Photodiagnostic services in the UK and Republic of Ireland: a British Photodermatology Group Workshop Report.

BACKGROUND: Photodiagnostic investigations are essential for the accurate diagnosis of abnormal cutaneous photosensitivity and provide important information for the management of patients with photodermatoses (cutaneous photosensitivity disorders). Although photodiagnosis has been undertaken since the early 1970s, specialist services in the United Kingdom (UK) and Republic of Ireland are limited and there is no formal guidance on diagnostic approach. Indeed, there is a limited literature in this area of methodology and diagnostic practice. OBJECTIVES: The primary objective was to undertake a British Photodermatology Group Workshop to review the role and activities of specialist centres in the UK and Republic of Ireland in order to ascertain whether there were consensus practices. Secondary objectives were to identify key priorities for service, training and research. METHODS: An initial detailed survey review of current activities was undertaken prior to the Workshop and data from this survey were used to inform discussion at the Workshop, which was attended by key photodermatology experts from the UK and Republic of Ireland. RESULTS/CONCLUSIONS: We have undertaken a detailed review of current Photodiagnostic Services in the UK and Republic of Ireland and report on our findings from the 12 centres and we have identified key areas of consensus practice. This is an important step in the process of standardising and optimising procedures and protocols and defining minimum clinical standards for photodiagnostic investigations, which are of such diagnostic importance in Dermatology.

The use of psoriasis biomarkers, including trajectory of clinical response, to predict clearance and remission duration to UVB phototherapy.

BACKGROUND: Remission duration and treatment response following phototherapy for psoriasis are highly variable and factors influencing these are poorly understood. OBJECTIVES: Our primary outcome was to investigate whether selected clinical/serum biomarkers were associated with remission duration, and secondly with psoriasis clearance at the end of phototherapy. In addition, we looked at whether early trajectory of UVB clearance was associated with final clearance outcome. METHODS: We performed a prospective cohort study of 100 psoriasis patients, routinely prescribed Narrowband UVB and measured selected clinical and biochemical biomarkers, including weekly PASI (psoriasis area and severity index) scores. Patients were followed up for 18 months. RESULTS: The median time to relapse was 6 months (95% CI 5-18) if PASI90 was achieved, and 4 months (95% CI 3-9) if less than PASI90 was achieved. Achieving PASI100 did not result in prolonged remission. On UVB completion, the median final PASI (n = 96) was 1.0 (IQR 0.5, 1.6) with 78 (81%) achieving PASI75 and 39 (41%) achieving PASI90. Improved PASI90 response was significantly associated with lower BMI, higher baseline PASI, non-smoking status and lower cumulative NbUVB. Serum levels of C-reactive protein (CRP) and vitamin D were not associated with clearance or remission duration. Early treatment response from weeks 2-3 was predictive of final outcome. For example, achieving PASI30 at week 3 was significantly associated with PASI90 at the end of the course [36/77 (51%) vs. 2/24 (8%), P < 0.001]. CONCLUSIONS: Raised BMI and positive smoking status predicted poorer phototherapy response. For the first time, we have shown that PASI clearance trajectory over the first 2-3 weeks of UVB, can predict psoriasis clearance. This is an important new step towards developing psoriasis personalized prescribing, which can now be formally tested in clinical trials. These simple clinical measures can be used to inform patient treatment expectations; allowing treatment modifications and/or switching to alternative therapies.

Should we be imaging lymph nodes at initial diagnosis of early-stage mycosis fungoides? Results from the PROspective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) international study.

BACKGROUND: Early-stage mycosis fungoides (MF) includes involvement of dermatopathic lymph nodes (LNs) or early lymphomatous LNs. There is a lack of unanimity among current guidelines regarding the indications for initial staging imaging in early-stage presentation of MF in the absence of enlarged palpable LNs. OBJECTIVES: To investigate how often imaging is performed in patients with early-stage presentation of MF, to assess the yield of LN imaging, and to determine what disease characteristics promoted imaging. METHODS: A review of clinicopathologically confirmed newly diagnosed patients with cutaneous patch/plaque (T1/T2) MF from PROspective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) data. RESULTS: PROCLIPI enrolled 375 patients with stage T1/T2 MF: 304 with classical MF and 71 with folliculotropic MF. Imaging was performed in 169 patients (45%): 83 with computed tomography, 18 with positron emission tomography-computed tomography and 68 with ultrasound. Only nine of these (5%) had palpable enlarged (≥ 15 mm) LNs, with an over-representation of plaques, irrespectively of the 10% body surface area cutoff that distinguishes T1 from T2. Folliculotropic MF was not more frequently imaged than classical MF. Radiologically enlarged LNs (≥ 15 mm) were detected in 30 patients (18%); only seven had clinical lymphadenopathy. On multivariate analysis, plaque presentation was the sole parameter significantly associated with radiologically enlarged LNs. Imaging of only clinically enlarged LNs upstaged 4% of patients (seven of 169) to at least IIA, whereas nonselective imaging upstaged another 14% (24 of 169). LN biopsy, performed in eight of 30 patients, identified N3 (extensive lymphomatous involvement) in two and N1 (dermatopathic changes) in six. CONCLUSIONS: Physical examination was a poor determinant of LN enlargement or involvement. Presence of plaques was associated with a significant increase in identification of enlarged or involved LNs in patients with early-stage presentation of MF, which may be important when deciding who to image. Imaging increases the detection rate of stage IIA MF, and identifies rare cases of extensive lymphomatous nodes, upstaging them to advanced-stage IVA2.

'I saw it on Facebook!' Assessing the influence of social media on patient presentation to a melanoma screening clinic.

BACKGROUND: The motivations for patients presenting to melanoma screening clinics (MSCs) with concerning skin lesions are poorly understood. Social media (SoMe) refers to online platforms designed to facilitate sharing of information with billions of users worldwide. There is evidence of patients posting skin lesion 'selfies' on SoMe, influencing internet searches. Interventions through SoMe may have positive impacts on health seeking behaviour. AIM: To identify the influence of SoMe on patients presenting to an MSC service, and to establish whether patients have been exposed to SoMe posts on skin cancer, from medical authorities or the public. METHOD: For this pilot study, qualitative data were collected from patient questionnaires over 7 consecutive weeks at MSCs in Newcastle upon Tyne hospitals. Questions involved demographics, factors influencing attendance, use of SoMe and exposure to content on skin lesions on SoMe. RESULTS: Questionnaires were collected from 249 patients across a range of ages. Self-examination of lesions was the most common driver. One person in the study population described SoMe as having motivated their attendance, while 30 patients recalled seeing posts from health authorities regarding skin cancer. Qualitative data indicated that patients could be influenced by targeted public health campaigns on SoMe. CONCLUSIONS: This study suggests that SoMe is not currently a major conscious driver to attend an MSC, even among SoMe-familiar populations. However, the fact that SoMe is ubiquitous in society, in conjunction with our qualitative data, may suggest that current strategies for SoMe melanoma information delivery are not of requisite quality to break through to target populations.

Characteristics associated with significantly worse quality of life in mycosis fungoides/Sézary syndrome from the Prospective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) study.

BACKGROUND: Mycosis fungoides (MF) and Sézary Syndrome (SS) are the most common cutaneous T-cell lymphomas. MF/SS is accompanied by considerable morbidity from pain, itching and disfigurement. AIM: To identify factors associated with poorer health-related quality of life (HRQoL) in patients newly diagnosed with MF/SS. METHODS: Patients enrolled into Prospective Cutaneous Lymphoma International Prognostic Index (PROCLIPI; an international observational study in MF/SS) had their HRQoL assessed using the Skindex-29 questionnaire. Skindex-29 scores were analysed in relation to patient- and disease-specific characteristics. RESULTS: The study population consisted of 237 patients [60·3% male; median age 60 years, (interquartile range 49-70)], of whom 179 had early MF and 58 had advanced MF/SS. In univariate analysis, HRQoL, as measured by Skindex-29, was worse in women, SS, late-stage MF, those with elevated lactate dehydrogenase, alopecia, high modified Severity Weighted Assessment Tool and confluent erythema. Linear regression models only identified female gender (ß = 8·61; P = 0·003) and alopecia (ß = 9·71, P = 0·02) as independent predictors of worse global HRQoL. Item-level analysis showed that the severe impairment in symptoms [odds ratio (OR) 2·14, 95% confidence interval (CI) 1·19-3·89] and emotions (OR 1·88, 95% CI 1·09-3·27) subscale scores seen in women was caused by more burning/stinging, pruritus, irritation and greater feelings of depression, shame, embarrassment and annoyance with their diagnosis of MF/SS. CONCLUSIONS: HRQoL is significantly more impaired in newly diagnosed women with MF/SS and in those with alopecia. As Skindex-29 does not include existential questions on cancer, which may cause additional worry and distress, a comprehensive validated cutaneous T-cell lymphoma-specific questionnaire is urgently needed to more accurately assess disease-specific HRQoL in these patients. What's already known about this topic? Cross-sectional studies of mixed populations of known and newly diagnosed patients with mycosis fungoides (MF)/Sézary syndrome (SS) have shown significant impairment in health-related quality of life (HRQoL). Previous studies on assessing gender-specific differences in HRQoL in MF/SS are conflicting. More advanced-stage disease and pruritus is associated with poorer HRQoL in patients with MF/SS. What does this study add? This is the first prospective study to investigate HRQoL in a homogenous group of newly diagnosed patients with MF/SS. In patients newly diagnosed with MF/SS, HRQoL is worse in women and in those with alopecia and confluent erythema. MF/SS diagnosis has a multidimensional impact on patient HRQoL, including a large burden of cutaneous symptoms, as well as a negative impact on emotional well-being.

Kidney disease in moderate-to-severe psoriasis: a critical appraisal.

AIM: Using a population-based cohort, Wan et al. examined the risk of moderate-to-advanced (stage 3-5) chronic kidney disease (CKD) in patients with psoriasis. SETTING AND DESIGN: A population-based cohort was constructed using The Health Improvement Network (THIN) database. THIN is an electronic primary healthcare records database containing routinely collected medical diagnosis and drug prescribing data on > 9 million patients in the U.K. Data were collected prospectively on 143 883 adults (aged 18-90 years) with psoriasis. Of these, 7354 had severe psoriasis, as defined by prescription codes for systemic medication or treatment codes for phototherapy. Patients with psoriasis were matched with up to five nonpsoriasis age- and practice-matched controls. Patients with a diagnosis of CKD before study entry were excluded. In addition, baseline data from the Incident Health Outcomes and Psoriasis Events (iHOPE) study, a cohort of 8731 primary care patients aged 25-64 years with psoriasis, was included. Psoriasis severity was categorized according to body surface area (BSA) involvement as estimated by general practitioners. A similar method using a patient-reported BSA assessment tool was previously validated by the same group. Patients were matched by age and practice with 10 nonpsoriasis controls. STUDY EXPOSURE: Psoriasis, identified on the basis of a recorded diagnostic code for psoriasis. OUTCOMES: Incident CKD was defined as the presence of a recorded diagnostic code consistent with moderate-to-advanced (stage 3-5) CKD or laboratory parameters consistent with the diagnosis (estimated glomerular filtration rate < 60 mL min(-1)  1·73 m(-2) ) during follow-up. Prevalent CKD (as defined above) in the cross-sectional data from the iHOPE study. RESULTS: The adjusted hazard ratios for incident CKD were 1·05 [95% confidence interval (CI) 1·02-1·07], 0·99 (95% CI 0·97-1·02) and 1·93 (95% CI 1·79-2·08) in the overall, mild and severe psoriasis groups, respectively. In the nested cross-sectional study (iHOPE) the adjusted prevalence odds ratios for CKD were 0·89 (95% CI 0·72-1·10), 1·36 (95% CI 1·06-1·74) and 1·58 (95% CI 1·07-2·34) in the mild, moderate and severe psoriasis groups, respectively. CONCLUSIONS: Moderate-to-severe psoriasis is associated with an increased risk of moderate-to-advanced CKD, independently of traditional risk factors.

Effect of tissue shrinkage on histological tumour-free margin after excision of basal cell carcinoma.

BACKGROUND: Histology reports of skin tumour excisions frequently describe a histological margin significantly less than the planned surgical excision margin. OBJECTIVES: A novel method of marking visible tumour margin was devised. This allowed us to evaluate the accuracy of tumour detection and to compare tissue contraction of the clinically normal perilesional skin with that of tumour tissue following excision and fixation. METHODS: Forty-four well-defined basal cell carcinomas were excised from 42 patients. The visible tumour edge was marked by scoring with a blade around its circumference prior to excision. This allowed comparison of visible and true histological tumour margin. The excision margin was carefully measured from the scored line and the tumour excised. After tissue fixation and processing the histological dimensions of tumour and perilesional margin skin were compared with the pre-excision measurements. RESULTS: The tumour edge was accurately identified to within 1 mm in 67% of margins and was underestimated in only 4%. The whole specimen contracted by a mean of 14%. Skin containing tumour contracted by a mean of 11% but adjacent tumour-free skin in the same plane contracted by a mean of 19%. There was no significant effect of age and site on difference in percentage shrinkage between tumour and margin. CONCLUSIONS: We underestimated tumour extent at only 4% of margins. Tissue shrinkage was the most important factor affecting eventual histological margin. Our novel technique allowed us to demonstrate that this shrinkage is not uniform across the specimen, but is disproportionately high in the tumour-free margin. This suggests that previous estimates of margin shrinkage, based on whole-specimen contraction measurements, may have been erroneously low.

An open-label, dose-ranging study of methotrexate for moderate-to-severe adult atopic eczema.

BACKGROUND: Treatment options for moderate-to-severe atopic eczema are limited. Although methotrexate (MTX) is a widely used and effective treatment for psoriasis, there have been no previous prospective trials of its use in refractory atopic eczema, despite a few small, retrospective reports suggesting that it is a well-tolerated and effective treatment. OBJECTIVES: We have assessed the safety and efficacy of oral MTX in 12 adults with moderate-to-severe atopic eczema in an open-label, dose-ranging, prospective trial using objective outcome measures. METHODS: All patients had previously received other second-line therapies and had disease only partially responsive to potent topical steroids and emollients. During the 24-week MTX treatment period, unrestricted use of standard topical therapy was permitted. We used an incremental MTX dose regime, starting at 10 mg per week (following a 5-mg test dose) and increasing by 2.5 mg weekly until response was achieved or treatment was limited by toxicity. Disease activity [six area six sign atopic dermatitis (SASSAD) score] was assessed every 4 weeks during treatment and 12 weeks after stopping MTX. The primary endpoint was 24-week change in disease activity. RESULTS: On average, disease activity improved by 52% from baseline (95% confidence interval 45-60%). There were significant improvements in quality of life, body surface area affected and loss of sleep and itch scores. Global response was rated as 'marked improvement' in five of 12 and six of 12 patients, by investigators and patients, respectively. In all patients, the majority of improvement in disease activity was seen by week 12, and, interestingly, patients who had not responded well over this period despite reaching a dose of 15 mg weekly failed to improve with further dose escalation. Only one patient withdrew due to minor adverse effects. MTX was well tolerated by the remaining 11 patients, all of whom completed treatment, achieving a median dose of 15 mg weekly. Importantly, eight of nine patients had a persistent improvement 12 weeks after stopping MTX, with mean disease activity remaining 34% below baseline. CONCLUSIONS: We have shown that MTX is an effective, well-tolerated treatment for moderate-to-severe atopic eczema, and response appears to compare favourably with other second-line therapies. A randomized, controlled trial is now warranted.

Melanomas arising from naevi and de novo melanomas--does origin matter?

BACKGROUND: It is widely accepted that some melanomas arise from pre-existing naevi, while others appear de novo. The proportions involved and the effect of melanoma origin on prognosis is unclear. OBJECTIVES: To determine whether melanomas reported by the patient to have developed from a pre-existing naevus are associated with a better or worse prognosis compared with those arising de novo when adjusted for confounding variables. METHODS: All patients attending a dedicated melanoma screening clinic between March 1997 and March 2002 were included. The distinction between melanoma arising without any pre-existing lesion (de novo) and those derived from a pre-existing lesion (naevus melanoma) was based on patient history. We categorized patients into three groups: those who gave a history of their lesion arising within a pre-existing naevus, those in whom the melanoma developed de novo and those in whom no conclusive history could be obtained. We compared prognostic indicators between the naevus and de novo melanoma groups. RESULTS: Of 8593 patients screened, 377 had a positive diagnosis of melanoma (in situ or invasive). Of these 42% had naevus melanomas, 34% new melanomas and 24% were uncertain. Patients presenting with a melanoma arising from a pre-existing naevus had a greater Breslow thickness despite presenting sooner than the de novo group, although no significant difference in thickness was found when other prognostic factors were controlled for. CONCLUSIONS: This prospective study shows that naevi that undergo malignant change may result in melanomas that are thicker and thus potentially have a worse prognosis than de novo melanomas. Although our results were not statistically significant when other risk factors were also taken into account, it is possible that a larger study would identify a significant association.

Melanoma screening clinics: are we detecting more melanomas or reassuring the worried well?

BACKGROUND: Melanoma screening clinics (MSCs) have been set up in the U.K. to help allay public anxiety about potential skin cancers, and to permit the early detection of thin melanomas, thus improving prognosis. Public health campaigns have led to increased awareness of melanoma and increased numbers of referrals to MSCs. OBJECTIVES: To determine whether the MSC has had an impact on the number and thickness of melanomas detected over the past 8 years. METHODS: Data was analysed retrospectively for all patients attending the MSC since it was set up in 1997, until the end of 2004. We categorized patients with melanoma according to Breslow thickness, examined trends in referral to the clinic and analysed changes in the proportion of patients with a new diagnosis of melanoma. RESULTS: There were 15 970 patients who attended for screening; 403 primary invasive melanomas were detected, and 190 in situ melanomas. The number of new patients seen each year increased by over 230%, although the proportion of patients with melanoma detected declined. The Breslow thickness did not change over time. CONCLUSIONS: Our experience suggests that public awareness has increased and that the general practitioner threshold for referral has fallen but there has been no reduction in the thickness of those melanomas diagnosed.

Managed substitution of modified release nitrates with an asymmetric dosing regimen.

BACKGROUND: Orally administered modified release organic nitrates are used commonly in the prophylaxis of myocardial ischaemia, although little evidence indicates a clinically superior response compared with standard formulated preparations administered symmetrically. AIM: To investigate the clinical success of transfer of suitable patients from MR to SF nitrates. METHOD: Suitable candidates for therapeutic substitution, assessed by a pharmacist, completed a baseline study to estimate frequency and timing of chest pain, the number of rescue doses of sublingual nitrates required, together with an assessment of adverse effects experienced. Following substitution to an eccentric dosing schedule, a further one month's assessment of chest pain frequency, rescue nitrate use and adverse effects was recorded and compared with baseline. RESULTS: Twelve (37.5%) patients from a possible 32 candidates were invited to complete a baseline symptoms and adverse event diary. Eight patients entered the study phase (66.7% of the 12 included in the baseline phase of the study). These candidates showed no evidence of loss of control of chest pain symptoms, 3.5 +/- 1.16 (mean +/- standard error of mean) episodes/patient/28 days compared with 1.9 +/- 0.96 episodes/patient/28 days during the test phase (P > 0.05). Similarly, there was no difference in the number of doses of rescue nitrates required when the trial phase (2.6 +/- 1.63 doses/patient/28 days) was compared with the control (2.0 +/- 1.31 doses/patient/28 days, P > 0.05). There was no evidence of an increased incidence of adverse effects during the trial period of the study. CONCLUSION: This small study suggests that, if selected carefully, therapeutic substitution of MR oral nitrates can be managed successfully without apparent risk of loss of symptom control or increased incidence of adverse effects.