) contiguous townships of this
north-central Connecticut county: Avon,
Berlin, Bloomfield, Bristol, Burlington,
East Granby, East Hartford, East Wind¬
sor, Farmington, Glastonbury, Granby,
Hartford, Manchester, New Britain, New-
ington, Plainville, Rocky Hill, Simsbury,
Southington, South Windsor, West Hart¬
ford, Wethersfield, Windsor, and Windsor
Locks. These towns are near one or more of
the medical care providers who partici¬
pated in our survey, and their residents are
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of onset and
1977.
Average Annual Incidence of Pemphigus
Connecticut, From 1972-1977, and in Jerusalem From 1952-1972'
Hartford
Jews
No. of cases 4 8
Rate* 3.2
95% Confidence llmitst 0.88-8.19
*Per 100,000 persons more than 20 years old.
fThe 95% confidence intervals of incidence rates for Jews and non-Jews do not overlap,
demonstrating a significant difference in these rates at the P < .05 level.
far less likely than those of the three
townships excluded from the study to seek
primary care outside the county. Census
data onthese 24 towns were used in calcu¬
lating the incidence of pemphigus for the
non-Jewish populations over the age of 20
years. Estimates published in the 128th
Registration Report on vital statistics by
the Connecticut Health Department show
that the 1975 population of Hartford Coun¬
ty was approximately 824,700 persons and
that the population of the 24 townships
included in our study was approximately
757,800. The number of persons over the
age of 20 years in the 24 survey towns was
estimated by multiplying the total popula¬
tion number of these towns by the propor¬
tion of people over the age of 20 years in
Hartford County as reported in the 1970
US census.
Estimates of the size of the Jewish pop¬
ulation of Hartford County were provided
by a research consultant of the Council of
Jewish Federations, Inc, New York. The
estimate of the Jewish population for all of
Hartford County is 24,500. This figure is
generated from a count of households (tak¬
en from lists of memberships in, clients of,
and contributors to all Jewish organiza¬
tions in the area) multiplied by a factor of
three, ie, according to a nationwide aver¬
age of three people per household. Several
communities have tried to determine the
percentage of Jewish households not on
any list of Jewish organizations and, in
some, underestimates of the Jewish popu¬
lation have been inferred.
Based on such data, it is unlikely that the
Jewish population of Hartford would be
underestimated by more than 20%, accord¬
ing to Alvin Chenkin (written communica¬
tion, July 25, 1979). Thus, the Jewish popu¬
lation there may be as high as 30,625; we
used this figure in calculating the inci¬
dence of pemphigus for Jewish people. We
estimated the size of the Jewish population
over the age of 20 years on the basis of the
age distribution reported by the National
Jewish Population Study of the Council of
Jewish Federations, Inc.3
The Poisson distribution2 was used for
significance testing and for constructing
95% confidence intervals around incidence
data.
diagnosis, Hart¬
in Persons in Hartford County,
County, Connecticut
Jerusalem
Non-Jews Total Jews
12 76
0.29 0.42 1.61
0.13-0.57 0.22-0.73
clearly
RESULTS
We found that pemphigus vulgaris
developed in 11 residents of the sur¬
vey area and pemphigus vegetans
developed in one resident between
Jan 1, 1972, and Dec 31, 1977.
Although six of 12 cases were diag¬
nosed in 1977, when the cases were
evaluated by year of onset rather than
by year of diagnosis (Fig 3), the distri¬
bution was not unusual and did not
support the suspicion that the inci¬
dence of pemphigus was rising in
Hartford County in the six-year sur¬
vey period.
Ten were women and two
patients
were men. All were white, as might be
expected from the 1970 US census
data, which showed that fewer than
10% of the Hartford County popula¬
tion were black. The mean age of
onset was 63.6 years (range, 33 to 84
years). The Table summarizes the
incidence rates. For the population
over 20 years, the average annual inci¬
dence of pemphigus for this six-year
period was 0.42 per 100,000 persons
(95% Poisson confidence interval, 0.22
to 0.73). Four of the 12 individuals
with pemphigus were Jewish, from
which we estimated an average
annual incidence of 3.2 cases per
100,000 Jewish residents over the age
of 20 years (95% Poisson confidence
limits, 0.88 to 8.29) and an average
annual incidence of 0.29 per 100,000
for non-Jewish residents over the age
of 20 years (95% Poisson confidence
limits, 0.13 to 0.57) (Table).
COMMENT
Our investigation did not show that
the incidence of pemphigus was rising
in Hartford County as of the latter
part of 1977, although the results pro¬
vided a basis for estimating the inci¬
dence of pemphigus in a specific pop-
 ulation. As in the only other published
incidence study from Jerusalem,1
more women than men had the dis¬
ease (P < .02). Our estimated average
annual incidence of 0.42 cases per
100,000 people over 20 years of age is
significantly lower than the 1.61 cases
per 100,000 reported for the adult pop¬
ulation of Jerusalem. Inadequate case
ascertainment in Hartford County
may partially explain these discrepant
rates, as may differences in the age
composition of the two populations.
However, the most likely explanation
for the higher rates reported for the
Jerusalem population is that pemphi¬
gus affects Jews more frequently
than others, as suggested by the eth¬
nic distribution of cases in several
clinical series.4" The findings in our
population-based study that the inci¬
dence of pemphigus for Jews was
more than ten times higher than that
1. Pisanti S, Sharav Y, Kaufman E, et al:
Pemphigus vulgaris: Incidence in Jews of differ-
ent ethnic groups, according to age, sex, and
initial lesion. Oral Surg 38:382-387, 1974.
2. Diem K (ed): Documenta Geigy: Scientific
Tables, ed 6. New York, Geigy Pharmaceuticals,
1962, pp 107, 191.
3. National Jewish Population Study, Demo-
graphic Highlights. New York, Council of Jewish
Federations Inc, 1973.
4. Gellis S, Glass FA: Pemphigus: A survey of
170 patients admitted to Bellevue Hospital from
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for non-Jews provides strong addi¬
tional support for such an interpreta¬
tion. Viewed in another way, a sub¬
group that comprised only 3.0% to
3.7% of the overall population ac¬
counted for 33% of all cases of pemphi¬
gus that developed in this population
from 1972 to 1977. Neither an assump¬
tion that we underestimated the Hart¬
ford County Jewish population by as
much as 25,000 people (50%) nor fur¬
ther age adjustment of the incidence
for adults based on the age distribu¬
tion of the nationwide Jewish popula¬
tion3 affects the findings that the
incidence of pemphigus was signifi¬
cantly higher for Jews than for others
(P < .05).
A genetic influence on the occur¬
rence of pemphigus has been sug¬
gested in several reports of an associa¬
tion between HLA-A10 and pemphi¬
gus vulgaris711 and in one suggesting
References
1911 to 1941. Arch Dermatol Syphilol 44:321-336,
1941.
5. Costello NJ: Treatment of pemphigus with
corticosteroids. JAMA 165:1249-1255, 1957.
6. Eller JJ, Kest LH: Pemphigus: Report of 77
cases. Arch Dermatol Syphilol 44:337-344, 1941.
7. Hasimoto K, Miki Y, Nakata S, et al: HLA\x=req-\
A10 in pemphigus among Japanese. Arch Der-
matol 113:1518-1519, 1977.
8. Krain LS, Terasaki PI, Newcomer VD, et al:
Increased frequency of HLA-A10 in pemphigus
vulgaris. Arch Dermatol 108:803-805, 1973.
an association with what is now
designated as HLA-B13.1" More
compelling evidence for a genetic role
derives from a recent study of 23
Jewish patients in California demon¬
strating a strong correlation between
pemphigus vulgaris and HLA-DRw4,
a gene linked to the HLA-A26 sub¬
group of HLA-A10.11 The correlation
seems to be far stronger for Jews than
for non-Jews. Further investigation
of geographic and ethnic influences on
the occurrence of pemphigus could
focus on Ashkenazic Jews who, in
Jerusalem,1 had an annual incidence
fourfold higher (2.70/100,000) than
that in other Jews (0.61/100,000). At
the same time, the data obtained in
our study of Hartford County need to
be confirmed with additional popula¬
tion-based studies.
Alvin Chenkin provided estimates of the
Jewish population of Hartford County.
9. Hasino K, Inouye H, Unokuchi M: HLA and
disease in Japanese, abstracted, in First Interna-
tional Symposium on HLA and Disease, 23-25
June 1976. Paris, Institut National de la Sant\l=e'\ret
de la Recherche M\l=e'\dicale,1976.
10. Katz SI, Dahl MV, Penneys N: HL-A anti-
gens in pemphigus. Arch Dermatol 108:53-55,
1973.
11. Park MS, Terasaki PI, Ahmed AR, et al:
HLA-DRW4 in 91% of Jewish pemphigus vulgar-
is patients. Lancet 2:441-442, 1979.