S3 guideline "actinic keratosis and cutaneous squamous cell carcinoma" - update 2023, part 2: epidemiology and etiology, diagnostics, surgical and systemic treatment of cutaneous squamous cell carcinoma (cSCC), surveillance and prevention.

Actinic keratosis (AK) are common lesions in light-skinned individuals that can potentially progress to cutaneous squamous cell carcinoma (cSCC). Both conditions may be associated with significant morbidity and constitute a major disease burden, especially among the elderly. To establish an evidence-based framework for clinical decision making, the guideline "actinic keratosis and cutaneous squamous cell carcinoma" was updated and expanded by the topics cutaneous squamous cell carcinoma in situ (Bowen's disease) and actinic cheilitis. The guideline is aimed at dermatologists, general practitioners, ear nose and throat specialists, surgeons, oncologists, radiologists and radiation oncologists in hospitals and office-based settings, as well as other medical specialties, policy makers and insurance funds involved in the diagnosis and treatment of patients with AK and cSCC. A separate guideline exists for patients and their relatives. In this part, we will address aspects relating to epidemiology and etiology, diagnostics, surgical and systemic treatment of cutaneous squamous cell carcinoma (cSCC), surveillance and prevention.

Causes of irritant contact dermatitis after occupational skin exposure: a systematic review.

PURPOSE: Irritant contact dermatitis (ICD) is a major cause of occupational disease. The aim was to review the relation between exposure to occupational irritants and ICD and the prognosis of ICD. METHODS: Through a systematic search, 1516 titles were identified, and 48 studies were included in the systematic review. RESULTS: We found that the evidence for an association between ICD and occupational irritants was strong for wet work, moderate for detergents and non-alcoholic disinfectants, and strong for a combination. The highest quality studies provided limited evidence for an association with use of occlusive gloves without other exposures and moderate evidence with simultaneous exposure to other wet work irritants. The evidence for an association between minor ICD and exposure to metalworking fluids was moderate. Regarding mechanical exposures, the literature was scarce and the evidence limited. We found that the prognosis for complete healing of ICD is poor, but improves after decrease of exposure through change of occupation or work tasks. There was no substantial evidence for an influence of gender, age, or household exposures. Inclusion of atopic dermatitis in the analysis did not alter the risk of ICD. Studies were at risk of bias, mainly due to selection and misclassification of exposure and outcome. This may have attenuated the results. CONCLUSION: This review reports strong evidence for an association between ICD and a combination of exposure to wet work and non-alcoholic disinfectants, moderate for metalworking fluids, limited for mechanical and glove exposure, and a strong evidence for a poor prognosis of ICD.

Update "Systemic treatment of atopic dermatitis" of the S2k-guideline on atopic dermatitis.

This guideline is an update from August 2020 the S2k-guideline "Atopic dermatitis" published in 2015. The reason for updating this chapter of the guideline were the current developments in the field of systemic therapy of atopic dermatitis. The agreed recommendations for systemic treatment in atopic dermatitis of the present guideline are based on current scientific data. Due to the approval of dupilumab for the treatment of moderate to severe atopic dermatitis, which cannot be treated sufficiently with topical drugs alone, this part of the guideline has now been adapted and newly consented. The indication for systemic therapy and the therapeutic response to topical and systemic treatment should be recorded and documented in a suitable form in clinic and practice. A standardized documentation of the indication for system therapy in atopic dermatitis can be recommended and is also part of the updated chapter of this guideline.

Assessment of the effects of a work-related allergy to seafood on the reduction of earning capacity in the context of BK No. 5101.

Fish, crustaceans, and mollusks are among the most potent allergenic foods of animal origin and are thus important triggers of work-related immediate-food allergies. In Germany, work-related seafood allergies are of great importance in the fishing and processing industries as well as in the areas of food preparation, food control, and food sales. There is no causal therapy of seafood allergy, only the strict and lifelong avoidance of allergens remains. The following recommendations serve to assess the impact of a seafood allergy with regard to the work opportunities ended by it for the assessment of the reduction of earning capacity (MdE (German for Minderung der Erwerbsfähigkeit)) in the context of the occupational disease number 5101 of the Annex to the German regulation for occupational diseases. As a special feature of work-related seafood allergy with regard to insurance law aspects, it must be taken into account that there is a potential risk of systemic reaction with subsequent multi-organ involvement. For the estimation of MdE in the general labor market, the impact of a seafood allergy can therefore be assessed, depending on its clinical severity, as generally "mild" to "severe" in justified individual cases.

No evidence of increased cancer incidence in children using topical tacrolimus for atopic dermatitis.

BACKGROUND: Long-term safety of topical calcineurin inhibitors is not well understood. APPLES (A Prospective Pediatric Longitudinal Evaluation to Assess the Long-Term Safety of Tacrolimus Ointment for the Treatment of Atopic Dermatitis; NCT00475605) examined incidence of lymphoma and other cancers in a pediatric population with atopic dermatitis. OBJECTIVE: To quantify incident malignancies during 10 years in children with atopic dermatitis who used topical tacrolimus for ≥6 weeks. METHODS: Standardized incidence ratios for cancer events were analyzed relative to sex-, age-, and race-matched control data from national cancer registries. RESULTS: There were 7954 eligible patients enrolled at 314 sites in 9 countries. During 44,629 person-years, 6 confirmed incident cancers occurred (standardized incidence ratio, 1.01; 95% confidence interval, 0.37-2.20). No lymphomas occurred. LIMITATIONS: Observational prospective cohort study. CONCLUSION: The cancer incidence was as expected, given matched background data. This finding provides no support for the hypothesis that topical tacrolimus increases long-term cancer risk in children with atopic dermatitis.

S3 guideline for actinic keratosis and cutaneous squamous cell carcinoma (cSCC) - short version, part 2: epidemiology, surgical and systemic treatment of cSCC, follow-up, prevention and occupational disease.

Actinic keratoses (AKs) are common lesions in light-skinned individuals that can potentially progress to cutaneous squamous cell carcinoma (cSCC). Both conditions may be associated with significant morbidity and constitute a major disease burden, especially among the elderly. To establish an evidence-based framework for clinical decision making, the guidelines for actinic keratosis and cutaneous squamous cell carcinoma were developed using the highest level of methodology (S3) according to regulations issued by the Association of Scientific Medical Societies in Germany (AWMF). The guidelines are aimed at dermatologists, general practitioners, ENT specialists, surgeons, oncologists, radiologists and radiation oncologists in hospitals and office-based settings as well as other medical specialties involved in the diagnosis and treatment of patients with AKs and cSCC. The guidelines are also aimed at affected patients, their relatives, policy makers and insurance funds. In the second part, we will address aspects relating to epidemiology, etiology, surgical and systemic treatment of cSCC, follow-up and disease prevention, and discuss AKs and cSCC in the context of occupational disease regulations.

Contact Allergy to Fragrance Mix II and Hydroxyisohexyl 3-Cyclohexene Carboxaldehyde: A Retrospective Study by International Contact Dermatitis Research Group.

BACKGROUND: Fragrance mix II (FM II) is included in the baseline patch test series recommended by the International Contact Dermatitis Research Group (ICDRG). Hydroxyisohexyl 3-cyclohexene carboxaldehyde (HICC) is the most important sensitizer of the 6 fragrance materials included in FM II. Besides being a part of FM II, HICC is also tested separately in the ICDRG baseline series. OBJECTIVES: The aim of the study was to investigate the prevalence of contact allergy to FM II and HICC in 2012-2016 with a focus on simultaneous reactions and the percentage of missed contact allergy to HICC provided that only FM II had been tested. PATIENTS AND METHODS: A total of 25,019 consecutive dermatitis patients in 13 dermatology clinics representing 12 countries in 5 continents were patch tested with FM II and HICC in the baseline series. RESULTS: Contact allergy to FM II and HICC was found in 3.9% and 1.6%, respectively. For FM II, the frequency varied from 1.5% to 7.6% in different centers. The corresponding range for HICC was 0.2% to 3.6%. Simultaneous contact allergy to FM II and HICC was noted in 1.4% with the range 0.2% to 2.6%. Seventy-seven patients (0.31%) with contact allergy to HICC did not test positively to FM II. The range for missed HICC allergy by testing only FM II in the different centers would be 0.04% to 0.74%. The ratio between the contact allergy rates for FM II and HICC was similar for all centers, except for Montreal having significantly more contact allergy to FM II than to HICC. CONCLUSIONS: The frequency of missed contact allergy to HICC when testing only with FM II was less than 0.5%, therefore questioning the need to test HICC separately in the ICDRG baseline series.

S3 guideline for actinic keratosis and cutaneous squamous cell carcinoma - short version, part 1: diagnosis, interventions for actinic keratoses, care structures and quality-of-care indicators.

Actinic keratoses (AK) are common lesions in light-skinned individuals that can potentially progress to cutaneous squamous cell carcinoma (cSCC). Both conditions may be associated with significant morbidity and constitute a major disease burden, especially among the elderly. To establish an evidence-based framework for clinical decision making, the guideline "actinic keratosis and cutaneous squamous cell carcinoma" was developed using the highest level of methodology (S3) according to regulations issued by the Association of Scientific Medical Societies in Germany (AWMF). The guideline is aimed at dermatologists, general practitioners, ENT specialists, surgeons, oncologists, radiologists and radiation oncologists in hospitals and office-based settings as well as other medical specialties involved in the diagnosis and treatment of patients with AK and cSCC. The guideline is also aimed at affected patients, their relatives, policy makers and insurance funds. In the first part, we will address aspects relating to diagnosis, interventions for AK, care structures and quality-of-care indicators.

Development of a Conceptual Model of Chronic Hand Eczema (CHE) Based on Qualitative Interviews with Patients and Expert Dermatologists.

INTRODUCTION: Chronic hand eczema (CHE) is a relapsing inflammatory dermatologic disease. Signs and symptoms can have a significant impact on patients' health-related quality of life (HRQoL). The aim of this study is to characterize the core signs, symptoms and impacts of CHE to develop a conceptual model. METHODS: A structured literature search and qualitative interviews with 20 adult CHE patients in the US and 5 expert dermatologists were conducted to explore the patient experience of CHE signs, symptoms and impacts. Findings were used to support the development of a conceptual model. RESULTS: There was a paucity of CHE qualitative research in the literature, supporting the need for the prospective qualitative research. The primary signs and symptoms identified from the literature review and interviews included itch, dryness, cracking, pain, thickened skin and bleeding. The most salient impacts included embarrassment and appearance concerns, frustration, impacts on work and sleep disturbance. Saturation was achieved for all signs, symptoms and impact concepts. CONCLUSIONS: Findings from this literature review and in-depth qualitative interviews supported the development of a comprehensive conceptual model documenting the signs, symptoms and impacts relevant to CHE patients. Such a model is of considerable value given the lack of existing studies in the literature focused on the qualitative exploration of the CHE patient experience. Limitations included the patient sample being only from the US and not including some CHE subtypes.

Ingenol mebutate as topical treatment for actinic keratosis based on a prospective, non-interventional, multicentre study of real-life clinical practice in Germany: efficacy and quality of life.

BACKGROUND: The use of ingenol mebutate (IM) as a field-directed therapy over a short period of time has been shown to be effective and well tolerated in randomized Phase III trials. OBJECTIVES: To assess the efficacy and patient-reported outcomes for IM as treatment for actinic keratosis (AK) under daily "real-life" practice conditions. MATERIALS AND METHODS: A total of 826 adult patients with AK were enrolled by 292 dermatologists in Germany in a prospective, open, non-interventional, non-controlled, multicentre study. All patients were treated with IM and followed for eight weeks. RESULTS: The mean number of clinically visible AK lesions decreased significantly from 7.1±6.8 to 2.8±4.5 (p<0.0001). Most dermatologists (79.0%) rated global efficacy of IM as "very good"/"good" and 82.6% of the patients were "very satisfied" or "rather satisfied" with the efficacy of IM. Patient-reported outcomes showed greater efficacy and treatment comfort with IM compared to any last previous AK treatment with a comparable tolerability profile. Skin-related QoL data revealed a significant improvement of 50.2% after IM treatment (p<0.0001). Adverse events were reported in 7.0% of all patients, which were in most cases mild in intensity. CONCLUSION: Field-directed treatment with IM over a short period was associated with a high level of treatment satisfaction, as reported by dermatologists and patients. This observational study demonstrates the effectiveness and tolerability of IM in everyday clinical practice in addition to the known efficacy and safety obtained by randomized controlled clinical trials.

Interventions for hand eczema.

BACKGROUND: Hand eczema is an inflammation of the skin of the hands that tends to run a chronic, relapsing course. This common condition is often associated with itch, social stigma, and impairment in employment. Many different interventions of unknown effectiveness are used to treat hand eczema. OBJECTIVES: To assess the effects of topical and systemic interventions for hand eczema in adults and children. SEARCH METHODS: We searched the following up to April 2018: Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, AMED, LILACS, GREAT, and four trials registries. We checked the reference lists of included studies for further references to relevant trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared interventions for hand eczema, regardless of hand eczema type and other affected sites, versus no treatment, placebo, vehicle, or active treatments. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Primary outcomes were participant- and investigator-rated good/excellent control of symptoms, and adverse events. MAIN RESULTS: We included 60 RCTs, conducted in secondary care (5469 participants with mild to severe chronic hand eczema). Most participants were over 18 years old. The duration of treatment was short, generally up to four months. Only 24 studies included a follow-up period. Clinical heterogeneity in treatments and outcome measures was evident. Few studies performed head-to-head comparisons of different interventions. Risk of bias varied considerably, with only five studies at low risk in all domains. Twenty-two studies were industry-funded.Eighteen trials studied topical corticosteroids or calcineurin inhibitors; 10 studies, phototherapy; three studies, systemic immunosuppressives; and five studies, oral retinoids. Most studies compared an active intervention against no treatment, variants of the same medication, or placebo (or vehicle). Below, we present results from the main comparisons.Corticosteroid creams/ointments: when assessed 15 days after the start of treatment, clobetasol propionate 0.05% foam probably improves participant-rated control of symptoms compared to vehicle (risk ratio (RR) 2.32, 95% confidence interval (CI) 1.38 to 3.91; number needed to treat for an additional beneficial outcome (NNTB) 3, 95% CI 2 to 8; 1 study, 125 participants); the effect of clobetasol compared to vehicle for investigator-rated improvement is less clear (RR 1.43, 95% CI 0.86 to 2.40). More participants had at least one adverse event with clobetasol (11/62 versus 5/63; RR 2.24, 95% CI 0.82 to 6.06), including application site burning/pruritus. This evidence was rated as moderate certainty.When assessed 36 weeks after the start of treatment, mometasone furoate cream used thrice weekly may slightly improve investigator-rated symptom control compared to twice weekly (RR 1.23, 95% CI 0.94 to 1.61; 1 study, 72 participants) after remission is reached. Participant-rated symptoms were not measured. Some mild atrophy was reported in both groups (RR 1.76, 95% CI 0.45 to 6.83; 5/35 versus 3/37). This evidence was rated as low certainty.Irradiation with ultraviolet (UV) light: local combination ultraviolet light therapy (PUVA) may lead to improvement in investigator-rated symptom control when compared to local narrow-band UVB after 12 weeks of treatment (RR 0.50, 95% CI 0.22 to 1.16; 1 study, 60 participants). However, the 95% CI indicates that PUVA might make little or no difference. Participant-rated symptoms were not measured. Adverse events (mainly erythema) were reported by 9/30 participants in the narrow-band UVB group versus none in the PUVA group. This evidence was rated as moderate certainty.Topical calcineurin inhibitors: tacrolimus 0.1% over two weeks probably improves investigator-rated symptom control measured after three weeks compared to vehicle (14/14 tacrolimus versus 0/14 vehicle; 1 study). Participant-rated symptoms were not measured. Four of 14 people in the tacrolimus group versus zero in the vehicle group had well-tolerated application site burning/itching.A within-participant study in 16 participants compared 0.1% tacrolimus to 0.1% mometasone furoate but did not measure investigator- or participant-rated symptoms. Both treatments were well tolerated when assessed at two weeks during four weeks of treatment.Evidence from these studies was rated as moderate certainty.Oral interventions: oral cyclosporin 3 mg/kg/d probably slightly improves investigator-rated (RR 1.88, 95% CI 0.88 to 3.99; 1 study, 34 participants) or participant-rated (RR 1.25, 95% CI 0.69 to 2.27) control of symptoms compared to topical betamethasone dipropionate 0.05% after six weeks of treatment. The risk of adverse events such as dizziness was similar between groups (up to 36 weeks; RR 1.22, 95% CI 0.80 to 1.86, n = 55; 15/27 betamethasone versus 19/28 cyclosporin). The evidence was rated as moderate certainty.Alitretinoin 10 mg improves investigator-rated symptom control compared with placebo (RR 1.58, 95% CI 1.20 to 2.07; NNTB 11, 95% CI 6.3 to 26.5; 2 studies, n = 781) and alitretinoin 30 mg also improves this outcome compared with placebo (RR 2.75, 95% CI 2.20 to 3.43; NNTB 4, 95% CI 3 to 5; 2 studies, n = 1210). Similar results were found for participant-rated symptom control: alitretinoin 10 mg RR 1.73 (95% CI 1.25 to 2.40) and 30 mg RR 2.75 (95% CI 2.18 to 3.48). Evidence was rated as high certainty. The number of adverse events (including headache) probably did not differ between alitretinoin 10 mg and placebo (RR 1.01, 95% CI 0.66 to 1.55; 1 study, n = 158; moderate-certainty evidence), but the risk of headache increased with alitretinoin 30 mg (RR 3.43, 95% CI 2.45 to 4.81; 2 studies, n = 1210; high-certainty evidence). Outcomes were assessed between 48 and 72 weeks. AUTHORS' CONCLUSIONS: Most findings were from single studies with low precision, so they should be interpreted with caution. Topical corticosteroids and UV phototherapy were two of the major standard treatments, but evidence is insufficient to support one specific treatment over another. The effect of topical calcineurin inhibitors is not certain. Alitretinoin is more effective than placebo in controlling symptoms, but advantages over other treatments need evaluating.Well-designed and well-reported, long-term (more than three months), head-to-head studies comparing different treatments are needed. Consensus is required regarding the definition of hand eczema and its subtypes, and a standard severity scale should be established.The main limitation was heterogeneity between studies. Small sample size impacted our ability to detect differences between treatments.

The significance of batch and patch test method in establishing contact allergy to fragrance mix I-EDEN Fragrance Study Group.

BACKGROUND: A fragrance mix consisting of eight separate fragrance ingredients (fragrance mix I [FM I]) is present in most baseline patch test series. Patch testing with the TRUE Test technique is considered to detect less contact allergy to FM I than testing with the Finn Chamber technique. OBJECTIVE: To investigate the possible significance of batch and patch test method in establishing contact allergy to FM I. METHODS: Three thousand one hundred and nineteen individuals representing a sample of the general population were patch tested with two batches of FM I with two patch test techniques at six dermatology clinics in five European countries. The TRUE Test technique and the Finn Chamber technique with pet. preparations were used. McNemar's test was used for statistical calculations. RESULTS: The contact allergy prevalences varied between 0.7% and 2.6%. The patch tests with the mixes containing Evernia prunastri (oak moss) with a high content of chloratranol/atranol resulted in substantially more positive reactions than the corresponding tests with the mixes containing oak moss with a low content of chloratranol/atranol. The Finn Chamber technique detected significantly more contact allergic reactions than the TRUE Test technique (P < 0.001). CONCLUSION: The Finn Chamber technique detects more contact allergy to FM I than the TRUE Test technique.

Chronic hand eczema in Germany: 5-year follow-up data from the CARPE registry.

BACKGROUND: The CARPE registry was set up in 2009 to prospectively investigate the management of patients with chronic hand eczema (CHE). OBJECTIVES: To report comprehensive follow-up data from the CARPE registry. PATIENTS AND METHODS: We investigated sociodemographic and clinical characteristics, provision of medical care, physician-assessed outcomes, and patient-reported outcomes (PROs). Data were collected between 2009 and 2016, with up to 5 years of follow-up, and are reported descriptively. RESULTS: Overall, 1281 patients were included in the registry (53.7% female). Mean age was 47.0 years. Of the patients, 793 and 231 completed the 2-year follow-up and 5-year follow-up, respectively. At baseline, 5.4% had changed or given up their job because of CHE, the average duration of CHE was 6.1 years, and, in 22.4%, the CHE was severe according to physician global assessment. Systemic treatment (alitretinoin, acitretin, and methotrexate) was prescribed at least once to 39.0% of the patients during the course of the follow-up. Disease severity, quality of life and treatment satisfaction improved over time, and the proportion of patients receiving systemic treatments decreased. CONCLUSIONS: Under continued dermatological care, substantial improvements in disease severity and PROs over time was achieved during the course of the CARPE registry, even in patients with long-standing and severe hand eczema.