Arch Dermatol Res
DOI 10.1007/s00403-014-1531-1
REVIEW
Geographic variations in epidemiology of two autoimmune
bullous diseases: pemphigus and bullous pemphigoid
Erkan Alpsoy • Ayse Akman-Karakas •
Soner Uzun
Received: 18 July 2014 / Revised: 11 November 2014 / Accepted: 29 November 2014
Ó Springer-Verlag Berlin Heidelberg 2015
Abstract Autoimmune bullous diseases are rare, organ-
specific, a group of blistering disease of skin and mucous
membranes. Recent studies suggest that the frequency of
the autoimmune bullous diseases has been increasing.
Pemphigus vulgaris and bullous pemphigoid are the most
frequently reported autoimmune bullous diseases. High
incidence of autoimmune bullous diseases in some ethnic
groups such as pemphigus in Ashkenazi Jewish, or in some
regions such as pemphigus foliaceus in Brazil has been
shown to be related to genetic and environmental factors,
respectively. Pemphigus has been reported more frequently
in the female gender. Although it is most frequently
diagnosed between the ages 50 and 60 in European coun-
tries, in the remaining countries in the world, it is seen
between the ages of 30 and 50. Bullous pemphigoid is
generally seen above 70 years of age. Although overall
incidence is slightly higher in females, after the age of
80 years it is more frequent in males. Both pemphigus
vulgaris and bullous pemphigoid has a chronic course with
recurrences. Mortality risk of the patients with bullous
pemphigoid was found at least 2 times higher and the
mortality risk of the patients with pemphigus was found
approximately 3 times higher than that of the general
population. In this review, the results obtained from the
epidemiological studies were analyzed according to geo-
graphic regions, and especially epidemiologic features of
two prevalent autoimmune bullous diseases, pemphigus
and bullous pemphigoid have been discussed.
E. Alpsoy (&)
A. Akman-Karakas
S. Uzun
Department of Dermatology and Venereology, Akdeniz
University School of Medicine, 07059 Antalya, Turkey
e-mail: ealpsoy@akdeniz.edu.tr
Keywords Autoimmune bullous diseases
Pemphigus

Bullous pemphigoid
Epidemiology
Introduction
Autoimmune bullous diseases (ABD) are rare, organ-spe-
cific, a group of blistering disease of skin and mucous
membranes mediated by autoantibodies directed against
the desmosomes and hemidesmosomes. Pemphigus and
bullous pemphigoid (BP) are the most prevalent ABD.
Pemphigus encompasses a group of autoimmune intraepi-
dermal blistering diseases classically divided into two
major variants: pemphigus vulgaris (PV) and pemphigus
foliaceus (PF). Pemphigus herpetiformis, IgA pemphigus,
paraneoplastic pemphigus and IgG/IgA pemphigus are
rarer forms. The pemphigoid group represents a group of
autoimmune disorders characterized by subepidermal
blistering. This group includes mainly BP, linear IgA dis-
ease, dermatitis herpetiformis, and epidermolysis bullosa
acquisita. ABD run a chronic course and are associated
with significant morbidity and even mortality.
Our knowledge about the epidemiology of these dis-
eases is still limited. ABD are reported from all around the
world. When the epidemiological data are reviewed, clear
regional differences are observed. Data regarding this
group of disease are mostly as a reflection of the hospital
records (frequently of university or teaching hospitals) with
retrospective study design. The number of studies per-
formed with the prospective study design which is more
realistic choice of research methodology when assessing
the frequency of ABD have been increasing in recent years.
Two recent studies performed with prospective study
design highlight information about the frequency of ABD
in population. Marazza et al. [44] from Switzerland,
123

reported the incidence of ABD as 14.5/million/year. Ber-
tram et al. [13] found this rate as 20.4/million/year for
Germany. Recent data suggest that the frequency of the
subepidermal ABD has been increasing. Zillikens et al.
[70] from Germany reported the incidence of BP as 6.6/
million/year in 1995. Bertram et al. [13] reported this rate
as 13.4/million/year in a recent study that they performed
in a similar area in Germany.
The large parts of the current studies regarding the ABD
are about PV and BP. In this review we focused, therefore,
on the epidemiological data of these diseases and tried to
summarize main geographic differences of both diseases.
Pemphigus
Incidence
Pemphigus incidence, in general, varies according to geo-
graphic area and ethnic groups (Table 1). The incidences
reported from the different regions of Europe range
between 0.5 and 8/million. The yearly pemphigus inci-
dences reported from the Northern Europe such as Finland
(0.76/million) [29], and Western Europe such as Germany
(0.5–0.98/million) [13, 28], Switzerland (0.6/million) [44]
and France (1.7/million) [10] are lower when compared to
the other countries. Interestingly, in the study of Langan
et al. [38] from UK, the incidence was reported with a
notably high frequency when compared to the other
Northern European countries with 6.8/million. In this
study, the data was obtained from a computerized longi-
tudinal general practice database (Health Improvement
Network Database). Thus, the data may not be safe enough
and more than one data entry may have been made for the
same patient. In Greece [47], Italy [46], Macedonia [65],
Serbia [26] located in the Southern Europe and Romania
[7], Bulgaria [61], located in the Eastern Europe, the fre-
quency of the disease is higher and ranges between 4 and
8/million. In the study of Uzun et al. [62] from the Medi-
terranean region of Turkey which is geographically closer
to countries above, the yearly incidence of pemphigus is
reported as 2.4/million.
When the remaining parts of the world are reviewed, the
yearly incidence in Asian countries varies between 1.6 and
16.1/million [16, 30, 37, 49, 53, 56, 60]. The highest fre-
quency in this region was reported from Israel with 16.1/
million [53]. As is known, although pemphigus could be
seen in all ethnical groups and races, it is more common
among Askhenazis, which is one of the biggest two Jewish
branch and people with Mediterranean roots. In the study
of Simon et al. [58] from North America, the frequency of
the disease was reported as 32/million in people with
Jewish roots and 4.2/million in people from other ethnical
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Arch Dermatol Res
races. In three studies performed in Africa, the yearly
incidence of pemphigus was reported as 2.9/million in Mali
[43] and 6.7 [10] and 8.62/million in Tunisia [69]
(Table 1).
In general, PV is the most frequently reported clinical
subtype among the pemphigus group. When the epidemi-
ologic data are reviewed, it is seen that at least 2/3 of the
patients are diagnosed as PV. In our study [62], 83.1 % of
the patients with pemphigus had the diagnosis of PV, 8.8 %
of them had PF, 4 % had pemphigus erythematosus, 2.7 %
had pemphigus herpetiformis and 0.7 % had pemphigus
vegetans.
While PF is seen all around the world sporadically, its
endemic form (fogo selvagem) is seen in Brazil. This form
of the disease is frequent in the rural and tropical regions in
Brazil. In these regions, PF is approximately 20 times more
frequent than PV. The frequency of the disease has been
reported almost 3 % in some parts of Brazil [19]. The
number of the new cases increases with the end of the rainy
season. The disease is more frequently seen among those
people who live in the riverside and whose economic
conditions are poor and it is rarely reported from the urban
areas. Again, in people who immigrated to the regions
having a better hygienic condition, the disease tends to get
better. Peru, Colombia, Algeria and Tunisia are countries
where PF is frequently seen. This form of pemphigus is
more frequent in the adolescence or around 20 years of age
[45]. Therefore, PF was reported to outnumber PV in Brasil
and other Latin American countries, and some African
countries such as Mali and Tunisia [10].
On the other hand, Zaraa et al. [69] recently reported
that although PF was relatively more prevalent especially
in central and south part of their country, PV (%61) was
more prevalent than PF (%36) in north Tunisia. Benchikhi
et al. [11] from Morocco reported equal frequency of PF
and PV, and Hietanen et al. [29] from Finland reported
pemphigus erythematosus as the predominant form of
pemphigus. In the study of Aboobaker et al. [1] from South
Africa, PF was reported to be the most frequent pemphigus
variant. The disease was especially frequent in black peo-
ple, while most Indian cases with pemphigus presented
with the PV subtype.
Age and sex
Pemphigus may occur in all age groups. When the Table 1
is reviewed, it is seen that the disease is most frequently
diagnosed between the ages 40 and 60. While the mean age
is between the ages of 50 and 60 in European countries, in
the remaining countries in the world, it is between the ages
of 30 and 50. Pemphigus has been reported more frequently
in the females. The female male ratio varies between 0.45
and 5. Interestingly, male dominance has been reported so
Arch Dermatol Res

Table 1 Demographic findings and incidences of pemphigus patients

References Study design Country Continent Patient Sex Mean age Incidence
(n) (F/M) (year) (cases/million)

Bertram et al. [13]a Prospective Germany Europe 41 – 62 0.5

a
Hahn-Ristic et al. [28] Retrospective Germany Europe 14 1.33 – 0.98
Hietanen et al. [29] Retrospective Finland Europe 44 1.1 57.5 0.76
Marazza et al. [44] Prospective Switzerland Europe 7 2.5 62.3 0.6
Langan et al. [38]a Retrospective UK Europe 138 1.93 71 6.8
Bastuji-Garin et al. [10] Retrospective France Europe 87 1.2 52 1.7
Micali et al. [46] Retrospective Italy Europe 84 1.6 56 6
Michailidou et al. [47]a Retrospective Greece Europe 129 2.25 59.6 8
V’lckova-Laskoska et al. [65] Retrospective Macedonia Europe 133 1.33 52 4.4
Tsankov et al. [61] Retrospective Bulgaria Europe 74 1.2 72.4 4.7
Golusin et al. [26] Retrospective Serbia Europe 51 1.55 55.6 6.6
Baican et al. [7] Prospective Romania Europe 68 1.75 53 4
Uzun et al. [62] Retrospective Turkey Europe 148 1.35 43 2.4
Simon et al. [58] Retrospective USA North America 12 5 63.6 32 (Jewish) 4.2 (Others)
Tallab et al. [60] Retrospective Saudi Arabia Asia 19 0.45 43.1 1.6
Salmanpour et al. [56] Retrospective Iran Asia 221 1.33 38 6.7
Chams-Davatchi et al. [16] Prospective Iran Asia 1209 1.5 42 10 (Iran) 16 (Tehran)
Kumar [37] Prospective India Asia 13 2.33 37 (F), 58 (M) 4.4
Pisanti et al. [53]a Prospective Israel Asia 76 1.62 – 16.1
Nanda et al. [49] Retrospective Kuwait Asia 60 0.9 36.5 4.57
Huang et al. [30]a Prospective Taiwan Asia 853 1.3 52.5 4.7
Mahé et al. [43] Retrospective Mali Africa 30 4 46.7 2.9
Bastuji-Garin et al. [10] Retrospective Tunisia Africa 198 4 36.7 6.7
Zaraa et al. [69] Retrospective Tunisia Africa 92 2 50 8.62
a
Studies including only pemphigus vulgaris patients

far from some Middle Eastern countries such as Saudi
Arabia [60], Kuwait [49], and Bangladesh [6] and China
[32].
Mortality
The disease has a long-term course, and is still associated
with severe morbidity and considerable mortality. The
mortality rate of pemphigus was very high until the 1950s.
If pemphigus is left untreated, during 2 years the mortality
is 50 % and at the end of 5 years, it is nearly 100 % [48].
The mortality rate has prominently decreased with the
usage of corticosteroids in treatment. Although several
effective treatments currently exist, none of them result in a
cure of the disease. Therefore, pemphigus is still an
important cause of significant mortality. There is relatively
little data about the mortality rate and specific causes of
mortality among patients with pemphigus compared with
general population. Most of the previous data are hospital-
based and show a relatively high mortality rates ranging in
the literature 5–15 % during various lengths of follow-up
[48]. In our series [62], the follow-up period varied
between 2 months and 6 years and during this period, 5 PV
patient in total died from septicemia (3 patients), myocar-
dial infarction (1 patient) and with unknown causes (1
patient). Recent population-based cohort studies by Langan
et al. [38] from UK and Huang et al. [30] from Taiwan
have given important epidemiologic data in this field.
Langan et al. [38] found that the age- and gender-adjusted
mortality rate was 3.3 times higher than that of controls.
Huang et al. [30] reported that pemphigus patients have a
2.36-fold increase in mortality compared with the general
population. Systemic and respiratory tract infections, car-
diovascular disease, and peptic ulcer were the most com-
mon events leading to death. Huang et al. [30] also pointed
out that patients with pemphigus onset after the age
60 years had worse prognoses and poorer survival rates
compared with those whose disease onset was before
60 years age. This finding is in line with the previous data.
Mortality rates can vary in different studies according to
the countries health care systems where the study is per-
formed, therefore they should be evaluated cautiously.

123

Associated diseases
Pemphigus has been reported to be associated with other
autoimmune diseases including autoimmune thyroid dis-
eases namely, Graves’ disease and Hashimoto’s thyroiditis
[40], myasthenia gravis [31], Sjogren’s disease, and rheu-
matoid arthritis [24]. Although, in a previous study Firooz
et al. [25] found thyroid disease, type 1 diabetes mellitus
and juvenile rheumatoid arthritis to be significantly more
common in the family members of PV patients than in a
control group, a recent study did not confirm these results.
In the study of Leshem et al. [40] first-degree relatives of
patients with pemphigus did not have a higher prevalence
of autoimmune diseases than the general population.
Oral lesions are a hallmark of PV and occur in almost all
cases, and represent the preliminary symptom in more than
half of the patients. Persistent lesions lead to lack of
effective oral hygiene, and more plaque accumulation may
increase the risk of long-term periodontal disease. Our
recent study detected the periodontal disease at a higher
frequency in the patients with pemphigus when compared
to the control group [5]. The results indicate that PV might
contribute to the development and/or progression of peri-
odontitis. This observation may also be due to the difficulty
to perform dental hygiene rather than the autoimmune
disease being a precipitating factor.
Triggering factors
Drugs seems to be the most common cause of the outbreak
of pemphigus. Thiol drugs (e.g., penicillamine, captopril,
penicillin, cephalosporins), phenol drugs (e.g., cephalo-
sporins, aspirin, rifampin, levodopa), and others (e.g., ACE
inhibitors, NSAID, nifedipine) are the most commonly
reported agents. Besides drugs, viral infections such as
herpesvirus infections, physical agents such as ultraviolet
radiation, contact allergens, diet, and smoking have also
been noted to be important environmental factors trigger-
ing pemphigus [55]. However, the portion of patients in
whom a particular triggering factor can be identified is
small.
Of note, V’lckova-Laskoska et al. [65] from Macedonia
reported an epidemiological peak in 2001 during the local
armed conflict. Women had a statistically significant
increase in the incidence of the disease. They speculated
that war-related elevated stress could be responsible for
this deviation in the disease incidence.
All these factors might trigger the disease by either
modifying the immune response or altering the antigenic
properties of the epidermal basement membrane and the
outbreak of disease symptoms may regress after the trig-
gering factor/s have been eliminated even in the absence of
any treatment.
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Arch Dermatol Res
On the other hand, findings suggest that tobacco
smoking may confer some protective effects and mitigate
pemphigus. The rate of smoking, both current and former
was found significantly lower in pemphigus patients com-
pared to age-matched controls [15, 59].
HLA
A genetic susceptibility associated with the HLA types has
been well documented in several populations. Furthermore,
population studies of patients with pemphigus and its
subtypes have shown that there are similarities among the
most prevalent alleles in various ethnic groups. For the first
time, Krain et al. [36] reported the increased frequency of
HLA-A*10 in Ashkenazi Jewish people. Regarding the
pemphigus, a strong association with HLA-DRB1*04,
DRB1*14 and DQB1*05 from HLA class II antigens have
been reported in the literature. HLA-DRB1*04 is seen
especially in Ashkenazi Jewish patients. HLA-DRB1*14
has been more frequently reported in European and
American Caucasians, Japanese, Chinese, Mexican, India
and Pakistani populations [3, 4, 21, 23, 52, 63]. In our
recent controlled study [35], distribution of HLA class I
and II antigens in Turkish patients with pemphigus was
evaluated. The frequencies of HLA-A*11, -CW*01,
-DRB1*04, -DRB1*14, -DQB1*05 and -DPB1*0401
antigens in the disease group were found to be statistically
higher compared to those of controls. Our results suggest
that besides carrying common Class II HLA antigens for
the genetic background of the pemphigus, Class I HLA
antigens namely HLA-A*11, CW*01 are also associated
with pemphigus in Southern Turkey. Furthermore, we
observed differences in linkage disequilibrium pattern
between patients and controls. Taking these factors toge-
ther, we concluded that the coexistence of the respected
antigens is strongly determinative for the predisposition
(DRB1*14/DQB1*05 and A*11/DQB1*05) or protective
(HLA-B*50/DQB1*02) against the disease.
Bullous pemphigoid
Incidence
The large part of the data regarding the subepidermal ABD
is about the BP, which is the most frequent disease among
this group. The incidence of all subepidermal ABD was
reported to be 19.9/million in the study of Bertram et al.
[13] from Germany. As expected, BP was the most fre-
quent subgroup (approximately 2/3 of all subepidermal
ABD). The yearly incidences reported from Europe varies
between 2.5 and 42.8/million [12, 18, 27, 33, 34, 57, 66,
70]. In some European countries, there are more than one
Arch Dermatol Res

epidemiological data which were performed at different
times. Among the studies performed in Germany at similar
[34, 70] and in France [12, 33] at different regions, BP
incidence is higher in the more recent ones. In a recent
study of Joly et al. [33] the annual incidence of BP was
estimated at 21.7 cases per million persons per year during
the 2000–2005 period for three French regions. It was
about threefold higher than the incidence that previously
estimated by Bernard et al. [12] during the 1986–1992
period for three French regions with similar demographic
characteristics and that reported by Zillikens et al. [70] in
Germany during the same period. The highest incidence
reported from Europe is the study of Langan et al. from UK
[38]. In this study, just as in pemphigus the BP incidence
was reported with a quite higher frequency (42.8/million)
when compared to the other European countries. Although
the limitation regarding the method of this study was dis-
cussed in the previous parts of the review an increase in the
age of their populations can be speculated as one of the
major causes for the raise in the incidence of BP observed
both in France and the UK over the last 15 years. Joly et al.
[33] suggested that increased incidence of dementia and
other disabling neurological disorders which are major risk
factors for BP among elderly patients, the increasing use of
some drugs such as diuretics and psycholeptics and
recently described clinical variants of BP which were not
recognized in the past might be other possible explanations
of the raise in the incidence of BP. On the other hand, the
lowest frequency reported from Europe (2.5/million)
belongs to the study of Baican et al. [7] from Romania. As
previously mentioned, in this study pemphigus was repor-
ted to be the most frequently observed ABD (Table 2.
The yearly BP incidences reported from Asian countries
are: 2.6/million for Kuwait [49], and 7.6/million for Sin-
gapore [67]. A very high incidence of BP in infancy was
reported by a study from Israel [66]. The incidence of BP
in the Israeli population of infants under age of 1 during the
study period was 23.6/million. Increased frequency of BP
alongside with pemphigus in Israel shows that the genetic
factors may play an important role in both disease groups
(Table 2). However, as emphasized by authors, because of
the relatively short period of time (3 years) of this study,
the calculated incidence rates may reflect a chance in
Israeli population over longer of periods time [66]. On the
other hand, there is only one study from the remaining part
of the World on the yearly BP incidences. In central and
south part of Tunisia from the Africa countries, Zaraa et al.
[69] recently reported the incidence of BP as 3.84.
Age and sex
The incidence of BP increases sharply with age and it is
most prevalent among elderly people. In the study of
Marazza et al. [44] BP frequency increased after the age of
70 and had the highest frequency above the age of 90.
Bertram et al. [13] reported the incidence of the disease

Table 2 Demographic findings References Study design Country Continent Patient Sex Mean age Incidence
and incidences of bullous (n) (F/M) (year)
pemphigoid
Serwin et al. [57] Prospective Poland Europe 35 5 68.9 (F), 4.47
67.3 (M)
Jung et al. [34] Retrospective Germany Europe 94 1.04 73.7 (F), 6.1
76.1 (M)
Zillikens et al. [70] Prospective Germany Europe 61 1.1 73.7 6.62
Bernard et al. [12] Prospective France Europe 69 1.48 82.4 7.4
Joly et al. [33] Retrospective France Europe 502 1.5 82.6 21.7
Cozzani et al. [18] Prospective Italy Europe 32 1.46 74 10
Bertram et al. [13] Prospective Germany Europe 27 1.2 74.6 13.4
Gudi et al. [27] Retrospective Scotland Europe 83 1.5 79.2 14
Langan et al. [38] Retrospective UK Europe 869 1.59 80 42.8
Baican et al. [7] Prospective Romania Europe 40 1.5 73 2.5
Marazza et al. [44] Prospective Switzerland Europe 140 1.3 77.2 12.1
Uzun et al. [62] Prospective Turkey Europe 29 1.41 64 0.047
Wong and Chua Retrospective Singapore Asia 59 2 77 7.6
[67]
Nanda et al. [49] Retrospective Kuwait Asia 43 5.1 65.2 2.6
Waisbourd-Zinman Retrospective Israel Asia 79 1.5 – 23.6
et al. [66]
Zaraa et al. [69] Retrospective Tunisia Africa 41 0.64 68.6 3.84

123

above the age of 80 as 189/million/year. While Joly et al.
[33] reported the incidence in the population aged 85 years
or above as 507/million/year, Jung et al. [34] reported the
incidence above the age of 90 as 485/million/year. In the
study of Jung et al. [34] the risk of having BP after the age
of 90 was calculated almost as 300 times higher when
compared to the patients at the age of 60 and younger.
These recent data shows that BP should not be considered
as a rare disease in the elderly especially in European
countries which have more elderly population. Interest-
ingly, Bourdon-Lanoy et al. [14] from France reported that
BP among young people is more severe and more active
than the usual form in the elderly.
BP was reported more frequently among females than
males in all studies except the study of Zaraa et al. [69]
from Tunisia. In the studies of Marazza et al. [44] and Joly
et al. [33] the overall incidence was higher in females
(yearly incidences 13.3/million and 25.7/million in
females, and 10.6/million and 17.5/millions in males,
respectively). However, above the age of 80 years BP was
more frequent in males. When demographic data of the
studies are reviewed, it can be seen that female and male
ratio varies between 0.64 and 5.1 (Table 2).
However, BP incidence in females is only slightly
higher as in males. For the estimation of sex distributions
in BP, the incidence of males and females in the general
population has to be taken into account. This is particularly
relevant, since BP is a disease of the elderly and the per-
centage of females tend to increase dramatically in the
elderly population.
Mortality
In most cases, BP has a chronic course with recurrences.
Despite recent improvements in BP treatment, it has a
significant morbidity and mortality risk. In the literature,
the mortality rate of BP is quite variable. Colbert et al.
[17] found the yearly mortality rate in US to be 6 %. The
same rate was reported as 41 % by Roujeau et al. [54]
from France. The study of Joly et al. [33] in France
showed a major excess of mortality in BP patients. The
mortality rate of BP patients was more than sixfold higher
than that in the general population of same age and sex
composition. Langan et al. [38] reported the mortality risk
of BP patients in UK as approximately twofold higher.
The poor prognosis of BP is largely due to old age,
side effects of treatment and associated other medical
conditions.
Associated diseases
Among the conditions associated with BP, neurological,
cardiovascular diseases and malignancy are those which
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Arch Dermatol Res
are emphasized the most. Association of BP with malig-
nancy or male patients with BP and malignancy has been
reported and it was considered as a marker of malignancy.
However, in the study of Lindelöf et al. [41] with 497
cases, which is the largest series in this respect, no asso-
ciation between BP and malignancy was detected. In a
recent study, Ong et al. [51] conducted a nationwide
record-linked study using national English hospital
admission and mortality dataset for all public hospitals in
England between 1999 and 2011. They found no evidence
of increased risk of BP in people with cancer overall, and
no evidence of increased risk of cancer overall in people
with BP when compared with a reference cohort.
Triggering factors
BP may also occur due to drugs. Especially diuretics,
analgesics, D-penicillamine, antibiotics and captopril are
reported to be cause of BP [39]. Bastuji-Garin et al. [8],
conducted a multicenter prospective case–control study
looking at the drugs used on a long-term basis before the
onset of the disease in 116 incident cases of BP. Two
classes of drugs, neuroleptics and diuretics (aldosterone
antagonists), were reported more frequently in BP patients
than control patients. Recently, Bastuji-Garin et al. [9]
revisited the issue with a multicenter case–control study,
and evaluated the risk factors for BP in 201 incident BP
cases. In a multivariate analysis, they identified chronic use
of spironolactone or phenothiazines to be independently
associated with BP besides major cognitive impairment,
bedridden condition, Parkinson’s disease, and unipolar or
bipolar disorder.
Physical agents (e.g., radiation therapy, ultraviolet
radiation, thermal or electrical burns, surgical procedures,
transplants) and infections, in particular human herpes
virus infections (cytomegalovirus, Epstein–Barr virus, and
HHV-6) have also been suggested as possible triggering
factors of BP in some cases [42].
It is wise to keep in mind that a great majority of cases
with BP occur apparently without any obvious triggering
factor. Venning and Wojnarowska [64] reported the prev-
alence of a recognizable triggering factor for BP in no more
than 15 % of patients.
HLA
HLA-DQB1*0301 antigen seems to be associated with
BP in Caucasians [22]. DRB1*04, DRB1*1101 and
DQB1*0302 antigens have been reported to be associated
with enhanced susceptibility to BP in Japanese society [50,
68]. Increased prevalence of BP in a specific geographical
area was not noted.
Arch Dermatol Res
In conclusion, pemphigus and BP are rare diseases and
the yearly worldwide incidence of pemphigus and BP
according to geographic region varies between 0.5 and 16.1
cases per million and 2.5–42.8 cases per million, respec-
tively. Among the pemphigus group, PV is the most fre-
quently seen clinical subtype usually occurring between the
ages of 50–60 in Europe and 30–50 in the remaining
countries in the World (Table 1). BP being the most
commonly observed subepidermal ABD is a typical elderly
disease and it is most frequently seen after the age of 70.
BP is reported to be the most prevalent ABD in Western
[13, 44] and Northern Europe [38], and Singapore [67]. On
the other hand, pemphigus is notified to be the commonest
ABD in Romania [7], Turkey [62], Iran [20], China [32],
Malaysia [2], Kuwait [49], and Tunisia [69]. BP relatively
has a benign course compared with PV and at least some
clinical forms respond more readily to low to mild doses of
systemic and/or even topical corticosteroids. Therefore,
fewer BP patients might be expected to be referred to
tertiary referral centers. BP is a disease of elderly people,
and it is most frequently seen in European countries,
probably due to longer life expectancy in these countries.
In agreement with this data, mean age of BP patients at
presentation is found to be lower in developing countries
compared with Western countries (Table 2). Nevertheless,
the possibility that a combination of genetic and environ-
mental factors may play a role in the occurrence of these
disorders cannot be ruled out.
References
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