Australian consensus: Treatment goals for moderate to severe psoriasis in the era of targeted therapies - Considerations for paediatric patients.

BACKGROUND: Treatment goals have been established in Australia to facilitate the management of adults with moderate to severe psoriasis. The Australasian College of Dermatologists sought to determine if and how these adult treatment goals could be modified to accommodate the needs of paediatric and adolescent patients. METHODS: A modified Delphi approach was used. Comprehensive literature review and guideline evaluation resulted in the development of statements and other questions to establish current clinical practices. Two rounds of anonymous voting were undertaken, with a collaborative meeting held in between to discuss areas of discordance. Overall, consensus was defined as achievement of ≥75% agreement in the range 7-9 on a 9-point scale (1 strongly disagree; 9 strongly agree). RESULTS: Consensus was achieved on 23/29 statements in round 1 and 17/18 statements in round 2. There was a high level of concordance with treatment criteria in the adult setting. The limitations of applying assessment tools developed for use in adult patients to the paediatric setting were highlighted. Treatment targets in the paediatric setting should include objective metrics for disease severity and psychological impact on the patients and their family, and be based on validated, age-appropriate tools. CONCLUSION: While the assessment, classification and management of moderate to severe psoriasis in paediatric patients aligns with metrics established for adults, it is vital that nuances in the transition from childhood to adolescence be taken into account. Future research should focus on psoriasis severity assessment scales specific to the paediatric setting.

Making Sense of Late Tissue Nodules Associated With Hyaluronic Acid Injections.

BACKGROUND: The pathogenesis of delayed-onset tissue nodules (DTNs) due to hyaluronic acid (HA) injections is uncertain. OBJECTIVES: To formulate a rational theory for DTN development and their avoidance and treatment. METHODS: A multidisciplinary and multicountry DTN consensus panel was established, with 20 questions posed and consensus sought. Consensus was set at 75% agreement. RESULTS: Consensus was reached in 16 of 20 questions regarding the pathogenesis of DTNs, forming the basis for a classification and treatment guide. CONCLUSIONS: The group believes that filler, pathogens, and inflammation are all involved in DTNs and that DTNs most likely are infection initiated with a variable immune response. Injected filler may incorporate surface bacteria, either a commensal or a true pathogen, if the skin barrier is altered. The initially high molecular weight HA filler is degraded to low molecular weight HA (LMWHA) at the edge of the filler. Commensals positioned within the filler bolus may be well tolerated until the filler is degraded and the commensal becomes visible to the immune system. LMWHA is particularly inflammatory in the presence of any local bacteria. Commensals may still be tolerated unless the immune system is generally heightened by viremia or vaccination. Systemic pathogenic bacteremia may also interact with the filler peripheral LMWHA, activating Toll-like receptors that induce DTN formation. Given this scenario, attention to practitioner and patient hygiene and early systemic infection treatment deserve attention. Classification and treatment systems were devised by considering each of the 3 factors-filler, inflammation, and infection-separately.

Factors associated with treatment satisfaction in patients with hidradenitis suppurativa: results from the Global VOICE project.

BACKGROUND: Nearly half of patients with hidradenitis suppurativa (HS) report dissatisfaction with their treatment. However, factors related to treatment satisfaction have not been explored. OBJECTIVES: To measure associations between treatment satisfaction and clinical and treatment-related characteristics among patients with HS. METHODS: Treatment satisfaction was evaluated utilizing data from a cross-sectional global survey of patients with HS recruited from 27 institutions, mainly HS referral centres, in 14 different countries from October 2017 to July 2018. The primary outcome was patients' self-reported overall satisfaction with their current treatments for HS, rated on a five-point scale from 'very dissatisfied' to 'very satisfied'. RESULTS: The final analysis cohort comprised 1418 patients with HS, most of whom were European (55%, 780 of 1418) or North American (38%, 542 of 1418), and female (85%, 1210 of 1418). Overall, 45% (640 of 1418) of participants were either dissatisfied or very dissatisfied with their current medical treatment. In adjusted analysis, patients primarily treated by a dermatologist for HS had 1·99 [95% confidence interval (CI) 1·62-2·44, P < 0·001] times the odds of being satisfied with current treatment than participants not primarily treated by a dermatologist. Treatment with biologics was associated with higher satisfaction [odds ratio (OR) 2·36, 95% CI 1·74-3·19, P < 0·001] relative to treatment with nonbiologic systemic medications. Factors associated with lower treatment satisfaction included smoking (OR 0·78, 95% CI 0·62-0·99; active vs. never), depression (OR 0·69, 95% CI 0·54-0·87), increasing number of comorbidities (OR 0·88 per comorbidity, 95% CI 0·81-0·96) and increasing flare frequency. CONCLUSIONS: There are several factors that appear to positively influence satisfaction with treatment among patients with HS, including treatment by a dermatologist and treatment with a biologic medication. Factors that appear to lower treatment satisfaction include active smoking, depression, accumulation of comorbid conditions and increasing flare frequency. Awareness of these factors may support partnered decision making with the goal of improving treatment outcomes. What is already known about this topic? Nearly half of patients with hidradenitis suppurativa report dissatisfaction with their treatments. What does this study add? Satisfaction with treatment is increased by receiving care from a dermatologist and treatment with biologics. Satisfaction with treatment is decreased by tobacco smoking, accumulation of comorbid conditions including depression, and higher flare frequency. What are the clinical implications of this work? Awareness of the identified factors associated with poor treatment satisfaction may support partnered decision making and improve treatment outcomes.

Comparative effectiveness of biologics in clinical practice: week 12 primary outcomes from an international observational psoriasis study of health outcomes (PSoHO).

BACKGROUND: Clinical trials study treatment outcomes under stringent conditions, capturing incompletely the heterogeneity of patient populations and treatment complexities encountered in real-world practice. OBJECTIVES: To compare the effectiveness of anti-interleukin (IL)-17A biologics relative to other approved biologics in patients with moderate-to-severe psoriasis. METHODS: The Psoriasis Study of Health Outcomes (PSoHO) is an ongoing 3-year observational cohort study in adults with chronic moderate-to-severe plaque psoriasis initiating or switching to a new biologic. Primary study endpoint is the proportion of patients achieving 90% improvement in Psoriasis Area and Severity Index (PASI 90) and/or static Physician Global Assessment (sPGA) 0/1 at Week 12 (W12) in the anti-IL-17A cohort (ixekizumab [IXE], secukinumab) vs. all other approved biologics. Secondary outcomes include the proportion of patients who achieve PASI 75/90/100, absolute PASI scores ≤5, ≤2 and ≤1, Dermatology Life Quality Index (DLQI) score of 0/1 at W12 between the two cohorts and among the individual biologics. Comparative effectiveness analyses were conducted using Frequentist Model Averaging (FMA), a novel causal inference machine learning approach. Missing data for binary outcomes were imputed as non-response. RESULTS: Patient profiles in the anti-IL-17A cohort and other biologics cohort were similar, with more frequent comorbid psoriatic arthritis and less frequent exposure to conventional treatments in the patients receiving anti-IL-17A biologics. At W12, 71.4% of patients who received an anti-IL-17A biologic achieved PASI 90 and/or sPGA 0/1 compared to 58.6% of patients who received other biologics (odds ratios [OR], 1.9; 95% confidence intervals [CI], [1.6, 2.4]). Similar findings were observed for secondary outcomes. CONCLUSIONS: These results reflect the high efficacy and early onset of skin clearance of IL-17A inhibitors observed in randomized clinical trials and confirm the effectiveness of anti-IL-17A biologics in the real-world setting.

Cannabinoids interaction with transient receptor potential family and implications in the treatment of rosacea.

With the recent interest in medical marijuana, research into cannabinoids is regaining wider attention. Cannabinoids are collectively a group of active compounds that can be produced by animals (endocannabinoids), plants (phytocannabinoids), or synthetically. By acting on a number of different receptors like cannabinoids receptors and transient receptor potential ion channel family, cannabinoids are known to modulate cutaneous inflammation, pain, and itch. Rosacea is a highly prevalent disease and can be associated with a significant degree of morbidity associated with its symptom. Transient receptor potential ion channels are known to be triggered in rosacea and may underlie a portion of rosacea's pathophysiology. This article aims to detail the transient receptor potential channel pathways in rosacea and the known effects of cannabinoids on these pathways and further discussing the potential role of cannabinoids in treating rosacea.

Perils & pearls of purchasing sun protection over the internet: A google project.

BACKGROUND/PURPOSE: Sunscreen use has been shown to reduce the incidence of skin cancers. Internet purchasing allows access to internationally sourced sunscreens, despite varying accepted active ingredients and regulations around the world. AIMS/OBJECTIVES: To determine the compliance of international sunscreen products advertised on the internet with the current Australian sunscreen standard (AS/NZS 2604:2012). MATERIALS AND METHODS: Six sunscreen-related search queries were executed on Google between January-November 2018. Qualitative analysis of the search results to determine compliance with the current Australian sunscreen standard (AS/NZS 2604:2012) was performed by collecting descriptive data, including listed active ingredients of each advertised product. These were compared against the AS/NZS 2604:2012 list of permitted active ingredients. The compliance status of each product, and reasons for non-compliance were annotated. A multiple regression contingency table test was performed to determine whether compliance was associated with the products' country of origin, and a post hoc analysis was performed to identify countries with significant differences in discrepancy in compliance rate. RESULTS: Execution of the sunscreen-related search queries on Google generated 1350 results. Only 613 of the 1291 (47.5%) included products were compliant with the AS/NZS 2604:2012 permitted sunscreen active ingredients. 552 of 1291 products were non-compliant due to insufficient information advertised. Australia, India and South Korea had significantly lower than expected compliance rates. CONCLUSIONS: Online marketing of sunscreen products from other countries has a significantly lower than expected compliance rate with the AS/NZS 2604:2012 permitted sunscreen active ingredients, with many lacking the disclosure of the active ingredients. Advertising regulations for online suppliers need to be tightened to ensure that online consumers purchasing sunscreen products can make informed decisions, as the international E-commerce market rapidly expands.

'Dimensions and tensions?': embracing the complexity of 'working in a rural area' through qualitative research interpreting perspectives of dermatologists and dermatology trainees.

INTRODUCTION: Challenges to addressing workforce maldistribution for equitable rural healthcare access continue, including for dermatology services. The conceptual complexity of the notion of 'rural' adds to the challenges, with the term 'rural' reflecting socially constructed meanings. In relation to healthcare workforce strategies, socially constructed meanings of 'rural' indicate preferences for quantifiable framings and tendencies towards deficit-based portrayals. While quantifiable framings provide impetus for implementing and evaluating important rural healthcare workforce strategies, their tendency towards deficit-based portrayals risks overlooking positives of rural healthcare practice and stereotyping rural areas as problematic environments for health care. The importance of balancing deficit-based portrayals of 'rural' with more positive orientations is recognised as important for addressing the maldistribution of the healthcare workforce. Adding further to the complexity of addressing workforce maldistribution is the range of strategies required. Encompassed in these strategies are socially constructed approaches and conflicting interests. The notion of 'tensions' has potential for making sense of, and addressing, the complexity of these competing interests. Importantly, not all 'tensions' need to be resolved. By identifying, embracing and holding 'tensions' rather than necessarily resolving them, space for ongoing rich discussion can be deliberately created. METHODS: This qualitative research used a wide-angle, strength-based lens to explore the topic of working in a rural area, from the perspectives of dermatologists and dermatology trainees. The wide-angle lens allowed consideration of the multiplicity of approaches. The strength-based lens allowed the research to go beyond deficit-based portrayals and embrace 'tensions' inherent in the complexities of addressing workforce maldistribution. This study, undertaken in the interpretive research paradigm, was informed by philosophical hermeneutics. The research question was, 'How can working in a rural area be conceptualised from the perspectives of dermatologists and dermatology trainees?'. Data collected through semi-structured interviews with 17 participants providing dermatology services in rural areas (11 dermatologists and 6 dermatology trainees) were iteratively interpreted. Data were initially coded descriptively, with iterations moving towards more conceptual themes. RESULTS: A conceptual model of dimensions and tensions of working in a rural area, from the perspective of dermatologists and dermatology trainees, is presented to illustrate the interpreted key themes, subthemes and implications. The four key themes are dimensions of working in a rural area: choosing to work in a rural area, transitioning out of a metropolitan area, embedding into the rural community and working within the complexity of 'rural'. As illustrated in the model, subthemes are characteristics capturing inherent diversity within each dimension, and the implications are 'tensions'. Issues for ongoing discussion arising from these 'tensions' include metropolitan as a gravitational force to be overcome; complexities of individual choice, including implications for absence of choice; importance of community as people at the core of the strategies; and the taken-for-granted language for 'rural' inadvertently reinforcing deficit-based portrayals. A set of reflective questions related to these issues is provided. CONCLUSION: The reflective questions posed can be discussed, grappled with and considered when developing strategies that address workforce maldistribution and when exploring different experiences within the complex social construction of 'rural'.

Evaluating patients' unmet needs in hidradenitis suppurativa: Results from the Global Survey Of Impact and Healthcare Needs (VOICE) Project.

BACKGROUND: A needs assessment for patients with hidradenitis suppurativa (HS) will support advancements in multidisciplinary care, treatment, research, advocacy, and philanthropy. OBJECTIVE: To evaluate unmet needs from the perspective of HS patients. METHODS: Prospective multinational survey of patients between October 2017 and July 2018. RESULTS: Before receiving a formal HS diagnosis, 63.7% (n = 827) of patients visited a physician ≥5 times. Mean delay in diagnosis was 10.2 ± 8.9 years. Patients experienced flare daily, weekly, or monthly in 23.0%, 29.8%, and 31.1%, respectively. Most (61.4% [n = 798]) rated recent HS-related pain as moderate or higher, and 4.5% described recent pain to be the worst possible. Access to dermatology was rated as difficult by 37.0% (n = 481). Patients reported visiting the emergency department and hospital ≥5 times for symptoms in 18.3% and 12.5%, respectively. An extreme impact on life was reported by 43.3% (n = 563), and 14.5% were disabled due to disease. Patients reported a high frequency of comorbidities, most commonly mood disorders. Patients were dissatisfied with medical or procedural treatments in 45.9% and 34.6%, respectively. LIMITATIONS: Data were self-reported. Patients with more severe disease may have been selected. CONCLUSION: HS patients have identified several critical unmet needs that will require stakeholder collaboration to meaningfully address.

Benign intracranial hypertension in a patient treated with ustekinumab for psoriasis.

Ustekinumab is a monoclonal antibody, which binds the p40 subunit of IL-12 and IL-23 so they are unable to bind to their receptors, ultimately reducing T-cell-mediated inflammation in psoriasis. Studies and cases have focused on the risk of infection and malignancy associated with the use of biologics medications; however, there have been limited data available on the potential neurological adverse effects of biologics. We report the case of a 44-year-old female with a longstanding history of psoriasis who developed benign intracranial hypertension while on ustekinumab for her psoriasis.

Dipeptidyl peptidase-4 inhibitors and bullous pemphigoid: A systematic review and adjusted meta-analysis.

BACKGROUND/OBJECTIVE: There have been a number of case reports and small clinical series reporting the potential association between dipeptidyl peptidase-4 inhibitors (DPPIs) for diabetes and the onset of bullous pemphigoid (BP). The aim of this study was to assess the association between DPPI use and BP, and whether this varied according to DPPI type. METHODS: We performed a systematic review and meta-analysis according to PRISMA guidelines. We identified five studies with cases and controls. We performed unadjusted and adjusted meta-analyses to assess the potential association. RESULTS: Adjusted meta-analysis revealed significant association between DPPI use and BP (OR 2.13, 95% CI 1.59-2.86, I2  = 46%, P < 0.00001). This association was stronger between vildagliptin and BP (OR 5.08, 95% CI 1.70-15.19, P = 0.004) compared to linagliptin (OR 2.87, 95%CI 1.06-7.79, P = 0.04), and no association was found between sitagliptin and BP (OR 1.29, 95%CI 0.79-2.08, P = 0.31). Subgroup analysis demonstrated that the association between DPPI use and BP remained significant in males (OR 2.35, 95% CI 1.46-3.78, P = 0.0005) and females (OR 1.88, 95%CI 1.10-3.22, P = 0.02). CONCLUSIONS: Limitations were that studies reviewed were retrospective by design which are susceptible to bias and lack of randomisation. Our adjusted analysis supports a significant association between DPPI use and onset of bullous pemphigoid. Vildagliptin had the highest odds of BP. These findings have clinical implications for dermatologists and the management of patients with diabetes and being treated with DPPI agents.

Synoptic reporting in Mohs micrographic surgery.

There is currently no standardised reporting format for Mohs surgery with its operation reports mostly written in a narrative form making them prone to unintentional errors and omission of necessary data. Synoptic histology reporting is used to describe excised skin cancers such as melanomas and, more recently, squamous cell and basal cell carcinomas. Since Mohs surgery is utilised as the gold standard treatment for locally invasive squamous and basal cell carcinomas, we propose the use of our model of synoptic reporting to ensure the completeness and consistency of Mohs surgery operation reports.

Hidradenitis suppurativa and polycystic ovarian syndrome: Systematic review and meta-analysis.

BACKGROUND/OBJECTIVES: Hidradenitis suppurativa has been associated with a number of pathologies, including various endocrine and autoimmune disorders. Although signs of hyperandrogenism are common in hidradenitis suppurativa, few formal studies have assessed the relationship between hidradenitis suppurativa and polycystic ovarian syndrome. Therefore, we performed a systematic review and meta-analysis to assess the association between hidradenitis suppurativa and polycystic ovarian syndrome. METHODS: We performed a systematic review and meta-analysis according to PRISMA guidelines. Odds ratio was used as the effect size, with random-effects meta-analysis. RESULTS: We identified five case-control studies for inclusion. From pooled data, we found a significantly higher proportion of polycystic ovarian syndrome in hidradenitis suppurativa cases compared with controls (OR 2.64; 95% CI 1.69-4.11; P < 0.00001). There was significant heterogeneity noted (I2  = 88%, P < 0.00001). Limitations included that studies reviewed were observational by design which are susceptible to bias, and lack of randomisation. CONCLUSIONS: In summary, pooled analysis of existing case-control studies supports a significant association between hidradenitis suppurativa and polycystic ovarian syndrome. Our results imply that hidradenitis suppurativa patients with signs of hyperandrogenism may benefit from screening for polycystic ovarian syndrome, and may potentially benefit from anti-androgen therapy.

Prevalence, incidence and management of atopic dermatitis in Australian general practice using routinely collected data from MedicineInsight.

BACKGROUND/OBJECTIVES: The prevalence of atopic dermatitis (AD) has increased significantly in industrialised countries in recent decades but data about the incidence or prevalence of AD in Australia are sparse. We aimed to determine the prevalence and incidence of AD among patients seen in Australian general practice and the use of specified medicines. METHODS: This was a cross-sectional study of 2.1 million patients attending 494 general practices in the MedicineInsight program from 1 January 2017 to 31 December 2018. We assessed the prevalence (lifetime and current), incidence, management and severity of AD. RESULTS: The lifetime (ever diagnosed) prevalence of AD in this general practice population was 16.4% and was greater in females (17.3%) than males (15.3%). One in five patients with AD were classified as having moderate-to-severe disease. Prevalence over the last two years was 6.3%. The incidence of AD in 2018 was 2.0% and was greater in females (2.2%) and for patients aged 0-4 years (3.9%). Patients with AD had an increased risk of insomnia, anxiety and depression, compared to those with no recorded AD. For AD patients, topical corticosteroids were the most commonly prescribed AD medication (36.5%) and topical calcineurin inhibitors the least (0.1%), with systemic corticosteroids (15.6%) more commonly prescribed than other immunosuppressants (0.9%). CONCLUSIONS: Our findings provide important insights into the epidemiology of AD and its management in Australian general practice. This information is likely to be useful in planning effective interventions to support GPs in the optimal management of patients with AD.

Trends in the incidence of Merkel cell carcinoma in Victoria, Australia, between 1986 and 2016.

BACKGROUND/OBJECTIVES: Merkel cell carcinoma (MCC) is a highly invasive cutaneous malignancy. The objective of this study was to investigate the incidence and trends of MCC in Victoria, Australia, between 1986 and 2016. METHODS: Population-based, descriptive analysis of Victorian Cancer Registry (VCR) data. The de-identified records of patients with MCC were obtained from Victoria residents diagnosed between 1986 and 2016. Trends in age-standardised incidences were examined using joinpoint analysis. RESULTS: A total of 1095 cases were found. Incidence of MCC was 3.9 per 100 000 for men and 1.5 per 100 000 for women. The incidence of MCC in men 66-85 is increasing at an annual rate of 4.2% (2.8-5.8%, 95% CI). However, since 2002 the incidence in women in the same age group has been decreasing. Whilst there is an overall stabilisation in the incidence of MCC, incidence of MCC for males is increasing. For MCC in males 85 years old and over, the incidence of MCC was 26.8 per 100 000 between 2012 and 2016. Relative 5-year survival for patients diagnosed between 2008 and 2012 is 50%. CONCLUSION: Merkel cell carcinoma remains an aggressive cancer, especially among older men. Differences in trends seen in local data can help target preventative and early intervention management strategies in specific groups.

Atopic dermatitis in adults: An Australian management consensus.

BACKGROUND/OBJECTIVES: Atopic dermatitis (AD) has significant negative impact on health-related quality of life, mood, sleep, work productivity and everyday activities. Research into the use of new drugs in the management of AD continues to develop, and international updates and recommendations have been published. However, questions remain in the Australian setting. This consensus aims to provide evidence-based insights and practical advice on the management of adult AD in Australia. METHODS: A panel (five dermatologists and one clinical immunologist) met to review the literature, critically examine clinical questions of relevance to Australian healthcare practitioners and develop a series of recommendation statements. A consensus panel, comprising the initial panel plus nine additional members, used a 2-round Delphi voting process to determine a set of final guidance statements. CONSENSUS: ≥75% agreement in the range 7-9. RESULTS: Round 1 voting comprised 66 guidance statements. Of these, consensus was reached on 26, which were retained, and five were removed. The remainder (35) were modified and one new guidance statement was added for inclusion in round 2 voting. After round 2, consensus was reached on 35, which were retained, and one was removed (considered redundant). The 61 guidance statements upon which consensus was reached were then used to support a series of core consensus recommendations and a management flow chart. CONCLUSIONS: Expert consensus recommendations providing practical guidance of clinical relevance to specialists and primary care physicians in Australia have been developed. Dissemination of this guidance and evaluation of its impact on patient outcomes remain to be undertaken.

Hidradenitis Suppurativa and Thyroid Disease: Systematic Review and Meta-Analysis.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disease characterized by painful nodules, sinus tracts, and significant scarring. Although the pathogenesis of this disease is not well established, there is increasing evidence to suggest that it is an immune-mediated disorder. Previous studies have suggested a relationship between HS and thyroid disease, which is also driven by an autoimmune process. We sought to assess whether an association exists between HS and thyroid disease. OBJECTIVES: To determine whether HS is associated with thyroid disease via meta-analysis of case-control studies. METHODS: A systematic review and meta-analysis was performed according to recommended PRISMA guidelines. Electronic searches were performed using 6 electronic databases from their inception until August 2018. Data were extracted and analyzed according to predefined clinical endpoints. Odds ratio (OR) was used as the summary effect size. RESULTS: We identified 5 case-controls studies included for meta-analysis. There were a total of 36 103 HS cases compared with 170 517 control cases. We found a significant association between HS and thyroid disease (OR 1.36, 95% CI 1.13-1.64, I 2 = 78%, P = .001). CONCLUSIONS: This pooled analysis of existing case-control studies to date supports an association between HS and any thyroid disease. Clinicians treating patients with HS should be aware of this potential association with thyroid disease.

Association between pemphigus and psoriasis: a systematic review and meta-analysis.

Pemphigus has been associated with other autoimmune and autoinflammatory disorders. Specifically, some case reports in the literature document coexistence of pemphigus with psoriasis, but this association is lacking larger scale investigation. With this in mind, we conducted a systematic review and meta-analysis to evaluate the association between pemphigus and psoriasis. In doing so, we found an association between the two conditions. Pemphigus was more common in patients with psoriasis than in controls (OR 2.64, 95% CI 1.24-5.59, P=0.01), with heterogeneity (I2=94%). We go on to propose pathophysiologic mechanisms and its relevance for diagnostic and management considerations.

Mycobacterium abscessus infection following penetrations through wetsuits.

Mycobacterium abscessus is a rapidly growing mycobacterium which is reportedly increasing in prevalence. Infection of the skin and soft tissue with M. abscessus is rare but typically associated with trauma. We present two cases of M. abscessus infection linked by penetration through wetsuits.