Lymphocytic infiltration of the skin is a photosensitive variant of lupus erythematosus: evidence by phototesting

BACKGROUND: Lymphocytic infiltration of the skin (LIS) is a disorder in which photosensitivity has been suspected but never proven. OBJECTIVES: To carry out a systematic photobiological investigation in patients with LIS and to compare the photobiological features of LIS with those of other photosensitive disorders. METHODS: We performed provocative phototesting with ultraviolet (UV) A and UVB in 10 patients with active LIS. RESULTS: In all patients, UVA and/or UVB elicited abnormal papular phototest reactions resembling lesions of LIS both clinically and histologically. Lesions typically developed 3--6 days (mean +/- SD 100.8 +/- 20.9 h) after the first UV exposure. CONCLUSIONS: This characteristic latency interval together with certain clinical features, i.e. onset in summer, predilection for the face and persistence of the lesions, indicate that LIS is a photosensitive disorder distinct from polymorphic light eruption but indistinct from lupus erythematosus (LE). Both our photobiological findings and the effective treatment with hydroxychloroquine in half of our patients strengthen the proposal that the two entities LIS and LE tumidus are identical. As diagnosis cannot be made by histological, immunofluorescence or laboratory criteria, provocative phototesting may be a diagnostic aid in this disorder.     

Proliferation and effects of UVA irradiation in cultured fibroblasts from lesions in cutaneous lupus erythematosus

Cutaneous lupus erythematosus (LE) often presents clinically as chronic cutaneous lesions, healing with scar formation, and acute cutaneous lesions that are seen in systemic and subacute LE and heal without scarring. UV-light plays a role in the pathogenesis of the skin lesions, but the pathomechanism is still unclear. The aim of this study was to compare fibroblast proliferation and response to UV-light by cultured fibroblasts from scarring and non-scarring LE lesions. Fibroblasts were cultured from skin lesions from 5 patients with classic discoid LE, 5 patients with subacute cutaneous LE and healthy, age-matched donors. Proliferation rate was assessed by cell counts at days 3, 6 and 9. The fibroblast cultures were irradiated with UVA and the supernatants were analysed for IL-6, TGF-beta, IL-4, soluble ICAM-1 and soluble VCAM-1. Fibroblast cultures from scarring lesions showed significantly lower cell-counts at days 3 (P = 0.01) and 9 (P = 0.009), than cultures from nonscarring lesions or controls. There were no significant differences in levels of IL-6 or TGF-beta in supernatants of irradiated fibroblasts from patients compared to controls and IL-4 and the soluble forms of ICAM-1 and VCAM-1 were below detection level. The response to UV-irradiation was similar to that of normal cells in the parameters studied. In summary, cultured fibroblasts from scarring LE lesions displayed significantly decreased proliferation rates compared to non-scarring LE lesions and controls. This may be secondary to inflammatory factors, or due to a functional defect in LE fibroblasts.     

Follicular lupus erythematosus: a new cutaneous manifestation of systemic lupus erythematosus

Summary We report the clinical, histopathological and immunological features of follicular erythema and petechiae in a 30-year-old Japanese woman with systemic lupus erythematosus (SLE). Histology showed this eruption to constitute a cutaneous manifestation of SLE. To our knowledge, this is the first reported case of follicular erythema and petechiae in association with SLE. Accordingly, we propose that this rare eruption be termed 'follicular lupus erythematosus'.     

Comparative analysis of subacute cutaneous lupus erythematosus and chronic cutaneous lupus erythematosus: clinical and immunological study of 270 patients

Background Lupus erythematosus (LE) is a chronic, autoimmune disease resulting from an interaction of genetic, environmental and hormonal factors and characterized by a spectrum of clinical forms with variable evolution from a localized cutaneous form to a life‐threatening systemic form. Objective To analyse and compare the prevalence and characteristics of the main clinical and immunological manifestations of subacute cutaneous LE (SCLE) and chronic CLE (CCLE). Methods A total of 270 patients with CLE (112 patients with SCLE and 158 patients with CCLE) were studied retrospectively. The clinical and serological characteristics of all the patients were collected in a chart review. Results The patients with SCLE had a higher prevalence of annular and papulosquamous lesions, Raynaud phenomenon, mucous membrane ulcers, malar rashes, photosensitivity, vasculitis and a lower frequency of discoid lesions and alopecia compared with patients with CCLE. Patients with SCLE had a higher prevalence of arthralgias (P < 0·001), xerophthalmia (P = 0·045), arthritis (P < 0·001), nephropathy (P = 0·003) and systemic LE (SLE) (P < 0·001) compared with patients with CCLE. Patients with SCLE also had a higher frequency of laboratory and serological abnormalities than patients with CCLE. Generalized discoid LE (DLE) was associated with a higher prevalence of photosensitivity (P < 0·001), panniculitis (P = 0·009) and SLE (P = 0·003) than localized DLE. In patients with SCLE and those with CCLE, photosensitivity, arthralgias, arthritis, nephropathy and xerophthalmia were associated with SLE. In patients with SCLE, significant correlations existed between clinical and immunological data. Conclusions In our series, differences in the expression of CCLE and SCLE were found with respect to the distribution and type of lesions, systemic features and immunological findings.     

Photosensitivity in patients with lupus erythematosus: a clinical and photobiological study of 100 patients using a prolonged phototest protocol

BACKGROUND: There is a clear relationship between ultraviolet (UV) radiation (UVR) and the clinical manifestations of patients with lupus erythematosus (LE). Cutaneous lesions are induced or exacerbated by exposure to UVR. Of patients with LE, 24-83% are reported to be photosensitive to UVR. LE tumidus appears to be the most photosensitive subtype of LE, followed by subacute cutaneous LE (SCLE). In general, the history of patients with LE correlates poorly with the presence or absence of photosensitivity, due to a delayed time interval between UV exposure and exacerbation of skin lesions. Phototesting using artificial UVR and visible light is a reliable way of diagnosing photosensitivity. OBJECTIVES: To investigate the photoreactivity of patients with various subtypes of LE using an individualized phototest protocol. The results of phototests were correlated with the history of photosensitivity, the subtype of LE, the presence of autoantibodies and the use of anti-inflammatory medication by these patients. METHODS: Phototesting with UVA, UVB and visible light was performed in 100 patients with LE. The diagnosis of LE was established both on clinical examination and skin histology. Serological studies were also performed in all patients. The phototests were performed on large skin areas of the forearm or trunk; the first dose was twice the minimal erythema dose and the dosage was increased according to the individual reactions of the patients at the test sites. Follow-up of skin reactions at the test sites was performed for up to 2 months. Histological examination of the photoprovoked skin lesions was carried out in 57 patients. RESULTS: Of the 100 patients included (81 women and 19 men; mean age 41 years, range 17-79), 46 had chronic discoid LE, 30 SCLE and 24 systemic LE. An abnormal reaction to UVR and visible light was found in 93% of our patients with LE. No clinical or histological evidence at the phototest sites of polymorphic light eruption was found. There was no correlation between photosensitivity and LE subtype, presence of autoantibodies or medical history. Concomitant use of anti-inflammatory medication seemed to exert only minimal influence on the results of phototesting. CONCLUSIONS: When using an extended phototesting protocol, almost all patients with LE in this study showed clinical and histological evidence of aberrant photosensitivity. Therefore, patients with LE should receive thorough advice and instruction on photoprotective measures, regardless of their history, LE subtype or presence of autoantibodies.     

沙利度胺治疗不同类型红斑狼疮皮损的疗效观察

目的：观察沙利度胺(thalidomide)对不同类型红斑狼疮(LE)皮肤损害的临床疗效。方法：选择56例不同类型的IE患者，包括慢性皮肤型红斑狼疮(CCLE)19例，深部红斑狼疮(LEP)2例，红斑狼疮-扁平苔藓综合征(LE-LP)2例，亚急性皮肤型红斑狼疮(SCLE)7例和系统性红斑狼疮(SLE)26例。患者口服沙利度胺，初始剂量为100—150mg／d，2周后根据疗效反应酌情减量，最后维持量为12．5—25mg／d；疗程6～8个月。结果：各型IE患者的皮肤损害均对沙利度胺有良好反应，56例中有41例皮损痊愈，近期治愈率达73．2％，复发率为21．9％。结论：沙利度胺对各型LE皮肤损害有较好的疗效。     

Photosensitivity in lupus erythematosus

BACKGROUND: Lupus erythematosus is a systemic disease process that may manifest with a variety of internal and cutaneous findings. Photosensitivity is one the most common manifestations of lupus erythematosus. In patients with lupus erythematosus, there is a relationship between exposure to ultraviolet light, autoantibodies, genetics and other factors in the development of photosensitivity. METHODS: Literature was reviewed on the topics of lupus erythematosus and photosensitivity discussed together and separately. The suggested mechanisms for their relationship were reviewed and analyzed. RESULTS: Photosensitivity's relationship to and influence on the systemic manifestations of lupus remain to be defined. Mechanisms for photosensitivity might include: modulation of autoantibody location, cytotoxic effects, apoptosis induction with autoantigens in apoptotic blebs, upregulation of adhesion molecules and cytokines, induction of nitric oxide synthase expression and ultraviolet-generated antigenic DNA. Tumor necrosis factor alpha also seems to play a role in the development of photosensitivity. CONCLUSION: The basis for photosensitivity in lupus has yet to be fully defined. It is more commonly associated with subacute and tumid lupus erythematosus than with other variants. Anti-Ro antibodies appear to relate to photosensitivity. Tumor necrosis factor alpha polymorphisms appear to be important in some variants of lupus with photosensitivity. There is no sine qua non antibody or mutation of photosensitivity in lupus. In patients with lupus, more work needs to be done to define the mechanisms of photosensitivity.     

UVB-induced leucocyte trafficking in the epidermis of photosensitive lupus erythematosus patients: normal depletion of Langerhans cells

BACKGROUND: The pathogenic mechanisms of UV-induced skin lesions of lupus erythematosus (LE) are unknown. In a recent study of pathogenic mechanisms of polymorphic light eruption (PLE), significantly more Langerhans cells (LCs) persisted in the epidermis after UVB overexposure than in healthy individuals. Interestingly, the same phenomenon was observed in one subacute cutaneous lupus erythematosus (SCLE) patient. It could therefore be hypothesized that both photodermatoses share a common pathogenic mechanism of photosensitivity. In the present study, we tested this hypothesis by investigating leucocyte trafficking in the initial phase of cutaneous LE after intense UVB exposure. METHODS: In 22 photosensitive LE patients (12 chronic discoid lupus erythematosus, seven systemic lupus erythematosus and three SCLE) and nine age/sex-matched controls, uninvolved buttock skin was exposed to six minimal erythemal dose (MED) UVB radiation. Subsequently, biopsies were taken after 24, 48 and 72 h, and one control biopsy was taken from unirradiated skin. Skin sections were stained for the presence of LCs, neutrophils and macrophages. Areal percentages of positively stained cells within the epidermis were quantified and compared between the patients and controls. RESULTS: A gradual decrease of epidermal LCs and a gradual increase of epidermal neutrophils and macrophages at several timepoints after six MED irradiation was observed equally in both LE patients and controls. CONCLUSION: Immunohistopathology of irradiated uninvolved skin of photosensitive LE patients did not reveal the same pathologic trafficking of LCs and neutrophils as described for PLE patients. We conclude that different mechanisms are operative in the pathogenesis of PLE and photosensitive LE.     

Lupus erythematosus tumidus is a separate subtype of cutaneous lupus erythematosus

Background  Lupus erythematosus tumidus (LET) is a rare disease which was first described in 1909 but has not always been considered as a separate entity of cutaneous lupus erythematosus (CLE) in the international literature.
Objectives  To compare characteristic features of different subtypes of CLE and to analyse whether LET can be distinguished as a separate entity in the classification system of the disease.
Methods  The study involved 44 patients with CLE, including 24 patients with LET, 12 with discoid lupus erythematosus (DLE) and eight with subacute CLE (SCLE), from two centres in Germany. A core set questionnaire and an SPSS database were designed to enable a consistent statistical analysis.
Results  Location of skin lesions did not differ significantly between the CLE subtypes; however, the activity score was significantly lower in LET than in DLE ( P  <   0·01), and the damage score was significantly lower in LET than in SCLE ( P  <   0·01) and DLE ( P  <   0·01). Photosensitivity and antinuclear antibodies were confirmed to be different in LET compared with SCLE and DLE but without statistical significance. Moreover, histological analysis of skin biopsy specimens showed that abundant mucin deposition is significantly more present in LET compared with SCLE ( P  <   0·01) and DLE ( P  <   0·01) while prominent interface dermatitis and alteration of hair follicles were absent in LET.
Conclusions  Several significant differences were found between LET and other subtypes of CLE with regard to clinical, histological and laboratory parameters. These data strongly indicate that LET should be defined as a separate entity in the classification of CLE.     

Recent advances in cytokines in cutaneous and systemic lupus erythematosus

Lupus erythematosus (LE) includes a broad spectrum of diseases from a cutaneous‐limited type to a systemic type. Systemic lupus erythematosus (SLE) is a systemic autoimmune disease which affects multiple organs. Cutaneous lupus erythematosus (CLE) includes skin symptoms seen in SLE and cutaneous‐limited LE. Although immune abnormalities, as well as heritable, hormonal and environmental factors, are involved in the pathology of LE, the actual pathogenesis is still unclear. Recently, the involvement of various cytokines has been shown in the pathogenesis of LE. Moreover, some trials with biological agents targeted specific cytokines are also ongoing for SLE. In this article, we review the contributions of major cytokines such as interferon, tumor necrosis factor‐α and interleukin‐18 to LE, especially SLE and CLE.     

Epidemiology of cutaneous lupus erythematosus in a tertiary referral centre in Singapore

The aim of this retrospective study was to investigate the epidemiology, yield of investigations and proportion of patients who develop systemic lupus erythematosus (SLE) among the subsets of cutaneous lupus erythematosus (LE) in the Singapore Asian population. One hundred and twenty-five patients were diagnosed with cutaneous LE on clinico-pathological correlation, of which 73 had discoid lupus erythematosus (DLE), eight had subacute cutaneous LE (SCLE), 22 had acute LE lesions and the remainder had other less common forms of cutaneous LE. Histology was consistent with LE in 94.4% and suggestive in 4.8%. Direct immunofluorescence was positive in 61% of DLE, 86% of SCLE and 80% of acute LE cases. Antinuclear antibody (ANA) was present in the majority of acute LE (85%) and SCLE (88%) but only in 25% of DLE. Eight patients (11%) presenting with DLE had definite SLE at first presentation and two (2.7%) subsequently several months later. Of these patients, six had only mucocutaneous and serological criteria but two had major organ involvement. Five SCLE patients (63%) fulfilled the criteria for SLE, including two with major organ involvement.     

Extracoporeal photochemotherapy in cutaneous lupus erythematosus

We report two female subjects with therapy-resistant cutaneous lupus erythematosus (LE), one with subacute cutaneous and the other chronic discoid LE, both treated with extracorporeal photochemotherapy (ECP). The responses after six and eight cycles of ECP led to a prolonged remission of 18 and 11 months, respectively. ECP seems to be a treatment option for patients not responding to or showing unwanted side-effects during conventional standard therapy.     

Cutaneous lupus erythematosus: a personal approach to management

SUMMARY Skin disease in patients with lupus erythematosus may be subdivided into two broad categories - those lesions that when biopsied demonstrate interface dermatitis and those that do not demonstrate interface dermatitis. The skin lesions that are represented by the interface dermatitis include discoid lupus erythematosus, subacute cutaneous lupus erythematosus and acute cutaneous lupus erythematosus. Patients with these 'specific' manifestations have varying degrees of systemic involvement from rare systemic disease in patients with localized discoid lupus erythematosus to common and often severe involvement in patients with acute cutaneous lupus erythematosus. Patients who do not demonstrate interface dermatitis also may have systemic disease and in some instances the skin manifestations are linked to some of the more severe systemic manifestations. Many patients with cutaneous lesions characterized by the interface dermatitis can be controlled with 'standard' therapies including sunscreens, protective clothing and behavioural alteration, and topical corticosteroids with or without an oral antimalarial agent. This review presents a brief summary of each common cutaneous manifestation of lupus erythematosus, its relationship to systemic involvement and treatment issues to effectively deal with the lupus erythematosus patient who has skin disease.     

Ticlopidine-induced subacute cutaneous lupus erythematosus: A case report and literature review

Many drugs have been reported to induce lupus in a minority of patients. Ticlopidine hydrochloride inhibits platelet aggregation and is widely used for the prevention of thrombosis. There have been only a few reports of ticlopidine-induced lupus. Here, we review 13 previously reported cases and describe the case of a 71-year-old man with ticlopidine-induced subacute cutaneous lupus erythematosus. His diagnosis was supported by the appearance of papulosquamous skin lesions on sun-exposed areas and detectable anti-Ro/SS-A antibodies, shortly after drug initiation as well as the gradual resolution of these symptoms after the discontinuation of ticlopidine. Our case highlights that when a patient presents with subacute cutaneous lupus erythematosus-like skin lesions, ticlopidine should be considered as a potential causative agent.