Chronic cutaneous Lupus erythematosus: study of 290 patients

Abstracts

FUNDAMENTO: Lúpus eritematoso cutâneo crônico é uma doença inflamatória crônica relativamente freqüente, mas pouco estudada entre nós. OBJETIVO: Caracterizar epidemiologia e clínica de pacientes com lúpus eritematoso cutâneo crônico, visando comparar dados obtidos com literatura mundial. PACIENTES E MÉTODOS: Foram estudados retrospectivamente 290 pacientes com lúpus eritematoso cutâneo crônico no período de 1982 a 1996, na Clínica de Dermatologia da Santa Casa de São Paulo. RESULTADOS: A média de idade da instalação da doença foi de 32,3 anos, houve predomínio do sexo feminino em relação ao masculino (3,4:1), a maior parte dos pacientes teve lesões localizadas no segmento cefálico (58,3%). Quanto às variedades clínicas, houve predomínio da placa discóide típica em 90,4% dos casos, seguida das variantes verrucosa ou hipertrófica (7,9%), lúpus eritematso pérnio (1,4%), e túmida (0,3%). Lesões em mucosas ou epitélios de transição ocorreram em 27,2% dos pacientes. CONCLUSÕES: Lúpus eritematoso cutâneo crônico é doença mais comum em mulher adulta, sendo a placa discóide típica a lesão mais comum. Lesões mucosas ocorreram em aproximadamente em um quarto dos casos.

lúpus; lúpus eritematoso cutâneo; lúpus eritematoso discóide

CLINICAL, LABORATORY AND THERAPEUTIC INVESTIGATION

Chronic cutaneous Lupus erythematosus: study of 290 patients^*

Thaís Helena Proença de Freitas^I; Nelson Guimarães Proença^II

^IAssistant Professor of Dermatology, Dept. of Clinical Medicine, Hospital Santa Casa de Sao Paulo

^IIFull professor of Dermatology and ex-titular of the Dermatology Clinic, Hospital Santa Casa de Sao Paulo

^{Correspondence}

SUMMARY

BACKGROUND: Chronic cutaneous lupus erythematosus is a chronic inflammatory disease, which albeit relatively frequent, has been the object of few studies.

OBJECTIVE: To characterize the epidemiological and clinical aspects of patients with chronic cutaneous lupus erythematosus, with a view to comparing the data obtained with the world literature.

PATIENTS AND METHODS: A retrospective study was done on 290 patients with chronic cutaneous lupus erythematosus from 1982 to 1996, attended at the Dermatology Clinic of Hospital Santa Casa de Sao Paulo.

RESULTS: The mean age at onset of the disease was 32.3 years, there was a female prevalence in relation to males (3.4:1), most of the patients had lesions located in the cephalic segment (58.3%). Regarding the clinical types, there was a prevalence of the typical discoid plaque in 90.4% of cases, followed by the verrucous or hypertrophic forms (7.9%), erythematous lupus pernio (1.4%) and tumid (0.3%). Lesions in the mucous membranes or transition epithelia occurred in 27.2% of the patients.

CONCLUSIONS: Chronic cutaneous lupus erythematosus is a disease more frequent in adult women and the most common lesion is the typical discoid plaque. Mucous lesions occurred in approximately one fourth of the cases.

Key words: lupus; lupus erythematosus, cutaneous; lupus erythematosus, discoid.

INTRODUCTION

Chronic cutaneous lupus erythematosus (CCLE), also known as lupus erythematosus discoid, is an inflammatory disease of the skin predominantly among adults that referentially involves those areas exposed to sunlight. It is characterized by well-delimited, erythematous and desquamative areas which can be of various sizes. These tend to leave atrophic scars and pigmentary alterations.¹

The diagnosis is confirmed by its characteristic histopathology. The frequent finding of immunoglobulins in the skin and, though less commonly, serological alterations demonstrating auto-antibodies suggestive of an auto-immune etiology. One of the most important triggering factors for the cutaneous lesions is ultraviolet radiation.²

Presently, the majority of researchers^3,4 consider CCLE to be part of a spectrum of the lupus erythematosus diseases (LE). According to these authors, the clinical expression of LE varies from CCLE, a benign and strictly cutaneous form, to a systemic form with an unfavorable prognostic, that presents mainly renal and neurological involvement, known as systemic lupus erythematosus (SLE). There is also an intermediate form that involves the skin and in 50% of cases it also presents systemic involvement, denominated subacute cutaneous lupus erythematosus (SCLE). Some cases diagnosed initially as CCLE can develop into SLE. Besides the prognostic, the therapeutic approach also differs according to the clinical form of the LE spectrum.

The epidemiology of CCLE shows that the age of onset is mostly between 20 to 40 years.⁵ The disease is rare in childhood or in individuals over 70 years of age. According to most of the international studies, there is a predominance in females of approximately 2:1.⁵ There is no racial bias. The literature describes familial cases of LE, which is verified in 4% of patients.⁶

The most common cutaneous clinical lesion of CCLE is discoid plaque, classically described as a macula or erythematous plaque, with well-defined borders and surface with adherent lamellar desquamation, on the underside of which there are keratotic spines corresponding to follicular hyperkeratosis, known as "upholsterer's tacks". These lesions develop in a centrifugal direction, assuming a disk form, often with dyschromic alterations, presence of telangiectasia and residual scars with an atrophic center. Cicatricial alopecia can be observed in the scalp. Other clinical presentations which are less frequent and more difficult to diagnose have also been described, such as the verrucosa or hypertrophic forms and lupus erythematosus pernio and tumid, besides others that are considerably rarer.¹ In general the lesions are asymptomatic; however it is common for some patients to complain of ardor and worsening of the lesions following solar exposure. There can be involvement of the mucous membranes, though there are only a few exceptional works in the literature specifically dealing with this.

Systemic manifestations are rarely found in patients with CCLE, however some of these complain about arthralgia or present Raynaud's phenomenon.

The serological exams, such as that for circulating auto-antibodies that are so valued in the diagnosis of SLE, are not useful for the diagnosis of CCLE, and only serve for the differential diagnosis between the systemic forms and to detect a possible development of CCLE into SLE.

The importance of CCLE in Brazil lies in the fact that in spite of not being a common disease (1/361 new consultations),⁷ its chronicity leads to an accumulation of cases in the out-patient clinics. Furthermore, although there is favorable course in most cases, any delay in the initiating treatment can lead to disfiguring scars, with deleterious consequences in the patient's social integration.

The objective of the present work was to present a study of 290 patients with CCLE treated at the dermatology clinic of Hospital Santa Casa de Sao Paulo from 1982 to 1996 and to make a descriptive analysis of the epidemiological and clinical aspects.

On reviewing the national and international literature regarding the epidemiology and clinical aspects of CCLE in the last 30 years, the authors only found works with smaller samples of patients than that of this study.

PATIENTS AND METHODS

The study was done at the Dermatology Clinic of Hospital Santa Casa de Sao Paulo, where a protocol destined to the study of CCLE was introduced in 1982. From 1982 to 1996, all the patients with cutaneous manifestations of SLE seen at that clinic were included in the protocol. Cases were excluded that had an immediate diagnosis SLE and SCLE, leaving 298 patients with an initial diagnosis of CCLE. The foremost inclusion criterion was the presence of the typical discoid plaque. Eight patients were later excluded from this group because they developed SLE, leaving a total of 290 cases for the study. The protocol included data on the epidemiological, clinical, histopathological, immunopathological and laboratorial aspects, besides enabling a follow-up of the treatment and course of the patients. In this work, the authors only presented the data related to the epidemiology (sex, age, color, familial occurrence) and to the clinical aspects of CCLE (clinical forms, topographical distribution of the lesions, involvement of the mucous membranes, and localized and general symptoms).

The statistical tests used for the evaluation of the results were: Chi square test, Student's t test (for the comparison of two non-paired means) and Mann-Whitney test.

RESULTS

Two hundred and ninety cases were diagnosed as CCLE and these remained as such throughout the observation period.

The age at disease onset varied from three to 73 years, with a mean value of 32.3 years (Table 1). In terms of gender, the mean age at which the first lesions appeared was lower among females (females, 31.8 yrs and males 33.9 yrs).

The distribution according to sex showed that 255 (77.6%) patients were female and 65 (22.4%) were male, therefore showing a sex bias of 3.4:1.

As for skin color, 164 patients were white, 92 black, 33 mixed race and one yellow. There were no significant differences in the cross comparison of the variables of color and sex.

The occurrence of familial cases of LE was reported by 13 (4.4%) of the 290 patients. The authors actually examined only three of these familial cases, with proven LE and attended at the dermatology clinic. Four patients reported that more than one family member had the disease, while the remaining nine only reported one familial case. Altogether these 13 patients referred to 17 familial cases of which, six with probable CCLE, three with SLE and eight with LE.

As for the questionnaire on local clinical symptoms (itch and aggravation following solar exposure), 179 (58.7%) patients answered that they had one or more symptoms: 45.7% reported pruritus, and 37.2% referred to aggravation with the sun; there was no significant difference between the sexes.

As for the presence of arthralgia, Raynaud's phenomenon and fever, 77 (26.6%) patients complained of one or more symptoms. Arthralgia was reported by 23.6%, Raynaud's phenomenon by 2.8%, and fever also by 2.8%. The results for arthralgia presented a significant difference between the sexes and was reported more frequently by women (p<0.05).

Regarding the topographical distribution of the lesions, they were predominantly located in the face/forehead, in 261 patients (90%). Other frequent locations were: trunk (32.4%), scalp (31.7%), ears (27.5%), upper limbs (26.8%); and with a lower frequency in the retroauricular region (8.6%), hands (6.5%), neck (3.4%), lower limbs (2.7%), feet (0.3%) and palmoplantar regions (0.9%). Disseminated skin lesions, with involvement above and below the cephalic segment were observed in 41.7% of the total patients.

Mucosal lesions and/or lesions of the transitional epithelium (lips, eyebrows and columella nasi) were observed in 79 patients (27.2%), and of these 20 (6.9%) presented involvement in more than one location. It is underscored that the anogenital mucous membrane was not examined. The inferior lip (vermilion zone) was the most frequently involved area - 56 (19.3%) of the patients presented lesions in this location either in isolation or associated with other mucous lesions or transitional epithelia (Table 2).

Table 3 shows the clinical varieties diagnosed according to sex. Note that all the patients had at least one discoid plaque and, occasionally, other types of plaque; in these cases, the form is indicated. There was a statistically significant predominance of the verrucosa form in male patients.

DISCUSSION

The authors consider it is appropriate to analyze the two topics presented in the introduction (epidemiology and clinical aspects) comparing the results with the data found in the medical literature.

In the works involving an epidemiological study of CCLE, in the literature over the last 35 years, it was seen that in the casuistry some authors did not exclude patients with discoid plaques present in SLE or included cases of SCLE or lupus profundus. Such a consideration is due to the fact their inclusion modifies the epidemiological characteristics of the studied group. Furthermore, the number of patients studied in eight epidemiological investigations (one national and seven international) was much smaller than in this study (290 cases), with the exception of that done by Burch and Rowell,⁸ who studied 234 cases, (Table 4).

The age at disease onset varied from 20 to 59 years (Table 1) in 86.6% of the patients, corroborating the data in the literature that indicates 87.5%⁸ and 89.0%.⁵ The highest concentration of cases was between 20 and 39 years, with 63.8% of the total patients, coinciding with the data of Burch and Rowell8 (61.1%) for the same age range. Therefore, CCLE is not a frequent disease in the extreme ages of life: below 20 years of age it accounted for only 11% of the casuistry presented here; and among the over 60s in 2.4%. There were only two cases (0.7%) of onset before 10 years of age, while Burch and Rowell⁸ reported 2% of their cases in this age group. Likewise, McMullen et ^al.12 consider its onset in childhood to be rare.

The mean age at disease onset, 32.3 years, was slightly under that verified by other authors: O'Loughlin et al.,¹³ 39 years, and le Bozec et al.,¹⁴ 34.6 years.

In this study there was a female bias, with 77.6% of the cases, giving a ratio of 3.4:1. In the works presented in the literature, although the predominance was maintained, the ratio varied considerably, from 1.6:1¹⁴ up to 5:1.¹⁵

As for the distribution of skin color, there was a prevalence among whites (56.6%), followed by blacks (31.7%) and mixed race (11.4%) (Table 3). The sum of the latter two reaching a total of 43.1%, results that do not differ from those of Prystowsky et al.,⁵ who found 55% of the patients were white against 45% black.

In response to the question on relatives with LE, 13 patients (4.4%) replied affirmatively. Their information allowed the inference that a total of 17 relatives were affected, of which six with CCLE, three with SLE, and in eight there was only reference to LE. Unfortunately, it was not possible to confirm the above diagnoses by clinical exam of all these family members, because only three presented at the clinic. Of these, there was a confirmed case of SLE and two of CCLE. As already stated, in the literature revision by the authors, the works regarding the familial occurrence of LE in patients with SLE^6,16 show high frequencies, varying between 12% and 18%. As for CCLE, Findlay and Lups,¹⁷ Prystowsky et al.⁵ and Le Bozec et al.¹⁴ make references to familial cases of LE in percentages of 1%, 4%, and 1.5%, respectively. The occurrence of different forms of LE in the same family is one more indicator that this is a disease with a broad spectrum.

The presence of discoid plaque was one of the criteria for inclusion in the study group. Most of the time, these plaques were already well-defined at the time of the first consultation and with cicatricial atrophy (82.8%), which enabled an immediate clinical diagnosis.

The verrucous form was presented by 23 patients (7.9%), in general with multiple lesions and disseminated plaques in the skin. The verrucous plaques were found alongside typical discoid lesions, and were either more numerous than the discoid lesions or very few in number. In these cases, the verrucous form was most common in the male sex (statistically significant). A fact that has not been attributed much importance in the literature is the almost obligatory association between pruritus and the onset of plaques with hyperkeratose characteristics, that eventually characterize the verrucous aspect. The pruritus causes the patients to react with a compulsive and constant scratching. The authors consider that this compulsive behavior leads to a modification in the surface of the plaques that assume a verrucous aspect.

Lupus erythematosus pernio is a rare variety LE, it was described in 1988, but to date there is still controversy as to its real existence.¹⁸ In the casuistry presented here, four cases were observed that in winter besides the discoid plaques presented lesions of the erythema pernio type in the hands; although the authors had suspected lupus erythematosus pernio, it was only possible to confirm this in one case through the characteristic histopathology and positive direct immunofluorescence (DIF).

Likewise, only one case of the tumid form was attended, corroborating the literature^18,19 that considers this to be a very rare form. Kuhn et al.¹⁹ have underscored the fact that this is one of the most photosensitive forms of cutaneous LE.

The topographical distribution of the lesions of the patients described here, as observed at the time of the first consultation, was most frequently in the exposed areas: 58.3% had lesions located in the head and neck (localized LE, according to O'Leary²⁰); while 41.7% also presented localized lesions in other areas, such as the trunk and limbs (classified as disseminated SLE by O'Leary). It is interesting to note that only in a single case (0.3%) were the lesions localized exclusively in areas other than the cephalic segment, especially considering that Pristowsky et al.⁵ had reported that 2% of their cases did not present involvement of the head or neck.

The classification of CCLE into localized and disseminated in the skin was made originally by O'Leary, in 1934, and is still accepted by more contemporary authors. In the original work, O'Leary denominated the localized form as that with lesions exclusively in the head and/or neck, and the disseminated or generalized form when, besides these, there are lesions in the trunk or members, irrespective of their number. In the casuistry presented here, 41.7% were disseminated cases, against 58.3% of localized cases. In the literature, 42% of cases are referred to as disseminated by Pristowsky et al.⁵ and 39% by Le Bozec et al.¹⁴

The importance of the contribution by O'Leary, albeit not perceived by himself, but by other authors, was the observation of clinical signs indicating a course to SLE in patients with very disseminated lesions in the skin.^4,21 However, it should be underscored that many of the works prior to 1979, when the concept of SCLE was concretized, included cases of this clinical form among sample populations of CCLE. This distorted the results, because systemic involvement is more common SCLE. Whatever, the authors' clinical experience also points to the need for a more complete and more constant observation of patients with disseminated skin lesions, with a view to eventually correcting the diagnosis to SCLE, or in other words, in order to detect a possible course to SLE.

The scalp and mucous membrane locations merit more detailed comment. The onset of the lesions of CCLE in the scalp was reported by 33 patients (11.4%); however, at the first consultation it was possible to observe involvement of this area in 92 patients (31.7%), and in 18 patients (6.2%) this was the only location found. Pristowsky et al.⁵ described a higher frequency, with 60% of the patients presenting lesions in the scalp, and in 12% of the cases this was the only location. The data of Wilson et al.,²² in turn, correlated closer with the present findings: 34% of scalp involvement in 89 cases examined.

It should be highlighted that the patients frequently complained of intense itching in the lesions of the scalp. The scratching delays the resolution of these lesions and often provokes exulceration and secondary infection.

In this casuistry, 79/290 patients (27.2%) presented in the initial exam, with involvement of the transitional epithelium and/or mucous membranes (Table 5). Multiple locations occurred in 20/290 (6.9%). The oral mucous membrane was involved in 22/290 (7.5%), either in isolation 10/290 (3.4%) or in association with transitional epithelium in 12/290 (4.1%). Of the transitional epithelia, the lips were the most frequently involved - 56/290 patients (19.3%), of which 39/290 (13.4%) in an isolated manner and 17/290 (5.9%) in association with the palpebrae, in 21/290 (7.2%) and the columella nasi in 7/290 (2.4%).

Lesions of the oral mucous membrane, characterized by asymptomatic chronic plaques, commonly went unnoticed by most of the patients. An aspect worth highlighting is that there was no relationship between lesions of the oral mucous membrane and activity of the cutaneous disease, since the former persisted even when the latter had already regressed. The same cannot be said, however, in relation to the palpebral lesions, which maintained a relationship with the cutaneous activity; and they are often symptomatic with the patient referring to ardor. Lesions of the columella nasi comprise erythematous, crusty and atrophic plaques, again the patients also often complain of local ardor.

In the recent literature, there are few works related to involvement of the mucous membranes in CCLE^14,23,24 and that present a significant number of patients. Just for comparison, table 5 shows the results side by side with those of the studies by Burge et al.²⁴ and Le Bozec et al.¹⁴ Burge et al.²⁴ studied 68 patients and found mucous lesions in 16 (24%) and Le Bozec et al.¹⁴ studied 136 cases and found them in 22 (16.2%). These results coincide with the authors' findings, 79/290 patients (27.2%).

Symptoms directly related to the cutaneous lesions were not uncommon: 45.7% of the patients complained of pruritus or ardor, specially following solar exposure, although only 37.2% reported their worsening after the exposure; many had more than one symptom.

The general symptoms complained of by the patients could not always be proven; for instance, articular pains were referred to by 68 patients, mainly females, but without special characteristics, and reports of Raynaud's phenomenon were accepted with reservation, due to the fact that they were not always confirmed by clinical exam.

CONCLUSION

Epidemiological and clinical data of a group of 290 patients with CCLE was analyzed. The mean age at disease onset was 32.3 years. There was a female bias (3.4:1). Familial occurrence of other cases of LE was reported by 4.4% of the patients. Regarding the topographical distribution of the lesions, 58.3% of the cases were localized (head and neck) and 41.7%, disseminated or generalized in the skin (also with lesions below the neck). As for the clinical forms, there was a prevalence of discoid plaque (90.4% of the cases), followed by verrucous (7.9%), lupus erythematosus pernio (1.4%) and tumid (0.3%). Lesions in mucous membranes or transitional epithelia occurred in 27.2% of the patients in the following order: vermilion zone, oral mucous membrane, palpebrae, nasal columella.

AKNOWLEDGEMENT

Financial support: CAPES.

REFERENCES

Received in March, 11^th of 2003

Approved by the Consultive Council and accepted for publication in September, 17^th of 2003

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*

Work done at "Clinica de Dermatologia do Hospital da Santa Casa de Misericórdia de SP".

Publication Dates

• Publication in this collection
  10 Feb 2004
• Date of issue
  Dec 2003

History

• Received
  11 Mar 2003
• Accepted
  17 Sept 2003