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.     

Discoid lupus erythematosus in children: clinical,histopathologic, and follow-up features in 27 cases

Among 27 pediatric patients with a clinicopathologic diagnosis of discoid lupus erythematosus (DLE), 15 had localized cutaneous lesions and 12 had disseminated lesions. During a mean follow-up period of 36 months, seven patients (26%) developed systemic lupus erythematosus (SLE). Four of these patients were less than 10 years of age. No correlation was found between localized and disseminated lesions and evolution to SLE. Three of four patients with a positive family history for rheumatoid disease developed SLE (p < 0.05). Hyperpigmentation was significantly more frequent (p < 0.04) in children less than 10 years of age. There was a female predominance of 5:1 among patients less than 10 years of age. Our findings suggest that onset of DLE prior to 10 years of age does not indicate a greater risk of developing SLE. The occurrence of localized or disseminated lesions does not seem to influence the outcome.     

Lupus mucinosis: a case report and review of cutaneous lupus

Lupus mucinosis (LM) is a rare disorder found only in patients with systemic lupus erythematosus (SLE) or discoid lupus erythematosus (DLE). We describe a patient with lupus mucinotic nodules as the initial presenting sign of SLE. We further discuss other forms of cutaneous lupus and contrast them with our findings.     

Lupus erythematosus panniculitis: a clinicopathologic study

BACKGROUND: Lupus erythematosus panniculitis is a clinical variant of lupus erythematosus which involves the deep dermis and the subcutaneous fat. The purpose of this study was to ascertain the clinical profile of Asian patients with this condition. METHODS: This was a retrospective study of all histologically confirmed lupus panniculitis seen at our center between 1992 and 1997. The age, sex, past history/subsequent diagnosis of systemic lupus erythematosus (SLE), presence of clinical discoid lupus erythematosus (DLE) changes on overlying skin, direct immunofluorescence, serologic, and histologic findings were analyzed. RESULTS: There were 12 cases of lupus panniculitis, two of which were in patients already diagnosed with SLE and one in which the patient subsequently evolved into SLE. The mean age at diagnosis was 31.3 years. The face (50%), upper limbs (33%), and scalp (25%) were the most common sites of involvement. Thirty-three per cent had clinical evidence of DLE on the overlying skin, whilst 67% had histologic features of DLE on the overlying skin. A lupus band was present in 36%. Antinuclear antibody (ANA) was positive in three of 11 cases; these were in the two patients who already had SLE and in the only patient who progressed to SLE. All of the cases showed fat necrosis and, in the majority of cases, there was associated lobular and paraseptal inflammation. Thirty-three per cent showed lymphocytic vasculitis and 75% had mucin deposition. None had lymphoid nodules, subepidermal hyalinization, or calcification. CONCLUSIONS: Lupus panniculitis affects a younger age group in Asians as compared with the Western population. Although about one-third of patients show clinical evidence of overlying DLE, two-thirds of patients show histologic evidence of DLE. It tends to have a mild disease course in the majority of cases.     

Tumid lupus erythematosus.

BACKGROUND: Tumid lupus erythematosus (TLE) is a subtype of discoid lupus erythematosus (DLE) whose clinical characteristics rarely have been described in the literature. OBJECTIVE: To describe the clinical, histopathologic, and other laboratory findings in tumid lupus erythematosus. METHODS: Clinical and laboratory findings were reviewed in four patients who had been diagnosed with tumid lupus erythematosus by conventional microscopy. The diagnoses were characterized by a superficial and deep perivascular infiltrate of lymphocytes and deposits of mucin in foci in the reticular dermis. RESULTS: All four patients were young women. Ages ranged from 16 to 39 years (mean 21 years). The lesions consisted of numerous erythematous papules and plaques, some with annular configuration situated in the face and neck, trunk, and upper extremities. All four patients had concurrent lesions of classic DLE, three of them had systemic lupus erythematosus (SLE). Direct immunofluorescence test results were negative in nonexposed lesional skin of two of the patients. CONCLUSION: The clinical findings of concurrent lesions of TLE and classic DLE in the same patient, the presence of lesions of TLE in patients with SLE, and the histologic findings demonstrate that TLE is a distinct manifestation of DLE, and as such, a cutaneous expression of SLE.     

Lupus erythematosus in children: a report of six cases

The clinical features of childhood discoid lupus erythematosus (DLE) are similar to those of adult DLE in presentation and chronic course. However, children have a particularly high levels of transition to systemic disease. Systemic lupus erythematosus (SLE) is the most common rheumatic disease associated with significant morbidity and mortality in children. This is a retrospective study reporting all cases of childhood lupus erythematosus observed in the dermatology department of Habib Thameur Hospital over a 14-year period. From 1989 to 2003, six cases of childhood lupus erythematosus are included, three patients with discoid lupus erythematosus (2 girls, 1 boy), and three patients with systemic lupus erythematosus (2 boys, 1 girl). The mean age of onset was 12 years (range 10-16 years). Skin manifestations were localized in sun exposed areas in both discoid and systemic lupus erythematosus. Photosensitivity was noted in all cases. The diagnosis was confirmed by histopathologic examination, direct immunofluorescence, and immunologic findings. Treatment included sun avoidance, oral hydroxychloroquine, and topical and systemic steroids. An average follow-up time was 18.1 months (1-96 months). The severity of onset of SLE is usually greater in children than adults. We note that lupus erythematosus is not a static disease and progression from DLE to SLE is possible.     

Comparative analysis of the quality of life of patients with discoid lupus erythematosus and systemic lupus erythematosus with skin injuries

Lupus erythematosus is an autoimmune disease of unknown etiology with cutaneous and vascular lesions. Both discoid lupus erythematosus (DLE) and systemic lupus (SLE) affect the skin. Visible skin lesions in young women can cause loss of self esteem. In the present study we aimed to evaluate and compare the quality of life in SLE and LED through an observational study of 64 patients. These patients were divided into 2 groups: Group 1: SLE (n = 38); group 2: DLE (n = 26) and then completed the quality of life questionnaire - Dermatology Life Quality Index or DLQI. It was found that patients with DLE have a worse quality of life than patients with SLE. It is believed that this fact is generated by the difference in the spectrum of injuries.     

Experience with the use of hydroxychloroquine for the treatment of lupus erythematosus

Hydroxychloroquine (HCQ) is generally used to treat systemic lupus erythematosus (SLE) in Western countries. However, chloroquine retinopathy became a problem in Japan, and chloroquine has never been used since then. Even now HCQ remains non‐approved. Therefore, the Japanese Hydroxychloroquine Study Group has been organized, and activities have started to have HCQ approved within Japan. In the present study, we investigated the effectiveness of HCQ against the skin manifestations of lupus erythematosus. There were seven patients, all female, and they consisted of four patients with SLE (skin lesion type: discoid lupus erythematosus [DLE] in three, subacute cutaneous lupus erythematosus in one and lupus erythematosus profundus in one), two patients with cutaneous lupus erythematosus (both DLE), and one patient with a combination of SLE and dermatomyositis. HCQ was effective in three patients and ineffective in the two patients. We could not judge the efficacy of HCQ in the other two patients. There were no adverse effects in any of the patients. Efficacy was exhibited against telangiectasia and erythema. HCQ is also an effective and safe treatment for Japanese patients, and it is hoped that it will be approved for use in Japan very soon.     

The circulating lymphocyte profiles in patients with discoid lupus erythematosus and systemic lupus erythematosus suggest a pathogenetic relationship

BACKGROUND: Discoid lupus erythematosus (DLE) and systemic lupus erythematosus (SLE) are chronic inflammatory diseases of unknown aetiology; the relationship of DLE with SLE has been a subject of debate for many years. OBJECTIVES; To find evidence for systemic immune activation in DLE by analysis of the immunophenotypic profiles of circulating lymphocytes, and to compare these changes with those in patients with SLE. METHODS: The immunophenotypic profile of peripheral blood lymphocyte subsets from 23 DLE patients without clinical or laboratory evidence of systemic disease, 25 SLE patients and 38 healthy donors was characterized by two-colour immunofluorescence flow cytometry analysis. None of the patients was receiving corticosteroid or immunosuppressive treatment. RESULTS: Patients with DLE had increased numbers of circulating HLA-DR+ CD3+ T cells and HLA-DR+ CD4+ T cells, indicating systemic T-cell activation, and an expansion of CD5+ CD19+ B cells. Decreased numbers of T-cell subsets expressing the differentiation markers CD11b and CD16/56, and of CD16/56+ natural killer cells were also found. In SLE, the changes were similar but more pronounced. In addition, a profound CD4+ T-cell lymphopenia and an increase of HLA-DR+ CD8+ T cells were found only in SLE. CONCLUSIONS: Our data provide evidence for systemic activation of the cellular immune system in patients with purely cutaneous DLE. Similarities in the lymphocyte immunophenotypic profiles in patients with DLE compared with SLE suggest that there are common immunopathological processes in these two conditions.     

Cutaneous manifestations of systemic lupus erythematosus

We have assessed the cutaneous signs in 73 patients with systemic lupus erythematosus (SLE), seen during a 5-year period in an English hospital. Most previous information about the cutaneous manifestations of SLE has been obtained from studies performed in the U.S.A. We classified lesions as specific cutaneous and mucosal LE (acute, subacute and chronic) or non-specific LE-related, e.g. photosensitivity, urticaria, erythema, Raynaud's phenomenon or vasculitis. Acute cutaneous LE lesions included a butterfly rash with erythematous macules, telangiectasia or papulosquamous lesions, seen in 37 patients (51%) and facial oedema seen in four patients (5%). Five patients (7%) had psoriasiform subacute cutaneous LE, Chronic cutaneous LE was common: 18 patients (25%) had chronic discoid lesions (DLE) and, in 12 (15%), these had preceded systemic disease. One patient had facial lupus profundus. Ten patients (14%) had scarring alopecia secondary to DLE. Fifteen patients (20.5%) had chronic chilblain lupus. Twenty-three patients (31.5%) had a history of mouth ulceration. Of these, 11 (15%) gave a history of ulcers at the onset of their disease. Three (4%) had erythema and superficial ulceration of the palate, not typical of aphthous ulcers, and three (4%) had chronic buccal plaques. Cheilitis due to DLE was seen in three (4%), episcleritis in three (4%), five (7%) had nasal disease, six (8%) bullous skin eruptions, one ‘the bullous eruption of SLE’, four bullae associated with cutaneous vasculitis, and one bullae associated with ultraviolet radiation. Forty-six (63%) observed photosensitivity. A non-scarring alopecia occurred in 29 (40%). Vascular phenomena were common: three patients (4%) had chronic palmar erythema. Raynaud's phenomenon occurred in 44 patients (60%), chronic urticaria, worsened by sun exposure, was noted by 32(44%) (in whom the lesions often lasted more than 36h), eight (11%) had cutaneous vasculitis and three (4%) livedo reticularis. Skin changes play a prominent part in SLE and may provide helpful diagnostic information. In this British population, chilblains and urticaria were particularly common. Lesions of subacute cutaneous LE were relatively unusual in this group of patients with SLE.     

Hyperkeratotic nail discoid lupus erythematosus evolving towards systemic lupus erythematosus: therapeutic difficulties

Nail changes occur in about 25% of systemic lupus erythematosus (SLE) cases. Onycholysis has been reported as the most frequent abnormality in SLE. Nailbed hyperkeratosis may be observed in both SLE and discoid lupus erythematosus (DLE). Involvement of the nail apparatus in DLE is extremely uncommon and never restricted to it. We report on a patient in whom the clinical features on the proximal nailfold were similar to those observed on the skin of a patient with typical DLE. This has, to the best of our knowledge, not yet been reported. The patient also exhibited a very distinctive prominent subungual hyperkeratosis. Interestingly, the patient developed biological alterations suggesting a systematization of the disease. Only a combination of systemic corticoids, retinoids and antimalarials was able to achieve nail improvement and this partial resistance to therapy may be explained by the very unusual subungual hyperkeratosis.     

Circulating T- and B-cell abnormalities in cutaneous lupus erythematosus

Seven patients with subacute cutaneous lupus erythematosus (SCLE), 11 patients with discoid lupus erythematosus (DLE), and 17 age-, sex-, and race-matched controls were examined for the number of circulating peripheral blood T and B cells, immunoglobulin (Ig) synthesizing cells, and Ig secreting cells. A significant alteration in T-cell subsets was detected only in SCLE patients who manifested a decreased number of OKT8 cells. Circulating B cells were significantly increased only in the SCLE patients. The percentage of Ig synthesizing and secreting cells was significantly increased in both the DLE and the SCLE groups. The somewhat unexpected increase in Ig synthesizing and secreting cells in the DLE patients could not be accounted for by antimalarial treatment or the concurrence of the HLA-DR3 phenotype. There was, however, a weak but significant correlation between the degree of B-cell activation in the DLE patients and the number of American Rheumatism Association criteria for the classification of systemic lupus erythematosus (SLE) possessed by these patients. These data demonstrate that abnormalities in B-cell function similar to those seen in SLE can also be found in a group of lupus erythematosus patients whose clinical disease expression is limited predominantly to the skin.     

Childhood discoid lupus erythematosus: a Tunisian retrospective study of 16 cases

Discoid lupus erythematosus (DLE) is uncommon in children. The clinical features of childhood DLE are similar to those of adult DLE in presentation and chronic course. However, children have a particularly high level of transition to systemic disease. We undertook a retrospective study of 16 children with DLE ranging in age from 2 to 15 years, seen over a 9-year period. Six were less than 10 years old at the onset of the disease. The sex ratio was equal. The frequency of childhood DLE was about 7% of the total number of DLE patients seen in our department. Photosensitivity was defined as a clinical history of induction or exacerbation of discoid lesions following sun exposure, and was present in 81% of patients. There was no progression to systemic lupus erythematosus (SLE); an average follow-up time was 10.5 months (2-30 months). We would like to emphasize the increased frequency of childhood DLE in our country and the importance of photosensitivity. However, follow-up data regarding transition to SLE is lacking, therefore we are unable to offer a prognosis to our patients.     

Histocompatibility antigens in discoid and systemic lupus erythematosus

A Study of histocompatibility (HLA) antigens in 6₉ patients with discoid lupus erythematosus (DLE) showed an increased incidence of HLA-B7 and HLA-B8 related to the age at onset and sex of the patient. Young females and males aged 15–39 years at onset were associated with HLA-B₇and females aged over 40 years with HLA-B8. This supports previous studies concerning sex and age specific onset rates in DLE which suggested that there is more than one genotype in this disorder. Female patients with systemic lupus erythematosus (SLE) at all ages of onset showed a significant association with HLA-B8. Female patients, with onset 15–39 years, with either SLE or DLE which has transformed to SLE, show a significant increase in HLA-B8 compared with the females in the same age at onset group who have the discoid disease. The presence of HLA-B8 in a young female with DLE may represent a risk factor for the development of the systemic disease.     

The interferon-regulated gene signature is elevated in subacute cutaneous lupus erythematosus and discoid lupus erythematosus and correlates with the cutaneous lupus area and severity index score

Background There is increased expression of type I interferon (IFN)‐regulated proteins in the blood and target tissues of patients with cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE). Patients with SLE have increased IFN‐regulated gene expression pointing towards a possible underlying genetic defect. Objectives To determine expression levels of five type I IFN‐regulated genes that are highly expressed in SLE in the peripheral blood of patients with CLE and to correlate the expression levels with cutaneous disease activity. Methods Peripheral blood was obtained from 10 healthy controls and 30 patients with CLE, including eight with concomitant SLE. Total RNA was extracted and reverse transcribed into complementary DNA. Gene expression levels were measured by real‐time polymerase chain reaction. Gene expression was normalized to GAPDH, standardized to healthy controls and then summed to calculate an IFN score for each patient. Disease activity was assessed with the Cutaneous Lupus Area and Severity Index (CLASI). Results Patients with subacute CLE (SCLE) and discoid lupus erythematosus (DLE) had elevated IFN scores compared with healthy controls regardless of concomitant SLE (P < 0·01 with SLE and P < 0·05 without SLE). There was no difference between patients with tumid lupus erythematosus (TLE) and healthy controls. The IFN score correlated with CLASI scores (Spearman’s rho = 0·55, P = 0·0017). Conclusions Patients with SCLE and DLE have an IFN signature, as seen in SLE. The level of gene expression correlates with cutaneous disease activity. These findings support a shared pathogenesis between SLE and some subtypes of CLE.     

Interferon response to dipyridamole in lupus erythematosus patients

Studies in patients with autoimmune disorders strongly support a role for interferon (IFN) in the disease process. In the present study we investigated the in vivo production of alpha-IFN in lupus erythematosus patients after stimulation with dipyridamole, recently characterized as an alpha-IFN inducer in mice and humans. Levels of IFN were measured in serum samples from 22 patients with systemic lupus erythematosus (SLE) and 12 patients with discoid lupus erythematosus (DLE) before and 24 h after dipyridamole administration. IFN activity was assayed on human and bovine cells in parallel. Initial serum concentrations of alpha-IFN in SLE patients were markedly elevated. The percentage of DLE positive responders to dipyridamole induction was about twice as high as that found for SLE. Studies of factors responsible for IFN production in lupus erythematosus might result in better understanding of the relationship between DLE and SLE.     

Investigating the presence of neutrophil extracellular traps in cutaneous lesions of different subtypes of lupus erythematosus

Neutrophil extracellular traps (NETs) are implicated in the pathogenesis of systemic lupus erythematosus (SLE). However, little is known about the implication of NETs in cutaneous lupus. In this case series of 30 patients, we compared the amounts of neutrophils producing NETs in cutaneous lesions of different subtypes of lupus (5 with discoid lupus or DLE, 5 with subacute cutaneous lupus or SCLE, 11 with acute cutaneous SLE, 7 with lupus panniculitis and 2 with chilblains). Immunofluorescence was performed on formalin‐fixed paraffin‐embedded skin biopsies using antibodies against neutrophilic granules (elastase, myeloperoxidase, PR‐3 proteins and citrullinated histone 3). Dihydroethidium staining was performed to detect reactive oxygen species (ROS), known inducers of NETs. NETs were detected in the different subtypes of cutaneous lupus as well as in cutaneous lesions of SLE. The amounts of neutrophils producing NETs were significantly higher in lupus panniculitis (49%), acute cutaneous SLE (41%) and DLE (32%), in comparison with SCLE (5%) and chilblains (0%). This suggests that NETs might be associated with more tissue damage and scarring. ROS were observed in the different cutaneous subtypes of lupus independent of NETs.     

The effect of systemic corticosteroid therapy on the expression of toll-like receptor 2 and toll-like receptor 4 in the cutaneous lesions of leprosy Type 1 reactions

Up to 28% of patients with discoid lupus erythematosus (DLE) are susceptible to developing systemic lupus erythematosus (SLE). To better characterize patients with DLE who have a higher potential of developing SLE, we reviewed studies contrasting, firstly, DLE-only patients (i.e. patients with DLE without SLE) and SLE patients with DLE (i.e. patients who are diagnosed with SLE and DLE simultaneously, and patients with SLE who later develop DLE), and secondly, DLE-only patients and patients with DLE who progress to SLE. These studies have commonly identified various clinical and laboratory indicators, such as widespread DLE lesions, arthralgias/arthritis, nail changes, anaemia, leucopenia, high erythrocyte sedimentation rates (ESRs) and high titres of antinuclear antibodies (ANAs), which are associated with progression to SLE in patients with DLE, and SLE patients with DLE. Limitations of these studies include inadequate follow-up time, small numbers of patients with DLE converting to SLE, outdated criteria for SLE diagnosis and retrospective study designs. However, because of the risk of SLE development in patients with DLE, complete skin examinations, joint assessments and laboratory tests including ANA, ESR and full blood counts should be performed regularly for patients with DLE. A prospective study following patients with DLE who do or do not develop SLE is currently underway through the Cutaneous Lupus Registry at the University of Texas Southwestern Medical Center. It will seek to identify clinical features and biomarkers that improve our assessment of risk of systemic spread in these patients.     

Time to progression from discoid lupus erythematosus to systemic lupus erythematosus: a retrospective cohort study

Determining the risk of progression to systemic lupus erythematosus (SLE) among patients diagnosed with discoid lupus erythematosus (DLE), and the time frame of this risk, are important clinical questions. Past reports have demonstrated a wide time frame of progression from DLE to SLE, with mean time to progression of approximately 8 years. Using data obtained from an academic lupus centre, we identified 32 patients who progressed from DLE to SLE. In our cohort, we found that the median time to progression from DLE to SLE was 453 days, much sooner than previously reported. We believe this information can help inform clinicians on monitoring visit intervals and how best to counsel patients on SLE progression.     

Abnormal laboratory test results and their relationship to prognosis in discoid lupus erythematosus. A long-term follow-up study of 92 patients.

Investigation of 92 patients with discoid lupus erythematosus, manifested initially by localized cutaneous lesions only, showed abnormal laboratory test results for 57 patients (62%) on admission and for 62 patients (67.4%) on review 16 to 20 years later. Patients with discoid lesions confined to the head and neck (DLE) showed fewer laboratory abnormalities than those patients with disseminated lesions involving trunk and limbs (disseminated discoid lupus erythematosus [DDLE]). Systemic lupus erythematosus (SLE) eventually developed in six (6.5%) of the patients, and all had shown persistent multiple abnormal laboratory findings from the beginning. Complete remission occurred in 46.7%. A persistent positive antinuclear factor of either speckled or homogeneous pattern with a titer greater than 1:50, leukopenia, thrombocytopenia, or a false-positive Wassermann reaction indicated those patients who may progress to DDLE or SLE.