An Emerging Role of Interferon Targeted Therapy in Mucocutaneous Sle: A Prospective Real-World Evaluation of Anifrolumab for Refractory Cutaneous Lupus

Background/Aims Advances in rational drug design and recent clinical trials are leading to emergence of a range of novel therapies for SLE and therapeutic options in clinical practice are expected to broaden rapidly. The optimal real-world place of emerging and established agents will be guided by understanding their differential efficacy on specific SLE manifestations as well as efficacy for more resistant disease. Anifrolumab, a type-I interferon receptor blocking monoclonal antibody, showed efficacy in SLE in phase III trials with a notable effect on mucocutaneous disease although specific lesion subtypes and chroncicity were not explored. Severe refractory mucocutaneous SLE such as scarring discoid lesions are an important and common clinical challenge in current practice. We therefore prospectively evaluated the real-world efficacy and quality of life impact of anifolumab for active mucocutaneous SLE, recalcitrant to multiple biologic and immunosuppressant therapies. Methods Seven patients commenced anifrolumab (300mg by monthly iv infusion) following application to the manufacturer's early access programme (NCT 04750057). Prior biologic therapies were discontinued at least 5 half-lives in advance. Mucocutaneous disease activity was captured by Cutaneous Lupus Disease Area and Severity Index (CLASI) activity score and medical photography. Patient reported health-related quality of life comprising the Dermatology Life Quality Index (DLQI);Lupus-QoL and EQ5D-5L were evaluated at baseline, three and six months. Results Seven female patients with active mucocutaneous SLE (Discoid LE n=5, chilblain LE n=1, subacute cutaneous LE n=1) and median disease duration of 17 years were evaluated. Median baseline CLASI activity score was 17 (range 10-26;higher scores indicating severe disease). Median number of previously failed therapies was 7 and included rituximab in 6/7, belimumab in 2/7 and thalidomide in 4/7. Rapid resolution of scale and erythema in DLE was established within 1 month of anifrolumab treatment. Improvements to chilblain lupus were evident by three months. CLASI activity score was improved >=75% in all patients at 3 months. Clinical responses were associated with significant improvements in DLQI (p<0.001) and EQ5D-VAS (p=0.002) by three months. Lupus-QoL trended toward improvement across all domains but most strongly for fatigue (p=0.01) and pain (p=0.002) by 6 months. One patient discontinued treatment after 4 months due to polydermatomal shingles complicated by sensorineural hearing loss. Infection coincided with background prednisolone dose >15mg daily, recent COVID-19 infection and new on-treatment hypogammaglobulinaemia (IgG <5g/L). Prolonged aciclovir treatment was required for lesion resolution. Conclusion We report rapid real-world efficacy and quality of life impact of anifrolumab on highly refractory mucocutaneous SLE, which exceeded that anticipated from existing clinical trial data. Findings suggest a unique role for emerging interferon targeting therapies in management of mucocutaneous SLE but emphasize need for enhanced VZV precautions among higher risk patients.

Mental health of patients with psoriasis during the COVID-19 pandemic: a cross-sectional study in a tertiary setting

Patients with psoriasis are at increased risk of depression. Furthermore, psoriasis is linked to social isolation, stress-related disorders and suicidality. The COVID-19 pandemic and social distancing represent potential stressors for patients, which may disproportionately affect the wellbeing of this vulnerable population. Our aim was to investigate whether the pandemic increased the affective burden of patients with psoriasis. We surveyed 194 patients with dermatologist-confirmed psoriasis attending our tertiary service. Ninety-three patients had completed questionnaires [Hospital Anxiety and Depression Scale (HADS);Quick Inventory of Depressive Symptomatology Self- Report (QIDS-SR);Sheehan Suicidality Tracking Scale;Dermatology Life Quality Index (DLQI)] before March 2020 in a pre-existing study. From May to October 2020, we recruited a different patient sample (n = 101) who completed the same questionnaires. We analysed separately data from 22 patients, who completed the survey both before and during the pandemic. Cases of depression and anxiety were defined as having a HADS subscale score of >= 8. Analysis was performed in R. Ninety-three patients completed the survey before the pandemic [49 5% female;mean (SD) age 42 (18) years] and 101 during the pandemic [38% female;mean (SD) age 52 (16) years;74% shielding]. Patient proportions across treatment groups did not differ before vs. during the pandemic (73 1% vs. 78 2% on biologics;P = 0 8). Depression, anxiety and suicidality were highly prevalent at both timepoints. However, there were no significant differences in depression [31% vs. 40%;adjusted odds ratio (aOR) 1 2, 95% confidence interval (CI) 0 6-2 5], anxiety (39% vs. 47 5%;aOR 1 7, 95% CI 0 8-3 5) or suicidal ideation prevalence (13% vs. 20%;aOR 2 19, 95% CI 0 8-5 9] before vs during the pandemic. During the pandemic, depression was not associated with living alone (P = 0 45) or shielding (P = 0 13). In the paired analysis, depression scores did not differ during compared with before the pandemic (QIDS-SR 9 4 x 5 8 vs. 8 8 x 6 1;P = 0 56). DLQI changes did not correlate with changes in QIDS-SR (r = 0 08, P = 0 7). At follow-up, three patients (14%) reported 12-month passive suicidal ideation;no patient reported 12- month active suicidality. Depression and the prevalence of anxiety are high in patients with psoriasis. Suicidal ideation rates appear to be higher than the rates in the general population during the COVID-19 pandemic. However, we did not observe a significant increase in the psychological burden or shielding of our patients during the pandemic compared with previous levels. Our findings are consistent with recent research on psoriasis-related quality of life during the COVID- 19 pandemic and may reflect population-specific resilience mechanisms. They also highlight the importance of continued monitoring of psychiatric comorbidity in this population, independently of acute stressors. Future research should address the long-term pandemic impact on patients.

The use of an online teledermatology platform with patient-submitted history and images for waiting list recovery in dermatology

While teledermatology has been a feature of some dermatology services for some time, the COVID-19 pandemic has led to both a deterioration in waiting lists for routine patients, and the use of distance consultation as a means of providing and improving access for such patients. The majority of teledermatology platforms rely on general practitioner (GP)-submitted information and images, and most data suggest that these systems result in around 50% of patients avoiding hospital attendance through the implementation of management plans suggested by hospital-based consultants (Mehrtens SH, Shall L, Halpern SM. A 14 year review of a UK teledermatology service: experience of over 40,000 teleconsultations. Clin Exp Dermatol 2019;44: 874-81). We now report the use of an online platform (Virtual LucyTM) using patient-provided information via a structured questionnaire, and patient images uploaded following clear online guidance, reinforced by call centre interaction. The data are derived from funded National Health Service (NHS) work: there was no specific funding for its generation. In total, 3500 patients from two hospital trusts with routine waiting list pressures were invited to use the system as an alternative to eventual hospital attendance. After secure registration, they completed dermatology and general health questionnaires based on conventional medical history taking, as well as a Dermatology Life Quality Index and then uploaded one or more images as appropriate. The patient data were reviewed by a consultant and a self-populated report provided to the patient, GP and trust within 72 h. Forty-eight per cent of patients were discharged to their GP with reassurance or a management plan. Patients requiring hospital attendance were signposted to appropriate clinics (e.g. isotretinoin, phototherapy, patch testing) or to surgical clinics for biopsy or excision. Hospital trust-based consultants were able to access the platform to view images prior to any surgery. Of patients directed to hospital clinics, 32% were reclassified as being urgent - waiting list duration was the main determinant of the need for reclassification. Of all images, 0.5% were unsatisfactory, and those patients were contacted through the platform to ask for a replacement image with specific advice. One per cent of patients were contacted by clinical staff by telephone or video to clarify or expand on the information given, and approximately 1% of patients used the platform to ask for additional treatment details. There were no patient complaints, and GP and hospital staff issues related to logistics were increasingly uncommon as iterative development of the system and support processes occurred. Teledermatology using patient-derived information and images gives similar outcomes to those seen in published conventional teledermatology, puts fewer demands on clinical staff, is popular with patients and has a significant benefit to the NHS.

Patient questionnaire-based triage improves outcomes for psoriasis referrals

COVID-19 has placed additional demands on a healthcare system that is already overstrained. While the National Health Service has coped extremely well in the face of new pressures, much of the pressure has transferred to a growing backlog of non-COVID outpatient care. Waiting lists have become unwieldy and new dermatology waiting times can be in excess of 18 months. We have developed a novel system to enable our tertiary referral dermatology department to triage rapidly and manage new patients with psoriasis, returning to target levels of activity, with minimum impact on patient care. Newly referred patients with psoriasis were sent a questionnaire, including the Dermatology Life Quality Index (DLQI), to direct their management appropriately. Patients were asked to estimate their affected body surface area using the palm measurements and affected body sites. Patients were also asked which treatment types they would be prepared to accept if offered (phototherapy, systemic therapy), as well as the type of clinic they would find acceptable. The latter included faceto- face only, telephone/video consultation or using a secure skin mobile phone app (MySkinSelfie), whereby photos are securely uploaded for viewing by the doctor but are still controlled by the patient. Of 265 patients, 222 responded (average response time 7 days). In total, 217 were offered an appointment. Thirty-one per cent were seen acutely (2 weeks) and the remainder in routine clinics. Two patients no longer wanted an appointment. An algorithm was used to place patients in appropriate clinics according to their responses. Patients who did not respond to the questionnaire within 4 weeks were sent a reminder letter and then discharged if there was still no reply (17%). Median DLQI was 15, with 63% of patients happy to have a telephone/video consultation, 72% were open to phototherapy, 80% were happy to use the MySkinSelfie App and 34% requested faceto- face appointments only. During the COVID-19 pandemic many dermatology units have had to limit the focus of their work on skin cancer, leaving little time for all but the most urgent patients with inflammatory disease. A previous systematic review and meta-analysis (Singh S, Taylor C, Kornmehl H, Armstrong AW. Psoriasis and suicidality: a systematic review and meta-analysis. J Am Acad Dermatol 2017;77: 425-40) of 1.7 million patients with psoriasis confirmed an increased risk of suicidal ideation [odds ratio (OR) 2.05] and suicidal behaviour (OR 1.26;Singh et al.), highlighting the importance of managing these patients in a timely manner. General practitioner letters can lack sufficient information on disease severity/ urgency, but our simple model allows the department to streamline referrals quickly, ensures that the patient still wants to be seen and minimizes unnecessary hospital visits. We propose that this approach is considered by other dermatology departments to streamline outpatient waiting lists and accelerate a return to normal activity during the pandemic.

Real-world response to dupilumab in patients with atopic dermatitis: a retrospective review of 100 patients

Dupilumab is a monoclonal antibody approved by the National Institute for Health and Care Excellence for the treatment of moderate-to-severe atopic dermatitis (AD) in 2018. It is indicated for patients who have not responded to at least one systemic medication or in whom these are contraindicated or not tolerated. Response criteria to allow continued treatment include at least a 50% reduction of Eczema Area and Severity Score (EASI) and/or at least a 4-point reduction in the Dermatology Life Quality Index (DLQI) score. Phase III clinical trials of dupilumab in AD reported a 75% reduction in EASI (EASI 75) of 51% in SOLO1 and 44% in SOLO2. Real clinic responses may differ from trials so we performed a retrospective review of 100 patients between June and August 2020 who had received dupilumab (44% female, 56% male;mean age 41 years). Fifty-eight per cent had a recorded diagnosis of asthma and 39% had a recorded diagnosis of allergic rhinitis. Seventy-six per cent of patients had received previous phototherapy. Ninety-seven per cent of patients received at least one systemic medication prior to commencing dupilumab. Thirty per cent (n = 29) received one, 33% (n = 32) received two, 33% (n = 32) received three and 4% (n = 4) received four prior to starting dupilumab. The most common were methotrexate (61%), followed by ciclosporin (22%) azathioprine (16%) and alitretinoin (1%). EASI scores were documented at baseline. The target time for EASI response assessment was 16 weeks, but we included outcome data recorded between 8 and 16 weeks, using the score nearest to 16 weeks where multiple scores were available. Seventy-five patients had response data recorded, 18 had stopped dupilumab and seven had missing data. Outcomes were 50% reduction in EASI [EASI 50;84% (n = 62)], EASI 75 [61% (n = 45)] and a 90% reduction in EASI [EASI 90;35% (n = 26)]. Mean (SE) EASI score pretreatment was 22 2 (1 2);at 16 weeks it was 5 8 (0 9). Sixty-five per cent of patients had a documented DLQI score at 8 and/or 16 weeks. Mean (SE) DLQI scores were 17 5 (0 7) predupilumab, 5 5 (1 1) at 8 weeks and 3 7 (0 8) at 16 weeks. Mean reduction was 13 8 (1 0). Eighty-six per cent (n = 56) had a reduction of four or more. Fifty-nine per cent of patients had Patient-Oriented Eczema Measure scores recorded. Mean (SE) values were 22 5 (0 5) predupilumab, 6 2 (1 2) at 8 weeks and 7 1 (1 1) at 16 weeks. Mean reduction was 15 4 (1 0). Compared with prospective clinical trials, real-world data have the limitations of missing data and slight scoring date variations, including the impact of the COVID-19 pandemic on missed appointments. Sixteen-week outcome data are not available for patients who withdrew from treatment. However, for the 75 patients with outcome data the proportion achieving EASI 75 and a 4-point reduction in DLQI is encouraging and similar to data from phase III trials.

Sensitivity to treatment and score bands of the Infants and Toddlers Dermatology Quality of Life questionnaire.

Background: The Infants and Toddlers Dermatology Quality of Life (InToDermQoL) questionnaire is the first dermatology-specific proxy health related QoL instrument for children from birth to 4 years. Score meaning bands and the sensitivity to successful therapeutic intervention are important to interpret the clinical meaning of an instrument. Objective: The aim of the present study was to check the sensitivity to successful therapeutic intervention and establish score bands of the InToDermQoL questionnaire. Methods: Parents or grandparents of 424 children with skin diseases from Spain, Malta, Croatia, Romania, Greece, and Ukraine filled in national language versions of the InToDermQoL questionnaire. Disease severity of children with atopic dermatitis was assessed by SCORAD (Scoring atopic dermatitis). Cohen's d was used to assess the responsiveness of the instrument. Results: The mean total InToDermQoL scores significantly decreased after treatment. Severity grading of the SCORAD scores gave stratification of the InToDermQoL severity grades based on 95% confidence intervals. Scores below a calculated minimal important difference of 2 corresponded to no effect on patient's health related QoL. Limitations: Score banding may be slightly different across patient population and study context. Conclusion: All 3 age-specific versions of the InToDermQoL questionnaire showed sensitivity to treatment. Score bands for the InToDermQoL questionnaire have been established.

Features of the post-COVID course of psoriasis

Background. Psoriasis is one of the most common dermatoses. The adverse impact of COVID-19 on psoriasis course is now increasingly be-ing reported. Objective. To study clinical and epidemiological features of psoriasis course after COVID-19. Material and methods. We reviewed outpatient records and case histories of 159 psoriasis patients (84 males and 75 females) who recov-ered from COVID-19. Results. The mean age of the patients was 49.9+/-1.9 years. The majority (55.3%) of patients were aged 50 to 60 years or older. The mean duration of illness was 4.74+/-0.69 years. The most common comorbidities were diabetes mellitus and obesity. Psoriasis vulgaris was diagnosed in 56% of patients, and different types of pustular psoriasis accounted for 4.4%. Psoriasis guttata was detected in 9 (5.7%) patients, arthropath-ic psoriasis in 13 (8.2%), exudative psoriasis in 15 (9.4%), psoriatic erythroderma in 14 (8.8%), and psoriatic onychodystrophy in 26 (16.3%) patients. The disease was mild in 12 (7.5%) patients, moderate in 55 (34.6%), and severe in 92 (57.9%) patients. The dermatological quality of life index was 26.6+/-3.2 points. Conclusion. Diabetes mellitus and obesity were the most common comorbidities. A significant part of the patients had pustular psoriasis, psoriasis guttata, and psoriatic erythroderma. In the post-COVID period, a moderate to severe course of psoriasis was observed in 78% of cas-es. A high DLQI value indicated an adverse impact of COVID-19 and psoriasis on patients' quality of life. The features of the psoriasis course in the post-COVID period should be considered when prescribing therapy and medical rehabilitation measures. Copyright © 2022, Media Sphera Publishing Group. All rights reserved.

SkinTracker: A novel smartphone app enabling remote clinical research in dermatology

A highly visual practice, dermatology as a field has significant potential to use emerging technology such as mobile applications for research and patient-centered mapping of the disease process. The UCSF team is working to create SkinTracker, a mobile application for patients with skin disease to remotely participate in clinical trials and research studies. The initial iteration of the application focuses on atopic dermatitis. The application includes an enrollment and consent module, validated surveys including the Patient Oriented Eczema Measure (POEM), Dermatology Life Quality Index (DLQI), Numerical Rating Scale (NRS) for itch, link to a wearable device that collects biometric data, a voice diary, and a patient-directed photography module to facilitate physician evaluation of disease. Also included is the ability to report medication use, adverse events, and the ability to chat with the study team. The patient information is available to the research team on a secure online website, where researchers can assess patient photographs to perform Eczema Area and Severity Index (EASI) scoring, note important patient observations from the voice diary, and view quantitative data from both patient surveys and health measures like physical activity, sleep, and environmental factors. We believe this application and website will facilitate patient interest and participation in research, continue research despite in-person restrictions placed during the COVID-19 pandemic, and allow enrollment of more diverse patients for clinical studies who would otherwise be less likely to participate in research due to time or financial constraints.

Evaluation of teledermatology during a pandemic indicates high patient satisfaction, positive impact on patient-related costs and clinical effectiveness

Aim: Telehealth is becoming an increasingly important way of delivering health services accelerated by the COVID-19 pandemic. The aim of the study is to evaluate teledermatology by assessing patient satisfaction, patientrelated costs and clinical effectiveness. Method: This was a single-centre cross-sectional study. A three-part questionnaire-Dermatology life quality index (DLQI), patient satisfaction questionnaire (PSQ) and cost evaluation questionnaire-was sent out to all teledermatology patients attending the Royal Melbourne Hospital. The Spearman rank-order correlation coefficient was used to measure the association between the DLQI and PSQ. We evaluated the clinical effectiveness in psoriasis patients on biologic therapy as a sub-cohort by comparing PASI and DLQI pre and post implementation of teledermatology, using Wilcoxon signed-rank test. Results: 191/747 patients responded (51% male, 73% living in metropolitan victoria). The mean DLQI was 5.2 +/- 6.25. PSQ was divided into four categories (Positive attitude, hotel, photo anxiety and interaction). There is a negative correlation between DLQI and PSQ, with all categories showing significant correlation except the 'positive attitude' category. Analysis of the cost evaluation questionnaire showed that a majority of patients reported that telehealth appointments save time (99%), reduce time off work (41%) and help avoid costs of transport (96%). When assessing patients with psoriasis on biologic therapy, there was no significant difference in PASI scores before (mean of 1.59) and after (mean of 1.44) implementation of teledermatology (p-value 0.542). There was a significant reduction in DLQI in 59 psoriasis patients on biologic therapy, as an indicator of clinical effectiveness. The mean DLQI before implementation of teledermatology was 2.73 and after implementation was 1.69 (p-value 0.0126). Conclusions: Overall this study indicates high patient satisfaction, positive impact on patient-related costs and good clinical effectiveness of teledermatology which warrant further evaluation in larger prospective studies.

Evaluation of clinical efficacy of synthetic tannin and polidocanol-based agents and modern emollients in the hand eczema treatment. Use of new hand antiseptics during the pandemic in patients with hand eczema

Background. Patients with hand eczema account for 30–40% of dermatological patients. With the pandemic of new coronavirus infection COVID-19 and the need for frequent antiseptics use, there has been a steady increase in hand eczema incidence. The dominant symptoms in exacerbating eczema are skin inflammation and itching, which requires effective and safe skincare that is effective and safe. Objective. To evaluate the efficacy of the therapy with synthetic tannin and polidocanol-based agents and modern emollients, the time of resolution and degree of severity of clinical symptoms of eczema in patients, as well as the time and duration of remission, safety and compliance with sodium hypochlorite hand antiseptic spray. Materials and methods. Thirty-four patients with exacerbation of hand eczema were examined. The study was conducted in two stages. At the stage 1, before the remission, the patients received synthetic tannin and polidocanol-based agents and modern emollients;at the stage 2, monotherapy with modern emollients was used. Patients used sodium hypochlorite spray as a hand sanitizer throughout the study period. Results. The NESCI score became zero in 33 (96%) patients after the complex treatment of hand eczema. The Dermatology Life Quality Index by the end of stage 2 decreased 6-fold compared to the beginning of the study. No exacerbation of the dermatosis was observed in any of the patients included in the study during the use of sodium hypochlorite hand spray. Conclusion. The complex therapy with synthetic tannin, polidocanol-based agents, and modern emollients in hand eczema helps to achieve stable medical remission, decreases the itching intensity, and improves the patients’ quality of life. The use of new hand sanitizers during the pandemic in patients with hand eczema did not result in dermatosis exacerbations.

Combination of breathing exercises, cold exposure, and meditation mitigate psoriasis – open label, randomized, controlled trial

Psoriasis is a skin disease of an unknown origin. Current understanding of its pathophysiology focuses on an undefined imbalance between the immune system and the nervous system. In this study we assessed the effects of a training program which was proven to affect both. A group of psoriatic patients volunteered, and were randomized to either the intervention (n = 19), or control group (n = 19). Subjects in the intervention group were trained for 10 weeks in breathing techniques, exposure to cold and meditation. The control group was not trained. After two weeks of the intervention, a full lockdown due to the COVID-19 pandemics was introduced. Modified protocol included exercises possible to conduct at home only. Two study visits (before and after the intervention) took place. Based on an analysis of blood and saliva samples, skin condition, and questionnaire answers, a flare up of psoriasis occurred among members of the control group. It was confirmed by an increase in hsCRP concentration, and decrease of seral interleukin-10 levels. 55% of those subjects declared intensification of the topical treatment. In the intervention group, a slight improvement was observed. Psoriasis Area Severity Index decreased, as well as interleukin 17 levels in saliva. Dermatology Life Quality Index improved fourfold. 68% of the subjects declared reduction of the topical treatment. Sleep quality, depressive symptoms and mindfulness improved as well. In conclusion, we demonstrate that this specific training program can potentially be an easy, safe to apply add-on therapy for psoriasis and its comorbidities.

Evaluation of skin problems and dermatology life quality index in health care workers who use personal protection measures during COVID-19 pandemic.

The aim of this study was to evaluate the skin problems and dermatological life quality of the health care workers (HCWs) due to personal protection equipment (PPE) use, who are at high risk for COVID-19 infection. A questionnaire about HCWs' PPE use, their skin symptoms, and prevention, management methods and Dermatology Life Quality Index (DLQI) was fulfilled. The median age of 440 participants was 33.5 (21.0-65.0) years old. Skin problems were found to be 90.2%, the most common were dryness, itching, cracking, burning, flaking, peeling and lichenification. The presence of skin problems (P < .001) was higher in those who did not use moisturizers. Of all, 22.3% (n = 98) stated that the use of PPE increased the severity of their previously diagnosed skin diseases and allergies (P < .01). Only 28.0% (n = 123) stated that they know the skin symptoms that may develop by using PPE. The proper hand washing rate was higher as education level increased (P < .001). Skin problems were higher in those using mask with metal nose bridge (P: .02 and P: .003, respectively). As the mask using period prolonged, acne was more common (P: .02). DLQI was significantly affected in women (P = .003), and with increased skin problems related to PPE (P < .001). It is important to organize trainings on prevention and management of possible skin symptoms due to PPE use according to guidelines.