Nicotinamide for Skin-Cancer Chemoprevention in Transplant Recipients.

BACKGROUND: Immunosuppressed organ-transplant recipients have an increased incidence of, and mortality from, skin cancer. Nicotinamide (vitamin B3) enhances the repair of ultraviolet (UV) radiation-induced DNA damage, reduces the cutaneous immunosuppressive effects of UV radiation, and reduces the incidence of keratinocyte cancers (including squamous-cell and basal-cell carcinomas) and actinic keratoses among high-risk immunocompetent patients. Whether oral nicotinamide is useful for skin-cancer chemoprevention in organ-transplant recipients is unclear. METHODS: In this phase 3 trial, we randomly assigned, in a 1:1 ratio, organ-transplant recipients who had had at least two keratinocyte cancers in the past 5 years to receive 500 mg of nicotinamide or placebo twice daily for 12 months. Participants were examined for skin lesions by dermatologists at 3-month intervals for 12 months. The primary end point was the number of new keratinocyte cancers during the 12-month intervention period. Secondary end points included the numbers of squamous-cell and basal-cell carcinomas during the 12-month intervention period, the number of actinic keratoses until 6 months after randomization, safety, and quality of life. RESULTS: A total of 158 participants were enrolled, with 79 assigned to the nicotinamide group and 79 to the placebo group. The trial was stopped early owing to poor recruitment. At 12 months, there were 207 new keratinocyte cancers in the nicotinamide group and 210 in the placebo group (rate ratio, 1.0; 95% confidence interval, 0.8 to 1.3; P = 0.96). No significant between-group differences in squamous-cell and basal-cell carcinoma counts, actinic keratosis counts, or quality-of-life scores were observed. Adverse events and changes in blood or urine laboratory variables were similar in the two groups. CONCLUSIONS: In this 12-month, placebo-controlled trial, oral nicotinamide therapy did not lead to lower numbers of keratinocyte cancers or actinic keratoses in immunosuppressed solid-organ transplant recipients. (Funded by the National Health and Medical Research Council; ONTRANS Australian New Zealand Clinical Trials Registry number, ACTRN12617000599370.).

Stage IA melanoma follow-up: Exploring the level of confidence of South Australian general practitioners in undertaking surveillance skin checks including considerations for shared care.

BACKGROUND: The literature highlights the role of Australian general practitioners (GP) in the management of skin cancers. With melanoma incidences on the rise, there have been discussions into whether lower-risk stage IA patients could safely be followed up by their GPs for annual surveillance full skin examinations (FSE). This study explores the level of confidence of South Australian (SA) GPs in undertaking FSEs including factors that could support discussions around shared care between GPs and dermatology units for lower-risk patients. METHODS: An online survey was designed and distributed to SA GPs via email, newsletters and social media between 5 December 2021 and 30 January 2022. Descriptive statistics were used to describe survey responses. Pearson's Chi-squared analysis was used to investigate associations between key variables of interest and explanatory variables. Logistic regression analysis was used to model odds ratios for associations between the dependent variable and independent variables. RESULTS: A total of 135 responses were obtained. Forty-four per cent of GPs were comfortable undertaking annual FSEs, 41% were uncomfortable and 15% were unsure. Scope of work, >20 years experience and additional training had statistically significant relationships (p < 0.05). Dermoscopy and detecting melanoma recurrences were reported to be skills with lower levels of confidence. With regards to shared care, 77% indicated that they would feel supported undertaking FSEs if rapid access referral pathways were allocated for patients who developed suspicious lesions. Preferred upskilling modalities included, face-to-face sessions in a dermatology unit (39%), dermatologist run webinars (25%) and certificate courses (20%). CONCLUSIONS: At present, there is a subset of SA GPs who are comfortable undertaking FSEs and therefore could be engaged in shared care with specialists. Further considerations have to be made in the areas of upskilling and supporting the workforce to enhance engagement in shared care.

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

BACKGROUND: Over the last decade, the treatment landscape for moderate-severe psoriasis has rapidly evolved. The Australasian College of Dermatologists sought to review and update previously published treatment goals for moderate-severe psoriasis. 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 26/29 statements in round 1 and a further 20 statements in round 2. There was strong agreement to expanding the classification/definition of psoriasis severity by including a choice of metrics, incorporating quality of life measures, and widening the scope of high-impact sites. Consensus was also reached on revised treatment response criteria, which were then incorporated into a new treatment algorithm. There was discordance with the current requirement to undertake a trial with established systemic agents before accessing targeted therapy. CONCLUSION: The ability of new targeted treatment options to change the narrative in psoriasis patient care can only be properly realised if challenges to timely and equitable access are addressed. The proposed framework for the assessment, classification and management of moderate-severe psoriasis aligns with international recommendations. Its adoption into Australian clinical practice is hoped to improve treatment outcomes and patients' satisfaction with their care.

Two cases of granulomatous mycosis fungoides mimicking interstitial granulomatous dermatosis.

Two patients presented with erythematous papules within larger patches and thin plaques. Following biopsies, each case was initially thought to represent interstitial granulomatous dermatitis (IGD); however, clinicopathological correlation led to a diagnosis of granulomatous mycosis fungoides (GMF). Drawing upon the similarities between these cases, this report explores the clinical and histological manifestations of GMF, features distinguishing GMF from other granulomatous diseases like IGD and the prognostic significance of distinguishing GMF from classic mycosis fungoides. This report also shows that despite the potential for histological overlap between GMF and IGD, the existing literature does not reveal an epidemiological or pathophysiological link between these two conditions.

Azathioprine-induced Sweet's syndrome: A case series and review of the literature.

We present three patients with azathioprine-induced Sweet's syndrome (AISS) who attended our tertiary institution within a 12-month period. Established associations exist between Sweet's syndrome and some medications; however, to date links to azathioprine are tentative. While there are case reports of AISS, most have occurred in patients with inflammatory bowel disease (IBD), an underlying predisposition for Sweet's syndrome. Our case series adds to the evidence that the entity of AISS truly exists independent of confounding factors such as concurrent IBD.

Heavy metal (monoclonal) bands: a link between cutaneous T-cell lymphoma and contact allergy to potassium dichromate, nickel and cobalt?

It has been proposed that chronic antigenic stimulation plays a role in the pathogenesis of cutaneous T-cell lymphoma (CTCL). By definition, antigenic stimulation triggers allergic contact dermatitis (ACD). It is therefore plausible that chronic ACD could serve as a precursor to CTCL. We report two cases of contact allergy to potassium dichromate, nickel and cobalt, where CTCL was diagnosed in one patient, and a diagnosis of CTCL is imminent in the other. We also review the literature on the diagnostic criteria for CTCL in the setting of ACD and explore potential mechanisms for the progression from ACD tos CTCL.

Cutaneous manifestations of peripheral T-cell lymphoma, not otherwise specified: a case series highlighting the diagnostic challenges for this heterogeneous group.

Peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) is a rare, heterogeneous group of nodal and extranodal mature T-cell lymphomas that do not correspond to any of the defined T-cell entities, according to the World Health Organization classification. Most cases present with late stage nodal disease; however extranodal involvement is common. Skin and subcutaneous involvement is reported in approximately 20% of cases. Little attention has been given to the highly variable skin manifestations in the literature. It is our experience that lesions can present in ways other than previously described nodular or tumourous lesions that often ulcerate. We present a case series from a large tertiary institution of seven cases of PTCL, NOS with skin involvement, highlighting the variable presentations and diagnostic challenges for this heterogeneous group.

Mycophenolate mofetil as a treatment for urticarial dermatitis.

We report two cases of adults with urticarial dermatitis who could not be managed by a variety of treatments but who obtained good control with mycophenolate mofetil (MMF). A clinical response was seen 6-8 weeks from treatment onset and they were maintained on MMF 1 g twice daily (case 1), and MMF 1 g omni mane and 500 mg omni nocte (case 2), with no major exacerbations for many years. MMF is an immunosuppressive agent, which is currently used off-label for many dermatological conditions. To date, there have been no studies investigating the use of MMF as a treatment for urticarial dermatitis. The cases we present suggest that MMF is an effective treatment for this condition, and we recommend that MMF be considered as a treatment option.

Circulating plakin autoantibodies in a patient with erythema multiforme major: are they pathogenic or a manifestation of epitope spreading?

Erythema multiforme is a well-recognised entity but its pathogenesis remains elusive. Theories hypothesise a cell-mediated immune pathogenesis, however recent case reports have observed autoantibodies to the plakin family of proteins, suggesting a role for the humoral immune system. We present a case of erythema multiforme major with circulating desmoplakin autoantibodies in a 36-year old woman who was previously diagnosed with pemphigoid gestationis. The close correlation between the concentration of these autoantibodies and the severity of clinical disease strongly suggests a pathogenic role in her disease. As previous case reports have proposed, these autoantibodies may be directly pathogenic. Alternatively, the epiphenomenon of epitope spreading must be considered in the subset of patients with erythema multiforme major.

Post-transplant plasmablastic lymphoma of the skin.

Plasmablastic lymphoma (PBL) is a recently described rare variant of diffuse large B-cell lymphoma characterised by its aggressive nature and plasmacytic differentiation. It most frequently arises in the oral cavity of human immunodeficiency virus (HIV)-infected patients. However extra-oral involvement is becoming increasingly recognised, particularly in HIV-negative patients. We report a case of PBL presenting as multiple violaceous nodules and plaques on the leg of a HIV-negative patient, 13-years post-renal transplant. To date, 20 cases of PBL presenting in the skin have been reported. We review and compare the clinico-pathological features of these cases.

Treatment goals for moderate to severe psoriasis: an Australian consensus.

BACKGROUND/OBJECTIVES: The high incidence of comorbidities in patients with psoriasis, significant impact on quality of life and patients' dissatisfaction with treatment led a European group to develop a consensus position on psoriasis treatment goals. There is an evident need for similar treatment goals in Australia. The aim of this project was to develop Australian treatment goals that reflect the local environment. METHODS: A panel of 12 representatives was drawn from across Australia consisting of nine dermatologists and a rheumatologist, a dermatology nurse and a general practitioner (GP)/dermatology trainee. The group met on three occasions between September 2011 and March 2012. The panel undertook a literature review and critically examined available evidence-based treatment goals. A questionnaire relating to psoriasis assessment and specific treatment outcomes was developed. Following discussion and debate, recommended treatment goals for psoriasis patients in Australia were determined. RESULTS: The panel agreed by consensus on recommended psoriasis treatment goals in the Australian environment. There was recognition that in addition to psoriasis area severity index (PASI) assessment, a quality of life assessment was highly relevant in determining psoriasis severity and treatment outcome. Mild psoriasis was defined as PASI ≤ 10 and a dermatology life quality index (DLQI) ≤ 10, with moderate to severe psoriasis defined as PASI > 10 and/or DLQI > 10. The presence of certain definedclinical features would elevate a patient's classification from mild to moderate/severe. The target for treatment was defined as a maintained change in PASI ≥ 75% improvement and DLQI ≤ 5. These largely concurred with the European treatment goals. A flow chart for psoriasis management in Australia based on outcome measures was developed. CONCLUSIONS: There is a need to identify and articulate treatment goals for psoriasis. Assessment of psoriasis severity requires both physical scoring (PASI) and consideration of quality of life measures (DLQI). Identification of treatment goals will guide clinicians in treatment decision-making, enhance the availability and appropriate use of therapies and increase patient satisfaction with their care.

Management pathway of skin conditions presenting to an Australian tertiary hospital emergency department.

There have been limited published data on the management pathway of patients presenting to the emergency department with skin conditions. We report the pathway of patients presenting with skin conditions to a large tertiary hospital for 1 year and make recommendations to optimise the available dermatological services.

Similar but different: distinguishing between pemphigus vegetans and pyostomatitis-pyodermatitis vegetans.

A 51-year-old woman presented with a 4-month history of painful ulcers in the mouth and vulva, and painful vegetative plaques at intertriginous sites. Skin biopsies showed squamous hyperplasia and intraepidermal eosinophilic pustulation. Skin direct immunofluorescence (DIF) revealed intercellular deposition of IgG and C3 in the lower part of the epidermis, while serum indirect immunofluorescence (IIF) confirmed the presence of antiepithelial antibodies. The patient was diagnosed with pemphigus vegetans, and successfully treated with dapsone, prednisolone and topical steroids. Although pemphigus vegetans and pyostomatitis-pyodermatitis vegetans can show identical clinical and histological features, the presence or absence of comorbid inflammatory bowel disease, and the results of both skin DIF and serum IIF can be used to distinguish between these two conditions. This case report explores the challenges in making this distinction, and the implications of establishing the correct diagnosis.

Frontal fibrosing alopecia associated with generalized hair loss.

We present six cases of frontal fibrosing alopecia, in which generalized hair loss is a feature. Although this variant of lichen planopilaris has been reported clinically in a number of patients, there is very little histological evidence that the condition exists in peripheral sites. We believe this pattern of involvement may be more common than is reported, and have provided histological evidence of lichen planopilaris being present at sites beyond the scalp and eyebrows.

Stevens Johnson syndrome and toxic epidermal necrolysis - an Australian analysis of treatment outcomes and mortality.

Background: Stevens Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are rare diseases with devastating consequences on morbidity and mortality. There are currently no standardized guidelines for treatment of SJS/TEN in Australia. Method: Retrospective chart review of all SJS/TEN cases treated at the Royal Adelaide Hospital from 2000 to 2017. Result: A total of 42 patients were identified (SJS = 18, TEN = 24). The average age of presentation for SJS was 45.8 years and 54.9 years for TEN. The overall mortality rate was 19%. Comparing the data between 2000-2009 and 2010-2017, there was an improvement in mortality in those who were treated with intravenous immunoglobulin (IVIg) compared to those who were treated with systemic steroids (mortality rate 27.2% vs. 50%). There were a total of 12 TEN patients admitted to the Burns unit, with only 2 observed deaths (mortality rate 16.7%). Conclusion: There was an improvement in mortality in those who were treated with IVIg and supportive care compared to those who were treated with systemic steroids and supportive care. Early admission into burns unit may also improve mortality outcomes. However, treatment paradigms in skin care and supportive measures have improved over the length of the study period, which makes definitive conclusions difficult.

A 30-year history of CD4+ vesiculo-bullous mycosis fungoides and multiple visceral malignancies.

An 83-year-old Caucasian woman presented with a 25-year history of an itchy, eczematous blistering eruption affecting her trunk and acral sites. She had a past history of adenocarcinoma of the lung, colorectal carcinoma and bladder carcinoma. Several skin biopsies consistently showed features of a spongiotic process. Direct and indirect immunofluorescence studies were repeatedly negative, excluding the possibility of an autoimmune blistering disorder. A skin biopsy several years later, however, showed histological and immunophenotypic features of mycosis fungoides. The literature on this rare phenotype of cutaneous T-cell lymphoma generally portrays a negative prognosis. Our case illustrates an excellent prognosis with stable disease 30 years after onset.