Varied responses to and efficacies of hydroxychloroquine treatment according to cutaneous lupus erythematosus subtypes in Japanese patients

Hydroxychloroquine is recommended as the first‐line systemic treatment for cutaneous lupus erythematosus (CLE) in Western countries, and it was approved in Japan in 2016. However, the efficacy of hydroxychloroquine in various cutaneous lupus erythematosus subtypes in Japanese patients has not been elucidated to date. Therefore, we investigated the efficacy of hydroxychloroquine for the treatment of cutaneous manifestations according to CLE subtypes in Japanese patients. We enrolled 35 patients (29 diagnosed with systemic lupus erythematosus and six with CLE) in this retrospective study. We analyzed the efficacy of hydroxychloroquine for the treatment of cutaneous manifestations according to cutaneous lupus erythematosus subtypes, time to the first skin improvement, as well as effects on laboratory data and reduction of concomitant immunosuppressive drug administration at 16 and 32 weeks of therapy. Complete improvement was observed at high rates for acute CLE (ACLE); however, partial or non‐improvement rates were higher for chronic CLE (CCLE) at 16 weeks. Several patients with alopecia without scarring achieved complete improvement at 32 weeks. CCLE tended to take more time to improve than ACLE. Overall, hydroxychloroquine was highly effective for skin: 87% of patients had at least some beneficial response at 16 weeks. Nevertheless, there were wide variations in complete improvement rates and duration for improvement among CLE subtypes. Our findings suggest that a therapeutic approach considering the subtypes of CLE will improve its management.     

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.     

Cicatricial alopecia: discoid lupus erythematosus

ABSTRACT:   Chronic cutaneous lupus erythematosus consists of three major dermatologic diseases: discoid lupus erythematosus (DLE), lupus panniculitis/lupus profundus, and lupus tumidus ( Table 1 ). DLE is estimated to be responsible for 50–85% of patients with chronic cutaneous lupus erythematosus. Scalp involvement is most often the presenting symptom. The clinical features and diagnosis of DLE, its pathophysiology and treatment, are reviewed.  

  Table 1.  Chronic cutaneous lupus erythematosus     

4.

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

Ng PP  Tan SH  Koh ET  Tan T 《The Australasian journal of dermatology》2000,41(4):229-233

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.     

5.

Photosensitivity in lupus erythematosus     

Scheinfeld N  Deleo VA 《Photodermatology, photoimmunology & photomedicine》2004,20(5):272-279

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.     

6.

Discoid lupus erythematosus     

AM Donnelly  AR Halbert  JB Rohr 《The Australasian journal of dermatology》1995,36(1):3-10

Discoid lupus erythematosus is a manifestation of chronic cutaneous lupus erythematosus with a small risk of systemic involvement. In this review article, the role of predisposing factors such as haplotype, hormones, antibodies and sunlight are discussed. The clinical features, including variants and associations, and management options are presented.     

7.

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

Yoko Momose  Satoru Arai  Hikaru Eto  Mitsumasa Kishimoto  Masato Okada 《The Journal of dermatology》2013,40(2):94-97

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.     

8.

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

Morihara K  Kishimoto S  Shibagaki R  Takenaka H  Yasuno H 《The British journal of dermatology》2002,147(1):157-159

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'.     

9.

Recent advances in cytokines in cutaneous and systemic lupus erythematosus     

Naoya MIKITA  Takaharu IKEDA  Mariko ISHIGURO  Fukumi FURUKAWA 《The Journal of dermatology》2011,38(9):839-849

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.     

10.

线状皮肤型红斑狼疮   总被引：2，自引：0，他引：2  

廖文俊  樊平申  付萌  王雷  高天文 《临床皮肤科杂志》2010,39(2)

目的:分析线状皮肤型红斑狼疮的临床表现、组织病理及免疫组化组织病理特点.方法:采用回顾性分析方法对7例线状皮肤型红斑狼绝患者的临床表现、组织病理改变、免疫荧光及实验窀检查资料进行分析.结果:7例患者中男2例,女5例;平均年龄23岁(4～40岁);平均发病年龄19.43岁(3～37岁),其中2例发病年龄<6岁.皮损部位:1例位于左下肢,其余6例均位于头面部.皮损均呈线状分布,其走向与Blasehko线一致;所有患者均无系统受累的证据.结合组织病理和免疫荧光检查,6例诊断为线状盘状红斑狼疮,1例为线状深在性红斑狼疮.结论:线状皮肤型红斑狼疮是红斑狼疮的罕见变异型,不引起系统受累.临床诊断有一定困难,需借助于组织病理和免疫荧光检查.     

11.

The circulating lymphocyte profiles in patients with discoid lupus erythematosus and systemic lupus erythematosus suggest a pathogenetic relationship   总被引：3，自引：0，他引：3  

Wouters CH  Diegenant C  Ceuppens JL  Degreef H  Stevens EA 《The British journal of dermatology》2004,150(4):693-700

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.     

12.

大疱性系统性红斑狼疮临床资料分析          下载免费PDF全文

温志华  姚煦 《中国麻风皮肤病杂志》2020,36(5):259-261

分析国内近20年发表的大疱性系统性红斑狼疮38篇文献,共57例,其中女47例,男10例,平均(26.6±11.8)岁;典型皮损为暗红色斑疹或正常皮肤上出现水疱大疱;常累及血液系统(64.9%)、肾脏(61.4%)及关节(57.9%);ANA阳性率为100%、dsDNA阳性率为66.7%、Sm抗体阳性率为59.6%;89.1%患者症状得到控制,其中23.6%患者单用糖皮质激素有效,76.4%患者联用DDS或其他免疫抑制剂。     

13.

Antidouble-stranded DNA isotypes in lupus erythematosus patients with prevalent cutaneous presentation   总被引：1，自引：0，他引：1  

Parodi A  Drosera M  Barbieri LB  Babbini G  Rebora A 《The British journal of dermatology》2002,147(4):754-756

BACKGROUND: Antidouble-stranded DNA antibodies (anti-dsDNA Ab), in particular of the IgG isotype, are usually considered a marker of systemic lupus erythematosus and often correlate with the disease activity. OBJECTIVES: To determine IgG, IgA and IgM anti-dsDNA Ab in a group of 330 patients with lupus erythematosus and prevalent cutaneous lesions. METHODS: The titre of anti-dsDNA Ab was determined by enzyme-linked immunosorbent assay, and disease activity was assessed by means of the systemic lupus activity measure. RESULTS: One hundred and six patients had anti-dsDNA Ab. Thirty-nine patients had antibodies of all three isotypes of immunoglobulins, 17 had IgG + IgM, five IgG + IgA, and two IgA + IgM. Forty-three patients had a single isotype of anti-dsDNA Ab. Patients with systemic disease and higher disease activity had antibodies of all three isotypes of immunoglobulins or of IgG isotype. Remarkably, anti-dsDNA Ab of the IgA isotype, alone or associated with IgM, marked dermatological patients with low disease activity, but often with disquieting clinical and/or laboratory alterations. CONCLUSIONS: These results indicate a correlation between disease activity and both frequency and isotype of anti-dsDNA Ab.     

14.

Cyclosporin combined with methotrexate in two patients with recalcitrant subacute cutaneous lupus erythematosus     

Klein A  Vogt T  Wenzel SM  Fleck M  Landthaler M 《The Australasian journal of dermatology》2011,52(1):43-47

The treatment of subacute cutaneous lupus erythematosus is a therapeutic challenge. Frequently, patients are resistant to or intolerant towards single selected immunosuppressants. In combination, lower doses of methotrexate and cyclosporin A might be used to minimize toxicity. This is the first report of a successful combination of these drugs in two patients suffering from subacute cutaneous lupus erythematosus refractory to standard treatment.     

15.

Cutaneous lupus erythematosus: a review of etiopathogenic,clinical, diagnostic and therapeutic aspects     

《Anais brasileiros de dermatologia》2023,98(3):355-372

Cutaneous lupus erythematosus is an autoimmune disease of varied clinical expression, which may present as an exclusively cutaneous disease or be one of the multiple manifestations of systemic lupus erythematosus. Its classification includes acute, subacute, intermittent, chronic and bullous subtypes, which are usually identified based on clinical features and histopathological and laboratory findings. Other non-specific cutaneous manifestations may be associated with systemic lupus erythematosus and are usually related to disease activity. Environmental, genetic and immunological factors play a role in the pathogenesis of skin lesions in lupus erythematosus. Recently, considerable progress has been made in elucidating the mechanisms involved in their development, which allows for foreseeing future targets for more effective treatments. This review proposes to discuss the main etiopathogenic, clinical, diagnostic and therapeutic aspects of cutaneous lupus erythematosus, aiming to update internists and specialists from different areas.     

16.

Hydroxychloroquine administration for Japanese lupus erythematosus in Wakayama: a pilot study     

Ikeda T  Kanazawa N  Furukawa F 《The Journal of dermatology》2012,39(6):531-535

Hydroxychloroquine (HCQ) is used as the first-line systemic treatment for severe, widespread or refractory cutaneous lupus erythematosus (CLE) in many countries. However HCQ is not an approved drug in Japan. For the establishment of HCQ therapy as the alternative treatment for CLE in Japan, we conducted a pilot study in Japanese patients with refractory CLE by administrating HCQ, and evaluated the improvements in the skin lesions using the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI). We administrated HCQ to seven CLE cases, including four systemic lupus erythematosus (SLE) cases. The skin lesions of the four cases improved dramatically, and their mean CLASI activity index decreased significantly following HCQ treatment. Arthralgia improved in all three cases with arthralgia and general malaise also improved in two of the three cases who had complained. In three cases who discontinued HCQ therapy after 16 weeks of treatment, their skin lesions and general malaise worsened soon, and after the resumption of HCQ therapy these symptoms improved again. The mean serum triglyceride and total cholesterol levels also decreased significantly at the end of this study. Our results suggest that HCQ might be effective for Japanese SLE skin lesions and CLE, and support the studies which reported that HCQ prevented clinical flare ups of SLE. An additional effect to improve lipid profiles was also observed in our Japanese cases. It is necessary to confirm that these effects are reproducible when Japanese lupus erythematosus cases are given HCQ.     

17.

Interleukin-6 expression in the skin of patients with lupus erythematosus   总被引：2，自引：0，他引：2  

W Nürnberg  N. Haas  D. Schadendorf  B. M. Czarnetzki 《Experimental dermatology》1995,4(1):52-57

Abstract It has been proposed that interleukin-6 may play a role in the pathogenesis of autoimmune diseases like lupus erythematosus. We have therefore investigated the immunoreactivity of IL-6 in 32 skin biopsies of 23 patients suffering from chronic discoid lupus erythematosus (n=16), subacute cutaneous lupus erythematosus (n=5) and systemic lupus erythematosus (n = 5) as well as in uninvolved skin (n = 6) and in normal skin from healthy volunteers (n = 3). Increased immunohistochemical staining was detectable in 14 of 26 biopsies from lesional skin. The remaining biopsies from lesional, non-lesional and normal skin displayed only minimal or no reactivity, but 8 out of 12 lupus erythematosus patients had been pretreated with local or systemic antiinflammatory drugs. Irrespective of the LE subtype, immunolabelling was generally most intense in the basal layer of the epidermis, with additional intense suprabasal staining in sections from 2 of 5 SLE patients. Preferential production of IL-6 in the lower parts of the epidermis was confirmed by RNA in situ hybridization. No correlation was found between the deposition of immuno-globulins and complement at the dermo-epidermal junction and IL-6 expression in keratinocytcs. These data suggest that IL-6 may be involved in LE although its exact role in the pathogenesis of the disease needs to be further elucidated.     

18.

Systemic lupus erythematosus presenting with oral mucosal lesions: easily missed?     

C.H. Orteu  J.A.G. Buchanan  I. Hutchison  †  I.M. Leigh  R.H. Bull 《The British journal of dermatology》2001,144(6):1219-1223

Two caucasian patients are described in whom oral mucosal lesions were the first manifestation of systemic lupus erythematosus. In both cases the diagnosis was delayed despite histological examination of oral lesions. Treatment with antimalarials and azathioprine was of significant benefit. In the absence of cutaneous or systemic features, distinguishing oral lupus erythematosus from lichen planus and epidermal dysplasia can be difficult, both clinically and on histology, and requires a high index of suspicion.     

19.

儿童大疱性系统性红斑狼疮临床特点分析          下载免费PDF全文

朱丽媛  杨文浩 《中国麻风皮肤病杂志》2023,39(3):151-155

目的:分析儿童大疱性系统性红斑狼疮的临床特点。方法:回顾性分析3例儿童大疱性系统性红斑狼疮资料,并总结文献报道的15例病例临床特点及治疗转归。结果:18例患儿中皮肤和肾脏病理资料完整者16例,平均年龄11.22岁,男女比例为2∶16;10例以皮肤大疱首发,12例大疱发生在狼疮肾炎之前;12例合并发热、9例合并口腔溃疡,14例出现贫血。所有病例ANA阳性,13例存在3种及以上血清自身抗体。皮肤病理特点为基底膜补体及免疫球蛋白沉积,10例24 h尿蛋白≥1.5 g; 16例患儿具有肾脏病理资料,其中Ⅴ型狼疮肾炎7例、Ⅳ型狼疮肾炎6例、Ⅲ型狼疮肾炎3例。氨苯砜对皮损有效,免疫抑制剂可减少大疱复发,利妥昔单抗和贝利尤单抗治疗对于难治性患儿可能有效。结论:多系统性受累、多种自身抗体阳性和狼疮肾炎是儿童大疱性系统性红斑狼疮的特点,免疫抑制治疗可改善预后,抗B细胞治疗可作为难治性病例的选择。     

20.

Systemic lupus erythematosus with C1q deficiency     

Stone NM  Williams A  Wilkinson JD  Bird G 《The British journal of dermatology》2000,142(3):521-524

We report a case of systemic lupus erythematosus associated with C1q deficiency. Our patient presented at the age of 6 years with cutaneous lupus. She later developed Raynaud's phenomenon, non-scarring alopecia, oral ulceration and grand mal seizures due to cerebral vasculitis. Complement C3 and C4 levels were consistently normal during flares of her lupus and haemolytic activity of her complement was absent, suggesting a deficiency of an early component of the complement cascade. No C1q could be detected.     

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.     

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.     

Discoid lupus erythematosus

Discoid lupus erythematosus is a manifestation of chronic cutaneous lupus erythematosus with a small risk of systemic involvement. In this review article, the role of predisposing factors such as haplotype, hormones, antibodies and sunlight are discussed. The clinical features, including variants and associations, and management options are presented.     

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.     

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'.     

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.     

线状皮肤型红斑狼疮

目的:分析线状皮肤型红斑狼疮的临床表现、组织病理及免疫组化组织病理特点.方法:采用回顾性分析方法对7例线状皮肤型红斑狼绝患者的临床表现、组织病理改变、免疫荧光及实验窀检查资料进行分析.结果:7例患者中男2例,女5例;平均年龄23岁(4～40岁);平均发病年龄19.43岁(3～37岁),其中2例发病年龄<6岁.皮损部位:1例位于左下肢,其余6例均位于头面部.皮损均呈线状分布,其走向与Blasehko线一致;所有患者均无系统受累的证据.结合组织病理和免疫荧光检查,6例诊断为线状盘状红斑狼疮,1例为线状深在性红斑狼疮.结论:线状皮肤型红斑狼疮是红斑狼疮的罕见变异型,不引起系统受累.临床诊断有一定困难,需借助于组织病理和免疫荧光检查.     

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.     

大疱性系统性红斑狼疮临床资料分析

分析国内近20年发表的大疱性系统性红斑狼疮38篇文献,共57例,其中女47例,男10例,平均(26.6±11.8)岁;典型皮损为暗红色斑疹或正常皮肤上出现水疱大疱;常累及血液系统(64.9%)、肾脏(61.4%)及关节(57.9%);ANA阳性率为100%、dsDNA阳性率为66.7%、Sm抗体阳性率为59.6%;89.1%患者症状得到控制,其中23.6%患者单用糖皮质激素有效,76.4%患者联用DDS或其他免疫抑制剂。     

Antidouble-stranded DNA isotypes in lupus erythematosus patients with prevalent cutaneous presentation

BACKGROUND: Antidouble-stranded DNA antibodies (anti-dsDNA Ab), in particular of the IgG isotype, are usually considered a marker of systemic lupus erythematosus and often correlate with the disease activity. OBJECTIVES: To determine IgG, IgA and IgM anti-dsDNA Ab in a group of 330 patients with lupus erythematosus and prevalent cutaneous lesions. METHODS: The titre of anti-dsDNA Ab was determined by enzyme-linked immunosorbent assay, and disease activity was assessed by means of the systemic lupus activity measure. RESULTS: One hundred and six patients had anti-dsDNA Ab. Thirty-nine patients had antibodies of all three isotypes of immunoglobulins, 17 had IgG + IgM, five IgG + IgA, and two IgA + IgM. Forty-three patients had a single isotype of anti-dsDNA Ab. Patients with systemic disease and higher disease activity had antibodies of all three isotypes of immunoglobulins or of IgG isotype. Remarkably, anti-dsDNA Ab of the IgA isotype, alone or associated with IgM, marked dermatological patients with low disease activity, but often with disquieting clinical and/or laboratory alterations. CONCLUSIONS: These results indicate a correlation between disease activity and both frequency and isotype of anti-dsDNA Ab.     

Cyclosporin combined with methotrexate in two patients with recalcitrant subacute cutaneous lupus erythematosus

The treatment of subacute cutaneous lupus erythematosus is a therapeutic challenge. Frequently, patients are resistant to or intolerant towards single selected immunosuppressants. In combination, lower doses of methotrexate and cyclosporin A might be used to minimize toxicity. This is the first report of a successful combination of these drugs in two patients suffering from subacute cutaneous lupus erythematosus refractory to standard treatment.     

Cutaneous lupus erythematosus: a review of etiopathogenic,clinical, diagnostic and therapeutic aspects

Cutaneous lupus erythematosus is an autoimmune disease of varied clinical expression, which may present as an exclusively cutaneous disease or be one of the multiple manifestations of systemic lupus erythematosus. Its classification includes acute, subacute, intermittent, chronic and bullous subtypes, which are usually identified based on clinical features and histopathological and laboratory findings. Other non-specific cutaneous manifestations may be associated with systemic lupus erythematosus and are usually related to disease activity. Environmental, genetic and immunological factors play a role in the pathogenesis of skin lesions in lupus erythematosus. Recently, considerable progress has been made in elucidating the mechanisms involved in their development, which allows for foreseeing future targets for more effective treatments. This review proposes to discuss the main etiopathogenic, clinical, diagnostic and therapeutic aspects of cutaneous lupus erythematosus, aiming to update internists and specialists from different areas.     

Hydroxychloroquine administration for Japanese lupus erythematosus in Wakayama: a pilot study

Hydroxychloroquine (HCQ) is used as the first-line systemic treatment for severe, widespread or refractory cutaneous lupus erythematosus (CLE) in many countries. However HCQ is not an approved drug in Japan. For the establishment of HCQ therapy as the alternative treatment for CLE in Japan, we conducted a pilot study in Japanese patients with refractory CLE by administrating HCQ, and evaluated the improvements in the skin lesions using the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI). We administrated HCQ to seven CLE cases, including four systemic lupus erythematosus (SLE) cases. The skin lesions of the four cases improved dramatically, and their mean CLASI activity index decreased significantly following HCQ treatment. Arthralgia improved in all three cases with arthralgia and general malaise also improved in two of the three cases who had complained. In three cases who discontinued HCQ therapy after 16 weeks of treatment, their skin lesions and general malaise worsened soon, and after the resumption of HCQ therapy these symptoms improved again. The mean serum triglyceride and total cholesterol levels also decreased significantly at the end of this study. Our results suggest that HCQ might be effective for Japanese SLE skin lesions and CLE, and support the studies which reported that HCQ prevented clinical flare ups of SLE. An additional effect to improve lipid profiles was also observed in our Japanese cases. It is necessary to confirm that these effects are reproducible when Japanese lupus erythematosus cases are given HCQ.     

Interleukin-6 expression in the skin of patients with lupus erythematosus

Abstract It has been proposed that interleukin-6 may play a role in the pathogenesis of autoimmune diseases like lupus erythematosus. We have therefore investigated the immunoreactivity of IL-6 in 32 skin biopsies of 23 patients suffering from chronic discoid lupus erythematosus (n=16), subacute cutaneous lupus erythematosus (n=5) and systemic lupus erythematosus (n = 5) as well as in uninvolved skin (n = 6) and in normal skin from healthy volunteers (n = 3). Increased immunohistochemical staining was detectable in 14 of 26 biopsies from lesional skin. The remaining biopsies from lesional, non-lesional and normal skin displayed only minimal or no reactivity, but 8 out of 12 lupus erythematosus patients had been pretreated with local or systemic antiinflammatory drugs. Irrespective of the LE subtype, immunolabelling was generally most intense in the basal layer of the epidermis, with additional intense suprabasal staining in sections from 2 of 5 SLE patients. Preferential production of IL-6 in the lower parts of the epidermis was confirmed by RNA in situ hybridization. No correlation was found between the deposition of immuno-globulins and complement at the dermo-epidermal junction and IL-6 expression in keratinocytcs. These data suggest that IL-6 may be involved in LE although its exact role in the pathogenesis of the disease needs to be further elucidated.     

Systemic lupus erythematosus presenting with oral mucosal lesions: easily missed?

Two caucasian patients are described in whom oral mucosal lesions were the first manifestation of systemic lupus erythematosus. In both cases the diagnosis was delayed despite histological examination of oral lesions. Treatment with antimalarials and azathioprine was of significant benefit. In the absence of cutaneous or systemic features, distinguishing oral lupus erythematosus from lichen planus and epidermal dysplasia can be difficult, both clinically and on histology, and requires a high index of suspicion.     

儿童大疱性系统性红斑狼疮临床特点分析

目的:分析儿童大疱性系统性红斑狼疮的临床特点。方法:回顾性分析3例儿童大疱性系统性红斑狼疮资料,并总结文献报道的15例病例临床特点及治疗转归。结果:18例患儿中皮肤和肾脏病理资料完整者16例,平均年龄11.22岁,男女比例为2∶16;10例以皮肤大疱首发,12例大疱发生在狼疮肾炎之前;12例合并发热、9例合并口腔溃疡,14例出现贫血。所有病例ANA阳性,13例存在3种及以上血清自身抗体。皮肤病理特点为基底膜补体及免疫球蛋白沉积,10例24 h尿蛋白≥1.5 g; 16例患儿具有肾脏病理资料,其中Ⅴ型狼疮肾炎7例、Ⅳ型狼疮肾炎6例、Ⅲ型狼疮肾炎3例。氨苯砜对皮损有效,免疫抑制剂可减少大疱复发,利妥昔单抗和贝利尤单抗治疗对于难治性患儿可能有效。结论:多系统性受累、多种自身抗体阳性和狼疮肾炎是儿童大疱性系统性红斑狼疮的特点,免疫抑制治疗可改善预后,抗B细胞治疗可作为难治性病例的选择。     

Systemic lupus erythematosus with C1q deficiency

We report a case of systemic lupus erythematosus associated with C1q deficiency. Our patient presented at the age of 6 years with cutaneous lupus. She later developed Raynaud's phenomenon, non-scarring alopecia, oral ulceration and grand mal seizures due to cerebral vasculitis. Complement C3 and C4 levels were consistently normal during flares of her lupus and haemolytic activity of her complement was absent, suggesting a deficiency of an early component of the complement cascade. No C1q could be detected.