Pharmacokinetic characterisation of a valproate Autism Spectrum Disorder rat model in a context of co-exposure to α-Hexabromocyclododecane.

Assessing the role of α-hexabromocyclododecane α-HBCDD as a factor of susceptibility for Autism Spectrum disorders by using valproic acid-exposed rat model (VPA) required characterizing VPA pharmacokinetic in the context of α-HBCDD-co-exposure in non-pregnant and pregnant rats. The animals were exposed to α-HBCDD by gavage (100 ng/kg/day) for 12 days. This was followed by a single intraperitoneal dose of VPA (500 mg/kg) or a daily oral dose of VPA (500 mg/kg) for 3 days. Exposure to α-HBCDD did not affect the pharmacokinetics of VPA in pregnant or non-pregnant rats. Surprisingly, VPA administration altered the pharmacokinetics of α-HBCDD. VPA also triggered higher foetal toxicity and lethality with the PO than IP route. α-HBCDD did not aggravate the embryotoxicity observed with VPA, regardless of the route of exposure. Based on this evidence, a single administration of 500 mg/kg IP is the most suitable VPA model to investigate α-HBCDD co-exposure.

Cryosurgery versus curettage for intraepidermal carcinoma: A randomized controlled trial.

BACKGROUND: Cryosurgery is a common destructive treatment method for intraepidermal carcinoma (IEC) above the knee. Curettage alone is a simple, non-aggressive and inexpensive treatment method commonly used on benign skin lesions. However, only one study has assessed curettage for treatment of IEC. OBJECTIVE: We aimed to (1) compare the effectiveness of cryosurgery (standard method) to curettage (experimental method) for treatment of IEC in regard to overall clearance rates at 1-year follow-up, and (2) investigate whether wound healing times differed between the treatment groups. METHODS: In this randomized and controlled, non-inferiority trial, adult patients with one or more IEC with a diameter of 5-20 mm, located above the knee and suitable for destructive treatment were recruited from Sahlgrenska University Hospital (Gothenburg, Sweden). Lesions were randomized to treatment with either cryosurgery or curettage. Wound healing was assessed by a nurse after 4-6 weeks and through self-report forms. Overall clearance was assessed by a dermatologist after 1 year. RESULTS: In total, 183 lesions in 147 patients were included, with 93 lesions randomized to cryosurgery and 90 to curettage. Eighty-eight (94.6%) of the lesions in the cryosurgery group and 71 (78.9%) in the curettage group showed an overall clearance at the 1-year follow-up visit (p = 0.002). The non-inferiority analysis was inconclusive. Curettage resulted in both shorter self-reported wound healing times (mean time 3.1 vs. 4.8 weeks, p < 0.001) and a larger proportion of healed wounds after 4-6 weeks (p < 0.001). CONCLUSIONS: Cryosurgery and curettage both result in high clearance rates for treatment of IEC, but cryosurgery is significantly more effective. On the other hand, curettage may result in shorter wound healing times.

Assessment of melanoma thickness based on dermoscopy images: an open, web-based, international, diagnostic study.

BACKGROUND: Preoperative assessment of whether a melanoma is invasive or in situ (MIS) is a common task that might have important implications for triage, prognosis and the selection of surgical margins. Several dermoscopic features suggestive of melanoma have been described, but only a few of these are useful in differentiating MIS from invasive melanoma. OBJECTIVE: The primary aim of this study was to evaluate how accurately a large number of international readers, individually as well as collectively, were able to discriminate between MIS and invasive melanomas as well as estimate the Breslow thickness of invasive melanomas based on dermoscopy images. The secondary aim was to compare the accuracy of two machine learning convolutional neural networks (CNNs) and the collective reader response. METHODS: We conducted an open, web-based, international, diagnostic reader study using an online platform. The online challenge opened on 10 May 2021 and closed on 19 July 2021 (71 days) and was advertised through several social media channels. The investigation included, 1456 dermoscopy images of melanomas (788 MIS; 474 melanomas ≤1.0 mm and 194 >1.0 mm). A test set comprising 277 MIS and 246 invasive melanomas was used to compare readers and CNNs. RESULTS: We analysed 22 314 readings by 438 international readers. The overall accuracy (95% confidence interval) for melanoma thickness was 56.4% (55.7%-57.0%), 63.4% (62.5%-64.2%) for MIS and 71.0% (70.3%-72.1%) for invasive melanoma. Readers accurately predicted the thickness in 85.9% (85.4%-86.4%) of melanomas ≤1.0 mm (including MIS) and in 70.8% (69.2%-72.5%) of melanomas >1.0 mm. The reader collective outperformed a de novo CNN but not a pretrained CNN in differentiating MIS from invasive melanoma. CONCLUSIONS: Using dermoscopy images, readers and CNNs predict melanoma thickness with fair to moderate accuracy. Readers most accurately discriminated between thin (≤1.0 mm including MIS) and thick melanomas (>1.0 mm).

Curettage vs. cryosurgery for superficial basal cell carcinoma: a prospective, randomised and controlled trial.

BACKGROUND: Basal cell carcinoma (BCC) is the most common cancer in the world and has a rising incidence. Current guidelines for low-risk BCC including superficial BCC (sBCC) recommend several treatment options including destructive treatment methods, such as cryosurgery with or without prior curettage or curettage and electrodesiccation. Curettage only (i.e. without subsequent cryosurgery or electrodesiccation) is a simple and quick destructive treatment method used for many benign skin lesions but has not been sufficiently evaluated for the treatment of sBCCs. OBJECTIVES: The objective was to compare the effectiveness of curettage vs. cryosurgery for sBCCs in terms of overall clinical clearance rates after 1 year as well as wound healing times. METHODS: A single-centre non-inferiority clinical trial was conducted. Non-facial sBCCs with a diameter of 5-20 mm were randomised to either cryosurgery using one freeze-thaw cycle or curettage. At follow-up visits, treatment areas were evaluated regarding the presence of residual tumour after 3-6 months and recurrence after 1 year. Further, wound healing times were assessed. RESULTS: In total, 228 sBCCs in 97 patients were included in the analysis. At 3-6 months, no residual tumours were seen in any of the treated areas. After 1 year, the clinical clearance rates for curettage and cryosurgery were 95.7% and 100%, respectively (P = 0.060). However, the non-inferiority analysis was inconclusive. Wound healing times were shorter for curettage (4 weeks) compared to cryosurgery (5 weeks; P < 0.0001). Overall, patient satisfaction at 1 year was high. CONCLUSIONS: Both treatment methods showed high clinical clearance rates after 1 year, whilst curettage reduced the wound healing time.

Dermoscopy of porokeratosis: results from a multicentre study of the International Dermoscopy Society.

BACKGROUND: The diagnosis of porokeratosis can be challenging, and knowledge about its dermoscopic features is limited. OBJECTIVES: To describe the dermoscopic features of porokeratosis of Mibelli and disseminated superficial actinic porokeratosis (DSAP) and the frequency of these features in a larger case series. The interobserver concordance was also assessed. METHODS: In this retrospective cohort study, members of the International Dermoscopy Society contributed macroscopic and dermoscopic images of histopathologically verified cases of porokeratosis of Mibelli or DSAP. Three observers independently reviewed the collected images to identify the presence of predefined dermoscopic features. Following this, a consensus meeting was held to agree upon which dermoscopic features were present in each lesion. RESULTS: In total, 78 clinical and dermoscopic images of porokeratoses were collected. The most common dermoscopic feature was keratin rim, which was present in 74 lesions (92.3%). The most common vascular structures were dotted or glomerular vessels which were present in almost half of the cases (48.7%). Other relatively frequent dermoscopic findings were as follows: non-peripheral scales (44.9%), grey-brown dots or pigmentation along the keratin rim (38.5%), and light-brown pigmentation within the keratin rim (33.3%). Shiny white structures and blood spots or erosions along the keratin rim were findings never before described in porokeratosis and were detected in 16.7% and 17.9% of the lesions, respectively. Dermoscopic findings in porokeratosis of Mibelli and DSAP were similar except for fewer blood spots or erosions along the keratin rim and more light-brown pigmentation within the keratin rim in DSAP. The interobserver concordance ranged from 0.44 (moderate) to 0.84 (almost perfect). CONCLUSIONS: The dermoscopic hallmark of porokeratosis is the keratin rim, a finding also allowing for almost perfect interobserver agreement. Pigmentation or erosions along the keratin rim, vascular structures, as well as scales, pigmentation or shiny white structures within the keratin rim are additional dermoscopic clues.

Which medical disciplines diagnose and treat melanoma in Europe in 2019? A survey of experts from melanoma centres in 27 European countries.

BACKGROUND AND OBJECTIVES: The incidence of melanoma is increasing. This places significant burden on societies to provide efficient cancer care. The European Cancer Organisation recently published the essential requirements for quality melanoma care. The present study is aimed for the first time to roughly estimate the extent to which these requirements have been met in Europe. MATERIALS AND METHODS: A web-based survey of experts from melanoma centres in 27 European countries was conducted from 1 February to 1 August 2019. Data on diagnostic techniques, surgical and medical treatment, organization of cancer care and education were collected and correlated with national health and economic indicators and mortality-to-incidence ratio (MIR) as a surrogate for survival. Univariate linear regression analysis was performed to evaluate the correlations. SPSS software was used. Statistical significance was set at P < 0.05. RESULTS: The MIR was lower in countries with a high health expenditure per capita and with a higher numbers of general practitioners (GPs) and surgeons (SURG) per million inhabitants. In these countries, GPs and dermatologists (DER) were involved in melanoma detection; high percentage of DER used dermatoscopy and were involved in the follow-up of all melanoma stages; both medical oncologists (ONC) and dermato-oncologists administered systemic treatments; and patients had better access to sentinel lymph node biopsy and were treated within multidisciplinary tumour boards. CONCLUSION: Based on these first estimates, the greater involvement of GPs in melanoma detection; the greater involvement of highly trained DER in dermatoscopy, dermatosurgery, follow-up and the systemic treatment of melanoma; and the provision of ongoing dermato-oncology training for pathologists, SURG, DER and ONC are necessary to provide an optimal melanoma care pathway. A comprehensive analysis of the melanoma care pathway based on clinical melanoma registries will be needed to more accurately evaluate these first insights.

Dermatoscopic features of thin (≤2 mm Breslow thickness) vs. thick (>2 mm Breslow thickness) nodular melanoma and predictors of nodular melanoma versus nodular non-melanoma tumours: a multicentric collaborative study by the International Dermoscopy Society.

BACKGROUND: Thin nodular melanoma (NM) often lacks conspicuous melanoma-specific dermatoscopic criteria and escapes clinical detection until it progresses to a thicker and more advanced tumour. OBJECTIVE: To investigate the dermatoscopic morphology of thin (≤2 mm Breslow thickness) vs. thick (>2 mm) NM and to identify dermatoscopic predictors of its differential diagnosis from other nodular tumours. METHODS: Retrospective, morphological case-control study, conducted on behalf of the International Dermoscopy Society. Dermatoscopic images of NM and other nodular tumours from 19 skin cancer centres worldwide were collected and analysed. RESULTS: Overall, 254 tumours were collected (69 NM of Breslow thickness ≤2 mm, 96 NM >2 mm and 89 non-melanoma nodular lesions). Light brown coloration (50.7%) and irregular brown dots/globules (42.0%) were most frequently observed in ≤2 mm NMs. Multivariate analysis revealed that dotted vessels (3.4-fold), white shiny streaks (2.9-fold) and irregular blue structureless area (2.4-fold) were predictors for thinner NM compared to non-melanoma nodular tumours. Overall, irregular blue structureless area (3.4-fold), dotted vessels (4.6-fold) and serpentine vessels (1.9-fold) were predictors of all NM compared to non-melanoma nodular lesions. LIMITATIONS: Absence of a centralized, consensus pathology review and cases selected form tertiary centres maybe not reflecting the broader community. CONCLUSIONS: Our study sheds light into the dermatoscopic morphology of thin NM in comparison to thicker NM and could provide useful clues for its differential diagnosis from other non-melanoma nodular tumours.

Methotrexate treatment for patients with psoriasis and risk of cutaneous melanoma: a nested case-control study.

BACKGROUND: Cutaneous malignant melanoma (CMM) is a highly immunogenic tumour. Patients with an impaired immune system have an enhanced risk for CMM and a worse prognosis. Methotrexate (MTX) is an anti-inflammatory and immunosuppressive drug frequently used to treat patients with psoriasis. An association between MTX and risk of CMM has previously been demonstrated in patients with rheumatoid arthritis. OBJECTIVES: To investigate whether MTX increases the risk of CMM among patients with psoriasis. METHODS: A nested case-control investigation from a Swedish cohort of patients with psoriasis was conducted. Data were obtained from available Swedish registers and included 395 patients with psoriasis who had previously been cancer-free and had a first CMM in the time period from 1 January 2010 to 31 December 2016. A total of 10 randomly selected cancer-free patients with psoriasis were matched per case with respect to age (same birth year) and sex. The accumulated MTX doses in both groups were obtained. Crude odds ratios (ORs) for the proportion of MTX in the respective group were calculated using conditional logistic regression analyses. RESULTS: Of 395 patients with psoriasis who had CMM, 97 (25%) had filled a prescription of MTX; of 3950 controls, the corresponding number was 954 (24%). In a conditional logistic regression analysis, no association between MTX exposure (ever use) and risk for CMM was observed (OR 1·0, 95% confidence interval 0·8-1·3). Moreover, no indication of a dose-response association was observed. CONCLUSIONS: In this Swedish nested case-control study, the use of MTX was not associated with an enhanced risk for CMM. These findings are reassuring for dermatologists in everyday clinical practice. What is already known about this topic? Methotrexate (MTX) treatment has been linked to an increased risk for cutaneous malignant melanoma (CMM) in an Australian cohort of patients with rheumatoid arthritis. In a previous retrospective Swedish cohort investigation, patients who had exclusively been prescribed MTX by a dermatologist did not have an enhanced risk for CMM compared with MTX-unexposed individuals. Nevertheless, this cohort did not specifically include patients with psoriasis. What does this study add? This Swedish nested case-control investigation included 395 previously cancer-free patients with psoriasis who had CMM (cases) and 3950 matched cancer-free patients with psoriasis (controls). No association between MTX exposure and risk for CMM in patients with psoriasis was observed. The results are reassuring for dermatologists using MTX to treat patients with psoriasis. Linked Comment: Haugaard and Egeberg. Br J Dermatol 2020; 183:608-609.

Standardization of dermoscopic terminology and basic dermoscopic parameters to evaluate in general dermatology (non-neoplastic dermatoses): an expert consensus on behalf of the International Dermoscopy Society.

BACKGROUND: Over the last few years, several articles on dermoscopy of non-neoplastic dermatoses have been published, yet there is poor consistency in the terminology among different studies. OBJECTIVES: We aimed to standardize the dermoscopic terminology and identify basic parameters to evaluate in non-neoplastic dermatoses through an expert consensus. METHODS: The modified Delphi method was followed, with two phases: (i) identification of a list of possible items based on a systematic literature review and (ii) selection of parameters by a panel of experts through a three-step iterative procedure (blinded e-mail interaction in rounds 1 and 3 and a face-to-face meeting in round 2). Initial panellists were recruited via e-mail from all over the world based on their expertise on dermoscopy of non-neoplastic dermatoses. RESULTS: Twenty-four international experts took part in all rounds of the consensus and 13 further international participants were also involved in round 2. Five standardized basic parameters were identified: (i) vessels (including morphology and distribution); (ii) scales (including colour and distribution); (iii) follicular findings; (iv) 'other structures' (including colour and morphology); and (v) 'specific clues'. For each of them, possible variables were selected, with a total of 31 different subitems reaching agreement at the end of the consensus (all of the 29 proposed initially plus two more added in the course of the consensus procedure). CONCLUSIONS: This expert consensus provides a set of standardized basic dermoscopic parameters to follow when evaluating inflammatory, infiltrative and infectious dermatoses. This tool, if adopted by clinicians and researchers in this field, is likely to enhance the reproducibility and comparability of existing and future research findings and uniformly expand the universal knowledge on dermoscopy in general dermatology. What's already known about this topic? Over the last few years, several papers have been published attempting to describe the dermoscopic features of non-neoplastic dermatoses, yet there is poor consistency in the terminology among different studies. What does this study add? The present expert consensus provides a set of standardized basic dermoscopic parameters to follow when evaluating inflammatory, infiltrative and infectious dermatoses. This consensus should enhance the reproducibility and comparability of existing and future research findings and uniformly expand the universal knowledge on dermoscopy in general dermatology.

Diagnostic accuracy and safety of short-term teledermoscopic monitoring of atypical melanocytic lesions.

BACKGROUND: Short-term dermoscopic monitoring (STDM) of atypical melanocytic lesions (AML) after 3.0-4.5 months can be used to detect featureless melanomas without performing countless unnecessary excisions of nevi. Recently, short-term teledermoscopic monitoring (STTM) was incorporated into the STDM clinical routine at Sahlgrenska University Hospital in Gothenburg, Sweden. Follow-up images for STTM were taken by an assistant nurse with subsequent teledermoscopic assessment by a dermatologist. OBJECTIVES: The purpose of this study was to evaluate the diagnostic accuracy and safety of STTM. METHODS: In this retrospective observational study, data from electronic health records of patients with teledermoscopically monitored AMLs were explored. The number of changed and excised AMLs and their histopathological diagnoses were recorded. The excised AMLs were categorized into three subgroups according to when they changed and were excised: (i) following STTM, (ii) after planned long-term follow-up or (iii) after unplanned long-term follow-up. RESULTS: A total of 686 patients with 883 AMLs were monitored with STTM. Sixty-two AMLs (7.0%) were excised following STTM, 14 (1.6%) after planned long-term follow-up and 10 (1,1%) after unplanned long-term follow-up. Twenty-one melanomas were detected using STTM, three after planned long-term follow-up and three after unplanned long-term follow-up. All melanomas were in situ (n = 20) or thin and non-ulcerated (n = 7; median Breslow thickness 0.4 mm, range 0.3-0.8 mm). The sensitivity for the diagnosis of melanoma by means of STTM with the option of additional planned follow-up was 88.9%, and the specificity was 93.9%. The number of AMLs needed to monitor in order to detect one melanoma with the STTM routine was 32.7, and the number needed to excise was 3.2. CONCLUSIONS: STTM of AMLs was safe and allowed for high diagnostic accuracy. All detected melanomas were in situ or thin and non-ulcerated. Furthermore, a considerable number of unnecessary excisions were spared.

Variability in the diagnosis of surgical-site infections after full-thickness skin grafting: an international survey.

BACKGROUND: Diagnosis of a surgical-site infection (SSI) in dermatological surgery can be based entirely on a subjective assessment, according to the fourth criterion of the most common definition of an SSI, which was established by the US Centers for Disease Control and Prevention. OBJECTIVES: To investigate the interobserver agreement between dermatologists in their diagnosis of SSI of dermatosurgical wounds. METHODS: An international electronic photographic survey with eight photographs of wounds 1 week after full-thickness skin grafting (FTSG) was sent to dermatologists. All wounds were assessed in terms of visual criteria beforehand. Data collected from respondents included physician characteristics and experience, and SSI assessments of all wounds. RESULTS: In total, 393 dermatologists from 27 countries enrolled. Most respondents were from the U.S.A. (25%), followed by Sweden (24%) and the U.K. (13%). There was only a slight interobserver agreement on SSI suspicion (κ = 0·19). SSI suspicion was lower for male physicians (P = 0·03), board-certified dermatologists (P = 0·001), physicians regularly assessing surgical wounds (P = 0·03) and physicians performing FTSG (P < 0·001). Swedish physicians diagnosed more SSIs than U.S. physicians (P = 0·002). Erythema was more common in cases with higher SSI suspicion. CONCLUSIONS: This study reveals broad inter-rater variability in the diagnosis of SSI, illustrating the need for novel objective diagnostic methods that can better capture the variables that constitute an SSI.

Teledermoscopy images acquired in primary health care and hospital settings - a comparative study of image quality.

BACKGROUND: The incidence of melanoma and non-melanoma skin cancer is increasing, which has also lead to an increase in referrals between primary health care (PHC) and dermatology departments, putting a strain on healthcare services. Teledermoscopy (TDS) referrals from PHC can improve the triage process for patients with suspicious skin tumours, but the quality of the images included could potentially affect its usefulness. OBJECTIVE: To critically appraise the quality of the dermoscopic images of a smartphone TDS system, by comparing the TDS referral images with images of the same tumours acquired at the department of dermatology. METHODS: Two dermatologists rated the image quality of two image sets from 172 skin tumours separately. The dermatologists also decided on a main diagnosis, differential diagnoses and described the visible dermoscopic structures. RESULTS: The images acquired in PHC were rated as having slightly lower quality, but there was no significant difference. PHC images and dermatology images were of intermediate-to-high quality in 95.5%-97.7% and 96.5%-98.8%, respectively. There was no difference in agreement between the TDS diagnosis based on the two image sets with the final clinical or histopathological diagnosis. Most image pairs (81.4% and 83.7%) received the same main diagnosis by the two evaluators. When this was not the case, the most common reasons were poor focus, excessive pressure applied when acquiring the image or inadequate amount of zoom. CONCLUSION: TDS performed in PHC with a smartphone-based system does not seem to negatively affect the usefulness of TDS referrals. Thus, physicians at PHC do not necessarily need to be trained photographers to ensure adequate TDS image quality. Knowledge about technical difficulties could however be used when training PHC staff, to improve the image quality further.

Diagnostic agreement and interobserver concordance with teledermoscopy referrals.

BACKGROUND: Malignant melanoma and non-melanoma skin cancers are among the fastest increasing malignancies in many countries. With the help of new tools, such as teledermoscopy referrals between primary health care and dermatology clinics, the management of these patients could be made more efficient. OBJECTIVE: To evaluate the diagnostic agreement and interobserver concordance achieved when assessing referrals sent through a mobile teledermoscopic referral system as compared to referrals sent via the current paper-based system without images. METHODS: The referral information from 80 teledermoscopy referrals and 77 paper referrals were evaluated by six Swedish dermatologists. They were asked to answer questions about the probable diagnosis, the priority, and a management decision. RESULTS: Teledermoscopy generally resulted in higher diagnostic agreement, better triaging and more malignant tumours being booked directly to surgery. The largest difference between the referral methods was seen for invasive melanomas. Referrals for benign lesions were significantly more often correctly resent to primary health care with teledermoscopy. However, referrals for cases of melanoma in situ were also incorrectly resent five times. The interobserver concordance was moderate with both methods. CONCLUSION: By adding clinical and dermoscopic images to referrals, the triage process for both benign and dangerous skin tumours can be improved. With teledermoscopy, patients with melanoma especially can receive treatment more swiftly.

Effectiveness of photodynamic therapy in Bowen's disease: a retrospective observational study in 423 lesions.

BACKGROUND: Photodynamic therapy (PDT) is a well-known technique that is often used for treating superficial precancerous and cancerous skin lesions. However, only a handful of studies, with a relatively small number of treated lesions, have been carried out on the effectiveness of PDT for Bowen's disease (BD). OBJECTIVES: This study aimed to assess the effectiveness and recurrence risk of PDT in the treatment of BD. The secondary objectives were to determine what factors affected the response rates and the cosmetic result of the treatment. METHOD: In this retrospective observational study, the electronic patient charts at Sahlgrenska University Hospital (SUH) in Gothenburg, Sweden, were searched to find all patients diagnosed with BD who were treated with PDT between 1 January 2002 and 31 December 2014. Data were collected regarding clinical response at the first follow-up visit, recurrences during later follow-up visits and other relevant patient and tumour characteristics. RESULTS: In total, 423 BD lesions in 335 patients were included in the study. The mean FU duration was 11.2 months (range 0.2-151 months). The complete response rate at the first FU visit was 77.5% for all BD lesions. During later FU visits, another 60 recurrences were observed, which resulted in a recurrence rate of 18.3%. Thus, the overall clearance rate after FU was 63.4% for all BD lesions. Significant risk factors for unsuccessful treatment in this study were large lesion size (>2 cm) and a single PDT session. CONCLUSION: This study shows that PDT is a relatively effective treatment modality for BD.

Alopecia areata totalis and universalis: a multicenter review of 132 patients in Spain.

BACKGROUND: Alopecia areata totalis (AAT) and universalis (AAU) pose a therapeutic challenge. OBJECTIVE: To describe the clinical and epidemiological features, therapeutic response and prognostic factors in a large series of patients diagnosed with AAT and AAU. METHODS: This retrospective multicenter study included patients diagnosed with AAT/AAU with a minimum follow-up of 12 months. Response was assessed based on the regrowth of scalp hair. RESULTS: In all, 132 patients (92 women and 40 men) - 80 (61%) diagnosed with AAU and 52 (39%) diagnosed with AAT - were included. The median time between the presentation of alopecia areata (AA) and the development of extensive AA was 1 year and it was less than 4 years in 121 patients (91%). There was an initial response to treatment in 64% of patients, although only 14% presented a persistent response. Adverse side effects from the medications used were detected in 33% of patients. The prognostic factors associated with poor response were the presence of AAU and a positive family history of AA. CONCLUSIONS: Treatment of AAT and AAU is challenging. Although an initial regrowth may be achieved, the duration of response is usually short. There were no significant differences on the effectiveness or duration of response between the various systemic therapies.

Methotrexate treatment and risk for cutaneous malignant melanoma: a retrospective comparative registry-based cohort study.

BACKGROUND: Methotrexate (MTX) is frequently used as an immunosuppressive drug in inflammatory diseases. It is controversial and it has not been thoroughly investigated whether MTX increases the risk of cutaneous malignant melanoma (CMM). OBJECTIVES: The aim of the present study was to investigate whether MTX exposure increases the risk for CMM. METHODS: A retrospective cohort study was conducted using statistics from the National Board of Health and Welfare. All patients over 18 years in the time period August 2005 to December 2014 that were dispensed MTX from Swedish pharmacies were registered (n = 101 966). For every MTX-exposed patient, five age- and sex-matched patients who had been dispensed a random drug other than MTX during the same time period were randomly selected (n = 509 279). The lists were matched with the Swedish Cancer Registry. RESULTS: Overall, a small but statistically significant (P < 0·001) risk increase for CMM was observed in MTX-exposed patients compared with patients without MTX exposure. The Kaplan-Meier estimates for the 5-year risk of CMM was 0·48% [95% confidence interval (CI) 0·43-0·53] in the MTX-exposed group and 0·41% (95% CI 0·39-0·43) in the MTX-unexposed group. However, in a subgroup analysis, the difference between the groups was preserved only in women older than 70 years at treatment start. Moreover, there was no significant difference in incidences between the MTX-exposed and MTX-unexposed patients in the time period. CONCLUSIONS: Our results suggest a small but significant increase in risk for CMM in patients treated with MTX. However, the risk increase observed was considerably lower than in earlier observations.