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.

Serum autoantibody reactivity in bullous pemphigoid is associated with neuropsychiatric disorders and the use of antidiabetics and antipsychotics: a large, prospective cohort study.

BACKGROUND: Bullous pemphigoid (BP), the by far most frequent autoimmune blistering skin disease (AIBD), is immunopathologically characterized by autoantibodies against the two hemidesmosomal proteins BP180 (collagen type XVII) and BP230 (BPAG1 or dystonin). Several comorbidities and potentially disease-inducing medication have been described in BP, yet a systematic analysis of these clinically relevant findings and autoantibody reactivities has not been performed. OBJECTIVE: To determine associations of autoantibody reactivities with comorbidities and concomitant medication. METHODS: In this prospective multicenter study, 499 patients diagnosed with BP in 16 European referral centers were included. The relation between anti-BP180 NC16A and anti-BP230 IgG ELISA values at the time of diagnosis as well as comorbidities and concomitant medication collected by a standardized form were analysed. RESULTS: An association between higher serum anti-BP180 reactivity and neuropsychiatric but not atopic and metabolic disorders was observed as well as with the use of insulin or antipsychotics but not with dipeptidyl peptidase-4 (DPP4) inhibitors, inhibitors of platelet aggregation and L-thyroxine. The use of DPP4 inhibitors was associated with less anti-BP180 and anti-BP230 reactivity compared with BP patients without these drugs. This finding was even more pronounced when compared with diabetic BP patients without DPP4 inhibitors. Associations between anti-BP180 and anti-BP230 reactivities were also found in patients using insulin and antipsychotics, respectively, compared with patients without this medication, but not for the use of inhibitors of platelet aggregation, and L-thyroxine. CONCLUSION: Taken together, these data imply a relation between autoantibody reactivities at the time of diagnosis and both neuropsychiatric comorbidities as well as distinct concomitant medication suggesting a link between the pathological immune mechanisms and clinical conditions that precede the clinically overt AIBD.

Updated S2 K guidelines for the management of bullous pemphigoid initiated by the European Academy of Dermatology and Venereology (EADV).

BACKGROUND: Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease of the skin and mucous membranes. This disease typically affects the elderly and presents with itch and localized or, most frequently, generalized bullous lesions. A subset of patients only develops excoriations, prurigo-like lesions, and eczematous and/or urticarial erythematous lesions. The disease, which is significantly associated with neurological disorders, has high morbidity and severely impacts the quality of life. OBJECTIVES AND METHODOLOGY: The Autoimmune blistering diseases Task Force of the European Academy of Dermatology and Venereology sought to update the guidelines for the management of BP based on new clinical information, and new evidence on diagnostic tools and interventions. The recommendations are either evidence-based or rely on expert opinion. The degree of consent among all task force members was included. RESULTS: Treatment depends on the severity of BP and patients' comorbidities. High-potency topical corticosteroids are recommended as the mainstay of treatment whenever possible. Oral prednisone at a dose of 0.5 mg/kg/day is a recommended alternative. In case of contraindications or resistance to corticosteroids, immunosuppressive therapies, such as methotrexate, azathioprine, mycophenolate mofetil or mycophenolate acid, may be recommended. The use of doxycycline and dapsone is controversial. They may be recommended, in particular, in patients with contraindications to oral corticosteroids. B-cell-depleting therapy and intravenous immunoglobulins may be considered in treatment-resistant cases. Omalizumab and dupilumab have recently shown promising results. The final version of the guideline was consented to by several patient organizations. CONCLUSIONS: The guidelines for the management of BP were updated. They summarize evidence- and expert-based recommendations useful in clinical practice.

International validation of the Bullous Pemphigoid Disease Area Index severity score and calculation of cut-off values for defining mild, moderate and severe types of bullous pemphigoid.

BACKGROUND: The Bullous Pemphigoid Disease Area Index (BPDAI) score has been proposed to provide an objective measure of bullous pemphigoid (BP) activity. OBJECTIVES: The objective of this study was to calculate BPDAI cut-off values defining mild, moderate and severe BP. We also aimed to assess the interrater reliability and correlation with the number of daily new blisters, and anti-BP180 and anti-BP230 antibodies. METHODS: Severity scores were recorded by two blinded investigators. Anti-BP180 and anti-BP230 antibodies were measured using an enzyme-linked immunosorbent assay (ELISA). Cut-off values defining mild, moderate and severe subgroups were calculated based on the 25th and 75th percentiles of the BPDAI score. RESULTS: In total, 285 patients with BP were enrolled from 50 dermatology departments in Europe. Median BPDAI activity was 37·5 points (range 0-164). Cut-off values corresponding to the first and third quartiles of the BPDAI score were 20 and 57, respectively; thus, these values were used to define mild (≤ 19), moderate (≥ 20 and ≤ 56) and severe (≥ 57) BP. The median BPDAI score for patients with ≤ 10 daily new blisters was 26 [interquartile range (IQR) 17-45], and for patients with > 10 daily new blisters the median score was 55 (IQR 39-82). The BPDAI intraclass correlation coefficient measured at baseline was 0·97 and remained higher than 0·90 up to month 6. The improvement in the BPDAI score was correlated with the absolute decrease in anti-BP180 ELISA value (Spearman's rank r = 0·34, P < 0·004), but not with anti-BP230 antibodies (r = 0·17, P = 0·15). CONCLUSIONS: This study suggests cut-off values of 20-57 for BPDAI to distinguish mild, moderate and severe BP, and confirms that it is a robust tool to assess BP severity precisely.

S2k guidelines (consensus statement) for diagnosis and therapy of dermatitis herpetiformis initiated by the European Academy of Dermatology and Venereology (EADV).

INTRODUCTION: Dermatitis herpetiformis (DH) is a chronic, pruritic, gluten-induced skin disorder characterized by subepidermal granular IgA deposition and a variable degree of enteropathy identical to that seen in coeliac disease. So far, there has been no European consensus about the management of DH. METHODS: The guidelines were created by small subgroups of a guideline committee consisting of 26 specialists from various medical fields and one patients' representative. The members of the committee then discussed the guidelines and voted for the final version at two consensus meetings. The guidelines were developed under the support of the European Academy of Dermatology and Venereology (EADV) and in collaboration with the European Dermatology Forum (EDF). RESULTS: The guidelines summarize evidence-based and expert-based recommendations (S2 level) for the management of DH (see Appendix). CONCLUSION: These guidelines will improve the quality of management of DH and support dermatologists in their diagnostic and therapeutic decisions.

Updated S2K guidelines on the management of pemphigus vulgaris and foliaceus initiated by the european academy of dermatology and venereology (EADV).

BACKGROUND: Pemphigus encompasses a group of life-threatening autoimmune bullous diseases characterized by blisters and erosions of the mucous membranes and skin. Before the era of immunosuppressive treatment, pemphigus was almost always fatal. Due to its rarity, only few randomized controlled therapeutic trials are available. Recently, rituximab has been approved as first-line treatment for moderate and severe pemphigus vulgaris in Europe and the United States. OBJECTIVES: The Autoimmune blistering diseases Task Force of the European Academy of Dermatology and Venereology (EADV) has initiated a throughout update of the guideline for the management of patients with pemphigus. RESULTS: The guidelines for the management of pemphigus were updated, and the degree of consent among all task force members was included. The final version of the guideline was consented by the European Dermatology Forum (EDF) and several patient organizations.

Inter-rater reliability of the BIOCHIP indirect immunofluorescence dermatology mosaic in bullous pemphigoid and pemphigus patients.

BACKGROUND: The BIOCHIP (Dermatology Mosaic 7; EUROIMMUN, Lubeck, Germany) is a novel multiplex indirect immunofluorescence (IIF) technique used in the serological diagnosis of bullous pemphigoid (BP) and pemphigus. OBJECTIVE: To validate the accuracy and inter-rater reliability (IRR) of the BIOCHIP in the diagnosis of BP, pemphigus foliaceus (PF) and pemphigus vulgaris (PV). METHODS: Sera from patients with BP (n = 38), PF (n = 8), PV (n = 23), control patients (n = 64) and healthy control volunteers (n = 39) were tested. Sera were collected and analysed during the course of the disease at 1-5 different time points. The BIOCHIP was performed for all patients, digital images were captured of each incubated field, and the images were shared with 10 dermatologists experienced in reading IF from around the world to report. There were 312 BIOCHIP slides consisting of 1872 photos in total. All patients were de-identified. Fleiss Kappa was used to estimate the IRR. RESULTS: Fleiss Kappa was computed for each category (Oesophagus, Oesophagus immunofluorescence pattern, Salt-Split Skin (SSS), SSS immunofluorescence location, BP180, BP230, Dsg 1 and Ds3). The inter-rater agreement between the 10 raters varied between fair and moderate for all categories. Those that demonstrated fair concordance included monkey oesophagus (k = 0.257, P < 0.0001), oesophagus pattern (k = 0.357, P < 0.0001), Dsg1 (k = 0.390, P < 0.0001) and BP230 (k = 0.281, P < 0.0001). Moderate agreement was demonstrated for SSS (k = 0.416, P < 0.0001), SSS immunofluorescence location (k = 0.505, P < 0.0001), Dsg3 (k = 0.437, P < 0.0001) and BP180 (k = 0.559, P < 0.0001). CONCLUSION: The BIOCHIP mosaic-based immunofluorescence test is a simple, time and effort saving test that can aid in the diagnosis and screening of BP, PV and PF. However, the level of agreement was relatively low. The authors found the most common causes to be variable levels of training, indicating the presence of a learning curve in the interpretation of the results and ambiguous staining patterns leading to incongruent results.

International Bullous Diseases Group: consensus on diagnostic criteria for epidermolysis bullosa acquisita.

BACKGROUND: Epidermolysis bullosa acquisita (EBA) is a complex autoimmune bullous disease disease with variable clinical presentations and multiple possible diagnostic tests, making an international consensus on the diagnosis of EBA essential. OBJECTIVES: To obtain an international consensus on the clinical and diagnostic criteria for EBA. METHODS: The International Bullous Diseases Group (IBDG) met three times to discuss the clinical and diagnostic criteria for EBA. For the final voting exercise, 22 experts from 14 different countries voted on 50 different items. When > 30% disagreed with a proposal, a discussion was held and re-voting carried out. RESULTS: In total, 48 of 50 proposals achieved consensus after discussion. This included nine diagnostic criteria, which are summarized in a flow chart. The IBDG was unable to determine one procedure that would be applicable worldwide. A limitation of the study is that differential diagnosis of bullous systemic lupus erythematosus has not been addressed. CONCLUSIONS: This first international consensus conference established generally agreed-upon clinical and laboratory criteria defining the clinical classification of and diagnostic testing for EBA. Holding these voting exercises in person with the possibility of discussion prior to voting has advantages in reaching consensus over Delphi exercises with remote voting.

Antimicrobial photosensitive reactions.

Photosensitivity reactions are recognized as unwanted adverse effects of an array of commonly administered topical or systemic medications, including nonsteroidal antiinflammatory agents, antifungals, and antimicrobials. When a drug induces photosensitivity, exogenous molecules in the skin absorb normally harmless doses of visible and UV light, leading to an acute inflammatory response. In phototoxic reactions, the damage to tissues is direct; in photoallergic reactions, it is immunologically mediated. In vitro and in vivo assay systems can assist in predicting or confirming drug photosensitivity. The incidence of photosensitivity reactions may be too low to be detected in clinical studies and may become recognized only in the postmarketing stage of drug development. Some drugs have been withdrawn because of photosensitivity effects that appeared after general release. Photosensitivity reactions have been studied for a number of topical antimicrobials and for the sulfonamides, griseofulvin, the tetracyclines, and the quinolones. Incidence and intensity of drug phototoxicity can vary widely among the different compounds of a given class of antimicrobials. When phototoxic effects are relatively low in incidence, mild, reversible, and clinically manageable, the benefits of an antimicrobial drug may well outweigh the potential for adverse photosensitivity effects.

An expert system applied to the physiological analysis of early stage of beer fermentation.

A fuzzy expert system was applied to the knowledge analysis of yeast physiology in the early stage of beer fermentation, when the wort was aerated. We used ergosterol and glycogen concentration in the wort as a suitable marker of physiological state of the cell population. The amount of both compounds influences the rate of fermentation, cell growth and the final taste of beer. The concentrations of ergosterol and glycogen including the number of cells can not be measured immediately during the relatively short aeration period, and incomplete experimental data are therefore found in laboratory logbooks. We therefore suggested that the fuzzy relation between the directly measurable dissolved oxygen concentration and the rate of ergosterol or glycogen formation should be identified and a fuzzy expert system should be used to analyze the behavior of the yeast.

[Occupationally-induced dyshidrosiform dermatitis of the hands following contact with cacti. Case report]. / Beruflich bedingte dyshidrosiforme Dermatitis der Hände nach Kontakt mit Kakteen. Kasuistische Mitteilung.

A patient, employed in a plant nursery where cacti are grown, developed wide spread dyshidrotic dermatitis of the hands. This patient was histologically studied and cactus spines were found in several biopsied vesicles.

[Comparative studies on lactate, proteins and enzymes in saliva of healthy and periodontitis sick juveniles]. / Sravnitelni prouchvaniia za laktat, proteini i niakoi enzimi v sliunkata pri zdravi i parodontozno bolni iunoshi.

Total protein, lactate and enzyme activity of alkaline and acid phosphatase and lactate dehydrogenase were determined in mixed non-stimulated saliva of healthy and periodontitis sick patients, aged from 15 to 17. Enzyme determination, expressed in U/l was performed with ready tests of Boehringer; total protein in g%--according to Netelsson, lactate--in mg/100 ml. Increased activity of alkaline phosphatase was observed, depending on the inflammatory processes of periodontium. With acid phosphatase the discrepancies were more negligible but with a marked tendency to increased enzyme activity. The changes in lactate quantity were also indicative. No statistically significant differences were established for lactate dehydrogenase and total protein. Conclusions have been drawn for the practice.

[Determination of the changes in the quantity, pH, protein and erythrocytes of gingival fluid in students with dental-jaw deformities and chronic catarrhal gingivitis after hygienic-therapeutic course with the toothpaste Propodent]. / Opredeliane na promenite v kolichestvoto, pH, beltuka i eritrotsitite na gingivalnata technost pri uchenitsi sus zubno-cheliustni deformatsii i khronichen kataralen gingivit sled khigienno-lecheben kurs s pasta Propodent.

The changes in the quantity, pH, protein and erythrocytes were studied in the gingival fluid of students with chronic catarrhal gingivitis and impaired oral hygiene due to dental-jaw deformities (DJD) after a 5-week hygienic-therapeutic course with the toothpaste "Propodent". The data about the indices studied in the experimental group--24 children and juveniles with DJD and chronica catarrhal gingivitis, aged from 8 to 16, were compared with the values of the indices studied in the control group of 10 children and juveniles without DJD and with clinically health periodontium of the same age. The comparison between the mean values of the quantity gingival fluid, pH, protein and erythrocytes of the experimental group, before and after the treatment, revealed: 78.6% reduction of the quantity of gingival fluid, 3.8% increase of pH, 93.74% reduction of protein and 95.98% reduction of erythrocytes. In this way, the indices studied in the experimental group after the treatment did not differ with statistical significance from those of the healthy children. The methods for determination of the quantity, pH, protein and erythrocytes, proposed by T. Dzemileva and P. Nenov, objectivized the clinically observed favourable changes in gingiva as a result from the hygienic-therapeutic course in the students with DJD and chronic catarrhal gingivitis.

Subacute cutaneous lupus erythematosus presenting with generalized poikiloderma.

A 64-year-old woman experienced progressive generalized poikiloderma after an episode of sunburn 4 years earlier. The diagnosis of subacute cutaneous lupus erythematosus (SCLE) was confirmed by the presence of anti-Ro/SS-A and antinuclear antibodies, the histology, and the direct immunofluorescent findings (ie, positive lupus band test and "dust-like" epidermal IgG staining pattern). Poikiloderma has not been previously reported in the spectrum of SCLE. As a major pathomechanism of SCLE, photosensitivity might explain this uncommon clinical manifestation of the disease.

Ultraviolet light-induced confluent and reticulated papillomatosis.

A 16-year-old girl initially had an eruption consisting of dark gray, flat, pin-sized, confluent papules with a slight hyperkeratotic surface. The lesions appeared after her summer holidays and were restricted to the tanned skin of sun-exposed areas, mainly the abdomen and back. Clinical and histologic findings were consistent with confluent and reticulated papillomatosis. If a basic disorder of keratinization is the cause of confluent and reticulated papillomatosis, it seems likely that the development of the disease in our patient may be due to an abnormal epidermal response to ultraviolet light.