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.

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.