A systematic review of sex and gender differences in treatment outcome of inflammatory skin diseases: Is it time for new guidelines?

Gender- and sex-specific differences in medicine were long-time disregarded. Despite numerous indications of gender- and sex-specific influences on the treatment of dermatological conditions, these have not yet been systematically investigated. To meet this unmet need, we conducted the present systematic review on the topic of gender and sex differences in the treatement outcome of skin diseases. Embase (via Ovid), PubMed Medline and Web of Science were searched, in between January 2001 and December 2022. English and german randomized controlled trials, prospective and retrospective cohorts and case-control studies that examined differences between men and women in treatment outcomes of skin diseases were included. Two authors independently screened the reports for eligibility, one extracted all data (the second double-checked) and critically appraised the quality and risk of bias of the studies. Eighty-three reports were included. The largest share of the identified publications focused on gender differences in psoriasis and psoriatic arthritis (n = 49), followed by melanoma (n = 8) and sporadic studies (n < 5) of inflammatory, infectious and autoimmune skin diseases. The main topics in which gender differences could be identified were choice of treatment, time to initiation of treatment, therapy response, adverse events, adherence and treatment satisfaction. For psoriasis, gender differences could be found in all aspects, while for the other skin diseases specific publications on gender differences are still missing. This systematic review shows numerous gender differences but also reveals major gaps in gender-specific care in dermatology which should be narrowed in the upcoming years to optimize a patient-centred, individualized, gender-equal healthcare. PROSPERO Registration: CRD42022306626.

Influence of hepatitis C virus infection and high virus serum load on biliary complications in liver transplantation.

BACKGROUND: Biliary complications (BCs) and recurrent hepatitis C virus (HCV) infection are among the major causes of morbidity and graft loss following liver transplantation. The influence of HCV on BCs has not been definitely clarified. PATIENTS AND METHODS: We performed a retrospective cohort study to analyze risk factors and outcome of post orthotopic liver transplantation (OLT) BCs in 352 liver transplant recipients over 12 years in Munich, Germany (n = 84 with HCV; living donor and re-OLT were excluded). BCs diagnosed with imaging techniques and abnormal liver enzyme pattern, requiring an intervention, were considered. RESULTS: In a multivariate analysis, HCV serostatus and a high pre-and post-surgery HCV RNA serum load were independent risk factors for anastomotic strictures. HCV positivity and BCs alone did not alter graft loss. HCV-positive patients with BCs, however, had a significantly worse graft outcome (P = 0.02). Non-anastomotic strictures, bile leaks, and the number of interventions needed to treat bile leaks led to worse graft outcome in all patients. CONCLUSION: HCV positivity and a high HCV RNA serum load were risk factors for anastomotic strictures. BCs and HCV had an additive effect on graft loss.

[Neutrophil-rich, anaplastic CD30+ T cell lymphoma in conjunction with lymphomatoid papulosis]. / Neutrophilenreiches, CD30+ anaplastisches T-Zell-Lymphom in Assoziation mit einer lymphomatoiden Papulose.

The 2005 EORTC/WHO classification includes three CD30+ lymphoproliferative disorders: 1) primary cutaneous anaplastic large cell lymphoma, 2) lymphomatoid papulosis and 3) borderline cases. These entities may present with many different clinical appearances. Therefore, a precise differentiation among them often is impossible. We present a 40-year-old female who initially presented with a neutrophil-rich, anaplastic CD30+ T cell lymphoma followed by lymphomatoid papulosis.

Stenotrophomonas maltophilia induced post-cataract-surgery endophthalmitis: Outbreak investigation and clinical courses of 26 patients.

BACKGROUND: Stenotrophomonas maltophilia, a microorganism which colonizes plastic material, is a rare causative agent of iatrogenic endophthalmitis. PATIENTS AND METHODS: A cluster of 26 cases of acute post-cataract-surgery endophthalmitis (PE) was identified. An outbreak investigation was performed. Information was abstracted from patients' charts and questionnaires sent to patients and their general practitioners. Vision was examined before, during, as well as one and six months after acute PE. Bacterial isolates were subjected to molecular typing. RESULTS: All patients initially received empiric systemic antibiotic treatment. The source of the infections was identified to be the rinsing solution used during cataract surgery, which was contaminated with two strains of S. maltophilia. Antibiotic therapy was subsequently changed to trimethoprim/sulfamethoxazol and ciprofloxacin for 30 days, complemented with iv fluocortolone and topical treatment with prednisolone, ciprofloxacin, and chloramphenicol. Twenty-one patients (81%) received pars plana vitrectomy and were additionally treated with intravitreal injections of vancomycin, amikacin and dexamethasone, or imipenem and dexamethasone, respectively. In addition, oxacillin, mezlocillin, and prednisolone were applied subconjunctivally after vitrectomy. Six months after acute infection, a final visual acuity of > or = 0.2 was achieved by 21/26 patients (80%), a visual acuity of > or = 0.5 by 14/26 patients (54%). Twenty of 26 patients (77%, 17 of whom had undergone vitrectomy) achieved a higher visual acuity than before surgery. Patients from the vitrectomy group had a median final visual acuity of 0.5 compared to 0.4 in the 5 patients without vitrectomy. There was 1 retinal ablation, 2 intra-retinal bleedings, and relapse of infection in 2/26 patients (8%), with isolation of S. maltophilia in one of the relapsing infection cases. CONCLUSIONS: Empiric antibiotic treatment of PE may not adequately treat rare pathogens such as S. maltophilia. Administration of an effective systemic or intravitreal antibiotic treatment after identification of S. maltophilia may have contributed to the favorable clinical course and relatively low relapse frequency in our patients. Despite the known problem of persistence of S. maltophilia, visual acuity outcome after treatment is comparable to PE induced by other Gram-positive or Gram-negative bacteria.

Influence of High Polyphenol Beverage on Stress-Induced Platelet Activation.

OBJECTIVES: Platelets are playing a crucial role in acute cardiovascular events. We investigated if physical stress activates platelets and whether this activation can be inhibited by a polyphenol-enriched diet. METHODS: Blood samples were taken from a total of 103 athletes three weeks before, one day before, immediately as well as 24 hours and 72 hours after a marathon run. Participants were randomized, double-blinded and divided into two groups. One group received a polyphenol-rich beverage the other the same beverage without polyphenols. Besides analysis of platelet counts and impedance-aggregometric-measurement of platelet activity, soluble P-selectin and Endothelin-A measurements were performed. RESULTS: In the control group, runners showed a 2.2-fold increased platelet aggregation directly after completing a marathon and within the following three days when compared with baseline values (p<0.01). In accordance, significant increases in sP-selectin (57.52ng/ml vs. 94.86ng/ml;p<0.01) were detectable. In contrast, for the group consuming a beverage with increased polyphenol content (upper quartile of study beverage intake) we did not find any increase of platelet aggregation. DISCUSSION: Physical stress causes a significant increase in platelet activity. Our results demonstrate that a diet enriched in polyphenols is capable of preventing platelet activation. These findings might indicate a diminished cardiovascular stress-reaction following pre-exposition to polyphenol-enriched diet.

Validity of carbohydrate-deficient transferrin (%CDT), gamma-glutamyltransferase (gamma-GT) and mean corpuscular erythrocyte volume (MCV) as biomarkers for chronic alcohol abuse: a study in patients with alcohol dependence and liver disorders of non-alcoholic and alcoholic origin.

AIM: To test the clinical performance of carbohydrate-deficient transferrin (%CDT), gamma-glutamyltransferase (gamma-GT) and mean corpuscular erythrocyte volume (MCV) as biomarkers for alcoholism with a special focus on patients suffering from liver diseases. DESIGN: Well-characterized collectives of alcohol-dependent patients with current consumption (ALC patients, n = 101), and relevant control groups (115 social drinkers, 46 patients with unspecifically increased gamma-GT, 51 hepatitis patients and 20/31 patients with non-alcohol/alcohol-dependent liver cirrhosis) were included into the study. The Positive Alcohol Use Disorders Test (AUDIT) score, International Classification of Diseases version 10 (ICD-10)/Diagnostic and Statistical Manual version IV (DSM-IV) criteria and blood drawn within 4 days of last drinking were inclusion criteria for subjects with regular heavy drinking. %CDT was determined using an automated assay which recently had been completely modified. FINDINGS: Median AUDIT scores of patients without/with regular heavy drinking were 1-3/27. The following medians/95th percentiles were obtained for %CDT: social drinkers 2.2/3.0, patients with unspecifically increased gamma-GT 2.1/3.0, hepatitis 2.0/4.4, non-alcohol-dependent liver cirrhosis 2.4/4.8, alcohol-dependent liver cirrhosis 3.0/5.9, ALC patients 3.9/14.9. Differences between patients without and with alcohol abuse were highly significant (P < 0.001). No differences in CDT values were found between males and females. There was no correlation between %CDT values, gamma-GT, MCV and the amount of alcohol consumed in ALC patients; 3.0%CDT (95th percentile social drinkers) is proposed as cut-off for the test used (Tina-quant %CDT 2nd-generation). At this cut-off, the sensitivity for ALC patients was 73.3%, whereas gamma-GT/MCV had a sensitivity of 71.3%/64.4%. Multivariate analysis performed at 95% specificity resulted in an improvement of the sensitivity by combining %CDT with gamma-GT (83.2%). A further enhancement of the sensitivity to 88.1% was obtained by combination of %CDT, gamma-GT and MCV. The diagnostic specificity of %CDT calculated at the cut-off of 3% was 93.5% in patients with unspecifically increased gamma-GT, 88.2% in hepatitis patients and 70.0% in patients with non-alcohol-dependent liver cirrhosis. %CDT was more specific in these patient collectives than MCV, and especially more than gamma-GT (specificity in hepatitis 52.9%, and 35.0% in non-alcohol-dependent liver cirrhosis). CONCLUSION: %CDT is of high diagnostic value to support diagnosis of alcohol-use disorders. The specificity of this marker in patient groups with liver disorders is superior to the biomarkers gamma-GT and MCV.

Type 2 segmental manifestation of Hailey-Hailey disease: poor therapeutic response to dermabrasion is due to severe involvement of adnexal structures.

In autosomal dominant skin conditions, two different types of segmental manifestation can be distinguished. Type 1 represents heterozygosity for a postzygotic mutation, resulting in a degree of severity similar to that of the nonmosaic phenotype. Type 2 reflects loss of heterozygosity and shows an excessively pronounced involvement superimposed on the ordinary nonsegmental phenotype. We describe the clinical, histopathological and therapeutic aspects of the first case of type 2 segmental manifestation of Hailey-Hailey disease (HHD). A 24-year-old woman with a family history of HHD comprising four generations, presented with lesions of erythema and blistering arranged in a unilateral pattern following the lines of Blaschko. The disorder was first noted at the age of 3 months. At the age of 24 years, additional scattered symmetrical lesions involving the axillary and inguinal folds were noted. Histopathological examination of the severely involved linear skin areas revealed pronounced acantholysis within the deep adnexal structures, whereas clinically unaffected skin showed the typical histopathological features of the heterozygous phenotype with suprabasal clefting and acantholysis sparing the adnexae. Dermabrasion was performed in the areas of segmental involvement. During a follow-up period of one year, no recurrence was noted, but 18 months after dermabrasion a recurrence was present in the left submammary and left perianal regions. This therapeutic resistance to dermabrasion may be explained by the presence of acantholysis within the adnexal structures of the skin as found in type 2 segmental HHD.

[Dyspnoea after complication-free tracheostomy]. / Atemnot nach komplikationsloser Tracheotomie.

HISTORY: A 70-year-old woman had been under oncological supervision for several years because of breast cancer with bone and lymph node metastases. For several weeks she had been treated for increasing vocal cord paresis of uncertain cause, requiring a tracheostomy, a speech cannula being inserted after eight days. Several days later the patient began to complain of dyspnea, but repeated inspection and cleaning of the cannula failed to reveal its cause. The increasingly anxious patient was given a benzodiazepine preparation to calm her. She was then transferred to the intensive care unit because of worsening respiratory insufficiency and impaired consciousness. DIAGNOSIS AND COURSE: A fiberoptic bronchoscopy was performed immediately, which revealed a black foreign body immediately distal to the tip of the tracheal cannula. The cannula was removed and the slightly sedated patient at once coughed up a large amount of bronchial secretion and a long, curved and fairly firm blood clot. Control bronchoscopy now revealed a flat, slightly hemorrhagic ulcer on the dorsal tracheal wall at the point where the cannula tip had made contact with the tracheal wall. CONCLUSION: Even trained personnel may have difficulty in recognizing intratracheal thrombi in patients with a tracheostomy. It is thus essential that an endoscopy is performed in patients with obstructive symptoms after a tracheostomy.

Comparing acoustic radiation force impulse imaging to transient elastography to assess liver stiffness in healthy volunteers with and without valsalva manoeuvre.

PURPOSE: Acoustic Radiation Force Impulse Imaging (ARFI) is a new ultrasound elastography technology (Siemens ACUSON S2000 Virtual Touch™ Tissue Quantification), which is integrated in conventional ultrasound equipment. In preliminary studies, ARFI sheer wave speed (SWS) in liver tissue correlated well with transient elastography (TE) values and liver fibrosis stages. MATERIALS AND METHODS: Sixty-eight healthy male and female volunteers were measured with ARFI with two ultrasound tranducers, three measuring positions and during valsalva manoeuvre. A TE (FibroScan™, Echosens, France) was performed in 60 volunteers. RESULTS: Volunteers had a mean age of 28 years and a mean BMI of 22.3. There was no significant difference of ARFI SWS between the 4C1 and 4V1 ultrasound probes in either intercostal or abdominal approach to liver segment 8 but a higher variance of ARFI SWS with the 4V1/abdominal compared to the intercostal approach (p = 0.0368). The 4C1/intercostal approach had the highest success rates (97.2%), comparable to those of TE (97.18%). Left liver lobe measurements obtained both significantly higher ARFI SWS and value variance (p = 0.0016 and p = 0.0198) compared to 4C1/intercostal approach. Mean ARFI SWS was 1.19 m/s (range 0.77-1.63). Mean TE was 5.39 kPa (range 3.3-9.0 kPa). Valsalva manoeuvre did not significantly alter ARFI SWS and variance. Skin-liver distance significantly influenced ARFI SWS (p < 0.05), while age and gender did not. CONCLUSION: These results might constitute a first impression of the chances of ARFI SWS to assess liver stiffness, especially in patients with liver diseases due to increased venous pressure.

Influence of antiretroviral therapy on immunogenicity of simultaneous vaccinations against influenza, pneumococcal disease and hepatitis A and B in human immunodeficiency virus positive individuals.

OBJECTIVES: Immune response to many vaccinations is impaired in human immunodeficiency virus (HIV) positive patients. METHODS: A total of n = 131 HIV positive patients were vaccinated against influenza, pneumococcal disease, hepatitis A and B, with n = 82 patients (62.6%) receiving 2 or more simultaneous vaccinations. Safety and immunogenicity of simultaneous vaccinations were assessed. Current antiretroviral therapy (ART) regimens were evaluated as potential predictors for antibody response. RESULTS: Immune response rates were 45% (influenza), 68% (pneumococcus), 63.6% (hepatitis A) and 62.5% (hepatitis B). Adverse reactions after vaccination were documented in 2 of 131 patients (1.5%). No statistically significant difference between pre- and post-vaccination CD4+ T-cell counts (CD4) and HIV plasma load was observed. 85% of patients received ART containing nucleotide reverse transcriptase inhibitors, non-nucleotide reverse transcriptase inhibitors and/or protease inhibitors (PI). Higher ratio of CD4 to CD8 and intake of PI were statistically significant, independent predictors for antibody response after influenza vaccination (OR 1.9 and 2.8, p = 0.01 and 0.04, respectively). CONCLUSIONS: Simultaneous vaccinations in HIV positive patients were safe and well tolerated. The positive effect of PI on antibody response after influenza vaccination should be confirmed in larger studies.

Alterations in the epidermal-dermal melanin axis and factor XIIIa melanophages in senile lentigo and ageing skin.

BACKGROUND: Senile lentigo (SL) is a pigmentation disorder that occurs predominantly on the dorsa of the hands, the forearms and the face; its incidence increases with age. Histological hallmarks of SL lesions are hyperpigmentation of the epidermis and elongation of the epidermal rete ridges. Various factors such as alpha-melanocyte-stimulating hormone, endothelin-1 or stem cell factor are involved in the onset and maintenance of the increased pigmentation. Alterations of the dermal compartment have not yet been analysed in detail in SL. OBJECTIVES: To study the occurrence and distribution of melanin in the dermis from SL and aged skin, biopsies from 12 subjects were morphologically analysed by light and electron microscopy in comparison with unaffected skin. METHODS: Punch biopsies of SL and adjacent skin from 12 male or female volunteers aged 52-81 years were prepared for light and electron microscopy and samples were analysed by morphological, morphometric, histochemical and immunohistochemical methods. RESULTS: The epidermis from SL revealed morphological features such as hyperpigmentation of basal keratinocytes and the formation of elongated rete ridges. S100+ melanocytes in the stratum basale were not markedly increased, indicating that the hyperpigmentation is predominantly due to changes in melanin synthesis, distribution or turnover. Quantification of epidermal cells expressing the proliferation marker Ki67 did not show an increase of this parameter in SL, indicating that at least in the established lesion cell proliferation is not enhanced. We further focused on the dermal compartment and observed granulated cells which were more abundant in SL. Electron microscopic and histochemical analysis revealed that the granulation of these cells is based on melanosomes, mostly present in large melanosomal complexes. Immunohistochemistry using antibodies to CD68 and factor XIIIa (FXIIIa) showed these melanophages to be predominantly FXIIIa+ dermal dendrocytes, which were about six times more abundant than CD68+ macrophages. CONCLUSIONS: In SL an increased number of melanophages was found compared with unaffected skin from the same subject. These melanophages were identified as FXIIIa+ dermal dendrocytes. Possible functional consequences of the massive melanin uptake by dermal dendrocytes are discussed.

HAART-prolonged life of HIV-infected patients should not be shortened by hepatitis C.

As highly active antiretroviral treatment (HAART) prolongs the life of HIV-infected individuals and reduces mortality associated with opportunistic infections, liver diseases have become a major challenge in the management of these patients. up to 45% of deaths of persons with HIV are related to endstage liver disease, some of which might have been avoided with a less hesitant approach to hepatitis C treatment in the setting of HIV/ hepatitis C (HCV) coinfection.

Treatment with levofloxacin does not resolve asymptomatic leucocytospermia--a randomized controlled study.

The manual of the World Health Organization defines leucocytospermia as the presence of >1 x 10(6) white blood cells per ml semen. Most authors consider leucocytospermia to be a consequence of inflammation due to bacterial infection. However, the efficacy of antibiotic therapy was not unequivocally demonstrated until now. We started a prospective, randomized, controlled study in 36 patients, who consulted our department for infertility with leucocytospermia. None of the patients reported any symptoms of genital infection. The patients were assigned randomly to two groups: group 1 received 250 mg levofloxacin once a day over 10 days, patients of group 2 received no therapy. Semen analysis was repeated 2 weeks later. After administration of levofloxacin, a mean decrease of leucocyte count of 45.8 +/- 72.2% compared with a decrease of only 3 +/- 109.2% in the untreated group was observed. However, this difference is not statistically significant. There were no significant differences between the two groups with respect to leucocyte count, sperm count and sperm cell after treatment. We conclude from our study that antibiotic therapy does not provide benefit for treatment of asymptomatic leucocytospermia.

[Anthrenus dermatitis]. / Anthrenus-Dermatitis.

A 31-year-old male presented with widespread itchy papules, especially on the legs, which had appeared 4 weeks previously. He reported that his wife and both daughters had developed similar lesions during the last week. Numerous small beetle larvae had been detected in his apartment, which were identified as museum beetle Anthrenus museorum L. Prick test with a larva extract caused a positive prick-test reaction, followed by a papular delayed type hypersensitivity reaction. History, clinical and histological examination led to the diagnosis of papular Anthrenus-dermatitis. Eradication of the beetle larvae from the patient's apartment, followed by topical glucocorticoid therapy led to a permanent remission of the dermatitis in all household members.

Cellular and biochemical markers in semen indicating male accessory gland inflammation.

Leucocytospermia is considered to be a sign of male accessory gland inflammation. The leucocytes in semen are mainly polymorphonuclear neutrophilic granulocytes. Leucocytospermia is not associated with the presence of bacteria and antibiotic treatment does not significantly lower the extent of leucocytospermia. A higher frequency of elevated herpes simplex antibodies titres were found in men with leucocytospermia. The concentration of inflammatory cytokines, interleukin-6 and -8, is closely correlated with the number of leucocytes. Their determination does not provide additional information. Reactive oxygen species (ROS) are generated at least in part by seminal leucocytes in response to stimulating factors. Purified leucocytes produce high levels of ROS. The determination of ROS appears to represent a parameter of functional activity of leucocytes. The role of chlamydiae in male accessory gland infection is unclear. Their determination in semen by DNA amplification and by immunological tests does not provide reliable results.

AIDS, multicentric Castleman's disease, and plasmablastic leukemia: report of a long-term survival.

Plasmablastic leukemia (PL) as a complication of human herpes virus 8 (HHV8)-associated Castleman's disease is marked by a rapid and fatal outcome. In patients with AIDS, survival of 7 to 14 days after diagnosis has been reported. Prompt splenectomy and chemotherapy might lead to a significant survival benefit. Here we report a case of long-term survival in a patient with AIDS and multicentric Castleman's disease (MCD) complicated by PL.

Kinetics of lactate metabolism after submaximal ergometric exercise in HIV-infected patients.

OBJECTIVES: It is unknown whether high levels of lactate result from enhanced production or decreased degradation. We therefore investigated differences in the kinetics of plasma lactic acid in HIV-infected patients receiving or not receiving highly active antiretroviral therapy (HAART) and in uninfected controls after submaximal ergometric exercise. METHODS: Ten healthy controls, 11 HIV-infected therapy-naïve patients, 15 HIV-infected patients on HAART with normal baseline lactate levels, and nine HIV-infected patients on HAART with elevated baseline lactate levels >2 mmol/L performed 10 min of ergometric exercise, with a heart rate of 200 beats/min minus age. Lactate levels were measured at baseline, at the end of exercise and 15, 30, 45, 60 and 120 min thereafter. RESULTS: Mean baseline lactate levels were 1.4, 1.5, 1.5 and 2.8 mmol/L in the controls, the therapy-naïve patients, the patients on HAART with normal lactate levels and the patients on HAART with elevated lactate levels, respectively. Maximum lactate levels after exercise were similar in all groups (9.7, 9.4, 9.0 and 10.1 mmol/L, respectively). Significant differences were found in the slope of lactate decline between controls and untreated individuals (P=0.038) and between patients on HAART with normal baseline lactate and patients on HAART with elevated baseline lactate (P=0.028). CONCLUSIONS: Differences in lactate metabolism do exist between healthy controls and HIV-infected therapy-naïve individuals. Thus, HIV infection in itself may influence lactate levels. Elevated baseline lactate levels are associated with a delayed decline of lactate after exercise. These results could be explained by impaired lactate clearance. Lactate production upon exercise does not seem to be affected by baseline lactate levels.