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.

Autologous Non-Cultured Epidermal Cellular Grafting in the Surgical Treatment of Stable Vitiligo: The Skin Hospital Protocol.

Autologous non-cultured epidermal cellular grafting is the treatment of choice for patients with stable refractory vitiligo. Recently, studies have shown cost-effective alternatives for this procedure, superseding previous techniques that required large research facilities or expensive pre-packaged kits. We provide modifications to current techniques, including the use of individual Petri dishes to allow for processing larger skin grafts, hyfrecation instead of conventional manual dermabrasion of the recipient site to reduce scar formation as well as better margin delineation, and an intravenous giving set with a filter for improved filtration of the mixed cell population. These modifications facilitated sufficient skin repigmentation in a cost-effective outpatient setting.

Australian experience and practical approach to the 308-nm excimer light therapy in dermatology.

The monochromatic excimer light therapy (308-nm excimer laser and lamp) is used to treat focal dermatoses with inflammation or hypopigmentation. In Australia, despite excimer light therapy being a proven effective treatment for many cutaneous conditions, barriers such as access and affordability provide considerable limitations to patients. This study aims to retrospectively evaluate the different applications of excimer light therapy in treating dermatologic conditions within the Australian setting and provide practical information for its use.

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.

The efficacy and safety of tacrolimus as mono- and adjunctive therapy for vitiligo: A systematic review of randomised clinical trials.

There is currently no definitive treatment for vitiligo; various modalities include immune modulators phototherapy and skin camouflage. We investigated the efficacy and safety of topical tacrolimus either as monotherapy or combined therapy in the treatment of vitiligo. Electronic systematic search of the literature was carried out using four major databases. Randomised clinical trials (RCTs) that reported the use of topical tacrolimus in the treatment of human vitiligo have been included in a systematic review and meta-analysis. Meta-analysis was conducted via RevMan, and risk of bias was assessed through the Cochrane quality assessment tool. The protocol was published through PROSPERO (CRD42018112430). A total of 19 studies including 814 patients were included in our systematic review. The random-effects-model meta-analysis of two studies revealed that the tacrolimus and narrowband ultraviolet B (NB-UVB) combination therapy rates is better than NB-UVB alone in inducing >75% repigmentation [RR 1.34 (95% CI: 01.05-1.71), P = 0.02]. Tacrolimus and steroids had similar potency in acheiving >75% repigmentation [RR 1.02 (95% CI: 0.19-5.51), P = 0.98]. Meta-analysis of two studies revealed that the fractional laser and tacrolimus combination therapy is no better than tacrolimus alone in causing >75% repigmentation [RR 2.11 (95% CI: 0.87-5.09), P = 0.10]. Further investigating tacrolimus as mono- or adjuvant therapy for vitiligo is highly recommended. Combining tacrolimus to other treatment options such as steroids, phototherapy and laser may be superior to using tacrolimus alone.

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.

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.

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 in those planning a family, pregnant or breast-feeding. The Australasian Psoriasis Collaboration.

The Australasian Psoriasis Collaboration has reviewed the evidence for managing moderate to severe psoriasis in those who are pregnant or are breast-feeding, or planning a family. The severity of the psoriasis, associated comorbidities and specific anti-psoriasis treatment, along with other exposures, can have a deleterious effect on pregnancy outcomes. Psoriasis itself increases the risk of preterm and low birthweight babies, along with spontaneous and induced abortions, but no specific birth defects have been otherwise demonstrated. The baseline risk for a live born baby to have a major birth defect is 3%, and significant neuro-developmental problem is 5%. In Australia, pregnant women with psoriasis are more likely to be overweight or obese, depressed, or smoke in their first trimester, and are also less likely to take prenatal vitamins or supplements. Preconception counselling to improve maternal, pregnancy and baby health is therefore strongly encouraged. The topical and systemic therapies commonly used in psoriasis are each discussed separately, with regards to pregnancy exposure, breast-feeding and effects on male fertility and mutagenicity. The systemic therapies included are acitretin, adalimumab, apremilast, certolizumab, ciclosporin, etanercept, infliximab, ixekizumab, methotrexate, NBUVB, prednisone, PUVA, secukinumab and ustekinumab. The topical therapies include dithranol (anthralin), calcipotriol, coal tar, corticosteroids (weak, potent and super-potent), moisturisers, salicylic acid, tacrolimus, and tazarotene. As a general recommendation, effective drugs that have been widely used for years are preferable to newer alternatives with less foetal safety data. It is equally important to evaluate the risks of not treating, as severe untreated disease may negatively impact both mother and the foetus.

The Australasian Psoriasis Collaboration view on methotrexate for psoriasis in the Australasian setting.

The Australasian Psoriasis Collaboration reviewed methotrexate (MTX) in the management of psoriasis in the Australian and New Zealand setting. The following comments are based on expert opinion and a literature review. Low-dose MTX (< 0.4 mg/kg per week) has a slow onset of action and has moderate to good efficacy, together with an acceptable safety profile. The mechanism of action is anti-inflammatory, rather than immunosuppressive. For pretreatment, consider testing full blood count (FBC), liver and renal function, non-fasting lipids, hepatitis serology, HbA1c and glucose. Body mass index and abdominal circumference should also be measured. Optional investigations in at-risk groups include an HIV test, a QuantiFERON-TB Gold test and a chest X-ray. In patients without complications, repeat the FBC at 2-4 weeks, then every 3-6 months and the liver/renal function test at 3 months and then every 6 months. There is little evidence that a MTX test dose is of value. Low-dose MTX rarely causes clinically significant hepatotoxicity in psoriasis. Most treatment-emergent liver toxicity is related to underlying metabolic syndrome and non-alcoholic fatty liver disease or non-alcoholic steatohepatitis. Alcohol itself is not contraindicated, but should be limited to < 20 gm/day. [Correction added on 6 January 2017, after first online publication: '20 mg/day' has been corrected to '20 gm/day'.] Although MTX is a potential teratogen post-conception, there is little evidence for this pre-conception. MTX does not affect the quality of sperm. There is no evidence that MTX reduces healing, so there is no specific need to stop MTX peri-surgery. MTX may be used in combination with cyclosporine, acitretin, prednisone and anti-tumour necrosis factor biologics.

Pruritus in the elderly - a guide to assessment and management.

BACKGROUND: Pruritus is the most common skin complaint in patients over the age of 65 years. These patients are in a unique population group that will require a comprehensive clinical approach. The symptoms of pruritus can be potentially debilitating and can have a significant impact on elderly patients by impairing their quality of life. OBJECTIVE: This article discusses the assessment and management of pruritus, with a specific focus on the elderly population. DISCUSSION: Pruritus in the elderly population remains both a diagnostic and therapeutic challenge. In the first instance, it has to be established whether the pruritus is arising from a primary dermatological condition or whether it is a manifestation of an underlying systemic disease. When a rash is present it could suggest an underlying primary dermatosis. Apart from lifestyle modifications, emollients, topical antipruritics (eg menthol 1% in aqueous cream), oral antihistamines, topical corticosteroids and phototherapy may prove useful.