ARTICLE
Auteur(s) : Martin Pfütze, Andrea Niedermeier, Michael
Hertl, Rüdiger
Eming
Department of Dermatology and Allergology, Philipps-University,
Marburg, Deutschhausstraße 9, 35037 Marburg, Germany
accepté le 11 Octobre 2006
Pemphigus is a potentially life threatening, chronic skin disorder
which is characterised clinically by blisters/erosions of the
mucous membranes and skin and serologically by circulating
autoantibodies against distinct adhesion molecules of the epidermis
[1, 2]. Great progress has been made in understanding the immune
pathogenesis of pemphigus which has led to the development of novel
therapeutic strategies aimed at reducing the side effects of
immunosuppressive treatment with corticosteroids and other
immunosuppressive adjuvants. As pemphigus is rare (incidence about
1-5 /106/year), only a few controlled studies have
been performed to demonstrate the therapeutic effects of distinct
immunosuppressive drugs [1, 3]. Most reports are based on a rather
subjective or non-specific rating of the clinical therapeutic
effects, or use of autoantibody titres to determine disease
activity. Furthermore, many authors use terms describing
therapeutic success or resistance such as “complete remission” and
“partial remission” without consistent definitions of these terms.
In addition, most studies lack standardised scores to evaluate the
clinical status of the patients.An objective scoring system for
pemphigus, which is effective and easy to use would thus be
desirable to compare the efficacy of different treatments,
including novel therapeutic approaches. During the past years
efforts have been made to develop such a scoring system. These
scores aim at comparing inter-individual differences in disease
activity. Pemphigus is a clinically heterogenous disorder: while
patients with pemphigus foliaceus (PF) suffer primarily from
cutaneous lesions, patients with pemphigus vulgaris (PV) are mainly
afflicted with blisters/erosions of the oral mucosa or both,
cutaneous and mucosal lesions [2, 3]. By classification of
heterogenous clinical phenotypes in broad score ranges slight and
sometimes even major intra-individual changes in disease activity
may not be properly reflected.The major focus of the present study
was to take the clinical variability of pemphigus into account to
develop a score which consists of different components, each
standing independently on its own and representing the clinically
most relevant areas of involvement: skin and oral mucosa. For all
other sites of clinical involvement we used a standardised method
of documentation instead of scoring each distinct area separately.
The present findings with ABSIS in pemphigus strongly suggest that
this scoring system is capable of assessing intra-individual
differences in disease activity in patients with pemphigus.
Moreover, ABSIS holds promise as a clinical scoring system for
additional autoimmune bullous disorders, such as bullous pemphigoid
and epidermolysis bullosa acquisita.
Methods
Scoring of skin involvement by ABSIS
The ABSIS skin score focused on two clinical criteria, i.e. 1) the
extent of the affected area and 2) the quality of the skin lesions.
The extent of skin lesions was assessed by the “rule of nine”.
According to this rule, defined areas equal to nine percent or to a
multiple of nine percent of the total body surface area (BSA) were
assessed; the palm of the patient’s hand (and areas of the
equivalent size) was set as one percent of BSA ( (figure 1) ). The extent of
BSA (in percentage) was then multiplied with a weighting factor
which was defined as: 1.5 for erosive, exsudative lesions, blisters
and/or positive Nikolsky’s sign; 1 for erosive, dry lesions; and
0.5 for re-epithelized lesions (excluding post inflammatory
erythema and/or hyperpigmentation) ( (figure 2) ). The most
dominant appearance of skin lesions determined the appropriate
weighting factor. ( Figure 3 ) shows a patient
with mucocutaneous PV to demonstrate how the above mentioned
different qualities of skin lesions were assessed.
As the scores of patients with different clinical patterns show
varying ABSIS score levels, the relative decrease or increase of
ABSIS compared to the initial score can be used to also compare
inter-individual changes of disease activity.
Scoring of oral involvement by ABSIS
For the evaluation of oral mucosal involvement we used a modified
grading system previously described by Saraswat and Kumar which
consists of two separate scores [4]. These allow us to represent
both the extent and severity of oral lesions (table 1( Table 1 )).
The first mucosal score is obtained by assessment of 11 distinct
anatomical sites: upper and lower gingival mucosa, upper and lower
lip mucosa, left and right buccal mucosa, tongue, floor of the
mouth, hard and soft palate and the pharynx. The presence or
absence of any lesion at all these sites is rated as 1 or 0,
respectively, resulting in a total score, ranging from 0 (no
lesions) to 11 (maximal extent).
The second mucosal score is based on the assessment of the
severity of symptoms and is based on a quantitative dysphagia
grading system introduced by Dakkak and Bennet [5]. Different
liquid and solid foods of increasing consistency are evaluated
concerning their ability to induce pain or bleeding in the
following manner: 1 point if pain/bleeding always occurred; 0.5
points if pain/bleeding occurred sometimes; and 0 points if the
patient never experienced problems during the last observation
period. If a particular food can not be eaten at all, that food and
all others listed below are rated 1 point. The score is then
calculated by multiplying each point with a food specific value and
adding the products, the total ranging from 0 (no symptoms) to 45
(severe symptoms) (table 2( Table 2 )).
The total oral mucosa score is then described as 0-11/0-45, with
the first score representing the extent and the second describing
the severity.
Table 1 Overview of the sites of involved and clinical
parameters assessed by the Autoimmune Bullous Skin Disorder
Intensity Score (ABSIS)
|
Body site of involvement
|
Parameters assessed by ABSIS
|
|
Skin involvement (two additive scores)
|
|
1. Extent (percent of BSA involvement): score:
0-100%
|
|
2. Weighting factor (measuring quality of lesions as a
multiplyer of value for)
|
|
• Bullae, erosions: factor 1.5
|
|
• Dry erosions: factor 1.0
|
|
• Re-epithelized erosions: factor 0.5
|
|
Total score: % of BSA * weighting factor = 0-150
points
|
|
Oral involvement (two independent scores)
|
Mucosal score 1
|
Extent (presence of lesions on defined sites): score:
0-11 points
|
|
Mucosal score 2
|
Severity (discomfort during eating/drinking): score: 0-45
points
|
Table 2 Assessment of oral mucosa severity score [4]
|
Water
|
|
(1 * x)
|
|
Soup
|
|
(2 * x)
|
|
Yogurt
|
|
(3 * x)
|
|
Custard
|
|
(4 * x)
|
|
Mashed potatoes/Scrambled egg
|
|
(5 * x)
|
|
Baked fish
|
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(6 * x)
|
|
White bread
|
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(7 * x)
|
|
Apple/raw carrot
|
|
(8 * x)
|
|
Fried steak/whole-grain bread
|
+
|
(9 * x)
|
|
Severity-Score:
|
0-45 points
|
Statistical analysis of clinical data generated by ABSIS
All clinical data was fed into the self-made ABSIS computer
database (based on Microsoft® Access) which facilitated
calculation of the scores. All parameters could be exported and
analysed in data processing programs. Table 1 gives an overview of
all parameters assessed by ABSIS.
Documentation of serum autoantibody titres by enzyme-linked
immunosorbent assay (ELISA)
Titres of IgG autoantibodies against desmoglein 1 and 3, the
autoantigens of pemphigus, were obtained by enzyme-linked
immunosorbent assay (ELISA) as previously described [6]. As
proposed by Amagai and coworkers, autoantibody titres were
expressed as protein index values (PIV) [6, 7]. These serological
parameters were not considered in the calculation of the ABSIS
score.
Results
Evaluation of cutaneous involvement in pemphigus by ABSIS
As shown in tables 1 and 2, the ABSIS skin score consists of a two
step procedure which assesses both the extent and quality of
cutaneous involvement in pemphigus. The extent of skin involvement
was calculated, applying the “rule of nine”. ( Figure 2 ) shows an example
of how the second ABSIS component, i.e. the weighting factor which
describes the quality of cutaneous lesions, was applied in a
patient with mucocutaneous pemphigus and how the final ABSIS skin
score was assessed.
Long term follow up of disease activity in individual pemphigus
patients by ABSIS
( Figure 3 )
illustrates the clinical course of a representative female patient
with severe mucocutaneous PV. Initially, she suffered from
extensive exsudative erosions of the chest, back, shoulders and
face, resulting in an ABSIS score of 25.5 points ( (figure 3A) ).
Immunosuppressive treatment led to a dramatic improvement of the
skin lesions which was reflected by a decrease of the ABSIS score
from 25.5 to 17 points ( (figure 3B) ). Four months
later, the patient presented with almost complete clinical
remission presenting as postinflammatory erythema, except for small
residual re-epithelized erosions on the face (not shown) and trunk
( (figure 3C) )
which resulted in an ABSIS score of 4 points.
Correlation of the ABSIS skin score with the clinical disease
activity of PV patients
To investigate the usefulness of ABSIS as a valid parameter for the
clinical activity of pemphigus, a group of 13 PV patients at
different disease stages were scored by ABSIS ( (figure 4) ). Disease
activity was defined as acute (acute onset with ≤ 3 month
duration), chronic (active disease with a duration of ≥ 3 month),
and remittent (no clinical lesions for ≥ 1 month). Our observations
demonstrate that the median ABSIS values for skin and mucosal
involvement were highest in the group of patients with acute onset
PV (skin: 6.5 (3-17.3); mucosa: 5 (4-5.5)) (all values given in:
“median (25. percentile - 75. percentile)”) followed by the score
for chronic active PV (skin: 1.8 (1.5-2), mucosa: 3(1.5-3.8)) and
finally, for remittent PV (skin: 0 (0-0); mucosa: 0 (0- 0)) ( (figure 4) ). There
was a distinct decrease of both ABSIS skin score and the mucosal
ABSIS score from acute to chronic and finally, remittent PV ( (figure 4) ). The
decrease of the ABSIS skin score was accompanied by a gradual
decrease of Dsg1- /Dsg3-reactive IgG autoantibodies. Not only the
difference of disease activity but also the decrease of disease
activity over a time course of 6 month was well represented by
ABSIS ( (figure
5) ). Thus, the ABSIS skin score was a valuable parameter
to assess disease activity in pemphigus not only intra-individually
but also inter-individually.
Since, upon initiation of immunosuppressive treatment, disease
duration is associated with clinical improvement of PV, we sought
to compare the value of the ABSIS score and serological analysis of
serum autoantibodies in a cohort of 13 patients with PV ( (figure 5) ). The
decrease of disease activity determined by ABSIS skin and mucosa
scores and titres of dsg1-/dsg3-specific IgG autoantibodies was
plotted over a time course of 6 months after initiation of
immunosuppressive therapy. Clinical improvement was documented by a
continuous decrease of ABSIS skin and mucosa scores which were at
baseline after 6 months. Autoantibody titers decreased but were
still detectable after 6 months and thus in discordance with the
observed clinical remission at this time point. Thus ABSIS scoring
truly reflected clinical disease activity while autoantibody titers
did not ( (figure
5) ).
Scoring of mucosal pemphigus by ABSIS
The assessment of oral lesions in PV is difficult since clinical
improvement is not only reflected by the extent of mucosal lesions
but also by the tendency of the blisters/erosions to healing. Thus,
for a more detailed classification the present ABSIS score for
mucosal lesions consists of two components, i.e. extent and quality
of mucosal lesions (tables 1 and 2). Applied to individual patients
with PV, the score reflects not only changes of extent but also
quality of oral mucosal lesions as shown in ( figure 6 ). A patient with
acute onset oral PV showed extensive erosions of the oral mucosa
without a visible tendency to healing. Erosions on 7 of 11 defined
areas (lower gingiva, upper lip, left and right buccal mucosa,
floor of the mouth, soft palate and the pharynx) resulted in an
extent score of 7. At this time the patient was able to eat/drink
water, soup, yogurt, custard and scrambled egg without pain or
bleeding, baked fish, white bread, fried steak with pain/bleeding
only sometimes and always expected pain/bleeding on eating apples
or raw carrots. Thus, according to table 2 resulting in a severity
score of 19. The combined mucosal ABSIS score (extent/quality of
lesions) was 7/19 ( (figure 6A) ). Fifteen days
of immunosuppressive treatment resulted in a qualitative but not
quantitative improvement of the erosions. At this point the patient
was able to eat baked fish and white bread without discomfort.
According to table 2 this was reflected by a decrease of ABSIS from
7/19 (extent/quality of lesions) to 7/12.5 points ( (figure 6B) ).
The majority of patients were scored retrospectively. Thus, we
were not able to analyse the functional part of the score in these
patients. Therefore, the data provided in figures 4 and 5
display only the first part of the mucosal score (extent).
Nevertheless, as shown by the clinical example above, in most
patients with mucosal pemphigus who were scored with both parts of
the score (1: extent; 2: quality of lesions) the subjective
clinical findings were well represented by the ABSIS mucosal
scores.
Discussion
We here present a novel clinical autoimmune bullous skin disorder
score, ABSIS, which we propose as an improved clinical score to
evaluate and monitor the status of both mucosal and cutaneous
lesions in patients with pemphigus. The advantage of the present
ABSIS score over previous scores is its suitability to monitor the
clinical status of individual patients over time while most of the
other scores were designed to compare disease activity among
different patients. ABSIS consists of a quality and quantity based
score for cutaneous lesions and two separate quantitative and
qualitative scores for oral mucosal involvement (table 1). Thus,
combining quantitative and qualitative scores allows for a more
comprehensive analysis of both the clinical status and the
individual impairment of patients with autoimmune bullous skin
disorders such as pemphigus.
Table 3( Table 3 ) shows an overview
of previously introduced clinical scores for autoimmune bullous
skin disorders. These scores aimed at comparing inter-individual
differences in disease activity. Pemphigus is a clinically
heterogenous disorder: while patients with pemphigus foliaceus
suffer primarily from cutaneous lesions, patients with PV are
mainly afflicted with blisters/erosions of the oral mucosa or both
cutaneous and mucosal lesions [2, 3]. By classification of
heterogenous clinical phenotypes in broad score ranges slight and
sometimes even major intra-individual changes in disease activity
may not be properly reflected.
Despite several studies that introduced different grading
systems for bullous skin disorders [4, 8-11], there is at present
no generally accepted score. This circumstance is based on
difficulties in creating an easy and comprehensive scoring system
for a group of rather heterogeneous disorders. Due to the clinical
variability of autoimmune bullous skin disorders it is a
challenging problem to involve all possible sites of disease
activity in a single score without under-representing the relative
impact of each location. For example, mild erosions of the oral
mucosa are usually more relevant for the patients’ well-being than
similar or more extensive cutaneous lesions. In particular,
erosions of distinct mucosal sites which appear similar to the
investigator may be of differential severity for the patient. Thus,
the different components of ABSIS (skin, oral mucosa) were
evaluated and regarded separately.
With regard to cutaneous involvement in pemphigus, Agarwal et
al. and Mahajan et al. proposed a scoring system which was mainly
based on the extent of skin involvement. Using these scores, the
extent of lesions was graded similarly to the psoriasis area and
severity index (table 1) [8, 11]. Since this technique of grading
depends on broad ranges of BSA involvement, only changes greater
than 10% of affected BSA (an area equal to the entire chest; (
figure 1 )) are
reflected within this score [8, 11]. Furthermore, using this
classification system higher area scores are only obtained when
skin involvement extends to more than 50% of BSA.
Another score for cutaneous involvement described by Agarwal et
al. and Harman et al. counts the number of newly arisen blisters
per time or the absolute number of blisters (table 1) [8, 10]. As
the number of lesions does not reflect the overall size of the
lesions, these scores do not always precisely reflect disease
activity.
A number of studies graded clinical disease severity in
pemphigus analogous to the scoring system introduced by Herbst and
Bystryn [9]. This score mainly considers the dose of
corticosteroids and/or adjuvant immunosuppressants in addition to
the presence or absence of involvement of defined body areas in
general (table 1). Applying this scoring system may not
appropriately reflect changes in disease activity within the same
body area. Furthermore, the score introduced by Herbst and Bystryn
may be not applicable to patients who show a differential clinical
involvement of mucosal and cutaneous lesions.
It has been repeatedly shown that scores using the affected BSA
underlie a substantial variation when used by different observers
[12-14]. Remarkably, in most of these studies people untrained in
BSA assessment were investigators. These persons showed a high
inter-observer variability in BSA assessment, whereas the
inter-observer variability was small in a subgroup of
dermatologists [14]. The authors even describe an intriguing
consistency of the results of three members within this subgroup
who had a research interest in measurement of body area.
Furthermore, the intra-observer variability did not show
significant differences, even in untrained observers [13]. In the
present study, ABSIS scores were calculated by a single
investigator (resident in dermatology) who was also involved in the
clinical follow-up of the patients. Based on our experience, 1)
training in BSA assessment is essential and 2) to further reduce
the inter-observer variability the group of investigators measuring
ABSIS in local facilities should preferably be restricted to one or
two, especially in clinical trials.
In a previous study conducted by Herbst and Bystryn, which
quantified defined sites according to the presence or absence of
involvement in general, alterations of the oral mucosa, which is
one of the defined areas, were not optimally reflected. This score
does not reveal subtle changes in oral mucosal involvement, as the
entire range of possible mucosal involvement is reflected by only
one point within a maximum extent score of four points [9].
Counting of oral mucosal lesions as described by Harman et al.
and Ishii et al. may not be sensitive enough for scoring of oral
involvement, since these scores only express changes in disease
activity when the number of lesions has changed dramatically (e.g.
from 10 to 3 erosions) [6, 10]. Furthermore, large erosions are
equally rated to small erosions and initial healing of oral
erosions has no impact on the assessment of the number of lesions.
Classifying these lesions as mild, moderate or severe bears the
risk of inter-observer variability [8].
As classification of oral mucosal involvement appears only
useful in combination with an objective severity factor, Saraswat
et al. and Mahajan et al. introduced scoring systems for oral
pemphigus, that were based on extent and severity [4, 11]. While
the score by Mahajan et al. [11] is based on the ability of food
intake and a rather subjective rating for the extent of the
disease, Saraswat et al. [4] proposed a compound scoring system
that is characterised by an objective score for both extent and
severity. The extent is expressed as a semi-quantitative score,
that is dependent on the number of involved sites of the oral
mucosa, whereas the second component of the score is based on
discomfort related to ingestion of defined liquid or solid food,
which is mostly increased according to the severity of oral
involvement. Thus, the combination of scores for the extent and
severity of oral mucosal lesions results in a comprehensive
validation of oral mucosal involvement in bullous skin disorders (
(figure 4) ).
Using ABSIS, we were able to express qualitative changes of mucosal
involvement even though the size of the mucosal lesions had not
changed ( (figure
4) ).
Apart from the present findings in pemphigus, ABSIS may be also
applicable to other autoimmune bullous skin disorders. Recently,
Niedermeier et al utilized the ABSIS skin and mucosa scores to
monitor the therapeutic effect of immunoadsorption and rituximab in
two patients with severe mechanobullous epidermolysis bullosa
acquisita [15]. Their findings demonstrate that the clinical
improvement/persistence of both cutaneous and mucosal lesions was
well reflected by ABSIS. Thus, ABSIS holds great promise for
scoring skin and mucosal lesions for clinical follow-up
studies.
Ocular involvement in pemphigus is rare and difficult to
quantify. Hence, conjunctival involvement was not documented in
ABSIS. For scoring of other autoimmune bullous skin diseases with
ocular involvement, such as mucous membrane pemphigoid, we propose
the classification introduced by Tauber et al. [16]. While less
detailed classifications are relatively insensitive in detecting
disease progression [16-18], the use of the former staging system
appears too extensive for routine dermatologic examination. Thus,
patients with predominantly ocular cicatrisation should be scored
with regard to eye involvement together with an
ophthalmologist.
In summary, even though several scoring systems have been
introduced in autoimmune bullous skin disorders, none of them is
generally accepted. This may be due to the inability of these
scores to reflect minor changes in the disease activity of
individual patients. The newly introduced ABSIS score provides
quantitative and qualitative parameters for the intra-individual
follow-up of both cutaneous and mucosal involvement in patients
with pemphigus, and potentially, with other autoimmune bullous skin
disorders.
Table 3 Overview of clinical activity scores for
autoimmune bullous skin disorders
|
Author (year)
|
Score range
|
Parameters assessed
|
Advantages
|
Disadvantages
|
|
Agarwal et al. (1998)
|
skin: 0-15
|
Area (0-6 points)
|
Activity (0-4 points)
|
- – body and oral mucosa score are separate but can be added
- – Nikolsky’s sign is used as a sensitive marker of disease
activity
|
- – higher area scores are only obtained by skin involvement
> 50%
- – slight changes in disease activity are not taken into
account
- – classification of activity (extension) is subjective
- – oral mucosa score is imprecise
|
|
|
- graded similar to PASI:
- none, 0-15; 16-30; 31-50; 51-70; 71-90 and >90
|
based on number of new blisters/day, extension of existing blisters
(none, mild, moderate, extensive) and Nikolsky’s sign (none,
perilesional, distant sites)
|
|
oral mucosa: 0-6
|
Area (0-3 points)
|
Severity (0-3 points)
|
|
|
- none; 1 site; 2 sites;
- > 2 sites
|
none, mild, moderate, severe
|
|
Herbst & Bystryn (2000)
|
0-10
|
Extent (0-4 points)
|
Therapy (0-6 points)
|
– includes information on required immuno-suppressive therapy
|
- – therapy overrepresented
- – dimension of single erosions has no influence on score
- – oral mucosa is under-represented; especially in patients with
oral lesions only
|
|
|
depending on affection or no affection of defined areas of the
body, incl. oral mucosa
|
- based on oral dose of corticosteroid (0-4 points), adjuvant
immunosuppressant and other adjuvant therapies
- (0-2 points)
|
|
Harman et al. (2000)
|
0-3 / —
|
Severity (0-3)
|
Antibody-titre level
|
– antibody levels are an easy gaugeable and objective marker
|
- – clinical score does not reflect any alteration without
changes in quantity of erosions
- – in short-term observation antibody levels are often not
directly correlated with disease activity
|
|
|
- depending on count of erosions
- (oral: ≤ 3 erosions; 3-10 erosions; > 10 erosions;
- skin: < 5 erosions; >5 and < 20 erosions; > 20
erosions)
|
- antibody levels as assessed by ELISA relate to severity of
- skin disease (Dsg1) and
- oral disease (Dsg3)
|
|
Saraswat et al.(2003)
|
0-11/0-45
|
Extent (0-11 points)
|
Severity (0-45 points)
|
– objective documen-tation of severity and extent
|
– scoring of oral mucosa only
|
|
|
presence of erosions on 11 defined sites of the oral mucosa
|
based on difficulties arising from consumption of 9 food with
varying consistency
|
|
Mahajan et al. (2005)
|
0-4
|
Cutaneous Involvement
|
Mucosal involvement
|
– skin and mucosal involvement are equally represented
|
– ranges of affected areas are too large to display slight changes
in disease activity
|
|
|
depending on affected body surface area (<10%; 10-25%; 25-50%;
>50) and ability of daily routine activities
|
based on localization of erosions and rating of ability to eat or
drink
|
Acknowledgements
Financial support: none. Conflict of interest: none
References
1 Bystryn JC, Rudolph JL. Pemphigus. Lancet 2005; 366:
61-73.
2 Hertl M. Humoral and cellular autoimmunity in autoimmune
bullous skin disorders. Int Arch Allergy Immunol 2000; 122:
91-100.
3 Harman KE, Albert S, Black MM, British
Association of Dermatologists. Guidelines for the management of
pemphigus vulgaris. Br J Dermatol 2003; 149: 926-37.
4 Saraswat A, Kumar B. A new grading system for oral
pemphigus. Int J Dermatol 2003; 42: 413-4.
5 Dakkak M, Bennett JR. A new dysphagia score with
objective validation. J Clin Gastroenterol 1992; 14: 99-100.
6 Ishii K, Amagai M, Hall RP, Hashimoto T,
Takayanagi A, Gamou S, Shimizu N, Nishikawa T.
Characterization of autoantibodies in pemphigus using
antigen-specific enzyme-linked immunosorbent assays with
baculovirus-expressed recombinant desmogleins. J Immunol 1997; 159:
2010-7.
7 Cheng SW, Kobayashi M, Kinoshita-Kuroda K,
Tanikawa A, Amagai M, Nishikawa T. Monitoring
disease activity in pemphigus with enzyme-linked immunosorbent
assay using recombinant desmogleins 1 and 3. Br J Dermatol 2002;
147: 261-5.
8 Agarwal M, Walia R, Kochhar AM, Chander R.
Pemphigus Area and Activity Score (PAAS)--a novel clinical scoring
method for monitoring of pemphigus vulgaris patients. Int J
Dermatol 1998; 37: 158-60.
9 Herbst A, Bystryn JC. Patterns of remission in
pemphigus vulgaris. J Am Acad Dermatol 2000; 42: 422-7.
10 Harman KE, Seed PT, Gratian MJ,
Bhogal BS, Challacombe SJ, Black MM. The severity of
cutaneous and oral pemphigus is related to desmoglein 1 and 3
antibody levels. Br J Dermatol 2001; 144: 775-80.
11 Mahajan VK, Sharma NL, Sharma RC, Garg G.
Twelve-year clinico-therapeutic experience in pemphigus: a
retrospective study of 54 cases. Int J Dermatol 2005; 44:
821-7.
12 Charman CR, Venn AJ, Williams HC. Measurement
of body surface area involvement in atopic eczema: an impossible
task? Br J Dermatol 1999; 140: 109-11.
13 Ramsay B, Lawrence CM. Measurement of involved
surface area in patients with psoriasis. Br J Dermatol 1991; 124:
565-70.
14 Tiling-Grosse S, Rees J. Assessment of area of
involvement in skin disease: a study using schematic figure
outlines. Br J Dermatol 1993; 128: 69-74.
15 Niedermeier A, Eming R, Pfütze M, Neumann CR, Happel C, Reich
K, Hertl M. Clinical response of severe mechanobullous
epidermolysis bullosa acquisita to combined treatment with
immunoadsorption and rituximab (anti-CD20 monoclonal antibody).
Arch Dermatol (in press).
16 Tauber J, Jabbur N, Foster CS. Improved
detection of disease progression in ocular cicatricial pemphigoid.
Cornea 1992; 11: 446-51.
17 Mondino BJ, Brown SI, Lempert S,
Jenkins MS. The acute manifestations of ocular cicatricial
pemphigoid: diagnosis and treatment. Ophthalmology 1979; 86:
543-55.
18 Foster CS. Cicatricial pemphigoid. Trans Am Ophthalmol
Soc 1986; 84: 527-663.
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