Cumulative incidence and risk factors for cutaneous squamous cell carcinoma metastases in organ transplant recipients: The Skin Care in Organ Transplant Patients in Europe-International Transplant Skin Cancer Collaborative metastases study, a prospective multicenter study.

INTRODUCTION: Solid organ transplant recipients (SOTRs) are believed to have an increased risk of metastatic cutaneous squamous cell carcinoma (cSCC), but reliable data are lacking regarding the precise incidence and associated risk factors. METHODS: In a prospective cohort study, including 19 specialist dermatology outpatient clinics in 15 countries, patient and tumor characteristics were collected using standardized questionnaires when SOTRs presented with a new cSCC. After a minimum of 2 years of follow-up, relevant data for all SOTRs were collected. Cumulative incidence of metastases was calculated by the Aalen-Johansen estimator. Fine and Gray models were used to assess multiple risk factors for metastases. RESULTS: Of 514 SOTRs who presented with 623 primary cSCCs, metastases developed in 37 with a 2-year patient-based cumulative incidence of 6.2%. Risk factors for metastases included location in the head and neck area, local recurrence, size > 2 cm, clinical ulceration, poor differentiation grade, perineural invasion, and deep invasion. A high-stage tumor that is also ulcerated showed the highest risk of metastasis, with a 2-year cumulative incidence of 46.2% (31.9%-68.4%). CONCLUSIONS: SOTRs have a high risk of cSCC metastases and well-established clinical and histologic risk factors have been confirmed. High-stage, ulcerated cSCCs have the highest risk of metastasis.

Exploring the Association Between Isotretinoin and Sexual Dysfunction: A Comprehensive Scoping Review.

BACKGROUND: The potential link between isotretinoin and sexual dysfunction has been reported in various studies. However, such an association has not been explored within the context of a literature review until now. OBJECTIVES: To evaluate the methodology and quality of studies investigating this association, and to examine the definitions of sexual dysfunction used. METHODS: A scoping review approach was used to identify peer-reviewed research articles. The search terms used were: "isotretinoin", "sexual dysfunction", "erectile dysfunction", "ejaculatory disorders" "decreased libido", "female sexual interest", "female arousal disorder", "libido", "pelvic pain", "dyspareunia", "orgasmic disorder", "impotence", "ovaries", "fertility" and "menstrual irregularity". RESULTS: 54 peer-reviewed manuscripts consisting of 8 animal studies and 46 human studies consisting of 2,420 patients were included. Of the studies in humans, there were 18 case reports/case series, 2 case-controls, 4 cross-sectional studies, 6 longitudinal studies, 3 pharmacovigilance reports and 13 cohort studies. The most frequently observed dose range of isotretinoin was 0.5-1.0mg/kg/day usually for a duration of 1-6 months. More than half of the studies (54%, n=25) reported a beneficial or neutral effect of isotretinoin on sexual function. The majority of studies (89%, n = 41) were categorized as Oxford evidenced-based-medicine level 4. CONCLUSIONS: This scoping review revealed very weak evidence supporting a link between isotretinoin and sexual dysfunction. Notably, the diverse definitions of sexual dysfunction pose a significant challenge for comparative analysis. The authors advocate for a standardized definition of sexual dysfunction and a framework for determining causality in order to contribute to a more comprehensive understanding of the relationship between isotretinoin and sexual dysfunction.

Combining treat-to-target principles and shared decision-making: International expert consensus-based recommendations with a novel concept for minimal disease activity criteria in atopic dermatitis.

BACKGROUND: Current treat-to-target recommendations for atopic dermatitis (AD) may not include high enough treatment targets and do not fully consider patient needs. OBJECTIVE: To develop recommendations for optimized AD management, including disease severity assessments, treatment goals and targets, and guidance for treatment escalation/modification. METHODS: An international group of expert dermatologists drafted a series of recommendations for AD management using insights from a global patient study and 87 expert dermatologists from 44 countries. Experts voted on recommendations using a modified eDelphi voting process. RESULTS: The Aiming High in Eczema/Atopic Dermatitis (AHEAD) recommendations establish a novel approach to AD management, incorporating shared decision-making and a concept for minimal disease activity (MDA). Consensus (≥70% agreement) was reached for all recommendations in 1 round of voting; strong consensus (≥90% agreement) was reached for 30/34 recommendations. In the AHEAD approach, patients select their most troublesome AD feature(s); the clinician chooses a corresponding patient-reported severity measure and objective severity measure. Treatment targets are chosen from a list of 'moderate' and 'optimal' targets, with achievement of 'optimal' targets defined as MDA. CONCLUSIONS: Patient and expert insights led to the development of AHEAD recommendations, which establish a novel approach to AD management. Patients were not involved in the eDelphi voting process used to generate consensus on each recommendation. However, patient perspectives were captured in a global, qualitative patient research study that was considered by the experts in their initial drafting of the recommendations.

Cross-sectional burden-of-illness study in atopic dermatitis (MEASURE-AD) in Australia and New Zealand reveals impacts on well-being.

OBJECTIVES: To describe disease burden in individuals with moderate-to-severe atopic dermatitis (AD) in Australia and New Zealand (ANZ) and compare it with other geographic regions. METHODS: This multicentre, cross-sectional, observational study (MEASURE-AD) recruited consecutive adolescent and adult patients attending dermatology clinics in 28 countries. Data collected included scores of pruritus, disease severity, sleep, pain, disease control, work and quality of life. RESULTS: This study included 112 ANZ participants (Australia n = 72; New Zealand n = 40) from December 2019 to December 2020. Treatments included topicals (85.7% of patients), non-biologic systemic therapy (28.6%), phototherapy (9.8%) and dupilumab (4.5%). Mean Eczema Area and Severity Index (EASI) score was 22.3 (95% CI 19.6-25.0) and Patient-Oriented Eczema Measurement (POEM) score was 18.4 (95% CI 16.8-20.0). Pruritus Numerical Rating Scale (NRS) was 6.0 (95% CI 5.5-6.6) (50% had severe pruritus) and Dermatology Life Quality Index (DLQI) 14.3 (95% CI 12.8-15.8). ADerm-Impact sleep domain score was 15.1 (95% CI 13.2-16.9). ADerm-Symptom Scale worst skin pain domain score was 5.0 (95% CI 4.3-5.6). Work Productivity and Activity Impairment (WPAI) percentages indicated work and productivity impairment. Inadequately controlled AD was self-reported by 41%, with 9.7 flares in the past 6 months. Scores of pruritus, disease severity, sleep, pain, disease control and quality of life in ANZ were often the highest of all the geographic regions studied. CONCLUSION: ANZ patients with AD have a high disease burden, which extends across multiple facets of daily life. Many are inadequately controlled with existing therapies.

Bullous pemphigoid: Its incidence, mortality and clinical outcome in New Zealand.

BACKGROUND/OBJECTIVES: Bullous pemphigoid (BP) is an uncommon autoimmune bullous disorder, with significant morbidity and mortality. Mortality may be as high as 23.5% in the first year after diagnosis. Clear epidemiologic data across Australasia are lacking. METHODS: A retrospective, multi-centred cohort study was designed to determine the incidence and mortality of bullous pemphigoid in New Zealand. Data from all histopathologically diagnosed patients with bullous pemphigoid between 2009 and 2015 from the Auckland region were obtained. Demographics, clinical characteristics and outcome 3 years from diagnosis (until 31 December 2018) were collected. Demographic data were compared against a denominator year-matched New Zealand Census population. RESULTS: One hundred sixty-one patients had confirmed bullous pemphigoid, with an incidence rate of 3.03/100 000 person-years [95% CI 2.58-3.54]; 70% were of European ethnicity; 12.4% were Pacific peoples; 11.2% were Asian; and 6.8% were Maori. 45.3% had associated cognitive impairment and/or stroke. In the 3-year follow-up, 25% had treatment complications mostly from prednisone therapy. The mortality rate was 40%, highest in the first year of diagnosis, with age at diagnosis a predictor. CONCLUSION: The incidence and mortality rates are comparable to the UK/Northern Europe. Knowledge of the epidemiology of bullous pemphigoid in New Zealand and within an international settling informs the provision of future care and treatments.

Virtual lesion clinic - Evaluation of a teledermatology triage system for referrals for suspected melanoma.

INTRODUCTION: The Virtual Lesion Clinic (VLC) of Waitemata District Health Board (WDHB) improves melanoma assessment and treatment using teledermatology. The VLC is reserved for pigmented lesions referred as suspected melanoma from primary care but indeterminate at the initial triage. OBJECTIVES: To assess the efficacy of the VLC diagnosis of melanoma. METHODS: A retrospective audit of suspected melanoma referrals (1 January 2012 to 31 December 2016) was conducted. Lesions were referred to the VLC if diagnostic uncertainty remained at the initial triage. VLC patients attended MoleMap imaging centres, a dermatologist reviewed history and images remotely and suggested a diagnosis and management plan. Post VLC provisional diagnosis of melanoma, all lesions subsequently excised were reviewed. A positive predictive value (PPV) was calculated using concordance between VLC diagnosis of melanoma and histopathological diagnosis of melanoma. Number needed to excise (NNE) for melanoma was derived, as well as an invasive to in-situ melanoma ratio (IM:MIS) and false negative rate (FNR). RESULTS: The VLC received 1874 referrals for 3546 lesions during the 5-year study period. Six hundred and seventy-nine lesions were recommended excision/biopsy or specialist face-to-face assessment, and 504 lesions were subsequently excised. The PPV was 62%, NNE 1.62 and IM:MIS 0.76 for lesions suspected to be melanoma at VLC assessment. The VLC had a melanoma-specific FNR of 7%. CONCLUSIONS: The VLC is effective in early diagnosis of melanoma with a high positive predictive value, low number needed to excise and low false negative rate amongst lesions referred as suspected melanoma.

Discoid (nummular) eczema in the paediatric setting - An Australian/New Zealand narrative.

Discoid (nummular) eczema is a common and distinctive eczema variant, which has not been studied in depth. Although the principles of management are similar to that of classic atopic dermatitis, distinctions are made due to its unique presentation and persistent clinical course in children. Australian and New Zealand dermatologists with an interest in paediatric eczema developed a consensus narrative to assist clinicians in diagnosing and treating this subtype of eczema. Identifying triggers, potent topical corticosteroids under occlusion, skin barrier support and management of pruritus are first-line therapies, however, many eventually require systemic immunomodulatory agents.

Biological Therapy Interruption and Re-Treatment in Chronic Plaque Psoriasis.

While biological treatments for chronic plaque psoriasis should be administered continuously to maximize and maintain efficacy, interruptions in therapy may be necessary for a number of reasons. We reviewed the evidence from clinical trials on efficacy, safety and immunogenicity in clinical trials for approved biologic agents for chronic plaque psoriasis. A systematic search of three major medical databases was performed and a total of 35 articles were included into the analysis, including 13 controlled trials. Trials assessing continuous therapy against dosing as-needed therapy (including infliximab, etanercept and secukinumab) have demonstrated superior efficacy for continuous regimes. However, randomized withdrawal trials for etanercept, adalimumab, ixekizumab, brodalumab, guselkumab, risankizumab and tildrakizumab, showed no significant impact on skin clearance rates in patients who are interrupted once and then re-treated. With the possible exception of infliximab, temporary interruption in biologic therapy appears to be safe and most agents will regain efficacy after re-introduction. J Drugs Dermatol. 2021;20(10):1063-1071. doi:10.36849/JDD.5716.

SARS-CoV-2 (COVID-19) vaccination in dermatology patients on immunomodulatory and biologic agents: Recommendations from the Australasian Medical Dermatology Group.

As the phase III COVID-19 vaccine trials excluded patients on immunosuppressive treatments, or patients with significant autoimmunity, the Australasian Medical Dermatology Group make the following preliminary recommendations around COVID-19 vaccination in dermatology patients on immunomodulatory and/or biologic agents. Vaccination against COVID-19 is strongly encouraged for all patients on immunomodulatory drugs and/or biologic agents. There are currently insufficient data to recommend one COVID-19 vaccine or vaccine type (mRNA, recombinant, inactivated virus) over another. No specific additional risk in patients on immunomodulatory or biologic therapies has so far been identified. Data on vaccine efficacy in patients on immunomodulatory or biologic therapies are missing, so standard vaccination protocols are recommended until otherwise advised.

Guidance on infection control and plume management with Laser and Energy-Based Devices taking into consideration COVID-19.

BACKGROUND: The COVID-19 pandemic has disrupted the practice of medicine. Dermatologic laser and energy-based device (EBD) treatments carry a potential risk for the transmission of SARS-CoV-2 both for the patient and the practitioner. These risks include close practitioner to patient proximity, the treatment of higher viral load areas such as the face, the potential for infective bioparticles being carried by generated plumes and aerosols, and the direct contact between device, practitioner and patient. OBJECTIVES: SARS-CoV-2 is a highly infective respiratory pathogen transmitted by respiratory droplets, respiratory/mucosal secretions, medically generated aerosols and via its transfer from contaminated fomites. This requires a review of the appropriateness of infection control protocols in regard to dermatologic laser and energy-based device treatments. METHODS: A critical evaluation of patient skin preparation including skin asepsis, device disinfection, laser and electrosurgical plume management and PPE in regard to SARS-CoV-2 was performed. RESULTS: The adherence to a high standard of skin preparation and asepsis, device disinfection, laser and electrosurgical plume and aerosol management and appropriate PPE should help mitigate or reduce some of the inherent treatment risks. Head and neck treatments along with aerosol and laser plume generating treatments likely carry greater risk. CONCLUSIONS: COVID-19 needs to be considered in the clinic set-up along with the planning, treatment and post-treatment care of patients utilising EBD procedures. Some of these treatment precautions are COVID-19 specific; however, most represent adherence to good infectious disease and established laser and EBD safety precautions.

A baseline patch test series for New Zealand.

BACKGROUND: Patch testing is the gold standard diagnostic test for allergic contact dermatitis and needs to be relevant to the region and the population being tested. The aim of this study was to develop a specific New Zealand baseline series (NZBS). METHOD: We performed a retrospective case note review of patients attending four regional patch test centres between 2008 and 2020. Demographic and diagnostic information was collected for each patient along with results of patch testing. Using the results of this review, a group of 11 dermatologists with an interest in contact dermatitis agreed on a core group of allergens for inclusion in an NZBS, based on the frequency of positive reactions and allergens of interest. The remaining potential allergens were ranked by each dermatologist using an online questionnaire, with inclusion in the final NZBS by consensus. RESULTS: Results from 2402 patients (67% female, mean age 44 years) from Auckland, Wellington, Palmerston North and Christchurch were collated. The 10 most frequent positive (relevant and non-relevant) allergens were nickel sulfate (22.0%), fragrance mix I (8.6%), cobalt chloride (7.3%), Myroxylon pereirae (5.6%), colophonium (5.1%), p-phenylenediamine (4.9%), methylisothiazolinone/methylchloroisothiazolinone (4.1%), fragrance mix II (3.9%), potassium dichromate (3.5%) and methylisothiazolinone (3.4%). Based on these results, a core series of 30 allergens was developed, with an additional 30 allergens added to form the extended series (total 60 allergens). CONCLUSION: The baseline series of patch test allergens for routine use in New Zealand (NZBS) is based on national patch test data and expert consensus.

Management of chronic hand and foot eczema. An Australia/New Zealand Clinical narrative.

Chronic hand/foot eczemas are common, but treatment is often challenging, with widespread dissatisfaction over current available options. Detailed history is important, particularly with regard to potential exposure to irritants and allergens. Patch testing should be regarded as a standard investigation. Individual treatment outcomes and targets, including systemic therapy, should be discussed early with patients, restoring function being the primary goal, with clearing the skin a secondary outcome. Each new treatment, where appropriate, should be considered additive or overlapping to any previous therapy. Management extends beyond mere pharmacological or physical treatment, and requires an encompassing approach including removal or avoidance of causative factors, behavioural changes and social support. To date, there is little evidence to guide sequences or combinations of therapies. Moderately symptomatic patients (e.g. DLQI ≥ 10) should be started on a potent/super-potent topical corticosteroid applied once or twice per day for 4 weeks, with tapering to twice weekly application. If response is inadequate, consider phototherapy, and then a 12-week trial of a retinoid (alitretinoin or acitretin). Second line systemic treatments include methotrexate, ciclosporin and azathioprine. For patients presenting with severe symptomatic disease (DLQI ≥ 15), consider predniso(lo)ne 0.5-1.0 mg/kg/day (or ciclosporin 3 - 5 mg/kg/day) for 4-6 weeks with tapering, and then treating as for moderate disease as above. In non-responders, botulinum toxin and/or iontophoresis, if associated with hyperhidrosis, may sometimes help. Some patients only respond to long-term systemic corticosteroids. The data on sequencing of newer agents, such as dupilumab or JAK inhibitors, are immature.

COVID-19 and the use of immunomodulatory and biologic agents for severe cutaneous disease: An Australian/New Zealand consensus statement.

Patients on immunomodulators, including biologic agents and new small molecular inhibitors, for cutaneous disease, represent a potentially vulnerable population during the COVID-19 pandemic. There is currently insufficient evidence to determine whether patients on systemic immunomodulators are at increased risk of developing COVID-19 disease or more likely to have severe disease. As such, clinicians need to assess the benefit-to-risk ratio on a case-by-case basis. In patients with suspected or confirmed COVID-19 disease, all immunomodulators used for skin diseases should be immediately withheld, with the possible exception of systemic corticosteroid therapy, which needs to be weaned. In patients who develop symptoms or signs of an upper respiratory tract infection, but COVID-19 is not yet confirmed, consider dose reduction or temporarily cessation for 1-2 weeks. In otherwise well patients, immunomodulators and biologics should be continued. In all patients, and their immediate close contacts, the importance of preventative measures to minimise human-to-human transmission cannot be overemphasised.

E-referrals and teledermatoscopy grading for melanoma: a successful model of care.

BACKGROUND/OBJECTIVES: An e-referral system was developed at a tertiary care hospital in Auckland, New Zealand in 2014 for suspected cutaneous malignancy. E-referrals include patient information, a description of the lesion(s), biopsy results and/or attached photograph(s). Experienced surgical oncologists prioritised the referrals and selected a management option or referred them for a teledermatoscopy opinion. Our aim was to review the efficacy of e-referrals for improving diagnostic accuracy for melanoma. METHODS: Referrals received in 2016 including images and categorisation as confirmed, likely or suspected melanoma by the triage specialist were evaluated. Concordance of the pathological diagnosis with the triage diagnosis and teledermatoscopy diagnosis was determined for each referral. RESULTS: 809 of 3470 e-referrals for skin cancer were categorised as confirmed, likely or suspected melanoma. 230 (28.4%) of these included a referral histopathology confirming melanoma/melanoma in situ. Of the remaining 579 referrals, 315 were sent for urgent diagnostic excision and 264 were referred for teledermatoscopy. 120 of the 315 sent for urgent excision were confirmed as melanoma (53) or melanoma in situ (67) on histopathology: a positive predictive value (PPV) of 38.1% and number needed to excise (NNE) of 2.6. Less than 10% of referrals triaged for teledermatoscopy were confirmed as melanoma (24/264). Almost half of all referrals (374/809, 45.6%) included melanoma/melanoma in situ. The melanoma: melanoma in situ ratio was 1: 1.18. CONCLUSIONS: The e-referral and teledermatoscopy service for suspected melanoma has proven fewer unnecessary excisions of benign lesions than previously reported.

Managing atopic dermatitis with systemic therapies in adults and adolescents: An Australian/New Zealand narrative.

With the rapid development of new, targeted therapies for the treatment of moderate/severe atopic dermatitis, it is opportune to review the available conventional systemic agents. We assess the published evidence for systemic therapies for atopic dermatitis and amalgamate this with real-world experience. Discussions are centred on when systemic therapy should be considered, which drug(s), what dose, how to sequence or combine these therapies, how long they should be continued for and what is considered success.

In situ and invasive melanoma in a high-risk, New Zealand, population: A population-based study.

BACKGROUND: Few population-based studies assess both invasive and in situ melanoma. We document all patients with a first biopsied melanoma in a general population in New Zealand (NZ). METHODS: All residents in a defined area of New Zealand with a biopsy showing a new primary invasive or in situ melanoma from 2010 to 2012 were identified, 974 patients; analysis used multivariate methods. RESULTS: Age-standardised incidence rates were 34.3 in females (F) and 41.4 in males (M) for invasive, 20.9 F and 27.6 M for in situ, and 55.2 F and 69.0 M for total melanoma. More in situ melanoma occurred in older patients and on the head and neck. Geometric mean Breslow thickness for invasive was 0.78 mm F and 0.85 mm M, with thicker lesions at ages over 60 and on the lower limb; there was no significant relationship with sex, distance from care or social deprivation assessed from residential address. Nodular melanomas (15%) were more frequent in older and male patients, and on the limbs, and were thicker. The estimated cumulative risk for melanoma is 4.4% F and 4.6% M by age 70. The body site distribution and sex differences were consistent with sun exposure patterns. Estimated incidence of melanoma in New Zealand in 2018 is 2500 invasive and 1700 in situ cases. CONCLUSIONS: Assessing both in situ and invasive melanoma expands the clinical picture, better estimating health care demand and costs. Results suggest that in situ disease is a more slowly growing lesion than the early phase of invasive disease. The features of thicker or nodular melanoma show priorities for prevention and early detection.

Psoriasis and cancer. An Australian/New Zealand narrative.

Patients with psoriasis have an increased risk of cancer, which may be due to impaired immune surveillance, immune modulatory treatments, chronic inflammation and/or co-risk factors such as obesity. The increase in treatment-independent solid cancers, including urinary/bladder cancers, oropharynx/larynx, liver/gallbladder and colon/rectal cancers, seem to be linked to alcohol and smoking. Lung cancer and nonmelanoma skin cancer are also increased in patients with psoriasis. The risk of nonmelanoma skin cancer increases with age and severity of psoriasis. It is also higher in men, particularly for squamous cell carcinoma, which may reflect previous exposure to PUVA and/or ciclosporin. The risk of cutaneous T-cell lymphoma is substantially higher in patients with moderate-to-severe psoriasis. Biologic therapies are independently associated with a slight increase risk of cancer, but this is less than ciclosporin, with the risk confounded by disease severity and other co-risk factors. The risk of cancer from low-dose methotrexate is likely minimal. In contrast, acitretin is likely protective against a variety of solid and haematological malignancies. The data on small molecule therapies such as apremilast are too immature for comment, although no signal has yet been identified. The decision whether to stop psoriasis immune modulatory treatments following a diagnosis of cancer, and when to resume, needs to be considered in the context of the patients' specific cancer. However, there is no absolute need to stop any treatment other than possibly ciclosporin, unless there is a concern over an increased risk of serious infection or drug-drug interaction with cancer-directed therapies, including radiotherapy.

Psoriasis and infection. A clinical practice narrative.

The Australasian Psoriasis Collaboration has developed a clinical practice narrative with respect to the relationship between psoriasis, its treatment and infection. The cutaneous microbiome of patients with psoriasis is different to those without psoriasis, although the significance of this is unclear. Whilst a wide range of microorganisms has been associated with psoriasis (including ß-haemolytic streptococci, Staphylococcus aureus, Porphyromonas gingivalis, Candida albicans, Chlamydia psittaci, human immunodeficiency virus and hepatitis C virus), there is limited evidence that antimicrobial therapy is of direct benefit in preventing flares of psoriasis. Psoriasis is independently associated with an increased risk of serious infection, but the absolute risk is low. The risk of serious infections is further increased with immune-modulatory treatments. The decision whether to, and when to, stop or resume immune-modulatory treatment after a serious infection has occurred depends on risk assessment for that patient, taking into account the infection being treated, the risk of recurrent infection, any interventions that can modify the risk and the need for psoriasis control. Live vaccines (e.g. MMR, varicella, zoster and yellow fever) are generally contraindicated in patients with psoriasis on immune-modulatory agents, but this depends on the degree of immune suppression and individual risk factors. Wound healing in psoriasis is normal. Treatment with infliximab, adalimumab, etanercept, methotrexate and ciclosporin can safely be continued through low-risk surgical procedures. For moderate- and high-risk surgeries, a case-by-case approach should be taken based on the patient's individual risk factors and comorbidities.