Background: Many treatments for actinic keratosis (AK) have been proven efficient in clinical trials. However, patients with AK may still experience unsatisfactory therapeutic outcomes in clinical practice. Objectives: To investigate patient adherence to self-applied topical interventions for AK and to explore factors associated with adherence in a real-world setting. Methods: A cross-sectional study was conducted. Patients presenting with AK were asked to complete a self-administered questionnaire about their last topical AK treatment. Results: A total of 113 patients participated with a median age of 78.5 years (range 58–94). Fifty-four patients (47.8%) received topical diclofenac, ten (8.8%) imiquimod, nine (8%) 5-fluorouracil, nine (8%) 5-fluorouracil plus salicylic acid, and eight (7.1%) photodynamic therapy. The non-adherence rate was 46.9% (n = 53), and only 30.9% (n = 35) used the topical treatments according to the summary of product characteristics (SmPC). These subgroups were compared. Patients of the non-compliant group were significantly less informed about the application time of the specific topical intervention (p = 0.002) and adjusted the timeframe (p < 0.001) and application frequency of the therapy (p = 0.02) independently of their physician. Conversely, patients reporting a sufficient pre-treatment consultation (p = 0.019) generally complied with the SmPC compliance application. Conclusions: A thorough pre-treatment consultation can help to increase treatment adherence and ensure lesion clearance.

Our purpose was to collect data on the incidence of malignant skin tumours presenting as chronic leg or foot ulcers in a tertiary centre, and to analyse the frequency and type of initial clinical misdiagnoses in these cases. A retrospective chart review of cases with melanoma or other malignant neoplasms of the skin of the lower extremity treated in a tertiary centre during January 2010 until February 2020 was conducted to identify cases that presented as chronic ulcers. Out of 673 cases, 26 (3.9%) were identified with a total of 27 malignant tumours presenting as chronic ulcers of the lower leg or foot. Therefrom, seven were diagnosed as melanoma, eight as squamous cell carcinoma, and twelve as basal cell carcinoma. The mean interval until diagnosis for all tumour types was 44.4 months (median 24 months). A delay in correct treatment occurred in 12 out of 26 cases (46%) as a result of misdiagnosis with subsequent treatment as chronic leg or foot ulcers of a different etiology. Misdiagnoses were venous ulcer, traumatic wound, mixed arterial and venous ulcer, arterial ulcer, and ulcer of an unknown origin. Malignant ulcers presenting as chronic ulcers are rare, but often lead to misdiagnosis.

BACKGROUND:Anti-PD1-based immunotherapy is currently used in most patients with advanced melanoma. Despite the remarkable data regarding overall survival, the optimal treatment duration is still unknown.METHODS:We evaluated the outcome of 125 patients with advanced melanoma with and without brain metastases (MBM), treated either with anti-PD1 monotherapy (N = 97) or combined with anti-CTLA4 (N = 28) after elective treatment discontinuation due to complete response (CR) (group A, N = 86), or treatment-limiting toxicity (N = 33) and investigator's decision (ID, N = 6) (group B) with subsequent CR.RESULTS:For group A, median duration of treatment (mDoT) was 22 months (range 5-49) and median time to CR 9 months (range 2-47). Accordingly, mDoT for group B was 3 months (range 0-36) and median time to CR 7 months (range 1-32). Seven patients from group A and three from group B experienced disease recurrence. Off-treatment survival was not reached. Median off-treatment response time (mOTRt) was 19 months (range 0-42) and 25 months (range 0-66), respectively. For MBM, mOTRt was 17 months (range 7-41) and 28 months (range 9-39), respectively. After a median follow-up of 38 months (range 9-70), seven (5.6%) patients had deceased, one (0.8%) due to melanoma.CONCLUSIONS:Treatment discontinuation is feasible also in patients with MBM. Efficacy outcomes seemed to be similar in both groups of patients who achieved CR, regardless of reason for discontinuation. In patients who experienced disease relapse, treatment re-challenge with anti-PD1 resulted in subsequent renewed response.

Actinic keratoses (AK) are common lesions of the skin that can be effectively treated with several lesion- and field-directed treatments. Clinical practice guidelines assist physicians in choosing the appropriate treatment options for their patients. Here, we aimed to systematically identify and evaluate the methodological quality of currently available guidelines for AK. Guidelines published within the last 5 years were identified in a systematic search of guideline databases, Medline and Embase. Then, six independent reviewers evaluated the methodological quality using the tools “Appraisal of Guidelines for Research and Evaluation” (AGREE II) and “Recommendation EXcellence” (AGREE-REX). The Kruskal–Wallis (H) test was used to explore differences among subgroups and Spearman’s correlation to examine the relationship between individual domains. Three guidelines developed by consortia from Canada, Germany and the United Kingdom were eligible for the evaluation. The German guideline achieved the highest scores, fulfilling 65 to 92% of the criteria in AGREE II and 67 to 84% in AGREE-REX, whereas the Canadian guideline scored 31 to 71% of the criteria in AGREE II and 33 to 46% in AGREE-REX. The domains “stakeholder involvement“ and “values and preferences“ were identified as methodological weaknesses requiring particular attention and improvement in future guideline efforts.

Dear Editor, Primary cutaneous CD8+ aggressive epidermotropic T-cell lymphoma (CD8+ AECTCL) is a very rare subtype of cutaneous T-cell lymphoma. The frequency is less than 1% of all primary cutaneous lymphomas and prognosis is poor, with a 5-year disease-specific survival rate of 31%.1 Because of the rarity of this entity, there are no evidence-based treatment options. We report the case of a 70-year-old female patient who presented with a red plaque with central ulceration on the left shin rapidly developing in 2 weeks. Skin biopsy revealed atypical lymphoid cells in the epidermis and dermis with atypical mitoses (Figure 1a). Immunohistochemical stains showed reactivity with CD3, CD8 (Figure 1b), TIA-1 and programmed cell death 1 ligand 1, with weak reactivity for programmed cell death protein 1 (PD-1) expression. CD2, CD4, CD20, CD30 and CD56 were negative. Cranial magnetic resonance imaging (MRI) and computed tomography (CT) scan of neck, thorax and abdomen showed no evidence of metastases. Bone marrow biopsy revealed no infiltration with lymphoma cells, and blood count was normal. Primary cutaneous CD8+ aggressive epidermotropic T-cell lymphoma was diagnosed. Chemotherapy with cyclophosphamide, doxorubicin, etoposide, vincristine and prednisone (CHOEP) every 21 days was started. After six cycles of chemotherapy the plaque was clearly regressive, and consolidating radiotherapy of the left lower leg was started. Still on radiotherapy, the patient developed disseminated, well demarcated erythematous patches and plaques, many with necrotic ulcerations, involving all extremities and trunk (Figure 1c), and ulceration on the hard palate. Cranial MRI, CT scan and fluorescence-activated cell sorting analysis ruled out extracutaneous manifestation. Photochemotherapy with psoralen plus ultraviolet A and treatment with topical corticosteroids class IV were initiated without significant improvement. Due to progression, therapy was changed to an anti-PD-1 antibody. After five infusions of nivolumab (2 mg kg–1) the patient experienced near complete remission of all lesions (Figure 1d). Only a singular new erythematous plaque with no ulceration appeared on the trunk during treatment. An additional skin biopsy was performed, which showed similar findings to the initial diagnostic specimen. After seven infusions of nivolumab she developed autoimmune diarrhoea grade 2 (Common Terminology Criteria for Adverse Events). Therapy was paused and treatment with prednisolone at 1 mg kg–1 orally was started and slowly tapered. Owing to persistent symptoms, one infusion with a tumour necrosis factor (TNF)-α inhibitor (infliximab) 5 mg kg–1 was applied. Diarrhoea improved and nivolumab was restarted 1 month after cessation. However, in the following 3 months, new disseminated erythematous and ulcerated plaques appeared and the patient developed a painful massive swelling in the preauricular region. MRI showed a mass in the parotid lodge infiltrating the masseter muscle. Treatment was switched to total body irradiation. However, the patient's condition deteriorated rapidly and she died from sepsis 14 months after diagnosis. Checkpoint inhibitors play an increasing role in the treatment of patients with solid and haematological malignancies. More recent studies evaluated the safety and efficacy of anti-PD-1 antibodies in patients with cutaneous T-cell lymphomas, including a phase Ib study for nivolumab that included 13 cases of mycosis fungoides and five cases of peripheral T-cell lymphoma. The objective response rate in that study was 15% among patients with mycosis fungoides and 40% among patients with peripheral T-cell lymphoma with no further specification of the subtype.2 A phase II study of 24 patients with pretreated mycosis fungoides and Sézary syndrome showed an overall response rate of 38%.3 To our knowledge, there are no descriptions of treatment of CD8+ AECTCL with anti-PD-1 antibody. Reported treatment regimens in cases of CD8+ AECTCL consist of polychemotherapies with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP). However, results are disappointing, with limited success and often rapid recurrence.4 So far the most promising results were achieved with allogeneic hematopoietic stem cell transplantation with a possible curative option,5, 6 which was not possible in our patient owing to rapid progression after multiagent chemotherapy, age and comorbidity. Our patient initially responded surprisingly well to therapy with anti-PD-1 antibody. However, after a short duration of nearly complete remission she required immunosuppressive medication including TNF-α inhibitor in steroid-refractory immune-related diarrhoea. Subsequently, the disease recurred with rapid progression and she finally died, 14 months after diagnosis of CD8+ AECTCL, due to sepsis. There is ongoing discussion of whether treatment with TNF-α inhibitors could induce progress of cutaneous lymphoma.7 Also in our case, it is not excluded that disease progression was accelerated by anti-TNF-α treatment. In conclusion, anti-PD-1 antibodies present a potential treatment option for CD8+ AECTCL, an entity with otherwise few options. open access funding enabled and organized by Projekt DEAL. Frédéric Toussaint: Conceptualization (lead); Visualization (lead); Writing-original draft (lead). Michael Erdmann: Resources (equal); Writing-review & editing (equal). Ella Grosch: Resources (equal); Writing-review & editing (equal). Stefan Schliep: Resources (equal); Writing-review & editing (equal). Gerold Schuler: Writing-review & editing (equal). Reinhard Dummer: Writing-review & editing (equal). Lucie Heinzerling: Supervision (lead); Writing-review & editing (equal).

Multiple guidelines on cutaneous melanoma (CM) are available from several consortia and countries. To provide up-to-date guidance in the rapidly changing field of melanoma treatment, guideline developers have to provide regular updates without compromises of quality. We performed a systematic search in guideline databases, Medline and Embase to identify guidelines on CM. The methodological quality of the identified guidelines was independently assessed by five reviewers using the instruments “Appraisal of Guidelines for Research and Evaluation” (AGREE II) and “Recommendation EXcellence” (AGREE-REX). We performed descriptive analysis, explored subgroup differences using the Kruskal–Wallis (H) test and examined the relationship between distinct domains and items of the instruments with Spearman’s correlation. Six guidelines by consortia from Australia, France, Germany, Scotland, Spain and the United States of America were included. The German guideline fulfilled 71%–98% of criteria in AGREE II and 78%–96% for AGREE-REX, obtaining the highest scores. Deficiencies in the domains of “applicability” and “values and preferences” were observed in all guidelines. The German and Spanish guidelines significantly differed from each other in most of the domains. The domains “applicability” and “values and preferences” were identified as methodological weaknesses requiring careful revision and improvement in the future.

Purpose Clinical practice guidelines provide recommendations for the management of diseases. In orphan conditions such as uveal melanoma (UM), guideline developers are challenged to provide practical and useful guidance even in the absence of high-quality evidence. Here, we assessed the methodological quality and identified deficiencies of international guidelines on UM as a base for future guideline development. Methods A systematic search was carried out in guideline databases, Medline and Embase until 27th May 2019 for guidelines on UM published between 2004 and 2019. Five independent reviewers assessed the methodological quality of the identified guidelines using the instruments “Appraisal of Guidelines for Research and Evaluation II” (AGREE II) and AGREE-REX (Recommendation EXcellence). Descriptive analysis was performed and subgroup differences were explored with the Kruskal–Wallis (H) test. The relationship between the individual domains and items of the instruments were examined using Spearman’s correlation. Results Five guidelines published from 2014 to 2018 by consortia of the United States of America, Canada and the United Kingdom (UK) were included. The highest scores were obtained by the UK guideline fulfilling 48–86% of criteria in AGREE II and 30–60% for AGREE-REX. All guidelines showed deficiencies in the domains “editorial independence”, “applicability”, and “recommendation”. Subgroup differences were identified only for the domain “editorial independence”. Conclusion The UK guideline achieved the highest scores with both instruments and may serve as a basis for future guideline development in UM. The domains “editorial independence”, “recommendation”, and “applicability” were identified as methodological weaknesses and require particular attention and improvement in future guidelines.

We report the case of a 52-year-old man who presented with a 10 year history of multiple nodules with purulent drainage on the upper extremities. Several attempts of treatment with oral antibiotics had been unsuccessful. A skin biopsy specimen showed a dermal abscess with branched septate hyphae. A mycological culture of pus and of the biopsy specimen revealed Trichophyton rubrum. Deeper dermatophytosis presenting as dermal abscesses is a rare disease which occurs normally in immunocompromised conditions. Our patient was on immunosuppressive therapy with methylprednisolone and azathioprine because of inflammatory demyelinating polyneuropathy and presented with extensive abscesses. In cases of dermal abscesses it is important to not only consider bacterial but also fungal infections as underlying cause.

e21042 Background: Immunotherapy (IT) has demonstrated an improved overall survival (OS) in advanced melanoma with 15% complete responses (CR) in treatment-naïve patients (pts) with brain metastases (met) in the anti-PD1/anti-CTLA4 combination. However, data on brain-met pts who discontinue treatment (EoT) after achieving a CR are lacking. Methods: Disease characteristics and clinical outcome were retrospectively collected from 6 centers on advanced melanoma pts treated with anti-PD1 or anti-PD1/anti-CTLA4. Pts were followed for at least 10 weeks (10.8 – 242). Off-treatment survival (OTS) was defined as time between last IT dose to disease progression or death. Results: Out of 890 pts, 62 achieved a CR; 40 pts stopped treatment due to CR, while 22 due to an adverse event (AE) (n = 19) or investigator decision (n = 3) with subsequent CR. 14 were treated with anti-PD1/anti-CTLA4 and 48 with anti-PD1. 24 had a BRAF mutation, of which 10 had previously received targeted therapy (TT). The median time to first CR was 31 weeks (6 – 138), median duration of response and OTS was 91.1 and 60.7 (10.6 – 242) weeks respectively. OTS was numerically longer for those pts with EoT after AE (85 weeks, 13-242) versus those with EoT due to CR (60 weeks, 11-130). Median OS was not reached. 6/62 (3%) progressed after EoT; 4 locoregionally while 2 were subsequently treated with IT. All pts were alive at last follow-up. 19 pts had brain mets. 8 were BRAF mutated. 10 were treatment naïve, 6 received previously anti-CTLA4, 1 chemotherapy and only 2 TT. Data on reasons for EoT and responses in brain mets are seen in the table. Conclusions: Early data suggest that OTS is numerically longer in patients with EoT due to AE with subsequent CR. EoT due to sustained CR is a feasible option also in brain mets. EoT due to AE with subsequent CR was a more frequent event in the combination treatment. [Table: see text]