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CHAPTER 5

Classification of Cutaneous Lupus


Erythematosus
Annegret Kuhn, Thomas Ruzicka

The clinical expression of skin involvement in patients with lupus erythematosus


(LE) is very common and shows great variation. Therefore, it has been difficult to
develop a unifying concept of the cutaneous manifestations of this disease, and much
attention has been paid to the issue of classifying LE from the dermatologic perspective in the past. However, the only universally accepted criteria for the classification
of LE are those of the American Rheumatism Association (ARA), now known as the
American College of Rheumatology (ACR), which were established in 1971 (Cohen et
al. 1971) and revised in 1982 (Tan et al. 1982) and 1997 (Hochberg 1997). This classification system includes 11 clinical and laboratory criteria for the classification of
systemic LE (SLE) primarily for the purpose of providing some degree of uniformity
to the patient populations of clinical studies. For rheumatologists and internists,
however, the ARA classification criteria for SLE might be most meaningful, whereas
a histologic classification of nephritis would likely be of greater value to nephrologists, and a clinical and histopathologic classification of the cutaneous manifestations
of LE would be most useful to dermatologists (Sontheimer 1997). Unfortunately, a
classification criteria system for the more mildly affected patients who suffer predominantly from cutaneous LE (CLE) has not yet been established. There is still continuous debate within the dermatology community concerning classification criteria
for patients having a form of CLE without systemic disease activity that would be
recognized by the ARA criteria system as SLE (Sontheimer 1997).
In 1977, Gilliam (Gilliam 1977) initially proposed a nomenclature for cutaneous
manifestations of LE, with several refinements soon thereafter (Gilliam and Sontheimer 1981, 1982), that was presented in the context of a new clinical-histopathologic
classification system. The new nomenclature attempted to bring some order to the
high level of confusion that existed in the literature resulting from the use of ambiguous and competing terms for the plethora of skin lesions that can be encountered in
patients with LE. The unique and clinically relevant relationships that exist between
individual skin lesions and aspects of the underlying systemic disease process should
not be overlooked, and the new developments in immunology should best be integrated into the management of patients with cutaneous manifestations of LE (Sontheimer 1997). The classification system developed by Gilliam divided all skin lesions
with any association to LE into those that are histologically specific for LE (LE-specific
skin disease) and those that do not share this pattern of histopathologic changes (LEnonspecific skin disease). Three broad categories of LE-specific skin lesions had been
suggested: acute CLE (ACLE), subacute CLE (SCLE), and chronic CLE (CCLE) with its
variants, such as discoid LE (DLE). The adjectives acute,subacute,and chronicused

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Annegret Kuhn, Thomas Ruzicka

in these designations conform to the classic dermatologic definitions of these terms. In


contrast, LE-nonspecific skin lesions, such as calcinosis cutis, sclerodactyly, cutaneous
vasculitis,and rheumatoid nodules,are those that in some way are related to the underlying LE autoimmune disease process but can also be encountered in other disease settings. This nomenclature by Gilliam was meant to be a more logical classification system for the extremely varied skin lesions that can be encountered in patients with LE,
and the various categories within this classification system were not meant to rigidly
define subsets of LE (Sontheimer 1997). In most patients, one form of LE-specific skin
involvement will predominate; however, with any arbitrary subdivision of a disease
continuum such as LE, overlapping features can occur. For example, patients who have
predominantly SCLE lesions can also develop ACLE or scarring CCLE lesions at some
point in the course of their disease. Furthermore, a small percentage of patients presenting with CCLE or SCLE skin lesions can subsequently die of complications of SLE.
However, there are certain patterns of systemic disease activity or inactivity that can
be seen to occur in conjunction with the three categories of LE-specific skin disease.
Since the initial formulation of the Gilliam nomenclature and classification system
more than 2 decades ago, several attempts have been made to improve on this system
or to provide altogether new approaches to the problem of classification of cutaneous
manifestations of LE. In 1991, Beutner et al. (Beutner et al. 1991) first presented the
results of their studies on a new criteria set developed by the European Academy of
Dermatology and Venereology (EADV) for the purpose of classification of patients
with CLE. The European system differs from the ARA classification criteria for SLE by
using a greater number of better-defined dermatologic criteria, such as Raynaud phenomenon, alopecia, and urticarial vasculitis. Furthermore, the group by Beutner et al.
(Beutner et al. 1992, 1993) subsequently presented additional work in this area, which
includes an effort to develop a new criteria set for identifying SLE in patients with cutaneous disease using a two-step model. However, although commendable in its goals
and its systemic approach, this classification scheme has not yet gained wide acceptance. As others have pointed out (Halmi et al. 1993), the approach advocated by Beutner et al. is more cumbersome to use than the ARA criteria classification system, and,
as a result, it is less useful to the practicing clinician. More recently, Parodi and Rebora
(Parodi and Rebora 1997) supported the value of the EADV criteria, finding them to be
somewhat less sensitive but more specific than the ARA criteria for patients with CLE.
This group strongly recommended that the ARA criteria should not be used in patients
with CLE as they are too sensitive, poorly specific, and altogether misleading. In 1993,
Halmi et al. (Halmi et al. 1993) proposed a new three-part classification scheme for LE
that included a bridging category between CLE and SLE that was termed intermediate
LE. Patients with this form were defined as those with skin lesions showing
histopathologic features of LE and fulfilling more than 1 but less than 4 of the 11 ARA
criteria for the diagnosis of SLE. In this system, CLE was defined as having only one
such criterion, namely, isolated CLE lesions, and SLE was defined as having four or
more such criteria. The positive and negative aspects of this classification system were
subsequently debated in a public forum by a panel of experienced clinicians (Rothfield
et al. 1994).Although attractive in some aspects, the mere counting up of classification
criteria can at times be misleading, especially when attempting to use such criteria for
diagnosis rather than classification.An identical classification system to that described
by Halmi et al. was used by Watanabe and Tsuchida in 1995 (Watanabe and Tsuchida

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1995) in their elegantly executed efforts to better document the relationships that exist
between the cutaneous and systemic manifestations of LE in Japanese patients.
Further efforts have been made to simplify the classification of LE by developing
classification trees through the methods of recursive partitioning (Edworthy et al.
1988). In addition, much work has been expanded to subclassify the cutaneous manifestations of this disease into more uniform patient groups (Costner et al. 2003, Sontheimer and Provost 1996), and a variety of subclassification criteria have been used:
clinical features, laboratory findings, histopathologic and immunohistologic patterns, genetic associations, and, more recently, phototesting results. Provocative phototesting has been crucial in further characterizing a highly photosensitive form of
CLE, namely, LE tumidus (LET) (Kuhn et al. 2000). Although LET was first mentioned
by Hoffmann in 1909 (Hoffmann 1909), and some years later by Gougerot and Bournier
(Gougerot and Burnier 1930), this subtype had since been somewhat forgotten or
rarely described in the literature. In 1990, Goerz et al. (Goerz et al. 1990) emphasized
for the first time the extreme photosensitivity as a major characteristic of LET, and
additional studies showed that these patients were more photosensitive than those
with other forms of CLE (Kuhn et al. 2001a). Furthermore, in our experience the prognosis in patients with LET is generally more favorable than in those with other forms
of CLE and, interestingly, LET lesions can disappear spontaneously within days or
weeks, even if the disease recurs chronically in these patients. Nevertheless, characteristic LET lesions can also occur in patients with SLE (Jolly et al. 2004). Recent
studies of more than 60 patients with LET further confirmed that this subtype of CLE
has so many characteristic features that it should be considered as a separate entity
and differentiated from ACLE, SCLE, and CCLE (Kuhn et al. 2000, 2001b, 2002a, b,
2003). Meanwhile, there is no doubt about LET being a separate entity, and further
case reports of this disease followed from groups other than our own (AlexiadesArmenakas et al. 2003, Hsu et al. 2002, Pacheco et al. 2002). Therefore, based on the
recent published data on LET we developed a modified classification system including
LET as an intermittent subtype of CLE (ICLE) (Kuhn 2003). In addition, bullous skin
lesions associated with different forms of LE (BLE) have also been added to the new
Table 5.1. Dsseldorf Classification of Cutaneous Lupus Erythematosus 2003

Acute cutaneous lupus erythematosus (ACLE)


Subacute cutaneous lupus erythematosus (SCLE)
Chronic cutaneous lupus erythematosus (CCLE)
Discoid lupus erythematosus (DLE)
Hypertrophic/verrucous variant
Teleangiectoid variant
Lupus erythematosus profundus (LEP)
Chilblain lupus erythematosus (CHLE)
Intermittent cutaneous lupus erythematosus (ICLE)
Lupus erythematosus tumidus (LET)
Bullous lesions in lupus erythematosus (BLE)
LE-specific bullous skin lesions
LE-nonspecific bullous skin lesions
Primarily bullous skin disorders associated with LE

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Dsseldorf classification of CLE 2003 (Table 5.1). The various types of vesicular and
bullous skin lesions that can occur in patients with LE have been divided into those
that show or do not show LE-specific histopathology (Sontheimer 1997, Yell and
Wojnarowska 1997). Furthermore, a number of primarily blistering diseases, such as
bullous pemphigoid, dermatitis herpetiformis, and pemphigus vulgaris, has been
reported in relationship to LE. Whether these bullous skin disorders are the result of
the LE autoimmune disease process or develop as a mere chance occurence in
patients who also have LE is not clear.

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