Skin lesions in lupus erythematosus: a marker of systemic involvement.

BACKGROUND: Lupus erythematosus (LE) is an autoimmune disorder with diverse clinical manifestation ranging from mild cutaneous disorder to life-threatening systemic illness (SLE). In some patients, it remains to persist in the skin-limited form while in others it evolves into SLE. Here comes the role of identifying the markers of systemic involvement, which could determine the course and prognosis of the disease. AIM: To identify those manifestations that could be used to identify the activity of the disease SLE.
MATERIALS AND METHODS: An institution based, descriptive, cross-sectional study carried out over 1 year period. Sixty patients (male : female 1 : 4) with cutaneous LE were recruited for the study. The patients were classified in two groups depending on the presence or absence of ARA criteria of SLE. Detailed account of LE-specific and nonspecific lesions were noted. Statistical significance of the results was compared between the two groups using the chi-square test.
RESULTS: Among the different cutaneous manifestations, highly significant (P value <0.001) was found between SLE and nonscarring alopecia, photosensitivity, oral ulcer, malar rash (in decreasing order of odds favoring the association with SLE). Dimorphic skin lesions (P value=0.0326) also showed significant association where as discoid lesion (especially localized variant) predicted toward a skin limited form of the disease with high probability of not developing SLE (P value <0.0001). No significant association was found between SLE and papulosquamous lesions, Raynaud's phenomenon or scarring alopecia.
CONCLUSION: Identification of lesions with high degree of association with SLE can alert the physician of the unfavorable prognosis and allow timely intervention and institution of appropriate management strategies.

Introduction

Lupus erythematosus (LE) is not just a cosmetic deformity; causing psychological upset due to the disfigurement arising thereof, but at times can be catastrophic and can damage various vital organ systems leading to perpetuating organ dysfunction and/or failure and subsequent death.

It is the dermatologists who primarily manage the cutaneous LE (CLE); on the other hand systemic LE (SLE) remains the domain of rheumatologists or internists. It is important to realize that a person with CLE will die not of the cutaneous lesion but of the systemic involvement. There comes the importance of bridging the gap between dermatologists and internists, which the present study will try to achieve.

The prevalence rate of SLE vary within 17–48/10,000 population worldwide[12] and CLE is thought to be 2–3 times more frequent than SLE itself.[1] It is note-worthy that cutaneous illness often precedes the systemic involvement, giving the opportunity to the dermatologist to recognize the disease process much before the systemic complaints are expressed. This will allow institution of appropriate management strategies and timely intervention, which could prevent the subsequent morbidity and/or mortality and the social burden arising thereof.

It is also important to recognize that some patients remain to persist in the skin-limited form through out their life, never developing the systemic complications. This necessitates the recognition of this group of patients with mild manifestations so that the battery of costly investigation may be minimized and limit the economic burden of the underdeveloped nations.

Here comes the role of identification of the markers of systemic involvement that could simplify the task of the attending physician to determine the course and prognosis of the disease. It has been seen in particular that American Rheumatism Association (ARA) criteria though sensitive enough for the diagnosis of SLE, are of limited value for determining its further course and prognosis.[34] It was also argued that during the generation of ARA criteria[5] the control group consisted of 95 patients with rheumatoid arthritis, 16 scleroderma, five to seven each of juvenile onset arthritis, dermatomyositis, ankylosing arthritis, and psoriatic arthritis and a few of each of several other diseases of interest to rheumatologists but only one case of DLE and none of the other dermatoses that dermatologists consider in their differential diagnosis.[6] So the diagnosis of CLE is not helped by ARA criteria for classification of SLE but rested on the clinical judgment of the dermatologist helped by the histopathology, serology, and direct immunofluorescence (if the facility is available). ARA criteria are also of no use in predicting the outcome of those cases who presents with CLE without any features of SLE.[78]

Studies exploring prognostic factors and markers of systemic involvement in patients with lupus will be a boon to the sufferers and to the society at large. The markers need not always be laboratory parameters and at times certain tale-tell clinical features serve as effective tool to foretell the future. Skin changes play a prominent part in SLE providing helpful diagnostic information.[9] Extrapolating the cutaneous manifestations beyond the diagnostic arena, to serve as prognostic indicator are also being attempted.[10]

The study was undertaken to identify those manifestations that could be used to identify the activity of the disease so as to prevent the severe and irreversible damage resulting from systemic involvement.

Materials and Methods

This study is an institution based, unicentric, descriptive, cross-sectional study carried out over a period of 1 year. All the patients attending the dermatology OPD of the study site, which is serves as a tertiary care institute of Eastern India, during the above-mentioned period, were screened for the presence of CLE.

A person was considered to be suffering form LE if he satisfied any 4 of the 10 preliminary, dermatologic first-step criteria.[4] If a patient has got positive finding for both the LE-type histology and discoid lesion were considered to be rated as having fulfilled three criteria.

They were categorized into two groups depending on the presence or absence of the SLE according to “1982 revised criteria for the classification of SLE” formulated by American College of Rheumatology and established by ARA.[5] We compared the association of the skin lesions as markers of systemic involvements between the two groups.

Statistical analysis

Statistical significance of the results were compared by using Chi-square test and unpaired t-test as applicable. Kolmogorov–Smirnov test was used to test the normal distribution. P values <0.05 were considered significant for the present study. The statistical analysis were carried out using the MedCalc® version 7.0.0.2 (http://www.medcalc.be) software.

Results

The study population consisted of 60 patients (30 had no features of SLE) with the male : female ratio of 1 : 4 (SLE group 1 : 14; non-SLE group 1 : 2; Chi-square 1.8; P value=0.18). The mean age of onset off disease was found to be 30.29 ± 11.34. Among the SLE group the age 27.59 ± 11.99; and non-SLE group 32.99 ± 10.15 (t-test, P value = 0.065).

Among the CLE patients with SLE, photosensitivity was found in 29 (48.33%) patients and absent in only one (1.67%) patient. The association was found to be highly significant with the odds in favor of having SLE in patients with photosensitivity is 67.67.

Among the two types of alopecia seen in LE, nonscarring alopecia [Figure 1] was found to be significantly associated with the patients developing SLE (odds in favor was 79.33); whereas no such association was found with scarring alopecia [Figure 2].

Figure 1

Nonscarring alopecia in a case of SLE

Figure 2

Scaring alopecia resulting from DLE

Raynaud's phenomenon, which was present in six (10%) of patients with SLE, failed to show any significant association with SLE. Similarly no association could be found between SLE and urticaria or vasculitis in the 95% confidence limit. On the other hand highly significant association was found between oral ulcer [Figure 3] and development of SLE (odds in favor was 42.25).

Figure 3

Palatal ulcer in a case of SLE

Among the LE specific skin lesion, highly significant association was found with malar rash (P value <0.0001) but the SCLE lesion failed to show any such association. On the other hand, presence of discoid lesions alone (i.e., DLE without simultaneous presence of other LE-specific lesions) predicted toward a skin limited form of the disease with high probability of not developing SLE (P value <0.0001). The Dimorphic skin lesion (concomitant presence of two pattern of LE-specific lesion) [Figure 4] when tested to know its association with SLE showed significant association with SLE P value <0.05). The results are presented in Table 1.

Figure 4

Hyper-pigmented variety acute cutaneous lupus erythematosus on malar area with papulosquamous subacute cutaneous lupus erythematosus on V-area of the chest

Table 1

The association of LE-specific and non-LE-specific skin lesion with presence of SLE in the study population

Discussion

The presence of SLE is an ominous feature in CLE that incapacitate a person and kill him as well. Measurement of disease process in CLE is of utmost important to safeguard those unfortunate people who could develop SLE in future. According to Parodi et al.[11] a disease may be measured through its activity or its severity. Severity denotes the gravity of manifestation whereas the activity implies a continuous phenomenon.[12] A manifestation may therefore be used to measure activity even though it is not severe, while severe lesions and their extent may represent permanent damage and may not be used to decide the prognosis. Our aim had been to identify those manifestations that could be used to identify the activity so as to prevent the severe and irreversible damage. This can be elucidated by the fact that nonscarring alopecia may not be a severe lesion but may serve as a measure of the activity in other words a marker of severity.[11]

Nonscaring alopecia, photosensitivity, oral ulcers, and malar rash were among the cutaneous manifestation, which were having highly significant association (P<0.0001) with the presence of systemic involvement (in decreasing order of odds favoring the association with SLE). Similar observation was noted by Parodi et al.[11] and Tebbe et al.[3] though the associations were not found to be that strong in their study population.

Dimorphic skin lesions (P value=0.0326) showed significant association but not as strong as the previous ones. These parameters were not tested in the past, so it is desirable that it is validated in larger study population. One important finding in the study is that presence of DLE (especially the localized variant) is a good prognostic sign. Thus, the treating physician can provide the patient the silver lining that in-spite of the disfiguring lesions he can expect reduced systemic involvement.

We found no significant association between SLE and Raynaud's phenomenon, papulosquamous skin lesion in SCLE, scarring alopecia or cutaneous vasculitis though some studies have documented their significance.[311] We also could find no association between SLE and urticaria, a parameters which was also not previously tested.

We conclude that diagnosis and management of a patient of CLE should not end with classifying him/her into the types of LE specific skin lesion and the presence/absence of SLE but with a thorough search of the factors, which can foretell the systemic involvement. Though such a search is being carried out in the Western world, on our part of the globe such studies are lacking. Our study is only the start of the pursuit of identifying the markers of systemic involvement in CLE in the Indian subcontinent. It will be expected to serve the ailing patients, their attending physician, and the society at large.