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A 3.5-month-old boy presented with a changing medium-sized congenital melanocytic nevus on his leg. Due to atypical features on dermoscopy and reflectance confocal microscopy (RCM), an excision of the area of concern was performed. Histopathology showed many of the pathological features usually associated with a diagnosis of melanoma in situ in older patients, but due to the young age of the patient, absence of mitoses, and the degree of atypia, a diagnosis of a dysplastic compound nevus arising in a congenital compound (predominantly dermal) nevus was favored. In our case, RCM corresponded to histopathology helped target the area of concern and map the clinical and subclinical components to facilitate an optimal biopsy.

Optical Coherence Tomography (OCT) is a useful non-invasive diagnostic tool for diagnosing and monitoring treatment of basal cell carcinomas. We describe the use of OCT in a patient with Basal Cell Naevus Syndrome. Through measuring tumour depth on OCT, management of individual tumours was triaged accordingly using 0.4 mm tumour depth as a cut-off for surgical and non-surgical management. OCT has potential to reduce unnecessary excisions and associated morbidity in this population of patients.

Background The success of clinical trials in Epidermolysis Bullosa (EB) is dependent upon the availability of a valid and reliable scoring tool that can accurately assess and monitor disease severity. The Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) and Instrument for Scoring Clinical Outcomes of Research for Epidermolysis Bullosa (iscorEB) were independently developed and validated against the Birmingham Epidermolysis Bullosa Severity Score but have never been directly compared. Objective To compare the reliability, convergent validity, and discriminant validity of the EBDASI and iscorEB scoring tools. Methods An observational cohort study was conducted in 15 patients with EB. Each patient was evaluated using the EBDASI and iscorEB-clinician scoring tools by 6 dermatologists with expertise in EB. Quality of life was assessed using the iscorEB-patient and Quality of Life in EB measures. Results The intraclass correlation coefficients for interrater reliability were 0.942 for the EBDASI and 0.852 for the iscorEB-clinician. The intraclass correlation coefficients for intrarater reliability was 0.99 for both scores. The two tools demonstrated strong convergent validity with each other. Conclusion Both scoring tools demonstrate excellent reliability. The EBDASI appears to better discriminate between EB types and disease severities.

Treatment with anti-PD1 inhibitors may enhance the risk for developing low grade squamoproliferative skin tumors. Immunohistochemical (IHC) analysis of the immune tumor microenvironment (TME) allows exploration of the pathogenesis and relationship with the PD1/PDL1 axis. Patients with eruptive keratoacanthoma (KA)-like lesions were recruited from the Melanoma Institute Australia, a tertiary referral specialist melanoma treatment center from January 2015 to August 2017. Clinicopathologic evaluation and IHC features of tumor cells (PDL1 expression) and peritumoral microenvironment (PD1, FOXP3, PDL1, CD4:CD8 expressing cells) in 12 eruptive KA-like lesions, were compared with solitary KAs in age and sex matched non-anti-PD1 treated controls. Four patients with repeated episodes of eruptive KA-like and lichenoid lesions developing 2-7 months after commencing pembrolizumab for AJCC stage IV melanoma, were recruited. Eruptive KA-like squamoproliferative lesions occurred in sun exposed sites and in areas of resolving, concomitant or delayed lichenoid reactions. Histologically, the lesions were well-differentiated squamoproliferative lesions resembling infundibulocystic squamous cell carcinoma or KA. IHC of cases and controls revealed low PDL1 expression of both squamous tumor cells and the TME immune cells. The numbers of immunosuppressive FOXP3 positive Tregs and PD1-expressing T-cells were higher in the cases than the controls but the CD4:CD8 ratio (2:1) was similar. The patients best responded to acitretin and were managed surgically if they demonstrated neoplastic features. Accelerated squamoproliferative growth in actinically damaged keratinocytes associated with lichenoid eruptions may be unmasked in patients treated with anti-PD1 immunotherapy potentially contributed to by a local cutaneous immunosuppressed TME.

IntroductionFear of cancer recurrence (FCR) is commonly reported by patients diagnosed with early-stage (0–II) melanoma and can have a significant impact on daily functioning. This study will pilot the implementation of the Melanoma Care Program, an evidence-based, psychological intervention to reduce FCR, into routine practice, using a stepped-care model.Methods and analysisIntervention effectiveness and level of implementation will be investigated using a hybrid type I design. Between 4 weeks before and 1 week after their next dermatological appointment, patients with melanoma will be invited to complete the Fear of Cancer Recurrence Inventory Short-Form, measuring self-reported FCR severity. Using a stepped-care model, clinical cut-off points will guide the level of support offered to patients. This includes: (1) usual care, (2) Melanoma: Questions and Answers psychoeducational booklet, and (3) three or five psychotherapeutic telehealth sessions. This longitudinal, mixed-methods pilot implementation study aims to recruit 108 patients previously diagnosed with stage 0–II melanoma. The primary effectiveness outcome is change in FCR severity over time. Secondary effectiveness outcomes include change in anxiety, depression, stress, health-related quality of life and melanoma-related knowledge over time. All outcomes are measured at baseline, within 1 week of the final telehealth session, and 6 and 12 months post-intervention. Implementation stakeholders at each study site and interested patients will provide feedback on intervention acceptability and appropriateness. Implementation stakeholders will also provide feedback on intervention cost, feasibility, fidelity and sustainability. These outcomes will be measured throughout implementation, using questionnaires and semistructured interviews/expert group discussions. Descriptive statistics, linear mixed-effects regression and thematic analysis will be used to analyse study data.Ethics and disseminationEthics approval was granted by the Sydney Local Health District–Royal Prince Alfred Zone (2020/ETH02518), protocol number: X20-0495. Results will be disseminated through peer-reviewed journals, conference presentations, social media and result summaries distributed to interested participants.Trial registration details(ACTRN12621000145808).

SummaryBackground Atopic dermatitis (AD) assessment is more difficult in patients with skin of colour (SOC). Objectives To compare the reliability of commonly used outcome measures for assessing AD in patients with SOC and to evaluate a novel greyscale in this population. Methods Twenty-five patients with AD each attended a 1-day scoring exercise based in either Sydney or Melbourne, Australia. Each patient was scored by the same five physicians using the Eczema Area and Severity Index (EASI), objective Scoring Atopic Dermatitis (oSCORAD), Investigator's Global Assessment (IGA) and a novel greyscale. Patients also completed the Patient-Oriented Eczema Measure and quality-of-life measures. A Mexameter was used to measure baseline melanin indices. Ten random patients were rescored to test intrarater reliability. Results We included 11 light-skinned patients (melanin index ≤ 200) and 14 patients with SOC (melanin index > 200) in the cohort. The inter-rater intraclass correlation coefficients (ICCs) were EASI 0·83 [95% confidence interval (CI) 0·66–0·94] for light skin and 0·77 (95% CI 0·60–0·91) for SOC; oSCORAD 0·68 (95% CI 0·44–0·88) for light skin and 0·74 (95% CI 0·54–0·89) for SOC; and IGA 0·80 (95% CI 0·62–0·93) for light skin and 0·70 (95% CI 0·49–0·87) for SOC. The greyscale had an ICC of 0·78 (95% CI 0·60–0·91) when replacing the EASI's erythema scale for patients with SOC. All scores showed excellent intrarater reliability for all skin types. Erythema component analysis showed that erythema did not contribute to variability. Conclusions EASI showed excellent reliability for patients of all skin colours, and is recommended as the optimal core measure for patients with all skin colours.

Background Diffuse melanosis cutis (DMC) is a rare presentation of metastatic melanoma characterized by a progressive blue-gray discoloration of the skin and mucous membranes. Objective To foster a better understanding of the clinical presentation, histological findings, and pathophysiology underlying DMC. Methods A systematic review of the literature was completed utilizing MEDLINE, CINAHL, Embase, and Google. Data were extracted using a protocol-driven spread sheet with all statistical analyses completed using SPSS. Results The review identified 68 original cases of DMC. The mean time from diagnosis of melanoma until development of DMC was 11.48 months (95% confidence interval [CI]: 0-48.16). The mean time to death following the onset of DMC was 4.43 months (95% CI: 0.00-11.11). Histological findings were relatively consistent demonstrating intracellular and extracellular melanin deposition in the dermis, with a pronounced perivascular distribution. The pathophysiological mechanisms underlying DMC could not be definitively elucidated; however, it is hypothesized that the melanin precursors, melanin, and melanosomes liberated by cytolytic metastatic melanoma deposits are phagocytosed by dermal histiocytes, manifesting clinically as diffuse melanosis. Limitations The cross-sectional nature of case reports, paucity of cases of DMC, and heterogeneity in reporting limit any conclusions being drawn regarding the pathophysiology of DMC definitively. Conclusion DMC heralds a poor prognosis for patients with metastatic melanoma and affected patients should be made aware of the implications of this condition on survival.

Midline mucinosis was observed in a 14-year-old man, which was confined to the midline of the back and appeared as asymptomatic, nonindurated, hyperpigmented plaques. Skin biopsies showed prominent interstitial mucinosis with perivascular lymphocytic infiltration. A literature review of plaque-like mucinosis revealed 14 previous cases with this distinct presentation that may overlap with reticular erythematous mucinosis and connective tissue disease. Midline mucinosis has been previously reported in prepubertal children but is rare.

Case Report A 79-year-old Caucasian male presented with a 1-week history of diffuse progressive blue-gray discoloration of the skin subsequently found to due to diffuse melanosis cutis (DMC) in the setting of metastatic melanoma. Mutation testing demonstrated BRAFV600E mutation status, an unexpected finding given his age. He died two weeks after presentation. Discussion As our understanding of the molecular subtypes of melanoma increases, in the future it may be possible to predict which melanoma patients have a predilection to developing DMC. Mutation testing of DMC patients should be considered as BRAF inhibitors, and other novel targeted therapies may improve the bleak prognosis associated with this unusual presentation of metastatic melanoma.

We present two female children aged 7 years with extensive multifocal venous malformations complicated by chronic localized intravascular coagulation. In both cases ultrasonography and magnetic resonance imaging revealed extensive venous malformations involving the skin, mucous membranes and pharynx, which were not apparent on clinical examination. Haematological investigations demonstrated persistent elevation of the D-dimer, consistent with chronic localized intravascular coagulation. The course of one patient was complicated by the development of multiple painful thromboses at distant sites following percutaneous sclerotherapy. Persistent elevation of the D-dimer occurring in association with large venous and veno-lymphatic malformations has been termed chronic localized intravascular coagulation, and is thought to occur due to thrombosis at sites of stagnant blood flow within venous malformations. It is of clinical concern due to the potential for transformation into serious thrombohaemorrhagic coagulation disorders, including disseminated intravascular coagulation. While previously described in association with large segmental venous malformations, these cases demonstrate the occurrence of chronic localized intravascular coagulation as a complication of disseminated multifocal venous malformations.

Our scientific knowledge of pemphigus has dramatically progressed in recent years. However, despite the availability of various therapeutic options for the treatment of inflammatory diseases, only a few multicenter controlled trials have helped to define effective therapies in pemphigus. A major obstacle in comparing therapeutic outcomes between centers is the lack of generally accepted definitions and measurements for the clinical evaluation of patients with pemphigus. Common terms and end points of pemphigus are needed so that experts in the field can accurately measure and assess disease extent, activity, severity, and therapeutic response, and thus facilitate and advance clinical trials. This consensus statement from the International Pemphigus Committee represents 2 years of collaborative efforts to attain mutually acceptable common definitions for pemphigus. These should assist in development of consistent reporting of outcomes in future studies.

SUMMARY A 48-year-old woman presented with acute unilateral ischaemia of the left hand. She had a background of chronic peripheral neuropathic pain, palpitations, anaemia and an episode of superficial thrombophlebitis. Physical examination revealed non-blanching purple discoloration of her left fingers and her left thumb, index finger and thenar eminance appeared ischaemic. Digital subtraction angiography of the left hand demonstrated reduced flow. Skin punch biopsy histology was unremarkable. The diagnosis of Fabry disease was made on urine lipid profile analysis and confirmed by reduced peripheral blood leukocyte α-galactosidase A activity.

Importance Quality-of-life (QOL) evaluation is an increasingly important outcome measure in dermatology, with disease-specific QOL instruments being the most sensitive to changes in disease status. Objective To develop a QOL instrument specific to autoimmune bullous disease (AIBD). Design A comprehensive item generation process was used to build a 45-item pilot Autoimmune Bullous Disease Quality of Life (ABQOL) questionnaire, distributed to 70 patients with AIBD. Experts in bullous disease refined the pilot ABQOL before factor analysis was performed to yield the final ABQOL questionnaire of 17 questions. We evaluated validity and reliability across a range of indices. Setting Australian dermatology outpatient clinics and private dermatology practices. Patients and Exposure Patients with a histological diagnosis of AIBD. Main Outcomes and Measures The development of an AIBD-specific QOL instrument. Results Face and content validity were established through the comprehensive patient interview process and expert review. In terms of convergent validity, the ABQOL was found to have a moderate correlation with scores on the Dermatology Life Quality Index ( R = 0.63) and the General Health subscale of the 36-Item Short Form Health Survey ( R = 0.69; P = .009) and low correlation with the Pemphigus Disease Area Index ( R = 0.42) and Autoimmune Bullous Disease Skin Disorder Intensity Score ( R = 0.48). In terms of discriminant validity, the ABQOL was found to be more sensitive than the Dermatology Life Quality Index ( P = .02). The ABQOL was also found to be a reliable instrument evaluated by internal consistency (Cronbach α coefficient, 0.84) and test-retest reliability (mean percentage variation, 0.92). Conclusions and Relevance The ABQOL has been shown to be a valid and reliable instrument that may serve as an end point in clinical trials. Future work should include incorporating patient weighting on questions to further increase content validity and translation of the measure to other languages. Clinical Trial Registration anzctr.org.au Identifier:ACTRN12612000750886

Background A range of interventions has been described for the treatment of pemphigus; however, the optimal therapeutic strategy has not been established. Objective We sought to evaluate the safety and efficacy of interventions for pemphigus vulgaris and pemphigus foliaceus. Methods We undertook a systematic review and meta-analysis according to the methodology of the Cochrane Collaboration. We selected randomized controlled trials including participants with the diagnosis of pemphigus vulgaris or pemphigus foliaceus confirmed with clinical, histopathological, and immunofluorescence criteria. All interventions were considered. Primary outcomes studied were remission and mortality. Secondary outcomes included disease control, relapse, pemphigus severity score, time to disease control, cumulative glucocorticoid dose, serum antibody titers, adverse events, and quality of life. Results Eleven studies with a total of 404 participants were identified. Interventions assessed included prednisolone dose regimen, pulsed dexamethasone, azathioprine, cyclophosphamide, cyclosporine, dapsone, mycophenolate, plasma exchange, topical epidermal growth factor, and traditional Chinese medicine. We found some interventions to be superior for certain outcomes, although we were unable to conclude which treatments are superior overall. Limitations Many interventions for pemphigus have not been evaluated in controlled trials. All studies were insufficiently powered to establish definitive results. Conclusions There is inadequate evidence available at present to ascertain the optimal therapy for pemphigus vulgaris and pemphigus foliaceus. Further randomized controlled trials are required.

Background A range of interventions have been described for treatment of pemphigus, however the optimal therapeutic strategy has not been established. Objectives To assess the efficacy and safety of all interventions used in the management of pemphigus vulgaris and pemphigus foliaceus. Search methods We searched the Cochrane Skin Group Specialised Register (October 2008), The Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4, 2008), MEDLINE (2003 to October 2008), EMBASE (2005 to October 2008), LILACS (1981 to October 2008), Ongoing Trials Registers, reference lists of articles, conference proceedings from international pemphigus meetings and contacted experts in the field. Selection criteria Randomised controlled trials of any intervention in pemphigus vulgaris or pemphigus foliaceus. Data collection and analysis Two authors independently assessed quality and extracted data from studies. All investigators were contacted for further information. Adverse events were identified from included studies. Main results Eleven studies with a total of 404 participants (337 pemphigus vulgaris, 27 pemphigus foliaceus and 40 not specified ) were identified. The quality of included studies was not high, the majority of studies did not report allocation concealment, and power was limited by very small sample sizes. Interventions assessed included prednisolone dose regimen, pulsed dexamethasone, azathioprine, cyclophosphamide, cyclosporine, dapsone, mycophenolate, plasma exchange, topical epidermal growth factor and traditional Chinese medicine. Ten studies included participants with newly diagnosed or newly active recurrent disease, and one trial included participants in maintenance phase. There was sufficient data for 4 meta-analyses, each pooling results of two studies only. For the majority of interventions, results were inconclusive. We found some interventions to be superior for certain outcomes, although we were unable to conclude which treatments are superior overall. Mycophenolate was more effective in achieving disease control than azathioprine (1 study; n=40; RR 0.72; 95% CI 0.52 to 0.99, NNT 3.7). There was evidence of a steroid-sparing benefit of azathioprine (1 study; n=57; MWD -3919 mg prednisolone; 95% CI -6712 to -1126) and cyclophosphamide (1 study; n=54; MWD -3355 mg prednisolone; 95% CI -6144 to -566) compared to glucocorticoids alone. Topical epidermal growth factor decreased time to control (1 study; n=20; HR 2.35; 95% CI 1.62 to 3.41). Authors' conclusions There is inadequate information available at present to ascertain the optimal therapy for pemphigus vulgaris or pemphigus foliaceus. Further research is required, especially to assess the optimal glucocorticoid dose, the role of adjuvant immunosuppressive medications, and long-term adverse events to improve harm:benefit analyses.

A 49-year-old man presented with a 20-year history of an asymptomatic reticular eruption on his upper trunk. On examination, there were well-demarcated orange-red patches with reticular margins and irregular central atrophy on the lateral chest and proximal upper limbs. Skin biopsies showed histological evidence of elastophagocytosis with scant lymphocytic inflammation. Elastin stains demonstrated focal loss of elastic fibers in the reticular dermis, consistent with mid-dermal elastolysis. Mid-dermal elastolysis is a rare disorder characterized by focal loss of elastic tissue in the mid-dermis. The etiology remains obscure. Reticular presentations of mid-dermal elastolysis have rarely been described and extend the clinical spectrum of dermal elastolytic disorders.

A 40-year-old woman presented with a delusion of warts on the forehead, for which she was applying podophyllin toxin. A skin biopsy was taken, which showed prominent mitotic figures in the basal and suprabasal layers of the epidermis and apoptotic keratinocytes. Histopathologically Bowen's disease was suspected, but was discounted after clinicopathological correlation was obtained and showed absence of epidermal atypia or disorganization. This case demonstrates the histological resemblance of podophyllin reaction to Bowen's disease. Differentiation of self-inflicted from organic skin disease may be difficult, especially where histopathological findings are confounded by cutaneous application of toxins.

■ Nurses can benefit from active participation in research activities. ■ Involvement in research is not just an academic pursuit but is essential for effective, quality care. ■ Nurses should actively seek the support of colleagues and research support structures to enable involvement in research. ■ Clinical nurses are capable of making an important research contribution.

E leven randomized controlled trials of the treatment of pemphigus have been published in the last 20 years, yet the optimal treatment for this serious condition remains elusive. So varied are the interventions, trial methodologies, patient groups, and outcome measures published, what role does a systematic review play in untangling the disparate treatment options? A systematic review, particularly within the rigorous methodological confines of the Cochrane Collaboration guidelines, provides three main benefits to our understanding of the management of pemphigus. First, it meticulously identifies and synthesizes the available evidence. Second, in the circumstances in which several trials examine the same intervention, the review allows meta-analysis of the data. Third, and perhaps most importantly, the review highlights the difficulty of performing research in this area and points the way to future research in profitable directions. The crux of the difficulty of researching pemphigus is its rarity. An incidence of only 1 to 16 per million population per annum means that all but the largest single centers are unable to recruit sufficient numbers of patients for adequate analysis. For example, assuming a baseline remission rate of 75% (as seen in the largest randomized controlled trial to date), to demonstrate a 20% difference between interventions with 80% power, a study of more than 196 patients is required. This calculation does not allow for withdrawals, so in reality an even higher number would be required. The implications of this are important. Studies that are underpowered add little to our knowledge of treatment options; the results are not statistically significant regardless of

Background Epidermolysis bullosa (EB) has a profound effect on quality of life (QOL); however, generic QOL assessments are poor indicators of the impact of EB. Objectives To develop a valid and reliable EB-specific QOL tool for use in measuring the effects of disease impact and interventions. Methods Open, nonstructured interviews were conducted with 26 patients with EB, along with 33 family members and 11 health professionals (70 individuals) for item generation. A pilot questionnaire was compiled, refined and distributed to 130 patients with EB. From the 115 returned questionnaires a principal axis factor analysis was undertaken producing a 17-item final questionnaire. Discriminative validity was assessed by differences in scores between EB subtypes. Content validity was assessed by expert ranking of items in terms of importance. Construct validity was evaluated by correlation with existing QOL tools. Test-retest reliability and internal consistency were evaluated. Factor analysis was performed. Results A 17-item questionnaire was developed: the QOLEB questionnaire. This gave distinguishing QOL scores to different EB subtypes, and correlated highly with existing QOL instruments. Conclusions The QOLEB questionnaire is the first EB-specific QOL measurement tool, and is a valid and reliable measurement tool for the quantification of QOL in patients with various subtypes of EB. In addition, the QOLEB has potential as a sensitive instrument to monitor QOL, and to identify dimensions of QOL as targets for interventions and research.

A 51 year old female was referred for evaluation of a transient pruritic blistering eruption located on the trunk and extremities. She had a complicated medical background including rheumatoid arthritis and drug-induced lupus erythematosus from the TNF blocker adalimubab. Her medications included prednisone 4 mg/day and hydroxychloroquine 400 mg/day. On examination a few large tense blisters were noted and the Nikolsky sign was negative. A routine skin biopsy showed intraepidermal vesicles, eosinophilic spongiosis and significant subepidermal oedema, but no acantholysis. Direct immunofluorescence (DIF) showed IgG depositions in an intercellular pattern in the upper epidermis, and IgM depositions in a granular pattern at the dermo-epidermal junction. Indirect immunofluorescence on monkey oesophagus and rat bladder was negative, whereas salt-split skin showed positive staining for IgG in the roof of the blister. As it was difficult to establish a unifying diagnosis given these clinical and histopathological features, the auto-antigenic targets were studied by ELISA and immunoblotting techniques. ELISA showed IgG reactivity to the 165 kd desmoglein 1 antigen, but not to desmoglein 3. Immunoblotting to basement membrane components was negative. These results supported a unifying final diagnosis of pemphigus foliaceus. She has been treated with minomycin and topical corticosteroids and has had a benign course. This case demonstrates the concurrence of multiple serious autoimmune diseases, which represent an ongoing diagnostic and management challenge. Although the molecular pathogenesis of autoimmune blistering diseases is well understood, clinico-pathological correlation may not always be achieved with routine dermatohistopathology and immunofluorescence examination. This case demonstrates the utility of additional molecular techniques in differentiating blistering diseases, which has important implications for management and prognosis.

Fifty mating events in free-living nurse sharks (Ginglymostoma cirratum) were observed over a nine-day period in the Dry Tortugas island cluster in the Florida Keys. Four stages of mating were identified: precoupling, coupling, positioning and alignment, and insertion and copulation. Copulation was observed and filmed in four of the mating events. Seminal fluid released into the water was obtained following one copulation and showed the presence of free, nonpackaged sperm cells. At least 10 of the events involved multiple males attempting copulation with single females.

and reproductive condition of elasmobranch fishes in Elkhorn Slough, California. Calif. Fish Game 71(4):210-229. WOURMS,J. P. 1977. Reproduction and development in chondrichthyan fishes. Amer. Zool. 17:379-410. Moss LANDING MARINE LABORATORIES, PO Box 450, Moss LANDING, CALIFORNIA 95039. Present address: (LKM) MONTEREY BAY AQUARIUM, 886 CANNERY Row, MONTEREY, CALIFORNIA 93940. Accepted 4 Dec. 1987.