Impact of COVID-19 on Influenza and Pneumococcal Vaccination of Psoriatic Patients in Germany: Results from Vac-Pso.

BACKGROUND: Suboptimal influenza and pneumococcal vaccination rates have been reported before the COVID-19 pandemics in certain populations at risk for severe infection. The aim of this longitudinal cohort study was to investigate changes in influenza and pneumococcal vaccination rates and patient perceptions in patients with psoriasis (PsO) before and during the pandemic. METHODS: Data on vaccination, patient and disease characteristics, comorbidity, and patient perceptions were collected with questionnaires before and during the pandemic approximately one year later. RESULTS: Over the whole cohort who participated in the follow-up visit (n = 287; 59.2% male; mean age: 56.3 years), both influenza and pneumococcal lifetime vaccination prevalences increased significantly from 50.5% to 66.2% and from 16.0% to 41.5%, respectively. A total of 88.5% of PsO patients were interested in a COVID-19 vaccination or had already received it. The reasons for and against vaccinations changed significantly before and during the pandemic. CONCLUSIONS: Despite a promising increase in the vaccination prevalence in our PsO cohort, it remains important that awareness for vaccinations is encouraged and closely monitored in future research, particularly in populations at risk.

Patients' preferences for systemic treatment of atopic dermatitis: safety and efficacy count the most.

BACKGROUND: The advent of biologics and janus kinase inhibitors has revolutionized treatment of atopic dermatitis (AD). OBJECTIVE: To investigate preferences of patients with AD for attributes of currently approved systemic treatments and assess influencing factors. METHODS: An online discrete choice experiment was conducted in patients with AD throughout Germany to analyze preferences for outcome (probability of (almost) clear skin at week 16, probability of significant itch improvement, time to onset of itch relief and type of side effects) and process attributes (application method and frequency of laboratory tests). RESULTS: Participants (n = 182, 75.3% female) considered side effects (Relative Importance Score (RIS): 31.2), (almost) clear skin (RIS: 24.2) and probability of itch improvement (RIS: 16.0) most important. Application method (RIS: 14.4), time to onset of itch relief (RIS: 7.4) and frequency of laboratory tests (RIS: 6.8) were less relevant. Preferences were significantly influenced by sex, age, psychiatric comorbidity, current therapy and health-related quality of life according to multivariate regression analysis. CONCLUSIONS: Participants attached great importance to safety and symptom control. However, preferences were also dependent on individual characteristics, underscoring the importance of personal counseling. Conjoined with medical considerations, patients' preferences have fundamental impact on shared decisions for treatment of AD.

Full-body blue light irradiation as treatment for atopic dermatitis: a randomized sham-controlled clinical trial (AD-Blue).

BACKGROUND: Visible blue light (wavelength 400-495 nm) is a promising new treatment option for both psoriasis and atopic dermatitis (AD). Whilst previous clinical trials featured various devices and blue light at a variety of wavelengths, none of these interventions were challenged in objective clinical criteria. PATIENTS AND METHODS: Eighty-seven patients diagnosed with AD were enrolled in AD-Blue, an international, prospective, double-blinded, three-armed (415 nm vs. 450 nm vs. sham control), randomized trial designed to investigate the safety and efficacy of prototype full-body blue light devices. RESULTS: Full-body irradiation with 450 nm blue light but not 415 nm had a significant impact on itch (Itch-VAS, -1.6 ± 2.3; p  =  0.023 vs. sham irradiation). PO-SCORAD values also decreased significantly in response to irradiation at 415 nm (-11.5 ± 18.4; p = 0.028 vs. sham irradiation). None of the other outcome measures (EASI, SCORAD, IGA, DLQI) changed significantly. No safety signals were observed. Evaluation of skin transcriptomes, cytokine levels in serum, and ELISpots from peripheral blood mononuclear cells isolated from a subset of patients revealed moderate decreases in IL-31 in response to irradiation with blue light. CONCLUSIONS: Despite its favorable safety profile and moderate reductions in itch and IL-31 levels, full-body blue light irradiation did not lead to an amelioration of any of the objective measures of AD.

Checkpoint blockade and BRAF/MEK therapy in the therapeutic setting improved the overall survival after sentinel node biopsy: A retrospective study comparing patients with primary care between 1998-2009 and 2010-2017.

Immunotherapies using checkpoint blockade and BRAF/MEK therapies have improved overall survival (OS) in patients with unresectable melanoma metastases. In this retrospective study, we aimed to demonstrate the resulting increase in melanoma-specific survival (MSS) and OS after the excision of primary melanomas (≥1 mm thick) and sentinel lymph node (SN) biopsy (SNB). Using Kaplan-Meier estimates and Cox models, we compared two consecutive cohorts. Patients in cohort 1 (N = 518) underwent SNB between 1998 and 2009, and patients in cohort 2 (N = 460) between 2010 and 2017, when checkpoint blockade and BRAF/(MEK) inhibition became available for the treatment of unresectable relapses. The median follow-up times were 120 and 73 months, respectively. While recurrence-free and distant metastasis-free survival rates remained very similar, MSS and OS increased in favor of cohort 2. The estimated 5-year OS rate of SN-positive patients increased by 14.3% (78.5% vs 64.2%, logrank test: P = .005). The MSS benefit was significant even with low SN tumor burden (metastasis diameter < 1 mm). On multivariate analyses, the risk-reduction in favor of cohort 2 was significant in the total population and in the SN-negative and SN-positive subgroups. In SN-positive patients, besides the availability of modern therapies, SN metastasis diameter and ulceration were independent factors of MSS and OS. Treatment of unresectable melanoma recurrences with modern drug therapies results in significantly higher survival rates in a population with SNB. The survival benefit measured from primary melanoma affects both the SN-positive and SN-negative subpopulations.

Interleukin-19 Levels Are Increased in Palmoplantar Pustulosis and Reduced following Apremilast Treatment.

Palmoplantar pustulosis (PPP) is a chronic inflammatory skin disease characterised by neutrophilic granulocyte (neutrophil)-filled pustules on the palms and soles. The pathogenesis of PPP is poorly understood. This study conducted an identification of the immune mediators associated with PPP and an exploration of apremilast treatment effects on them. We screened for immune mediators elevated in blood taken from 68 patients with PPP versus control participants and included the most promising parameters in the protocol of phase the 2, multicentre study of apremilast (PDE4 inhibitor) in 21 patients with moderate-to-severe PPP (APLANTUS; EudraCT 2016-005122-11) for respective analysis of blood and skin samples of study patients. We investigated stimulated neutrophils and three-dimensional reconstituted epidermis cultures. Interleukin (IL)-19 was found to be the most upregulated immune mediator in the blood of PPP patients. IL-19 serum levels were independent of patients' age, gender, and BMI but were associated with strongly upregulated cutaneous IL-19 expression and correlated with the number of palmoplantar pustules. In patients participating in the APLANTUS study, apremilast reduced pustules more effectively than erythema and scaling. Moreover, this treatment significantly reduced IL-19 blood and skin levels. The reduction in IL-19 blood levels at week 4 correlated with the reduction in pustule counts at week 20 (end of treatment). IL-19 was expressed by neutrophils activated in vitro and induced CXCL6, a neutrophil-attracting chemokine, in epidermis models. This work demonstrates elevated IL-19 levels in the blood and skin of PPP patients and suggests a relevant role of this cytokine in the appearance of pustules in this disorder. It also suggests the suitability of IL-19 blood levels as a predictive biomarker for the treatment response of PPP patients, which should be validated in further studies.

Patient Preferences in Hidradenitis Suppurativa (APProach-HS): a discrete choice experiment.

BACKGROUND AND OBJECTIVES: Treatment options for moderate-to-severe hidradenitis suppurativa (HS) comprise antibiotics, biologics, and different surgical methods. These approaches differ substantially regarding the treatment process, success rates, and adverse events. However, information on patient preferences for HS therapies is hitherto scarce. Our aim was to assess patient preferences for medicamentous and surgical treatment of HS with conjoint analysis. PATIENTS AND METHODS: In this cross-section study, computerized discrete choice experiments were used to quantify patient preferences for HS therapies decomposed into treatment modality (tablets, subcutaneous injections, surgery with secondary-intention healing or primary closure), probability of sustained therapeutic success, probability of mild or severe adverse events, and duration of treatment or wound healing. RESULTS: Averaged over the cohort (n  =  216 patients with HS), sustained therapeutic success was considered as most important (Relative Importance Score [RIS]: 36.2), followed by the treatment modality (RIS: 24.0), and duration of treatment/wound healing (RIS: 19.9), whereas mild or severe adverse events (RIS: 10.7 or 9.3) were regarded as less relevant. Patients preferred tablets, followed by subcutaneous injections, and disliked surgery with primary closure. Preferences differed significantly dependent on age and affected body regions. CONCLUSIONS: Awareness of patient preferences is essential for patient-centered care in HS.

Low Pneumococcal Vaccination among Patients with Psoriasis in Germany: Results from Vac-Pso.

While suboptimal pneumococcal vaccination rates have been reported in immunosuppressed patients with rheumatic diseases, data for patients with psoriasis (PsO) or atopic dermatitis (AD) are scarce. Pneumococcal vaccination in Germany is recommended in patients with certain comorbidities, immunosuppression, and/or aged 60 years or above. The aim of this multicenter cross-sectional study was to investigate the pneumococcal vaccination rate in patients with PsO compared to patients with AD and to evaluate patient perceptions. All patients completed a questionnaire on vaccination status and perceptions, patient and disease characteristics, as well as comorbidity. Medical records and vaccination certificates were reviewed. Over the whole cohort (n = 327 PsO (41.9% female), n = 98 AD (42.9% female)), 83.8% and 42.9% of PsO and AD patients, respectively, had an indication for pneumococcal vaccination due to immunosuppressive treatment. The pneumococcal vaccination rate was 14.4% and 10.2% in PsO and AD patients, respectively. The vaccination rate depended significantly on age, working status and presence of psoriatic arthritis. The most common reason for nonvaccination was lacking recommendation by physicians. Higher awareness, particularly for vaccination indication due to immunosuppression among dermatologists, general physicians, and patients, is warranted.

Melanocytic nevi in sentinel lymph nodes: association with cutaneous nevi and clinical relevance in patients with cutaneous melanomas.

PURPOSE: Melanocytic nevi in lymph nodes (NNs) are an important histological differential diagnosis of initial sentinel lymph node (SN) metastasis in melanoma. Our aim was to associate NN in SNs with clinicopathologic features and survival rates in 1, 250 patients with SN biopsy for melanoma. METHODS: To compare patients with present and absent NN, we used Fisher's exact test, Mann-Whitney U test, and multivariate logistic regression models in this retrospective observational study based on a prospectively maintained institutional database. RESULTS: NN prevalence in axillary, cervical, and groin SNs was 16.5%, 19.4%, and 9.8%, respectively. NN were observed in combination with all growth patterns of melanoma, but more frequently when the primary was histologically associated with a cutaneous nevus. We observed a decreasing NN prevalence with increasing SN metastasis diameter. Multiple logistic regression determined a significantly increased NN probability for SNs of the neck or axilla, for individuals with ≥ 50 cutaneous nevi, midline primary melanomas, and for individuals who reported non-cutaneous malignancies in their parents. Cancer in parents was also significantly more frequently reported by melanoma patients who had more than 50 cutaneous nevi. In SN-negative patients, NN indicated a tendency for slightly lower melanoma-specific survival. CONCLUSIONS: We found a highly significant association between NN diagnosis and multiple cutaneous nevi and provided circumstantial evidence that cutaneous nevi in the drainage area of lymph nodes are particularly important. The trend toward lower melanoma-specific survival in SN-negative patients with NN suggests that careful differentiation of SN metastases is important.

Response of eosinophilic fasciitis associated with Waldenström macroglobulinemia to rituximab.

Eosinophilic fasciitis (EF) and generalized morphea (GM) are rare and difficult-to-treat sclerosing skin diseases which may occur in association with hematologic disorders. We present a 66-year-old man with EF and associated Waldenström macroglobulinemia who received combination therapy with rituximab (375mg/m2 every other week, gradually extended to every eight weeks), prednisolone (1.25-30mg/d), and methotrexate (7.5-15mg/w). Three months after rituximab initiation, his skin condition improved steadily accompanied by a significant improvement in joint mobility with only mild and transitory flares (observation period: 59 months under treatment with rituximab). To date, there are five case reports on rituximab treatment of EF/GM with an association to hypergammaglobulinemia in three of those cases. Therapy effected significant improvement in four patients. Our case adds to the hitherto limited evidence that rituximab may be a promising therapeutic strategy for EF/GM in association with hypergammaglobulinemia.