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 nephrolo-gists, 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 (LE-nonspecific 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 "chronic" used 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
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 pho-totesting 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 (Alexiades-Armenakas 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. Düsseldorf 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
"Düsseldorf 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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Rosacea and Eczema are two skin conditions that are fairly commonly found throughout the world. Each of them is characterized by different features, and can be both discomfiting as well as result in undesirable appearance features. In a nutshell, theyre problems that many would want to deal with.