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.

Vulval lichen sclerosus: An Australasian management consensus.

BACKGROUND/OBJECTIVES: Vulval lichen sclerosus (VLS) is a chronic inflammatory skin condition predominantly affecting the anogenital region in women and children. To date, there is lack of agreement amongst experts on a severity scale to aid assessment, research and treatment stratification on VLS. Furthermore, literature on best practice for long-term management of VLS is lacking. The aim of this consensus is to provide broad guidelines on the short and long-term management of VLS. METHODS: An initial focus group of Australasian experts in vulval dermatology developed a draft consensus statement for the management of VLS. Based on the results of the draft statement, a consensus panel of 22 Australasian experts, comprised of the initial and additional members, participated in an anonymous four-stage eDelphi process. Round 1 involved generation and voting on statements from the draft consensus statement developed by the focus group. In Rounds 2, 3 & 4, panel members were presented formal feedback from previous rounds and asked to indicate their level of agreement. Consensus was reached if there was ≥70% agreement on the importance of an item in the 4 (agree) to 5 (strongly agree) range. RESULTS: The expert panel, with a total of 504 collective years of experience in the field of VLS, reached consensus on a core set of 51 management statements related to diagnosis, severity, initial and long-term management, follow-up, and complications of VLS. CONCLUSIONS: This study has identified a set of management statements for VLS that may be useful in clinical practice in the Australasian population.

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.

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.

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.

Scalp Basal Cell Carcinoma: Review of 2,202 Cases.

BACKGROUND: Increases in the incidence of basal cell carcinoma (BCC) in women, younger age groups and in aggressive scalp subtypes in younger women have been reported. OBJECTIVE: To describe lesion and patient characteristics in scalp BCC. MATERIALS AND METHODS: Retrospective audit of scalp BCCs from 3 pathology laboratories in Adelaide, South Australia, January 2009-December 2013. RESULTS: Scalp BCC was 2.6% of all BCC. Of 2,202 patients with scalp BCC, 62% were male and 78% were >60 years. Histologic subtypes included nodular (55%), mixed (30%), and superficial (8%). The concordance between biopsy and excision was 83% for division into nonaggressive and aggressive subtypes. The incomplete excision rate was 16%. Aggressive subtypes were larger and had perineural invasion (PNI) in 8.5% and incomplete excision in 26%. CONCLUSION: Basal cell carcinoma on the scalp was less common. Men and the elderly had the majority of cases, with no predilection for women, including aggressive histologic subtypes in younger women. Aggressive subtypes were associated with increased size, incomplete excision, and PNI. A preliminary biopsy assisted division into aggressive and nonaggressive histologic subtypes. Incomplete excision rates were higher and increased in aggressive histologic subtypes and PNI. Mohs surgery or wider margins are suggested in these cases.

Biological therapies for psoriasis: Adherence and outcome analysis from a clinical perspective.

We evaluated and compared patients' long-term adherence to biological therapies in a real-life clinical setting. Secondary aims included weight changes on biological therapy and reporting adverse effects. This prospective case-note review included 58 patients, undergoing 84 treatment series including etanercept (21), adalimumab (24), infliximab (14) and ustekinumab (25). Patients' adherence was greatest with ustekinumab (being 6.7-fold less likely to withdraw from treatment than etanercept, P = 0.014), while the difference in treatment adherence of adalimumab and infliximab compared to etanercept was not statistically significant. Adalimumab and infliximab were associated with an increase in weight, while ustekinumab was associated with weight loss compared with etanercept (not statistically significant). Long-term patient adherence to biologic therapy in patients with psoriasis is greatest with ustekinumab.

Methicillin-resistant Staphylococcus aureus in children with atopic dermatitis from 1999 to 2014: A longitudinal study.

BACKGROUND/OBJECTIVES: With the increase in rates of methicillin-resistant Staphylococcus aureus (MRSA) skin infections in the general population, there may be a similar increase of such infections in patients with atopic dermatitis (AD). There are few studies on MRSA prevalence in the AD population, and no previous studies in Australia. This study investigated the prevalence of MRSA and other organisms in the paediatric AD population over the previous 15 years. METHODS: Skin swab results and other significant data, including patients' characteristics and comorbidities, were collected on patients with AD aged 0-18 years, admitted to a large teaching hospital in South Australia from 1999 to 2014 (N = 298). This longitudinal, retrospective study investigated, using logistic regression, the change of prevalence of MRSA, methicillin-sensitive S. aureus (MSSA) and Streptococcus spp. in AD over the past 15 years. RESULTS: Compared with 1999-2002, in 2003-2006 patients were approximately threefold more likely (P = 0.350), in 2007-2010 they were approximately 13-fold more likely (P = 0.030) and in 2011-2014 they were approximately 24-fold more likely to test positive for MRSA (P = 0.008), despite low absolute MRSA numbers. There was a positive association between the number of previous hospital admissions per patient and MRSA (OR = 1.16 [1.08-1.25], P = 0.000). In contrast, there was no change in the prevalence of MSSA or Streptococcus spp. over time. CONCLUSION: The prevalence of MRSA in children with AD is clearly on the rise. This has negative consequences for individuals with AD and is also a major public health problem.

Durable dermatology life quality index improvements in patients on biologics associated with psoriasis areas and severity index: a longitudinal study.

BACKGROUND/OBJECTIVES: Patients with psoriasis experience higher rates of depression, anxiety and suicidal ideation than the general population. With effective treatment, there is evidence that with the initial decrease in the psoriasis area and severity index (PASI) score, patients' quality of life (QoL), measured by the dermatology life quality index (DLQI) improves. However, to date, there have been no studies demonstrating that patients' QoL remains improved. We investigated the association between the DLQI and PASI of patients with psoriasis on biologic agents for an extended period of time of up to 6.5 years. METHODS: The data for this longitudinal, retrospective study was collected from a large tertiary teaching hospital in South Australia. Data was collected from all patients with psoriasis who had been on biologic agents for 2 or more years (n = 54). RESULTS: PASI and DLQI were highly correlated over all time points (ρ = 0.50), P < 0.001. DLQI scores significantly decreased by 0.8 (95% CI: 0.30, 1.26) units per year from 12 months to 6.5 years, P = 0.002. After 12 months, PASI scores declined by 0.19 (95% CI: 0.13, 0.52) units per year, P = 0.24. CONCLUSION: This study demonstrates that DLQI and PASI remain low after 12 months, and, in fact, both gradually decline further with time. Patients on biologic agents for prolonged periods maintained their improvement in QoL for up to 6.5 years.

Zoster Immunoglobulin-VF: A Potential Treatment for Molluscum Contagiosum in Immunosuppressed Children.

We present a brief observational report of clearance of significant molluscum contagiosum infection in a child taking methotrexate after one dose of intramuscular zoster immunoglobulin-VF (human) and suggest that this may indicate a potential new treatment option.

Leprosy: a review on elimination, reducing the disease burden, and future research.

Leprosy, one of the oldest diseases known to man, is a stigmatising, potentially disabling disease. Throughout history, leprosy has been associated with fear, prejudice and immense social stigma. It remains one of the leading causes of deformity and physical disability from an infectious disease. Tremendous advances in leprosy control were made by the World Health Organization, and the 'elimination of leprosy', defined as a decrease of disease prevalence to less than 1 case per 10,000 population, was achieved by 2000. However, the reality is that true 'elimination' is yet to be achieved. Despite almost 30 years of effective multidrug treatment, the prevalence and incidence of leprosy have plateaued since 2005. Moreover, new cases with Grade 2 disability and new cases occurring in children remain unchanged since 2010, reflecting a failure in early leprosy detection, and indicating that transmission is clearly continuing. This review examines the challenges of elimination, and proposes further measures to reduce the disease burden, including future research possibilities.

Nephrogenic systemic fibrosis in a gadolinium-naïve patient: successful treatment with oral sirolimus.

A 52-year old woman with chronic renal failure presented with tender buttock nodules, bilateral non-tender periocular papules and yellow scleral plaques. The patient then developed sclerodermoid changes of the hands, as well as woody induration, oedema and hyperpigmentation of lower limbs. There was no previous exposure to gadolinium contrast. Her histology and clinical features were consistent with nephrogenic systemic fibrosis. Treatment with oral sirolimus resulted in a marked reduction of induration and oedema, and an improvement in distal upper limb and lower limb joint mobility.

Late diagnosis of ectodermal dysplasia syndrome.

This case study reports the clinical, skin biopsy and molecular findings in a 56-year-old Filipino man with the autosomal recessive ectodermal dysplasia disorder, Schöpf-Schulz-Passarge syndrome, the precise nature of which was established only after reading of a similar case in this journal. In addition to the late diagnosis, successful clinical management of his acral hyperkeratosis and ulceration has been difficult, with oral retinoids exacerbating the skin fragility.

Toxic epidermal necrolysis-like subacute cutaneous lupus erythematosus.

Toxic epidermal necrolysis (TEN)-like presentations have been described in non-drug-induced settings. We describe a case of subacute cutaneous lupus erythematosus (SCLE) in a 53-year old woman, which evolved into a TEN-like presentation over the course of 4 weeks. The patient responded rapidly to treatment with intravenous methylprednisolone. This article draws attention to features that may be used to differentiate classical TEN from TEN-like SCLE.

Success treatment of post-irradiation morphoea with acitretin and narrowband UVB.

Post-irradiation morphoea is a rare but under-recognised complication of radiotherapy treatment for breast cancer. Management of this condition is difficult, and many cases are recalcitrant to therapy. A 43-year-old woman with breast cancer received radiotherapy following a mastectomy and partial axillary lymph node dissection, shortly after which she developed a hot, tender, erythematous and indurated plaque at the mastectomy site. Subsequently the skin became retracted, depressed and hyperpigmented. The clinical features, along with histological findings, were consistent with post-irradiation morphoea. Treatment with narrowband ultraviolet B and acitretin 10 mg daily was commenced 5 years following radiotherapy. After 2 months of therapy the patient reported significant improvement in tenderness and range of left arm movement. Objectively the plaque was less indurated and softer to palpation. We propose that this treatment regimen is an option in the management of post-irradiation morphoea.

Dermatophytosis and Sjögren-Larsson syndrome: foe or friend?

We report the patchy normalization of lamellar ichthyotic skin in Sjögren-Larsson syndrome (SLS) following a cutaneous Trichophyton rubrum infection. The dermatophytosis was pruritic and pustular, requiring treatment which was followed by the return of the lamellar ichthyosis. We discuss the possible mechanism of this clinical observation, which in turn may direct future therapy for difficult to treat ichthyotic skin seen in conditions such as SLS.