EuroGuiderm guideline on lichen sclerosus-introduction into lichen sclerosus.

INTRODUCTION: Lichen sclerosus (LS) is an inflammatory skin disease affecting all ages. LS typically involves the anogenital site where it causes itching and soreness. It may lead to sexual and urinary dysfunction in females and males; however, it may be asymptomatic. First signs of LS are redness and oedema, typically followed by whitening of the genital skin; sometimes fissuring, scarring, shrinkage and fusion of structures may follow in its course. LS is associated with an increased risk of genital cancer. LS has a huge impact on the quality of life of affected patients, and it is important to raise more awareness of this not uncommon disease in order to diagnose and treat it early. OBJECTIVES: The guideline intends to provide guidance on the diagnostic of LS, highlight important aspects in the care of LS patients (part 1), generate recommendations and treatment algorithms (part 2) on topical, interventional and surgical therapy, based on the latest evidence, provide guidance in the management of LS patients during pregnancy, provide guidance for the follow-up of patients with LS and inform about new developments and potential research aspects. MATERIALS AND METHODS: The guideline was developed in accordance with the EuroGuiDerm Methods Manual v1.3 https://www.edf.one/de/home/Guidelines/EDF-EuroGuiDerm.html. The wording of the recommendations was standardized (as suggested by the GRADE Working Group). The guideline development group is comprised of 34 experts from 16 countries, including 5 patient representatives. RESULTS: Ultrapotent or potent topical corticosteroids in females and males, adults and children remain gold standard of care for genital LS; co-treatment with emollients is recommended. If standard treatment fails in males, a surgical intervention is recommended, complete circumcision may cure LS in males. UV light treatment is recommended for extragenital LS; however, there is limited scientific evidence. Topical calcineurin inhibitors are second line treatment. Laser treatment, using various wave lengths, is under investigation, and it can currently not be recommended for the treatment of LS. Treatment with biologics is only reported in single cases. CONCLUSIONS: LS has to be diagnosed and treated as early as possible in order to minimize sequelae like scarring and cancer development. Topical potent and ultrapotent corticosteroids are the gold standard of care; genital LS is often a lifelong disease and needs to be treated long-term.

EuroGuiderm guideline on lichen sclerosus-Treatment of lichen sclerosus.

INTRODUCTION: Lichen sclerosus (LS) is an inflammatory skin disease affecting all ages. LS typically involves the anogenital site where it causes itching and soreness; it may lead to sexual and urinary dysfunction in females and males; however, it may be asymptomatic. First signs of LS are usually a whitening of the genital skin, sometimes preceded by redness and oedema; fissuring, scarring, shrinkage and fusion of structures may follow in its course. LS is associated with an increased risk of genital cancer. LS has a huge impact on the quality of life of affected patients, and it is important to raise more awareness of this not uncommon disease in order to diagnose and treat it early. OBJECTIVES: The guideline intends to provide guidance on the diagnostic of LS (part 1), highlight important aspects in the care of LS patients, generate recommendations and treatment algorithms (part 2) on topical, interventional and surgical therapy, based on the latest evidence, provide guidance in the management of LS patients during pregnancy, provide guidance for the follow-up of patients with LS and inform about new developments and potential research aspects. MATERIALS AND METHODS: The guideline was developed in accordance with the EuroGuiDerm Methods Manual v1.3 https://www.edf.one/de/home/Guidelines/EDF-EuroGuiDerm.html. The wording of the recommendations was standardized (as suggested by the GRADE Working Group). The guideline development group is comprised of 34 experts from 16 countries, including 5 patient representatives. RESULTS: Ultrapotent or potent topical corticosteroids in females and males, adults and children remain gold standard of care for genital LS; co-treatment with emollients is recommended. If standard treatment fails in males, a surgical intervention is recommended, complete circumcision may cure LS in males. UV light treatment is recommended for extragenital LS; however, there is limited scientific evidence. Topical calcineurin inhibitors are second line treatment. Laser treatment, using various wave lengths, is under investigation, and it can currently not be recommended for the treatment of LS. Treatment with biologics is only reported in single cases. CONCLUSIONS: LS has to be diagnosed and treated as early as possible in order to minimize sequelae like scarring and cancer development. Topical potent and ultrapotent corticosteroids are the gold standard of care; genital LS is often a lifelong disease and needs to be treated long-term.

Smoking is highly associated with discoid lupus erythematosus and lupus erythematosus tumidus: analysis of 405 patients.

BACKGROUND: Environmental factors appear to play a role in the pathogenesis of lupus erythematosus (LE). OBJECTIVE: To determine the association between cigarette smoking and various types of cutaneous LE. DESIGN: Retrospective descriptive study at a dermatology clinic of a tertiary referral hospital. METHODS: All patients diagnosed with cutaneous and/or systemic LE from January 2000 to December 2012 at the outpatient clinic for dermatological autoimmune diseases were analyzed. RESULTS: 405 patients were diagnosed with LE. Smokers were more common among patients with cutaneous LE, especially those with LE tumidus or discoid LE. The frequency of cigarette smokers was not significantly higher among patients with other LE-specific skin lesions and patients with systemic LE compared to the general population. Smoking at the onset of disease was associated with LE tumidus (odds ratio OR 4.5), discoid LE (OR 2.05), the male gender (OR 3.31), age < 50 years (OR 1.03), and photosensitivity (OR 2.07). LIMITATIONS: A retrospective descriptive study at a tertiary referral hospital. CONCLUSION: Smoking is highly associated with cutaneous LE, but not systemic LE. Various risk factors appear to be involved in the pathogenesis of cutaneous and systemic LE.

Cerebral large vessel vasculitis in systemic lupus erythematosus.

Neuropsychiatric systemic lupus erythematosus (NPSLE) is defined by involvement of the central nervous system in systemic lupus erythematosus (SLE), with a wide range of both neurological and psychiatric manifestations. Although its aetiopathogenesis is not fully elucidated, NPSLE seems to be a consequence of cerebral vascular pathology including thromboembolism, small-vessel vasculopathy and, in rare cases, true vasculitis. Cerebral vasculitis is rare, and cerebral large-vessel vasculitis in SLE is even more unusual. We report the case of a female patient with the diagnosis of SLE. She presented with stroke-like symptoms, headache and vertigo, and palpable purpura on her legs. Further investigations revealed that she suffered from both vasculitis of the cerebral large vessels and coexisting cutaneous small-vessel vasculitis.

Analysis of 303 Ro/SS-A antibody-positive patients: is this antibody a possible marker for malignancy?

BACKGROUND: The risk of cancer in patients with autoimmune diseases has been investigated in several studies. Ro/SS-A antibodies are frequent and specific autoantibodies among patients with various autoimmune diseases. OBJECTIVES: To assess the risk of cancer in individuals with positive Ro/SS-A antibodies and to analyse their clinical and laboratory characteristics. METHODS: Consecutive patients (n = 303) with Ro/SS-A antibody positivity were collected during 11 years in our outpatient clinic for autoimmune diseases and were retrospectively analysed. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for all cancers were calculated. In addition, we identified further clinical and laboratory characteristics of Ro/SS-A antibody-positive patients indicating the development or existence of a malignancy. RESULTS: Fifty (16·5%) patients were diagnosed with malignancies. Ro/SS-A antibody was strongly associated with malignant diseases (SIR 2·6, 95% CI 1·9-6·1), particularly melanoma (SIR 33·3, 95% CI 5·2-188·6), T-cell lymphoma (SIR 16·7, 95% CI 2·9-128·9), non-Hodgkin lymphoma (SIR 10·6, 95% CI 1·5-78·9) and breast carcinoma (SIR 4·98, 95% CI 1·3-28·3). Logistic regression modelling revealed that Ro/SS-A antibody-positive patients aged 55 years or older, presenting with fever, anaemia and cutaneous lupus erythematosus, have a greater probability of developing cancer and are considered high-risk patients, as compared with Ro/SS-A antibody-positive patients with none of the mentioned clinical criteria. CONCLUSIONS: In our cohort of Ro/SS-A antibody-positive patients, an overall increased risk of malignancy was noticed. Regular screening tests including imaging and laboratory values are justified in Ro/SS-A antibody-positive patients who exhibit the mentioned clinical criteria.

Hepatitis C and autoimmunity: a therapeutic challenge.

Hepatitis C virus (HCV) infection causes not only acute and chronic liver disease, but also extrahepatic symptoms. To our knowledge, this is the first case report of a patient who developed simultaneously subacute cutaneous lupus erythematosus and a small CD20+ B-cell clone because of chronic HCV infection and relapse after standard of care therapy (pegylated interferon plus ribavirin). Treatment with rituximab, a chimeric anti-CD20 monoclonal antibody, was successful.

Successful use of anakinra to treat refractory Schnitzler's syndrome.

Schnitzler's syndrome is a rather rare disease which may appear in a rheumatologist's office because patients often report rheumatic symptoms with joint, bone and muscle pain. However, it is characterized by chronic urticaria, recurrent fever, liver and spleen enlargement, osteosclerosis, and lymphadenopathy, in conjunction with a serum IgM M component. A patient who had been treated with relatively high doses of corticosteroids for 10 years with insufficient response was treated with the IL-1 receptor antagonist anakinra, this led to a complete resolution of symptoms.

Fallopian tube cancer associated with paraneoplastic dermatomyositis -- asymptomatic multivisceral exacerbated dermatomyositis mimicking recurrent widespread malignant disease: case report.

OBJECTIVE: To report an uncommon case of a recurrent episode of primarily paraneoplastic dermatomyositis which was completely disconnected from the initially triggering malignancy and manifested as a silent pure multivisceral exacerbation. CASE: A 70-year-old woman presented with a pure multivisceral episode of dermatomyositis without characteristic musculo-cutaneous symptoms one year after successful treatment of fallopian tube carcinoma with complete resolvement of a concomittant paraneoplastic dermatomyositis. The uncommon manifestation of recurrent dermatomyositis involving the lungs, spleen and liver, both adrenal glands and abdominal lymph nodes, mimicked a highly disseminated recurrence of the fallopian tube cancer. Physicians participating in the interdisciplinary tumor board were misled to opt for reinductive chemotherapy. Only histologic diagnosis obtained from multiple biopsies uncovered the inflammatory nature of the disease and spared the patient unneeded chemotherapy. CONCLUSION: Asymptomatic multivisceral dermatomyositis may mimic metastatic spread of the initially underlying malignancy and may misdirect therapeutic strategies towards inadequate antineoplastic treatment.

DC-sign+ CD163+ macrophages expressing hyaluronan receptor LYVE-1 are located within chorion villi of the placenta.

The purpose of this study was to investigate with immunohistochemical methods antigen presenting cells and their relationship to blood and lymphatic vessels in human term placenta. Fetal placental antigen presenting cells, historically also known as Hofbauer cells, were located in the chorionic villi below the syncytiotrophoblast and in the vicinity of fetal capillaries. DC-SIGN/CD209 expression was observed on CD163+, CD68+, CD45+, HLA-A,B,C+, DC-LAMP/CD208-, CD86-, Langerin/CD207-, FXIIIa-, CD1a- cells consistent with the macrophage nature of these cells. These fetal DC-SIGN+ cells lack HLA-DR, -DP, -DQ expression. Moreover, we show for the first time that they co-express the hyaluronan receptor LYVE-1. In contrast, no LYVE-1+ vessel structures, i.e. lymphatic vessels, were detected. Human term decidua hosted a variety of CD45+ cells, further phenotyped as CD163+, DC-SIGN+, CD68+, HLA-DR+, HLA-A,B,C+. Mature dendritic cells were never observed in human term placenta. In summary, human term placenta is an immunoprivileged organ without lymphatic drainage and with numerous DC-SIGN+ macrophages within the chorionic villi. We hypothesize that these cells may fulfil a function in innate responses against pathogens as well as be involved in the homeostasis of hyaluronan metabolism in the rapidly differentiating placenta.

Sézary syndrome is a unique cutaneous T-cell lymphoma as identified by an expanded gene signature including diagnostic marker molecules CDO1 and DNM3.

Sezary syndrome (SS) is a rare, aggressive CD4+ cutaneous T-cell lymphoma (CTCL); molecular traits differentiating SS from nonleukemic mycosis fungoides (MF) and from inflammatory skin diseases (ID) are not sufficiently characterized. Peripheral blood mononuclear cells (PBMC) of 10 SS patients and 10 healthy donors (HD) were screened by Affymetrix U133Plus2.0 chips for differential gene expression. Ten candidate genes were confirmed by qRT-PCR to be significantly overexpressed in CD4+ T cells of SS versus HD/ID. For easier clinical use, these genes were re-analyzed in PBMC; qRT-PCR confirmed five novel (DNM3, IGFL2, CDO1, NEDD4L, KLHDC5) and two known genes (PLS3, TNFSF11) to be significantly overexpressed in SS. Multiple logistic regression analysis revealed that CDO1 and DNM3 had the highest discriminative power in combination. Upon comparison of PBMC and skin samples of SS versus MF, CDO1 and DNM3 were found upregulated only in SS. Using anti-CDO1 antisera, differential expression of CDO1 protein was confirmed in SS CD4+ T cells. Interestingly, DNM3 and CDO1 are known to be regulated by SS-associated transcription factors TWIST1 and c-myb, respectively. Furthermore, CDO1 catalyzes taurine synthesis and taurine inhibits apoptosis and promotes chemoprotection. In summary, CDO1 and DNM3 may improve the diagnosis of SS and open novel clues to its pathogenesis.

Cheilitis granulomatosa and Melkersson-Rosenthal syndrome: evaluation of gastrointestinal involvement and therapeutic regimens in a series of 14 patients.

BACKGROUND: Cheilitis granulomatosa and Melkersson-Rosenthal syndrome are both rare and benign diseases. Because of their granulomatous character, a relationship to Crohn's disease has been suggested. Furthermore, because of their unknown aetiology, treatment is difficult, and evaluation of response is hampered by the natural tendency to spontaneous resolution and recurrence. OBJECTIVES AND METHODS: To evaluate gastrointestinal involvement by clinical history, conventional endoscopy, and capsule endoscopy as well as to compare efficacy of treatment modalities on a series of 14 patients, one of the biggest collectives reported. RESULTS: Four patients (4 of 14) were previously, simultaneously, or subsequently diagnosed with Crohn's disease. In six patients (6 of 14) with minor gastrointestinal symptoms as flatulence, occasional constipation, diarrhoea, or admixture of mucus with the stool, we could not detect any signs of inflammatory bowel disease by capsule endoscopy. Nine patients received clofazimine, and eight patients responded to treatment (four complete responses, four partial responses). Two patients were successfully treated with infliximab. Systemic methylprednisone was not successful in two patients. CONCLUSION: Close to 30% of patients showed an association of cheilitis granulomatosa and Crohn's disease. Forty-three per cent of patients reported minor gastrointestinal irregularities without any detectable changes of Crohn's disease. Clofazimine seems to be an effective treatment, although long-term application is necessary with frequent aggravation in the beginning. Infliximab, an effective drug in Crohn's disease, could be a promising treatment option for severe cases.