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.

Three-Day Combination Treatment for Vulvovaginal Candidosis with 200 mg Clotrimazol Vaginal Suppositories and Clotrimazol Cream for the Vulva is Significantly Better than Treatment with Vaginal Suppositories Alone - an Earlier, Multi-Centre, Placebo-Controlled Double Blind Study.

Problem: According to the guidelines, acute vulvovaginal candidosis (VVC) may be treated vaginally, through a combination of vaginal treatment and cream for the vulva or orally. However, there is a lack of investigations into whether combined treatment for the vagina and vulva achieves better results than vaginal treatment alone. Method: In 1999, 160 patients with vulvovaginal candidosis from ten German gynaecological practices were included in a study and treated on a randomised basis with three 200 mg clotrimazol vaginal suppositories = clotrimazol 2 % cream (verum n = 79) or + placebo (active-ingredient-free cream base n = 79). The examinations took place before treatment (T1), six to eight days following the end of treatment (T2) and approximately four weeks following the end of treatment (T3). In addition to demographic data, the clinical findings of each investigation were documented in a standardised way and a native preparation and a fungal culture were taken. The doctor and patient evaluated the healing process and tolerance. The main efficacy variables were the pre/post difference scores for extravaginal redness. Results: On T1, there was no difference between the two groups. By T2, there was a significant difference in the extent of extravaginal redness between the verum and the placebo groups (p = 0.0002), as well as in the subgroup of the per-protocol analysis (verum 64, placebo 70 patients, p = 0.0015). Genital itching or burning had entirely disappeared in 51 % and 56 % of patients respectively in the verum group and in only 30 % and 45 % of patients in the placebo group on T2 (p = 0.0181). There was no difference in intravaginal redness on T1 and T2 in either group. The overall assessment by the doctor went accordingly (p = 0.0004). On T1, the extravaginal fungal culture was positive in 75 women in the verum group and in 76 women in the placebo group. On T2, however, this was positive in 51.9 % (verum) and 73.1 % (placebo) of cases, and a positive culture was evinced in the vagina in 6 vs. 8 women (7.5 vs. 10.1 %, p = 0.3802). The local tolerance in both groups was 70 % very good, and 29 vs. 27 % good. After four weeks (T3), 16 out of 23 patients in the verum group and only 8 out of 21 in the placebo group had negative extravaginal fungal cultures. Discussion: There is a lack of studies into the issue of whether vaginal treatment or combined vulvovaginal treatment of acute VVC would be more advantageous. However, there are two studies that support the significant results of this paper that when it comes to acute VVC, the combination of three 200 mg clotrimazol vaginal suppositories with clotrimazol cream 2 % is better than with vaginal suppositories alone.

Guideline vulvovaginal candidosis (2010) of the German Society for Gynecology and Obstetrics, the Working Group for Infections and Infectimmunology in Gynecology and Obstetrics, the German Society of Dermatology, the Board of German Dermatologists and the German Speaking Mycological Society.

Candida (C.) species colonize the estrogenized vagina in at least 20% of all women. This statistic rises to 30% in late pregnancy and in immunosuppressed patients. The most often occurring species is Candida albicans. Host factors, especially local defense deficiencies, gene polymorphisms, allergic factors, serum glucose levels, antibiotics, psychosocial stress and estrogens influence the risk for a Candida vulvovaginitis. In less than 10% of all cases, non-albicans species, especially C. glabrata, but in rare cases also Saccharomyces cerevisiae, cause a vulvovaginitis, often with fewer clinical signs and symptoms. Typical symptoms include premenstrual itching, burning, redness and non-odorous discharge. Although pruritus and inflammation of the vaginal introitus are typical symptoms, only less than 50% of women with genital pruritus suffer from a Candida vulvovaginitis. Diagnostic tools are anamnesis, evaluation of clinical signs, the microscopic investigation of the vaginal fluid by phase contrast (400 x), vaginal pH-value and, in clinically and microscopically uncertain or in recurrent cases, yeast culture with species determination. The success rate for treatment of acute vaginal candidosis is approximately 80%. Vaginal preparations containing polyenes, imidazoles and ciclopiroxolamine or oral triazoles, which are not allowed during pregnancy, are all equally effective. C. glabrata is resistant to the usual dosages of all local antimycotics. Therefore, vaginal boric acid suppositories or vaginal flucytosine are recommended, but not allowed or available in all countries. Therefore, high doses of 800 mg fluconazole/day for 2-3 weeks are recommended in Germany. Due to increasing resistence, oral posaconazole 2 × 400 mg/day plus local ciclopiroxolamine or nystatin for 15 days was discussed. C. krusei is resistant to triazoles. Side effects, toxicity, embryotoxicity and allergy are not clinically important. A vaginal clotrimazole treatment in the first trimester of pregnancy has shown to reduce the rate of preterm births in two studies. Resistance of C. albicans does not play a clinically important role in vulvovaginal candidosis. Although it is not necessary to treat vaginal candida colonization in healthy women, it is recommended in the third trimester of pregnancy in Germany, because the rate of oral thrush and diaper dermatitis in mature healthy newborns, induced by the colonization during vaginal delivery, is significantly reduced through prophylaxis. Chronic recurrent vulvovaginal candidosis requires a "chronic recurrent" suppression therapy, until immunological treatment becomes available. Weekly to monthly oral fluconazole regimes suppress relapses well, but cessation of therapy after 6 or 12 months leads to relapses in 50% of cases. Decreasing-dose maintenance regime of 200 mg fluconazole from an initial 3 times a week to once monthly (Donders 2008) leads to more acceptable results. Future studies should include candida autovaccination, antibodies against candida virulence factors and other immunological trials. Probiotics should also be considered in further studies. Over the counter (OTC) treatment must be reduced.

Quality of care of VLBW neonates: relationship between unit volume and outcome is different between metropolitan and rural regions.

BACKGROUND: Recent studies from predominantly rural areas in Germany show that neonatal outcome of very low birth weight (VLBW) neonates is (on average) inferior with lower NICU (neonatal intensive care unit) volume. However, there are no data available which show that study results of one specific region can be transferred to other areas with possibly different medical infrastructure and needs. AIM: It was investigated whether a systematic difference of treatment quality between smaller (1000-2000 births/year; < or =20 neonatal beds) vs. larger neonatal centres in Berlin (>3000 births/year; >20 neonatal beds) exists. Furthermore, the results are compared to data from a rural region in order to discuss transferability between regions. METHODS: Retrospectively, completely, and for the first time, the data of all centres which treat VLBW neonates (< or =1500 g birth weight) in the city-state of Berlin, Germany, from the years 2003/2004 were reviewed. RESULTS: Our study showed no difference in the treatment quality of smaller vs. larger neonatal units in Berlin. This result differs from those of a study in Baden-Württemberg, a predominantly rural state, with different medical infrastructure than Berlin. CONCLUSION: The present study suggests that regional investigations on the infrastructure vs. treatment outcome are not transferable between areas. Patient volume/unit appears inadequate for predicting the future treatment quality of neonatal departments. Direct quality indicators are stable for the assessed departments and should be preferably used to organize medical infrastructure.

Guideline vulvovaginal candidosis: guideline of the German Dermatological Society, the German Speaking Mycological Society and the Working Group for Infections and Infectimmunology of the German Society for Gynecology and Obstetrics.

The Guideline vulvovaginal candidosis, as passed by three German medical societies, is presented.

[Torsion of pregnant uterus--a case report]. / Torsion des schwangeren Uterus. Ein Fallbericht.

The 29 year old woman with a caesarian section 5 years before was hospitalized in the 23 rd gestational week bleeding by a placenta praevia totalis and was intravenously tocolized. In the 26 nd gestational week a caesaran re-section was necessary because of heavy acute abdominal symptoms. The uterus presented torquated for 180 degrees to right. The male child (720 g, pH 7.22) died the next night by extreme immaturity. The mother was discharged after 8 days without complications.

Strain specificity of yeasts isolated from different locations of women suffering from vaginal candidosis, and their partners.

Sexual partners often harbour identical yeast strains in the vagina, in the orointestinal tract and in semen in cases of recurrent vulvovaginal candidoses. Specimen were collected from vagina, oral cavity and faeces of the patients, and from semen, oral cavity and faeces of their male partners. Mycological cultures were grown on Sabouraud glucose-agar and, if positive, specified by Candida-ID-Agar (BioMérieux), by formation of chlamydospores on rice agar, and by biochemotyping with the System Walkaway (Dade) or the API-32C system (BioMérieux). A polymerase chain reaction finger-printing technique with the T3B oligonucleotide as single primer was used for strain typing. Candida albicans was isolated from the vagina of 18 out of 21 patients, the vagina of one patient harboured a strain of Candida glabrata. The cultures obtained from vagina, oral cavity and faeces were genetically identical in 12 patients. From the partners of 15 patients C. albicans was cultured in at least one of the clinical samples. Identical strains were observed for eight of 15 couples, whereas four of these identical strains were cultured from semen. Further prospective investigations will prove whether a consequent treatment of both partners will eradicate identical yeast strains and will be able to improve the results of treatment in such women.

[Vulvovaginal mycoses]. / Vulvovaginalmykosen.

Due to its pathogenety Candida albicans is the most frequent yeast in cases of vaginal candidosis, probably mostly caused by local immunological weakness. In 5-30% one can expect a vaginal yeast colonisation depending on age, estrogen influence, pregnancy and dispositions by illness. Prepartal vaginal yeast colonisation should be treated to protect the newborn. The only typical symptom of acute vaginal candidosis is itching. Beside history and clinical symptoms, examination of vaginal secretion by phase contrast microscopy and the yeast culture are cornerstones of the diagnosis. Antimycotic resistance should be investigated only by specialists. Acute Candida albicans vaginitis should be treated locally by one or three day therapy. Candida glabrata vaginitis can be treated with high doses of oral fluconazole.

[Comparison of strain specificity of yeasts from various organs of women with vaginal candidiasis]. / Vergleich der Stammspezifität von Hefepilzen verschiedener Lokalisation bei Frauen mit Vaginalcandidosen.

Sexual partners harbour often identical yeast strains in the vagina, orointestinal tract and sperm in cases of recurrent vulvovaginal candidoses. Mycologic cultures from the vagina, mouth and stool of the patient and from the mouth and sperm of her partner were cultured on Sabouraud-Glucose-Agar and, if positive, specified by Candida ID-Agar (Biomerieux), rice agar and the system Walk away (Dade). Equal species were compared by DNR-fingerprinting using PCR. The vagina of 22 women was in 21 cases infected by Candida albicans and in one case by Candida glabrata. The culture of mouth or stool of 18 women was in 11 cases identical with those of the vagina. In 13 cases of 18 sexual male partners Candida albicans was found being identical with the strain of the female partner in 8 cases. 4 of the identical strains were grown from the sperm. Future prospective investigations shall prove whether a consequent treatment of both partners to eradicate all identical yeasts is able to improve the treatment results in such women.

[Past and present of mycology in German gynecology and obstetrics]. / Zur Vergangenheit und Gegenwart der Mykologie in der deutschsprachigen Gynäkologie und Geburtshilfe.

After the detection of yeasts in 1839, German speaking mycology was first performed in obstetrics to find out the source of neonatal thrush. The authors are Berg (1846), Mayer (1862), Martin (1856), Winckel (1866), Haussmann (1870), Kehrer (1883), Epstein (1924), Rüther, Rieth and Koch (1958), Malicke (1963), Blaschke-Hellmessen (1968) and Schnell (1981) and others. In the gynecological field yeasts, vaginal mycoses and therapeutic problems had been investigated by the gynecologists Döderlein (1892), Spitzbart (1960), Lachenicht and Potel (1971), Neumann and Kaben (1971), Müller and Nold (1981) and Mendling (1987, 1995). Many gynecological papers, however, had also been written by dermatologists and microbiologists.

[Is Candida septicemia in premature infants a nosocomial infection?]. / Ist die Candida-Septikämie bei Frühgeborenen eine nosokomiale Infektion?

Yeast colonization of the vagina is found in about 30% of all pregnant women. Premature infants are severely endangered by generalized fungal infections due to their immature immune system. The objective of this study was to elucidate the relationship between vaginal yeast colonization of the mothers and Candida septicemia in their premature babies. In a prospective study, running from 12/1994 to 8/1996, 176 mothers, facing probable premature birth, were investigated, when hospitalized, for vaginal yeast colonization. 150 premature infants (birth weights ranging from 550 to 2390 g) of these mothers were culturally examined for yeasts in specimens from the mouth, ear, stool and urine immediately after birth as well as once weekly in the following weeks. The patients were divided into two groups. In group A, oral prophylaxis with nystatin was practiced only in infants with at least one positive yeast culture. In group B, all patients received nystatin prophylaxis. Candida septicemia developed one or two weeks after birth mainly in infants with birth weights below 1000 g. Primary oral prophylaxis with nystatin lowers considerably the risk of developing Candida infection.

[Oral contraceptive use and vaginal candida colonization]. / Einnahme oraler Kontrazeptiva und vaginale Kandidabesiedlung.

Fungal vaginal infections/colonisations can be divided into a symptomatic vaginal candidiasis and an asymptomatic vaginal Candida-carriage. The latter seems to be a predisposing factor for the development of a symptomatic vaginal candidiasis. The fungal organism isolated most frequently is Candida albicans, followed by Candida glabrata, which was previously also known as Torulopsis glabrata. To a lower extend, other Candida species such as Candida tropicalis and Candida krusei can be prevalent in the vulvovaginal region. Predisposing factors for vaginal candidiasis are gravidity, diabetes mellitus or a therapy with immunosuppressive agents. Also gestagenes showed to be a pre-disposing factor for vaginal candidiasis. Divergent results concerning the predisposition to vaginal candidiasis or colonisation due to oral contraception have so far been reported. Therefore we performed a study with two healthy collectives of female volunteers (n = 2 x 60) which were different concerning the taking of oral contraceptives. Overall, in 17% of the subjects (20/120) yeast could be cultured out of the vaginal secretions. There was no evidence for a higher rate of Candida-colonisation in subjects taking oral contraceptives. Further, there was no evidence for a relationship between the length of the taking of oral contraceptives and the rate of vaginal yeast-carriage. Also the type of oral contraceptive (combination or sequential contraceptive) had no influence on the frequency of Candida-carriage. Candida albicans was the most prevalent yeast (16/20), followed by Candida glabrata (4/20).

Immunological investigations in vaginal mycoses.

In 42 women with chronically recurrent and 20 women with acute Candida albicans vulvovaginitis, as well as 14 women with Candida glabrata vaginitis, the following investigations were carried out: determination of protein content and secretory immunoglobulin A (sIgA) in the cervicovaginal secretion by a self-modified ELISA technique; determination of immunocells and cellbound IgA in the cervicovaginal secretion by immunofluorescence and nephelometric analysis of IgA in the serum. The results were compared with those of 77 pre-menopausal non-pregnant women with or without intake of anti-ovulants, 17 healthy pregnant women and four hysterectomised pre-menopausal women. Due to inflammation, women with acute and chronically recurrent Candida albicans vulvovaginitis had a higher protein content in the cervicovaginal secretion than healthy women. However, the content of secretory IgA was not increased but even slightly decreased in chronic cases. The number of macrophages and granulocytes in the vaginal content was not increased compared with healthy patients. In only a few cases was IgA detected on yeast cells and in the cervicovaginal secretion by fluorescence microscopy. In chronically-relapsing vaginal candidosis, the frequency of the serotype B of C. albicans was strikingly high. Women with Candida glabrata vaginitis showed lower values of secretory sIgA in the vaginal secretion compared with healthy patients as well as women with vaginitis caused by C. albicans. However, like healthy women, they had normal protein values in the cervicovaginal secretion and also lower values of IgA in the serum compared with women of C. albicans vulvovaginitis patients. Macrophages and granulocytes were demonstrable in the cervicovaginal secretion just as in healthy persons. Women with C. glabrata vaginitis showed a more conspicuous, although not a significantly more frequent, binding of IgA to budding cells demonstrated by fluorescence microscopy than women with C. albicans.

Investigations by cell-mediated immunologic tests and therapeutic trials with thymopentin in vaginal mycoses.

OBJECTIVE: According to unsatisfactory therapeutic results in patients with chronically recurrent vaginal candidosis, we investigated if immunologic patient factors could be found and treated. METHODS: In 42 women with chronically recurrent and 20 women with acute Candida albicans vulvovaginitis, as well as 14 women with C. glabrata vaginitis, the following investigations were carried out: identification of yeast species; quantification of T lymphocytes and their subpopulations in sera; proliferation tests of T lymphocytes in vitro; treatment of 18 patients with chronically recurrent vaginal candidosis with the synthetic T-lymphocyte- stimulator thymopentin; and, finally, control of the above-mentioned parameters in the clinical course. RESULTS: Women with C. albicans vulvovaginitis showed fewer T lymphocytes and subpopulations in the peripheral blood than healthy women. Only the number of non-specific killer (NK) cells, however, was significantly lower in cases of acute C. albicans vulvovaginitis. In women with C. glabrata vaginitis, the number of T lymphocytes in the blood was within the normal range. In vitro proliferation tests using mitogens, bacterial antigens, and commercially available candida antigens with and without addition of thymopentin were carried out on the T lymphocytes of women with chronically recurrent C. albicans vulvovaginitis. These tests revealed no significant differences compared with the other patients with C. albicans infections. The patients were treated with thymopentin. Those women who revealed an increase of initially low numbers of T-helper cells recovered from vaginal candidosis after thymopentin treatment. CONCLUSIONS: The peripheral T lymphocytes may be diminished in patients with chronically recurrent C. albicans vaginitis, and immunologic treatment can reduce the relapse rate.

[Determination of secretory immunoglobulin A in cervicovaginal secretions of healthy women with an ELISA method]. / Bestimmung des sekretorischen Immunoglobulin A im Zervikovaginalsekret gesunder Frauen mit einer ELISA-Methode.

Secretory IgA of the cervico-vaginal secretions was determined for the first time using a modified ELISA method following the recommendations of Sohl Akerlund et al. (Scand. J. Immunol. 6 [1977] 1275). The results were compared with the total protein content of the cervico-vaginal secretions, which were within the normal limits reported in literature. Women in the middle of the menstrual cycle and those taking anti-ovulants, showed lower and those during pregnancy higher values. Secretory sIgA could not be detected in vaginal secretions of hysterectomised women.