The New England Journal of Medicine



Original Article
Volume 346:321-327

January 31, 2002

Number 5
A Comparison of Oral and Topical Corticosteroids in Patients with Bullous
Pemphigoid
Pascal Joly, M.D., Ph.D., Jean-Claude Roujeau, M.D., Jacques Benichou, M.D.,
Ph.D., Catherine Picard, M.D., Brigitte Dreno, M.D., Ph.D., Emmanuel
Delaporte, M.D., Ph.D., Loïc Vaillant, M.D., Ph.D., Michel D'Incan, M.D.,
Ph.D., Patrice Plantin, M.D., Christophe Bedane, M.D., Ph.D., Paul Young,
M.D., Philippe Bernard, M.D., Ph.D., for the Bullous Diseases French Study
GroupABSTRACT
Background Bullous pemphigoid is the most common autoimmune blistering skin
disease of the elderly. Because elderly people have low tolerance for
standard regimens of oral corticosteroids, we studied whether highly potent
topical corticosteroids could decrease mortality while controlling disease.
Methods A total of 341 patients with bullous pemphigoid were enrolled in a
randomized, multicenter trial and stratified according to the severity of
their disease (moderate or extensive). Patients were randomly assigned to
receive either topical clobetasol propionate cream (40 g per day) or oral
prednisone (0.5 mg per kilogram of body weight per day for those with
moderate disease and 1 mg per kilogram per day for those with extensive
disease). The primary end point was overall survival.
Results Among the 188 patients with extensive bullous pemphigoid, topical
corticosteroids were superior to oral prednisone (P=0.02). The one-year
survival rate was 76 percent in the topical-corticosteroid group and 58
percent in the oral-prednisone group. Disease was controlled at three weeks
in 92 of the 93 patients in the topical-corticosteroid group (99 percent)
and 86 of the 95 patients in the oral-prednisone group (91 percent, P=0.02).
Severe complications occurred in 27 of the 93 patients in the
topical-corticosteroid group (29 percent) and in 51 of the 95 patients in
the oral-prednisone group (54 percent, P=0.006). Among the 153 patients with
moderate bullous pemphigoid, there were no significant differences between
the topical-corticosteroid group and the oral-prednisone group in terms of
overall survival, the rate of control at three weeks, or the incidence of
severe complications.
Conclusions Topical corticosteroid therapy is effective for both moderate
and severe bullous pemphigoid and is superior to oral corticosteroid therapy
for extensive disease.
  _____

Bullous pemphigoid is the most common blistering autoimmune disease of the
skin 1 <http://content.nejm.org/cgi/content/full/346/5/#R1> , 2
<http://content.nejm.org/cgi/content/full/346/5/#R2> ; it is manifested by
cutaneous blisters without mucosal involvement. 3
<http://content.nejm.org/cgi/content/full/346/5/#R3>  Histologic features
include subepidermal blisters. 4
<http://content.nejm.org/cgi/content/full/346/5/#R4>  Autoantibodies
directed against two proteins of the basement-membrane zone, bullous
pemphigoid antigens 1 and 2, are detectable by both direct and indirect
immunofluorescence. 5 <http://content.nejm.org/cgi/content/full/346/5/#R5> ,
6 <http://content.nejm.org/cgi/content/full/346/5/#R6> , 7
<http://content.nejm.org/cgi/content/full/346/5/#R7> , 8
<http://content.nejm.org/cgi/content/full/346/5/#R8> , 9
<http://content.nejm.org/cgi/content/full/346/5/#R9> , 10
<http://content.nejm.org/cgi/content/full/346/5/#R10>  Bullous pemphigoid is
most common in elderly persons. 11
<http://content.nejm.org/cgi/content/full/346/5/#R11> , 12
<http://content.nejm.org/cgi/content/full/346/5/#R12> , 13
<http://content.nejm.org/cgi/content/full/346/5/#R13> , 14
<http://content.nejm.org/cgi/content/full/346/5/#R14>  Systemic
corticosteroids are considered the standard treatment for bullous
pemphigoid. 3 <http://content.nejm.org/cgi/content/full/346/5/#R3> , 15
<http://content.nejm.org/cgi/content/full/346/5/#R15>  A dose of prednisone
of 1 mg per kilogram of body weight per day is usually recommended for the
treatment of patients with severe disease; a lower dose may be used for
patients with moderate disease. 15
<http://content.nejm.org/cgi/content/full/346/5/#R15>  Systemic
corticosteroids are poorly tolerated by elderly patients, however, and have
been suspected of contributing to the high rates of death observed in some
series. 11 <http://content.nejm.org/cgi/content/full/346/5/#R11> , 12
<http://content.nejm.org/cgi/content/full/346/5/#R12> , 16
<http://content.nejm.org/cgi/content/full/346/5/#R16> , 17
<http://content.nejm.org/cgi/content/full/346/5/#R17> , 18
<http://content.nejm.org/cgi/content/full/346/5/#R18>
Many efforts have been devoted to finding corticosteroid-sparing agents for
the treatment of bullous pemphigoid. Uncontrolled studies have suggested the
usefulness of immunosuppressive drugs. 19
<http://content.nejm.org/cgi/content/full/346/5/#R19> , 20
<http://content.nejm.org/cgi/content/full/346/5/#R20> , 21
<http://content.nejm.org/cgi/content/full/346/5/#R21> , 22
<http://content.nejm.org/cgi/content/full/346/5/#R22> , 23
<http://content.nejm.org/cgi/content/full/346/5/#R23> , 24
<http://content.nejm.org/cgi/content/full/346/5/#R24> , 25
<http://content.nejm.org/cgi/content/full/346/5/#R25> , 26
<http://content.nejm.org/cgi/content/full/346/5/#R26>  Unfortunately, the
single controlled study published to date failed to demonstrate a benefit
from the addition of azathioprine to corticosteroid therapy. 27
<http://content.nejm.org/cgi/content/full/346/5/#R27>  Topical
corticosteroids have been proposed as possible treatments for mild forms of
bullous pemphigoid. 28 <http://content.nejm.org/cgi/content/full/346/5/#R28>
, 29 <http://content.nejm.org/cgi/content/full/346/5/#R29> , 30
<http://content.nejm.org/cgi/content/full/346/5/#R30>  Because complications
attributable to oral corticosteroids may contribute to the poor prognosis of
patients with bullous pemphigoid, we conducted a randomized trial comparing
topical corticosteroid treatment with oral corticosteroid treatment in
patients with bullous pemphigoid. The aim of the present study was to assess
whether topical corticosteroids could substantially increase the rate of
survival among patients with bullous pemphigoid and whether they could
effectively control the disease.
Methods
Study Patients
Twenty dermatologic centers in France participated in this prospective,
randomized study. The study was approved by the ethics committee of Seine
Maritime, and written informed consent was obtained from each patient.
Consecutive patients with newly diagnosed bullous pemphigoid were eligible
for entry if the following criteria were met: clinical features suggestive
of bullous pemphigoid 14
<http://content.nejm.org/cgi/content/full/346/5/#R14> ; subepidermal blister
on skin biopsy; and linear deposits of IgG and C3 along the
basement-membrane zone. Exclusion criteria were predominant or exclusive
mucosal involvement and treatment with oral or topical corticosteroids,
dapsone, or immunosuppressive drugs during the previous six months.
Study Design
This randomized, nonblinded study compared two parallel groups of patients
treated with topical or oral corticosteroids. Since overall survival was the
primary outcome, blinding was not deemed necessary. Randomization was
stratified according to the clinical center and the severity of disease,
which was determined on the basis of the mean number of new bullae that had
appeared daily during the three previous days (moderate disease was defined
by <=10 new bullae daily and extensive disease by >10). Randomization was
performed centrally with the use of random numbers in permuted blocks of
four within each stratum. Patients were randomly assigned to receive either
topical applications of 0.05 percent clobetasol propionate cream (Dermoval
cream, Glaxo SmithKline, Philadelphia), or oral prednisone (Cortancyl,
Roussel, Paris). Prednisone was administered once daily at a dose of 0.5 mg
per kilogram of body weight per day in patients with moderate disease and a
dose of 1 mg per kilogram per day in those with extensive disease. The
initial dose was maintained for 15 days after control of the disease had
been attained; thereafter, the dose was reduced by 15 percent every 3 weeks.
Treatment was stopped after 12 months.
Irrespective of the severity of their disease, patients who were assigned to
receive topical corticosteroids received a daily dose of 40 g of clobetasol
propionate that was applied twice daily on the entire surface of the body
until 15 days after control of the disease had been attained. The doses were
then gradually reduced — to 20 g daily for one month, 10 g daily for two
months, 10 g every other day for four months, and finally 10 g twice a week
for four months. When possible, topical corticosteroids were applied by the
patients themselves or by members of their households. A nurse performed
this task for patients who were in poor condition generally.
Relapse was defined as the occurrence of at least three new bullae daily for
three consecutive days during treatment. In patients who had a relapse
during the period when the dose was being reduced, the dose was increased to
the previous level that had permitted control of the disease. Other therapy
that might affect the activity of bullous pemphigoid was avoided throughout
the study period. Investigators stopped treatment if a life-threatening side
effect occurred, irrespective of the patient's treatment group.
Base-Line and Follow-up Measurements
At base line, each patient underwent physical examination. The Karnofsky
score was assessed. The score is a measure of the patient's general
condition and degree of autonomy on a scale ranging from 0 to 100, with
higher scores indicating better condition and greater autonomy. 31
<http://content.nejm.org/cgi/content/full/346/5/#R31>  The number of new
bullae that appeared daily was noted by a nurse who was not otherwise
involved in the study. Because of the high mortality reported in recent
studies during the first year after the diagnosis of bullous pemphigoid, we
planned 12 months of follow-up. At each follow-up visit (on days 7, 14, 21,
30, 90, 180, and 360), the patients underwent physical examination, and the
number of new bullae that appeared daily was noted, as was the number of
units of clobetasol propionate cream that had been used. The date of any
relapse was recorded, as were the date and cause of death in any patient who
had died. Any side effects of treatment were assessed, and their severity
was graded 1 for mild effects, 2 for moderate effects, 3 for severe effects,
or 4 for life-threatening effects, according to standard criteria of the
World Health Organization. 32
<http://content.nejm.org/cgi/content/full/346/5/#R32>
Statistical Analysis
The primary end point was overall survival during the first year after the
onset of bullous pemphigoid. Secondary end points were control of the
disease at day 21, defined as the absence of new bullae for three
consecutive days; occurrence of severe (grade 3 or 4) side effects (adverse
events requiring hospitalization or prolongation of hospitalization or
life-threatening events) during the first year; and cumulative hospital days
(including the initial hospitalization plus all rehospitalizations).
The study was designed to have 80 percent power to detect a 50 percent
reduction in the one-year mortality rate for both moderate and extensive
bullous pemphigoid, from 40 to 20 percent, with the two-sided log-rank test
and a type I error of 5 percent. To achieve this power, 75 patients were
needed in each treatment group. Separate intention-to-treat analyses were
performed for patients with moderate and severe bullous pemphigoid. No
interim efficacy analysis was either scheduled or performed.
Distributions of overall survival according to treatment group were
estimated by the Kaplan–Meier method and compared with the use of the
log-rank test. A Cox model was used to adjust the comparisons between
treatment groups for base-line characteristics that were suspected a priori
to have prognostic significance — namely, older age (>=80 years vs. <80
years) and poor general condition as measured by the Karnofsky score (<=40
vs. >40). 11 <http://content.nejm.org/cgi/content/full/346/5/#R11>  Fisher's
exact test was used to compare the treatment groups in terms of the
proportions of patients with controlled bullous pemphigoid at day 21, as
well as the frequency of severe side effects. Exact binomial probabilities
were used to estimate 95 percent confidence intervals for the rates of
control of disease. Student's t-test was used to compare the mean durations
of hospitalization. For all tests, two-sided P values of less than 0.05 were
considered to indicate statistical significance. Continuous variables are
expressed as means ±SD.
Results
Patients
Between January 1996 and December 1998, 364 patients were assessed for
eligibility. Eight declined to provide informed consent. Previous use of
medication effective against bullous pemphigoid (in eight patients),
diagnosis of another autoimmune blistering-skin disease (in four patients),
spontaneous healing of skin lesions (in two patients), and immediate
withdrawal of consent (in one patient) were other reasons for exclusion. Of
the 341 remaining patients, 153 had 10 or fewer new bullae daily (moderate
disease) and 188 had more than 10 new bullae daily (extensive disease). A
total of 77 patients with moderate disease were randomly assigned to receive
clobetasol propionate cream and 76 to receive oral prednisone at a dose of
0.5 mg per kilogram per day. A total of 93 patients with extensive disease
were randomly assigned to receive clobetasol propionate cream and 95 to
receive oral prednisone at a dose of 1 mg per kilogram per day. The
base-line characteristics of the patients are shown in Table 1
<http://content.nejm.org/cgi/content/full/346/5/#T1> . Among both patients
with moderate bullous pemphigoid and patients with extensive bullous
pemphigoid, the treatment groups were well balanced in terms of the
base-line characteristics. The mean duration of follow-up among surviving
patients with severe bullous pemphigoid was 360 days in the oral-prednisone
group and 359 days in the topical-corticosteroid group. The corresponding
figures among surviving patients with moderate bullous pemphigoid were 361
and 360 days, respectively. One patient with moderate bullous pemphigoid who
was randomly assigned to the topical-corticosteroid group decided to stop
treatment during the third month of the study.


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Table 1. Base-Line Characteristics of the Patients.

Overall Survival
A total of 107 patients died during the one-year follow-up; 46 of these had
moderate bullous pemphigoid, and 61 had extensive bullous pemphigoid. The
causes of death were determined in 71 cases; the main causes were sepsis (in
27 patients, including 20 with pneumonia), cardiovascular disease (in 13
patients), and stroke (in 9 patients).
Among the patients with moderate bullous pemphigoid, 23 patients in the
topical-corticosteroid group died (30 percent), and 23 in the
oral-prednisone group died (30 percent). The log-rank test did not indicate
any difference in overall survival between the two treatment groups
(P=0.95). The one-year Kaplan–Meier survival rate was 69 percent in both
groups ( Figure 1A <http://content.nejm.org/cgi/content/full/346/5/#F1> ).
Similarly, no difference was evident in the Cox regression model that
included age and Karnofsky score (P=0.69).


  <http://content.nejm.org/cgi/content/full/346/5/321/F1>
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Figure 1. Kaplan–Meier Estimates of the Overall Survival of Patients with
Moderate Bullous Pemphigoid (Panel A) or Extensive Bullous Pemphigoid (Panel
B), According to Treatment-Group Assignment.
P values were determined by the log-rank test.

Among the patients with extensive bullous pemphigoid, 22 patients in the
topical-corticosteroid group died (24 percent), and 39 patients in the
oral-prednisone group died (41 percent). Overall survival was significantly
longer with topical corticosteroids than with oral prednisone (P=0.02).
One-year Kaplan–Meier survival rates were 76 percent and 58 percent,
respectively ( Figure 1B
<http://content.nejm.org/cgi/content/full/346/5/#F1> ). With the use of the
Cox regression model, this beneficial effect of clobetasol propionate was
confirmed after adjustment for age and Karnofsky score (P=0.009).
Disease Control and Relapse
In all 77 patients with moderate bullous pemphigoid who were assigned to the
topical-corticosteroid group (100 percent; 95 percent confidence interval,
95 to 100 percent) and 72 of the 76 patients with moderate bullous
pemphigoid who were assigned to the oral-prednisone group (95 percent; 95
percent confidence interval, 87 to 99 percent), control of bullous
pemphigoid was achieved by day 21 (P=0.06). Control was achieved by day 21
in 92 of the 93 patients with extensive bullous pemphigoid in the
topical-corticosteroid group (99 percent; 95 percent confidence interval, 94
to 100 percent) and in 86 of the 95 patients with extensive bullous
pemphigoid in the oral-prednisone group (91 percent; 95 percent confidence
interval, 83 to 96 percent; P=0.02).
A total of 30 of the 76 patients with moderate disease in the
oral-prednisone group (39 percent; 95 percent confidence interval, 28 to 50
percent) and 27 of the 77 patients in the topical-corticosteroid group (35
percent; 95 percent confidence interval, 24 to 46 percent) had relapses
during follow-up after a mean interval of 149±109 days and 178±118 days,
respectively. The corresponding figures among the patients with extensive
disease were 44 of the 95 patients in the oral-prednisone group (46 percent;
95 percent confidence interval, 36 to 56 percent) after a mean interval of
210±133 days and 34 of the 93 patients in the topical-corticosteroid group
(37 percent; 95 percent confidence interval, 27 to 46 percent) after a mean
interval of 187±118 days.
Compliance with Treatment and Adverse Effects
In accordance with the study protocol, the investigators switched three
patients with moderate bullous pemphigoid and four with extensive bullous
pemphigoid from the oral-prednisone group to the topical-corticosteroid
group because of side effects of treatment. The life-threatening side
effects in these patients were septicemia (in two patients), severe
pneumonia with respiratory distress (in two patients), postoperative sepsis
after hip fracture (in one patient), necrotizing cellulitis of the leg (in
one patient), and myocardial infarction with acute cardiac failure (in one
patient). Two of these seven patients died during the study period. There
were no life-threatening side effects in patients assigned to the
topical-corticosteroid group. One patient with severe bullous pemphigoid who
was initially assigned to the topical-corticosteroid group was later treated
with oral prednisone, at a dose of 1 mg per kilogram per day, by a physician
who was not aware of the protocol; this patient died of pneumonia 15 days
after the treatment was changed.
Overall, 172 severe (grade 3) or life-threatening (grade 4) side effects
were reported in 132 patients ( Table 2
<http://content.nejm.org/cgi/content/full/346/5/#T2> ). Severe side effects
were reported in 29 of the 76 patients with moderate disease in the
oral-prednisone group (38 percent), as compared with 25 of the 77 patients
with moderate disease in the topical-corticosteroid group (32 percent,
P=0.46). Severe side effects were observed in 51 of the 95 patients with
extensive disease in the oral-prednisone group (54 percent), as compared
with 27 of the 93 patients with extensive disease in the topical
corticosteroid group (29 percent, P=0.006). Among the 10 patients with
extensive bullous pemphigoid in whom disease was not controlled by day 21,
severe adverse events occurred in 5 of the 9 patients in the oral-prednisone
group, and 3 of the 9 patients in that group died, whereas neither a severe
adverse event nor death occurred in the 1 patient in the
topical-corticosteroid group.


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Table 2. Incidence of Grade 3 or 4 Adverse Events after the Initiation of
Treatment.

Duration of Hospitalization
Most patients were initially hospitalized during the acute phase of their
disease. Some patients were rehospitalized during the follow-up period
because of relapse or side effects. The length of hospital stay according to
treatment group is shown in Table 3
<http://content.nejm.org/cgi/content/full/346/5/#T3> . The mean cumulative
duration of hospitalization was shorter in the topical-corticosteroid group
than in the oral-prednisone group: 11±11 days and 17±14 days, respectively,
among patients with moderate bullous pemphigoid (P=0.02) and 17±14 days and
25±20 days, respectively, among those with extensive bullous pemphigoid
(P=0.002).


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Table 3. Number of Hospital Stays and Duration of Hospitalization.

Discussion
Systemic corticosteroids have been considered the mainstay of treatment for
bullous pemphigoid for 40 years. 3
<http://content.nejm.org/cgi/content/full/346/5/#R3>  However, this
treatment is responsible for numerous side effects in elderly people and has
been suspected of being associated with a mortality rate of up to 40 percent
per year among elderly persons with bullous pemphigoid. 11
<http://content.nejm.org/cgi/content/full/346/5/#R11> , 12
<http://content.nejm.org/cgi/content/full/346/5/#R12> , 16
<http://content.nejm.org/cgi/content/full/346/5/#R16> , 17
<http://content.nejm.org/cgi/content/full/346/5/#R17> , 18
<http://content.nejm.org/cgi/content/full/346/5/#R18> , 33
<http://content.nejm.org/cgi/content/full/346/5/#R33> , 34
<http://content.nejm.org/cgi/content/full/346/5/#R34>  The present study
confirms the poor prognosis of patients with bullous pemphigoid who are
treated with 1 mg of prednisone per kilogram per day, among whom the
one-year mortality rate was 41 percent. Among the patients who received
topical treatment, there was no difference in overall survival between
patients with moderate bullous pemphigoid and those with extensive bullous
pemphigoid, suggesting that survival of patients with bullous pemphigoid is
more likely to be related to the type of treatment than to the severity of
disease. 11 <http://content.nejm.org/cgi/content/full/346/5/#R11> , 27
<http://content.nejm.org/cgi/content/full/346/5/#R27>
The present study was designed to test the hypothesis that topical
corticosteroids could be an effective alternative treatment for patients
with bullous pemphigoid and would result in a decrease in the incidence of
severe adverse events. Our results clearly demonstrate the efficacy of
clobetasol propionate cream. In all patients with moderate bullous
pemphigoid and 99 percent of those with extensive bullous pemphigoid, the
disease was controlled by day 21 — an improvement over oral-corticosteroid
treatment that was significant among those with extensive disease. Moreover,
the rates of control of disease in both subgroups of the oral-prednisone
group were higher than those usually reported with oral corticosteroids. 27
<http://content.nejm.org/cgi/content/full/346/5/#R27> , 35
<http://content.nejm.org/cgi/content/full/346/5/#R35>  This finding may be
related to the high bioavailability of prednisone and seems consistent with
the greater effectiveness reported for prednisone than for prednisolone in
controlling bullous pemphigoid. 35
<http://content.nejm.org/cgi/content/full/346/5/#R35>
The main finding of this study is the significant and substantial
improvement in outcome among patients with extensive bullous pemphigoid who
were treated with clobetasol propionate cream, as compared with those
treated with 1 mg per kilogram per day of oral prednisone. This difference
was observed consistently for all the outcomes we studied: overall survival,
control of disease, occurrence of severe side effects, and duration of
hospitalization.
It is important to consider whether the nonblinded nature of the study may
have biased our results. We think such bias is unlikely, for several
reasons. First, it is unlikely that overall survival, our primary end point,
could be subject to such bias. Moreover, bias concerning secondary end
points is unlikely as well, because most were graded semiquantitatively and
were not directly dependent on subjective judgment. Indeed, assessment of
the control of disease was based on the determination of the number of new
bullae that appeared daily by nurses who were not directly involved in the
study, and most grade 3 and grade 4 side effects represented well-known side
effects of corticosteroids that were characterized biologically (diabetes
mellitus), radiologically (stroke, pneumonia, and bone fracture), or
bacteriologically (septicemia, arthritis, and peritonitis). Differences in
the cumulative duration of hospitalization were due, at least in part, to
rehospitalizations initiated by the patients' general practitioners — not by
study investigators — because of side effects of the treatments.
Our study demonstrates the superiority of an alternative treatment regimen
over oral corticosteroids in the treatment of extensive bullous pemphigoid,
in terms of both the control of disease and survival. In patients with
extensive bullous pemphigoid, topical corticosteroids led to a 43 percent
reduction (95 percent confidence interval, 19 to 69 percent) in the one-year
mortality rate. This benefit is further supported by the demonstration of a
50 percent reduction in the mortality rate (95 percent confidence interval,
15 to 71 percent) after adjustment by Cox regression for age and Karnofsky
score — two factors strongly suspected to be related to the prognosis in
patients with bullous pemphigoid. 11
<http://content.nejm.org/cgi/content/full/346/5/#R11>  The chief explanation
for the present results is the fact that topical treatment has lower
toxicity than 1 mg of prednisone per kilogram per day, as demonstrated by
the fact that fewer patients in the topical-corticosteroid group had severe
side effects of treatment. This difference was particularly marked in the
case of side effects, such as sepsis and diabetes mellitus requiring
insulin, that are classically reported with high-dose systemic
corticosteroids. Our results suggest that topical corticosteroids should be
considered the standard treatment for patients with extensive bullous
pemphigoid.
Supported by research grants from Rouen University Hospital and the French
Society of Dermatology.
We are indebted to the patients who participated in the study; to Veronique
Chambaretaud for technical assistance during the study; and to Annick
Horville and Richard Medeiros for their assistance in the preparation of the
manuscript.
* Other participants in the Bullous Diseases French Study Group are listed
in the Appendix. <http://content.nejm.org/cgi/content/full/346/5/#RFN1>

Source Information
From the Departments of Dermatology and Biostatistics, INSERM Unite 519,
University of Rouen, Rouen (P.J., J.B., P.Y.); and the Departments of
Dermatology at the University of Paris XII, Creteil (J.-C.R.); Bichat
University, Paris (C.P.); the University of Nantes, Nantes (B.D.); the
University of Lille, Lille (E.D.); the University of Tours, Tours (L.V.);
the University of Clermont-Ferrand, Clermont-Ferrand (M.D.); the General
Hospital of Quimper, Quimper (P.P.); the University of Limoges, Limoges
(C.B.); and the University of Reims, Reims (P.B.) — all in France.
Address reprint requests to Dr. Joly at the Clinique Dermatologique, Hôpital
Charles Nicolle, 1, rue de Germont, 76031 Rouen CEDEX, France, or at
[log in to unmask] <mailto:[log in to unmask]> .
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Appendix
The following persons also participated in the Bullous Diseases French
Study. Investigators: P. Saiag, M.D., Ph.D., Boulogne Billancourt; E.
Tancrede-Bohin, M.D., Paris; B. Sassolas, M.D., Brest; C. Lok, M.D., Ph.D.,
Amiens; B. Labeille, M.D., Valence; J.C. Guillaume, M.D., Colmar; F. Loche,
M.D., Toulouse; M.S. Doutre, M.D., Ph.D., Bordeaux; I. Gorin, M.D., Paris;
O. Chosidow, M.D., Ph.D., Paris; C. Pauwels, M.D., Saint Germain en Laye.
Contributors: C. Neveu, M.D., Lillebonne; M.F. Hellot, M.Sc., Rouen; I.
Noblesse, M.D., Rouen.


This article has been cited by other articles:
*       Stern, R. S. (2002). Bullous Pemphigoid Therapy -- Think Globally, Act
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Edward E. Rylander, M.D.
Diplomat American Board of Family Practice.
Diplomat American Board of Palliative Medicine.