Association of sex and systemic therapy treatment outcomes in psoriasis: a two-country, multicentre, prospective, noninterventional registry study.

BACKGROUND: Few systematic data on sex-related treatment responses exist for psoriasis. OBJECTIVES: To evaluate sex differences with respect to systemic antipsoriatic treatment. METHODS: Data from patients with moderate-to-severe psoriasis in the PsoBest or Swiss Dermatology Network of Targeted Therapies (SDNTT) registries were analysed. Treatment response was defined as achieving a ≥ 75% reduction in Psoriasis Area and Severity Index (PASI 75) or PASI ≤ 3 at treatment months 3, 6 and 12, supplemented by patient-reported outcomes [i.e. Dermatology Life Quality Index (DLQI) ≤ 1 and delta DLQI ≥ 4]. RESULTS: In total, 5346 patients registered between 2007 and 2016 were included (PsoBest, n = 4896; SDNTT, n = 450). The majority received nonbiological treatment (67·3% male, 69·8% female). Women showed slightly higher PASI response rates after 3 (54·8% vs. 47·2%; P ≤ 0·001), 6 (70·8% vs. 63·8%; P ≤ 0·001) and 12 months (72·3% vs. 66·1%; P ≤ 0·004). A significantly higher proportion of women achieved a reduction in DLQI ≥ 4 [month 3: 61·4% vs 54·8% (P ≤ 0·001); month 6: 69·6% vs. 62·4% (P ≤ 0·001); month 12: 70·7% vs. 64·4% (P ≤ 0·002)]. Regarding PASI ≤ 3, women on biologics showed a significantly superior treatment response compared with men at 3 (57·8% vs. 48·5%; P ≤ 0·004) and 6 months (69·2% vs. 60·9%; P ≤ 0·018). Women in the nonbiological treatment group had a significantly better treatment response (PASI response, PASI 75 and PASI ≤ 3) over 12 months compared with men. CONCLUSIONS: We provide evidence that women experience better treatment outcomes with systemic antipsoriatic therapy than men.

Linkage between patients' characteristics and prescribed systemic treatments for psoriasis: a semantic connectivity map analysis of the Swiss Dermatology Network for Targeted Therapies registry.

BACKGROUND: Several treatment options are currently available for the treatment of psoriasis. OBJECTIVE: To explore the main associations between patients' characteristics and systemic treatments prescribed for psoriasis in a large group of patients observed in real-life clinical practice. METHODS: This was a retrospective analysis of baseline data collected within the Swiss Dermatology Network for Targeted Therapies registry in Switzerland between March 2011 and December 2017. Semantic map analysis was used in order to capture the best associations between variables taking into account other covariates in the system. RESULTS: A total of 549 patients (mean age 46.7 ± 14.7 years) were included in the analysis. Conventional therapies such as retinoids and methotrexate were associated with no previous systemic therapies for psoriasis, a moderate quality of life (QoL) at therapy onset and older age (≥60 years). Fumaric acid derivatives were associated with mild psoriasis (psoriasis area severity index < 10) and long disease duration (≥20 years). On the other side, cyclosporine and psoralen and ultraviolet A/ultraviolet B treatments were linked to a more severe condition, including impaired QoL, hospitalization and inability to work. Regarding biological therapies, both infliximab and adalimumab were connected to the presence of psoriatic arthritis, severe disease condition and other comorbidities, including chronic liver or kidney diseases and tuberculosis. Etanercept, ustekinumab and secukinumab were all connected to a complex history of previous systemic treatments for psoriasis, moderate disease condition, overweight and university education. CONCLUSIONS: The analysis shows multifaceted associations between patients' characteristics, comorbidities, disease severity and systemic treatments prescribed for psoriasis. In particular, our semantic map indicates that comorbidities play a central role in decision-making of systemic treatments usage for psoriasis. Future studies should further investigate specific connections emerging from our data.

Gender and age significantly determine patient needs and treatment goals in psoriasis - a lesson for practice.

BACKGROUND: Though patient needs are key drivers of treatment decisions, they are rarely systematically investigated in routine care. OBJECTIVE: This study aimed at analysing needs and expectations from the patient perspective in the German and Swiss psoriasis registries PsoBest and Swiss Dermatology Network of Targeted Therapies (SDNTT) with respect to treatment choice, age and gender. METHODS: The German and Swiss psoriasis registries observe patients recruited at first-time use of systemic drugs. Within 10 years, clinical [Psoriasis Area Severity Index (PASI), Body Surface Area (BSA)] and patient-reported outcomes are documented, including the Dermatology Quality of Life Index (DLQI) and the Patient Benefit Index (PBI), characterizing patient needs for treatment. The analysis data set includes n = 4894 patients from PsoBest and n = 449 from SDNTT with mean follow-up time of 7.5 months. RESULTS: A total of 5343 patients registered between 2008 and 2016 were included in the analyses (at baseline: 59.6% male, mean age 47.6 years ± 14.5, PASI 14.2 ± 9.7, BSA 22.7 ± 19.7, DLQI 11.3 ± 7.2). The most important patient needs were to 'get better skin quickly' and to 'be healed of all skin defects'. Subgroup analyses by age revealed significant differences in needs, especially higher needs regarding social impairments in patients younger than 65 years. Patients 65 years or older attributed more importance to sleep quality, less dependency on medical visits, fewer side-effects and confidence in the therapy. Out of 25 items reflecting patient needs, 20 items were rated significantly more important by women than men, with the greatest differences regarding feeling of depression, sleep quality and everyday productivity. Divided by treatment, needs were rated differently, recommending individualized and targeted choice of therapy. CONCLUSION: Age and gender stratify patient needs. Women showed higher expectations and rated specific needs in psoriasis treatment higher than men. Analysing the patient needs on an individual level will facilitate shared decisions by patient and physician in finding the optimal personalized treatment.

Swiss S1 guideline for the treatment of rosacea.

Rosacea (in German sometimes called 'Kupferfinne', in French 'Couperose' and in Italian 'Copparosa') is a chronic and frequently relapsing inflammatory skin disease primarily affecting the central areas of the face. Its geographic prevalence varies from 1% to 22%. The differential diagnosis is wide, and the treatment is sometimes difficult and varies by stage of rosacea. For erythematous lesions and telangiectasia, intense pulsed light (IPL) therapy and lasers are popular treatment option. In addition, a vasoconstrictor agent, brimonidine, has recently been developed. For papulopustular rosacea, topical antibiotics, topical and systemic retinoids, as well as systemic antibiotics are used. A topical acaricidal agent, ivermectin, has undergone clinical development and is now on the market. In the later stages, hyperplasia of the sebaceous glands develops, resulting in phymatous growths such as the frequently observed bulbous nose or rhinophyma. Ablative laser treatments have largely replaced classical abrasive tools. Here, we reviewed the current evidence on the treatment of rosacea, provide a guideline (S1 level) and discuss the differential diagnosis of rosacea.

Consensus on performing skin biopsies, laboratory workup, evaluation of tissue samples and reporting of the results in patients with suspected cutaneous graft-versus-host disease.

BACKGROUND: Histopathological diagnosis including selection of lesions, the determination of the best point of time for biopsy and workup is not trivial in cutaneous graft-versus-host disease (GvHD). OBJECTIVES: To develop interdisciplinary recommendations on performing, the laboratory work up and reporting of the results of skin biopsies in patients with suspected cutaneous GvHD. METHODS: A working group consisting of dermatopathologists, dermatologists, transplant-physicians and transplant-pathologists prepared recommendations for performing skin biopsies, laboratory workup and evaluation of tissue samples, and reporting of the results in patients with cutaneous GvHD. After achieving a consensus within the working group, a survey that comprised the core issues of the recommendations was electronically sent out to 72 alloHSCT centres within Germany, Austria, and Switzerland and their Departments of Pathology. The answers were discussed in a Consensus Conference and final recommendations were established. RESULTS: Twenty-five centres responded to the clinical and 17 centres to the histopathological survey. Questions addressed to the clinicians comprised the indication for skin biopsy in chronic GvHD (cGvHD) and acute GvHD (aGvHD) and the appropriate point of time for skin biopsy. Eighty-eight per cent agreed that the skin biopsy is generally indicated in patients with suspected cGvHD lacking diagnostic features. In contrast, with suspected aGvHD, only 62% of respondents felt that skin biopsy was necessary even if GvHD had not been confirmed in another organ. Although restricted due to the fact that immunosuppression is often applied in an emergency setting most centres supported skin biopsies before initiation of topical or systemic immunosuppression. The majority of pathologists agreed that in non-sclerotic GvHD a punch biopsy is adequate, whereas in sclerotic GvHD a scalpel biopsy is preferred. CONCLUSION: While a consensus on the need for biopsies in cGvHD was reached the value of skin biopsies in aGvHD and subsequent biopsies during therapy requires further evaluation.

German-Austrian-Swiss Consensus Conference on clinical practice in chronic graft-versus-host disease (GVHD): guidance for supportive therapy of chronic cutaneous and musculoskeletal GVHD.

Supportive therapy plays a central role in the management of cutaneous and musculoskeletal manifestations of chronic graft-versus-host disease (cGVHD), either alone or in combination with systemic approaches. We present results from the German-Austrian-Swiss Consensus Conference on clinical practice in cGVHD, held in Regensburg, Germany, in November 2009. The intention was to achieve a consensus on current evidence-based treatment options as well as to provide guidelines for daily clinical practice. Skin is the most common organ involved in cGVHD. Its clinical presentation varies considerably. Patients may have pruritus, rash, pain, dyspigmentation and fibrotic or sclerodermatous lesions, often leading to contractures. Treatment options for supportive therapy in cutaneous cGVHD include topical therapies such as topical steroids and topical calcineurin inhibitors, as well as phototherapy and physiotherapy. The most relevant manifestation in musculoskeletal cGVHD is fasciitis which must be distinguished from sclerodermatous skin cGVHD. Physiotherapy is the mainstay of supportive treatment in fasciitis in cGVHD. Successful therapy of cutaneous and musculoskeletal cGVHD depends on interdisciplinary management to improve patients' quality of life.

Simplifying the WHO 'how to hand rub' technique: three steps are as effective as six-results from an experimental randomized crossover trial.

OBJECTIVES: The World Health Organization (WHO) issued guidelines on hand hygiene recommending a six-step 'how to hand rub' technique for applying alcohol-based hand rub. However, adherence to all six steps is poor. We assessed a simplified three-step technique and compared it to the conventional WHO six-step technique in terms of bacterial count reduction on healthcare workers' hands. METHODS: Thirty-two participants were randomly assigned to clean their hands following the six-step 'how to hand rub' technique (WHO reference group) or a simplified three-step technique (intervention group). Assignments were reversed after 1 day. The degree of bacterial killing was assessed following the European norm for testing hand hygiene products. Hands were contaminated with Escherichia coli, and the mean logarithmic reduction in bacterial counts was compared between both techniques. RESULTS: Bacterial density before hand hygiene performance did not differ between the WHO reference group (median 6.37 log10 CFU, interquartile range (IQR) 6.19-6.54) and the intervention group (median 6.34 log10 CFU, IQR 6.17-6.60, p 0.513). After hand hygiene, the logarithmic reduction factor was higher in the intervention group (median 4.45, IQR 4.04-5.15) compared to the WHO reference group (median 3.91, IQR 3.69-4.62, p 0.021). CONCLUSIONS: The WHO six-step 'how to hand rub' technique can be simplified to a 3-step procedure based on the reduction of bacterial counts on healthcare workers' hands achieved under experimental conditions. The proposed technique is easier to perform and could improve adherence to the execution of hand hygiene action.

[Skin manifestations of lupus erythematosus]. / Hautmanifestationen bei Lupus Erythematodes.

There are multiple forms of cutaneous manifestations of lupus erythematosus. In general strictly cutaneous forms are distinguished from systemic lupus erythematosus with cutaneous involvement. Systemic lupus erythematosus can be regarded either as primarily with skin signs or secundarily after initial involvement of the skin. Typical forms of cutaneous lupus erythematosus are the subacute cutaneous and the discoid form.

Clinical guidelines for gynecologic care after hematopoietic SCT. Report from the international consensus project on clinical practice in chronic GVHD.

Despite similarities relevant age- and gender-specific issues exist in the care of patients after allogeneic hematopoietic SCT (HSCT). Female genital chronic GVHD (cGVHD) has been markedly underreported in the past but has a significant impact on the patients' health and quality of life. Data on prevention and treatment of this complication are still limited. Here we present a comprehensive review summarizing the current knowledge, which was discussed during several meetings of the German, Austrian and Swiss Consensus Project on clinical practice in cGVHD. In this report, we provide recommendations for post-transplant gynecological care of cGVHD manifestations agreed upon by all participants. This includes guidelines for diagnosis, prevention, and therapeutic options and topical treatments in female patients with genital cGVHD and hormonal replacement treatment of premature ovarian failure for adult and pediatric patients and underlines the necessity for regular gynecological care and screening programs for women after HSCT.

Sicca symptoms and their impact on quality of life among very long-term survivors after hematopoietic SCT.

The objective of this prospective cross-sectional case-control study was to examine the prevalence of dryness symptoms and its impact on quality of life (QoL) among very long-term survivors after hematopoietic SCT (HSCT) in comparison with their respective sibling donors. Forty-four allogeneic HSCT recipients with a long-term survival (median: 17.5; range: 11-26 years) were included. Their respective, HLA-identical sibling donors served as controls. Clinical examinations included saliva flow rates (SFR) and the Schirmer's test. The presence of sicca symptoms of mouth, eyes and skin were inquired. The social functioning (SF)-36 questionnaire was applied. Recipients had lower (P<0.01) unstimulated and stimulated mean SFR than donors. Schirmer's test results <5 mm was found in 45% of the recipients in comparison with 27% of the donors (P = 0.07). Xerostomia (34 vs 4 subjects), xerophtalmia (23 vs 3) and dry skin (32 vs 12) were reported more often by the recipients than donors (P<0.001). Sicca symptoms and their objective findings correlated with QoL. The mean SF-36 scores of the donors were significantly higher than those of the recipients for physical component summary. In conclusion, sicca symptoms are common amongst long-term survivors of HSCT and affect remarkably the QoL.

[Asymptomatic facial infiltrated papules in an HIV-positive male]. / Unklare asymptomatische infiltrierte Papeln im Gesicht eines HIV-infizierten Mannes.

A 65 year old HIV-infected patient (CDC A2, diagnosed in 07/2008) presented with facial, erythematous infiltrated papular lesions. Consistent with progressive immunodeficiency a low CD4+ T-cell count and an increase of the viral load was seen simultaneously and an eosinophilic pustular folliculitis (EPF) was assumed. Though, the lesional biopsy revealed a follicular eosinophilic infiltration and endotrichial hyphae, proving for an infiltrating dermatophytosis. This shows how an infiltrating Tinea faciei is mimicking clinically and histologically an HIV-associated EPF of the face.

Gli2 upregulates cFlip and renders basal cell carcinoma cells resistant to death ligand-mediated apoptosis.

Mutations in the Hedgehog signaling pathway is responsible for the formation of various cancers, including some forms of basal cell carcinoma (BCC). Uncontrolled Hedgehog signaling leads to overexpression of the zinc-finger Gli transcription factors, among which Gli2 plays a central role. We found that high Gli2 expression induced the concomitant high expression of the caspase 8 inhibitor, cFlip, and thereby counteracts death-ligand-mediated apoptosis. By investigating the cFlip promoter, Gli2 binding sites were identified and confirmed. Gli2 gene silencing by RNA interference broke the apoptosis resistance via cFlip downregulation. The direct functional connection between Gli2 and cFlip was not only demonstrated in a keratinocytic cell line but also in BCC tissue. As cFlip and Bcl-2 are highly expressed in BCCs, as a consequence of high Gli2 expression, this may explain the marked resistance of the tumor to the extrinsic and intrinsic apoptotic pathway. We could now demonstrate that Gli2 gene silencing in BCC tissues made the tumor sensitive to TRAIL (tumor necrosis factor-related apoptosis-inducing ligand)-mediated cell death by downregulating cFlip. As Gli2 silencing does not only downregulate cFlip, but also Bcl-2, Gli2 could be a key target for a novel therapeutic approach in tumors with dysregulated Hedgehog signaling.

[Urticaria and parasites: case report and general view over the most common pathogens of chronic urticaria]. / Urtikaria und Parasiten: Fall- bericht und Ubersicht uber die häufigsten parasitären Erreger der chronischen Urtikaria.

Chronic urticaria is a disease with numerous aetiologies. In case of blood hypereosinophilia a parasitosis is probable an should be mentioned. Infections with echinococcus and helminths can cause IgE mediated release of histamine. Different cytokines are involved and lead to chronic urticaria as well. There are only a few case repoorts about chronic urticaria caused by amoebiasis. The transmission of amoebas is faeco oral and the pathogen can be detected with stool examinations or with testing of antigens or molecular methods. This case showed a remission of chronic urticaria after treatment of the amboebiasis with metronidazole and paromomycine. Therfore a direct causal connection of the amoebiasis and chronic urticaria can be assumed.

[Livid facial erythema: marker lesion of a multi-facet systemic illness]. / Livides Gesichtserythem: Markerläsion einer Systemkrankheit mit vielen Facetten.

We present a 53 year old woman with a progressive violaceous erythema (heliotrop rash) of the face with periorbital oedema. A clinical diagnosis of dermatomyositis was proposed. Except for the cutaneous manifestation there was no further clinical evidence of systemic disease and specifically of muscle involvement. The lesions developed about six months earlier and an amyopathic dermatomyositis was diagnosed. The patient was treated with hydroxychloroquine. The risk of malignant disease is increased in primary idiopathic and amyopathic adult onset dermatomyositis. Therefore an adequate work-up is mandatory.

Recurrent flexural exanthema (SDRIFE or baboon syndrome) after administration of two different iodinated radio contrast media.

In 1984, the baboon syndrome was described as a particular form of systemic contact dermatitis that occurred after the administration of a contact allergen in individuals previously sensitized by topical exposure to the same allergen. Its clinical picture presents as an erythema of the buttocks and upper inner thighs resembling the red bottom of baboons. This specific reaction was originally observed with mercury, nickel and ampicillin. Since then over 100 cases have been described, most of them without known prior sensitization to the causative agent. In 2004, our group proposed the acronym SDRIFE specifically for cases associated with systemic drugs; it stands for symmetrical drug-related intertriginous and flexural exanthema, as a distinct reaction pattern related to systemic drugs. Here we describe a case of SDRIFE after administration of the iodinated radio contrast medium (RCM) iomeprol (Iomeron), accidentally reproduced by the RCM iopromide (Ultravist). Positive delayed skin tests with both drugs were observed indicating that the pathomechanism of SDRIFE is likely a cell-mediated type IV allergy. Oral potassium iodide and a skin-test-negative RCM were administered and both tolerated, indicating that the antigen is related to the molecules and not to iodine itself. Therefore, in our case skin tests had a good positive and negative predictive value.

Dermatoscope as vector for transmissible diseases - no apparent risk of nosocomial infections in outpatients.

PURPOSE: To determine nonpathogenic and potentially pathogenic bacterial growth isolated from dermatoscopes of dermatologists using oil as contact medium in the daily routine at two outpatient sections in Switzerland. METHODS: We investigated the microbiologic colonization of dermatoscopes (Dermatoskop Delta 10, Heine Optotechnik, or Dermogeniusbasic, Rodenstock) during routine use in the outpatient sections of the Departments of Dermatology at the University of Basel and Kantonsspital Aarau. 112 swabs (4 from Aarau, 108 from Basel) taken under standardized conditions were microbiologically worked up in the same laboratory. Oil (101) and 63% isopropyl alcohol (11) were used as contact medium. RESULTS: 39 of 112 swabs showed no bacterial growth. 73 of 112 showed growth of nonpathogenic bacteria (skin flora). Additionally to the cultivation of nonpathogenic bacteria, 3 swabs showed growth of oxacillin-sensitive potentially pathogenic Staphylococcus aureus. Of 11 swabs taken after using 63% isopropyl alcohol as a contact medium, 6 revealed no bacterial growth and 5 showed the growth of skin flora. CONCLUSIONS: The potential risk of nosocomial infection related to the routine use of dermatoscopes in outpatients is small, and the use of oil as a contact medium for dermatoscopy to enhance the optical quality seems to be unproblematic.

Ciprofloxacin-induced acute generalized exanthematous pustulosis mimicking bullous drug eruption confirmed by a positive patch test.

We report the case of an 80-year-old woman presenting with ciprofloxacin-induced acute generalized exanthematous pustulosis (AGEP) confirmed by a positive patch test. Cutaneous morphology, course and histological findings were consistent with a definite diagnosis according to the AGEP validation score of the EuroSCAR study group. We point to the rarity of quinolone-induced AGEP and discuss immunological mechanisms, the value of in vivo and in vitro tests as well as the main differential diagnosis. Furthermore, we highlight in this particular case the challenging differentiation from bullous drug eruption.

[Skin manifestations in kidney diseases]. / Hauterscheinungen bei Nierenkrankheiten.

Skin irritations in conjunction with renal disorders are often specific. Therefore a close inspection of the integument may point to an internal organ pathology. A selection of hereditary syndromes and a summary table are shown including acquired diseases displaying symptoms of the skin and the kidneys. A special emphasis is laid on specific and unspecific skin alterations under chronic renal failure. Instead of a detailed list of therapeutic possibilities, priority is given to the exact description of macroscopic and microscopic skin alterations including pathophysiologic mechanisms.

Baboon syndrome resulting from systemic drugs: is there strife between SDRIFE and allergic contact dermatitis syndrome?

The term 'baboon syndrome' (BS) was introduced 20 years ago to classify patients in whom a specific skin eruption resembling the red gluteal area of baboons occurred after systemic exposure to contact allergens. Thereafter, similar eruptions have been reported after systemic exposure to beta-lactam antibiotics and other drugs. In addition to the presentation of 2 of our own cases, we have reviewed and characterized the main clinical and histological aspects of published reports of drug-related baboon syndrome (DRBS) and compared the primary clinical signs from such cases to those found in other distinct drug eruptions. Of approximately 100 published baboon syndrome cases, 50 were identified as drug-induced. Of these, 8 were representatives of systemically induced contact dermatitis (SCD), and 42 were examples of drug eruptions elicited by systemic administration of either oral or intravenous drugs. The main clinical findings included a sharply defined symmetrical erythema of the gluteal area and in the flexural or intertriginous folds without any systemic symptoms and signs. 14 of 42 cases were elicited by amoxicillin, 30 of the 42 patients were male, and latency periods were between a few hours and a few days after exposure. DRBS is a rare, prognostically benign and often underdiagnosed drug eruption with distinct clinical features. The term baboon syndrome, however, does not reflect the complete range of symptoms and signs and is ethically and culturally problematic. Moreover, baboon syndrome is historically often equated with a mercury-induced exanthem in patients with previous contact sensitization. Symmetrical drug-related intertriginous and flexural exanthema, or SDRIFE, specifically refers to the distinctive clinical pattern of this drug eruption, and the following diagnostic criteria are proposed: 1) exposure to a systemically administered drug either at the first or repeated dose (excluding contact allergens); 2) sharply demarcated erythema of the gluteal/perianal area and/or V-shaped erythema of the inguinal/perigenital area; 3) involvement of at least one other intertriginous/flexural localization; 4) symmetry of affected areas; and 5) absence of systemic symptoms and signs.