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.

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.

[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.

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.

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.

[Pre-eclampsia with haemolytic anaemia, thrombocytopenia, liver and kidney involvement--an uncommon form of severe gestosis. A case report]. / Präeklampsie mit hämolytischer Anämie, Thrombozytopenie, Leber- und Nierenbeteiligung - eine ungewöhnliche Form der schweren Gestose. Ein Fallbericht.

The case of a 22-year-old primigravida in the 33rd week of pregnancy is presented, showing an uncommon form of EPH-gestosis which so far has been described very rarely in German literature. It is a case of pre-eclampsia with haemolytic anaemia, thrombocytopenia, increased liver values and beginning kidney failure. The key to the survival of mother and child lies in rapid delivery and an adequate substitution of erythrocytes and blood plasma. Symptomatics, differential diagnosis and therapy are discussed. Reference literature is given.

[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.

[Torulopsis in gynecology]. / Die Torulopsidose in der Frauenheilkunde.

Torulopsis glabrata, a pathogenic yeast, causes a vulvovaginal mycosis in about 10% of all cases, whereas mostly candida albicans is identified. Yeasts of the genus Torulopsis seem to occur especially on healthy women, whereas in cases of the well-known risk factors the growth of Candida albicans is advanced. Torulopsidosis of the vagina commonly takes a mild course. The diagnosis is ensured only in cooperation with special laboratories. However, microscopic traps are absence of pseudomycelia and relatively small buds which contrast with the big buds of candida albicans. Although the clinical course is usually less heavy than in cases of candidosis, a six- to ten-day treatment with local imidazole or Polyene antimycotics is necessary to avoid recurrences. The fact that yeasts of the genus Torulopsis form no pseudomycelia is perhaps an explanation for the mostly mild course of illness on the one hand and for the weak response to cellwall-synthesis blocking antimycotics on the other hand.

[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.

[Bacteriologic findings and therapeutic consequences in adnexitis]. / Bakteriologische Befunde und therapeutische Konsequenzen bei Adnexitis.

After laparoscopic confirmation of adnexitis, a bacteriological examination was made of specimens taken from the small pelvis of 63 patients, with an average age of 26.4 years, at the Rheinischen Landesfrauenklinik (Gynecological Hospital) in Wuppertal. To this end, various aerobic and anaerobic optimal and selective culture media were used. The cultured germs were identified with API systems, other conventional methods, and by using gas chromatography. All bacilli were tested for their sensitivity to mezlocillin and metronidazole. In 40 cases (63.5%), it was possible to determine 1-10 bacilli from the inner genital tract. In most cases there was an aerobic/anaerobic mixed infection, with participation of streptococci, staphylococci, enteric bacteria, as well as peptococci, peptostreptococci and bacteroid types. Neisseria gonorrhoeae was only identified three times. In 23 cases (36.5%), it was not possible to determine bacilli in spite of definite inflammatory symptoms. Since, according to international literature, Chlamydia trachomatis was to be found on the inflamed tubes of roughly one third of cases of adnexitis, the presence of this bacillus is suspected even in the many bacteriologically negative cases in the author's own study. Only in one case of a monoinfection by Staphylococcus aureus did the combination of mezlocillin and metronidazole prove to be unsuitable. In 25% of the cases where the presence of bacilli was proved, metronidazole was even necessary, since bacilli of the Bacteroides fragilis and Bacteroides bivius and disiens groups were involved, all of which are capable of inactivating penicillins and cephalosporins by formation of a beta-lactamase.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunological findings in patients with chronically recurrent vaginal candidosis and new therapeutic approaches.

Eighteen patients with chronically recurrent vaginal candidosis showed low T-lymphocyte counts twice as frequent as a control group of 55 women. The patients were treated with azoles locally and lymphocyte stimulating pentapeptide thymopentin. The prolongation of disease-free intervals and a cure was mainly seen in the patients with low T-cell values before therapy. In vitro-proliferation assays upon stimulation with Candida albicans bore no correlation with the course of the disease. We suspect a failure in the co-operation of the immune cells, caused by differing strong responses to the Candida albicans stimulation.

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.

[Maternal mortality in the Rheinische Landesfrauenklinik Wuppertal from 1917 to 1979 (author's transl)]. / Die Müttersterblichkeit in der Rheinischen Landes-frauenklinik Wuppertal von 1917 bis 1979.

From 1917 to 1979, the maternal mortality in the Rheinische Landesfrauenklinik Wuppertal has been investigated on the basis of 136084 live births. From 1917 to 1921, it was 10.1% and decreased to 0.16% in the period from 1973 to 1979. The maternal mortality in association with caesarean section, which was 11.8% in the period from 1917 to 1921 with a frequency of caesarean sections of 2.5%, decreased to zero since 1973 with a frequency of 6.3%. A caesarean section preceded more than 50% of the deaths since 1962. Most of the decreased (24.4%) were in the group of 30-34 years of age and 48.3% aged more than 30 years. 51.5% were primiparas and 14.6% of the women were at least para 4's. From 1917 to 1936, infection was the main cause of maternal mortality with 39.6%; from 1957 to 1966, however, thrombo-embolism advanced to the leading cause with 27.3%. Since 1960, 4 of 35 deaths were anaesthetic deaths. During all the examined periods, non-specific reasons of maternal mortality were an important factor with more than 30%.

Vaginal secretion levels after 6 days, 3 days and 1 day of treatment with 100, 200 and 500 mg vaginal tablets of clotrimazole and their therapeutic efficacy.

Patients with a mycologically confirmed vaginal mycosis were treated either with one 100-mg vaginal ovule of clotrimazole each for 6 days, or with one 200-mg vaginal ovule of clotrimazole each for 3 days, or with one 500-mg vaginal ovule of clotrimazole for 1 day, the ovule having been supplied in a novel, acid formulation. 24, 48 and 72 h after the last dose, samples of secretion were taken from the fornix vaginae. The intravaginal secretion levels were determined semiquantitatively on the basis of the measured inhibition zones obtained with Candida albicans growth on agar plates, and the levels obtained with the different treatment regimens were compared. The vaginal secretion levels after a single 500-mg dose of the new formulation were higher, even after 3 days, than those measured in the 6-day treatment, while administration of 200 mg clotrimazole on 3 days resulted in no increase of the secretion levels over those seen in 6-day treatment with 100 mg.

[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.