Safety of biologic therapy in combination with methotrexate in moderate to severe psoriasis: a cohort study from the BIOBADADERM registry.

BACKGROUND: Safety is an important consideration in decisions on treatment for patients with moderate-to-severe psoriasis and the study of drug safety is the main purpose of the BIOBADADERM registry. The combination of a biologic agent and a conventional systemic drug [generally methotrexate (MTX)] is a common treatment in clinical practice. However, there is a paucity of evidence from real-world practice on the safety of such combination regimens in the treatment of psoriasis. OBJECTIVES: The primary objective of this study was to ascertain whether the use of regimens combining biologic drugs with MTX in the management of moderate-to-severe psoriasis increases the risk of adverse events (AEs) or serious AEs (SAEs). We compared monotherapy using tumour necrosis factor (TNF), interleukin (IL)-17 and IL-23 inhibitors with the use of the same drugs in combination with MTX. METHODS: Using data from the BIOBADADERM registry, we compared biologic monotherapies with therapies that were combined with MTX. We estimated adjusted incidence rate ratios (aIRR) using a random effects Poisson regression with 95% confidence intervals for all AEs, SAEs, infections and serious infections and other AEs by system organ class. RESULTS: We analysed data from 2829 patients and 5441 treatment cycles, a total of 12 853 patient-years. The combination of a biologic with MTX was not associated with statistically significant increases in overall risk of AEs or SAEs in any treatment group. No increase in the total number of infections or serious infections in patients receiving combined therapy was observed for any group. However, treatment with a TNF inhibitor combined with MTX was associated with an increase in the incidence of gastrointestinal AEs (aIRR 2.50, 95% CI 1.57-3.98; P < 0.002). CONCLUSIONS: The risk of AEs and SAEs was not significantly increased in patients with moderate-to-severe psoriasis receiving different classes of biologic drugs combined with MTX compared with those on biologic monotherapy.

Extrafacial lentigo maligna: A progression model and enhanced diagnostic techniques using dermatoscopy and reflectance confocal microscopy.

Lentigo maligna (LM) is a subtype of lentiginous melanoma confined to the epidermis, which is associated with chronic sun exposure. Its clinical, dermatoscopic, and histopathological diagnosis can be challenging, particularly in the early and advanced stages, requiring appropriate clinicopathological correlation. This article reviews the clinical presentation, diagnosis through noninvasive methods (dermoscopy and confocal microscopy), and provides insights for diagnosis of extrafacial LM through the presentation of four representative clinical cases from different phases of a theoretical-practical progression model. Recognizing these lesions is crucial, as once they invade the dermis, they can behave like any other type of melanoma.

Monkeypox: a new differential diagnosis when addressing genital ulcer disease.

We describe a case of genital ulcer and inguinal adenopathies that were attributable to monkeypox virus infection. We suggest clinicians adopt a low threshold for suspicion, particularly when evaluating genital ulcer disease.

Guselkumab effectiveness and survival in patients with psoriasis and psoriatic arthritis: Multicenter analysis in daily clinical practice by the Spanish Psoriasis Group.

Guselkumab is a monoclonal antibody that selectively blocks the p19 subunit of interleukin 23 and has been approved for the treatment of moderate to severe psoriasis and active psoriatic arthritis in adult patients due to its efficacy in different clinical trials. Therefore, itis important to know the performance of guselkumab in this setting of patients in clinical practice given that a high percentage of them are not represented in these clinical trials. Our objective was to evaluate the effectiveness and tolerability of guselkumab in clinical practice in the first patients with psoriasis and psoriatic arthritis treated since the date of its approval for psoriasis in Spain, in joint dermatology-rheumatology clinics. A multicenter retrospective data collection was carried out, in which 14 hospitals participated, including a total of 90 patients with psoriatic arthritis confirmed by a rheumatologist. Data collection was recorded at baseline and at weeks 12, 24, and 52 for both the articular and cutaneous domains. Ninety PsA patients started treatment with guselkumab and therefore were included in this study. The vast majority had already failed to at least to one biologic therapyprior guselkumab prescription. The median age was 55 years, 61% were female and 46% had a BMI ≥ 30 kg/m2 . Sixty-nine percent suffered from peripheral arthritis, and in 34% an axial involvement was also detected; dactylitis or enthesitis was present in 24% and 29% of patients, respectively. Guselkumab was effective in controlling both articular and skin manifestations of PsA patients. Absolute PASI significantly decreased from 10.5 to 4.8, 1.9 and 1.3 at weeks 12, 24, and 52, respectively. In 29 out of 61 (48%) of cases, DAPSA was moderate or high, and patients showed a significant reduction in DAPSA at 12, 24, and 52 weeks of treatment (mean DAPSA values at baseline and follow up were 29, 20, 16, and 14, respectively). Patients with DAPSA in low activity or in remission at the time of initiation of guselkumab maintained response at the end of the study period. No new safety concerns were detected. Seventy-eight out of 90 patients (84.4%) persisted on treatment after 2 years follow-up. Our experience suggests that guselkumab isan effective drug for PsA and PsO patients in clinical practice with good tolerability and no additional safety signals, making it a new therapeutic alternative for the treatment of PsA and PsO patients.

Complications Associated with Mohs Micrographic Surgery: Data from the Nationwide Prospective Cohort REGESMOHS.

BACKGROUND: Large prospective studies on the safety of Mohs micrographic (MMS) surgery are scarce, and most focus on a single type of surgical adverse event. Mid-term scar alterations and functional loss have not been described. OBJECTIVES: To describe the risk of MMS complications and the risk factors for them. METHODS: A nationwide prospective cohort collected all adverse events on consecutive patients in 22 specialised centres. We used multilevel mixed-effects logistic regression to find out factors associated with adverse events. RESULTS: 5,017 patients were included, with 14,421 patient-years of follow-up. 7.0% had some perioperative morbidity and 6.5% had mid-term and scar-related complications. The overall risk of complications was mainly associated with use of antiaggregant/anticoagulant and larger tumours, affecting deeper structures, not reaching a tumour-free border, and requiring complex repair. Age and outpatient setting were not linked to the incidence of adverse events. Risk factors for haemorrhage (0.9%) were therapy with antiaggregant/anticoagulants, tumour size, duration of surgery, and unfinished surgery. Wound necrosis (1.9%) and dehiscence (1.0%) were associated with larger defects and complex closures. Immunosuppression was only associated with an increased risk of necrosis. Surgeries reaching deeper structures, larger tumours and previous surgical treatments were associated with wound infection (0.9%). Aesthetic scar alterations (5.4%) were more common in younger patients, with larger tumours, in H-area, and in flap and complex closures. Risk factors for functional scar alterations (1.7%) were the need for general anaesthesia, larger tumours that had received previous surgery, and flaps or complex closures. CONCLUSIONS: MMS shows a low risk of complications. Most of the risk factors for complications were related to tumour size and depth, and the resulting need for complex surgery. Antiaggregant/anticoagulant intake was associated with a small increase in the risk of haemorrhage, that probably does not justify withdrawal. Age and outpatient setting were not linked to the risk of adverse events.

Effect of Sex in Systemic Psoriasis Therapy: Differences in Prescription, Effectiveness and Safety in the BIOBADADERM Prospective Cohort.

The effect of sex on systemic therapy for psoriasis has not been well studied. The aim of this study was to analyse a large multicentre Spanish cohort of 2,881 patients with psoriasis (58.3% males), followed from January 2008 to November 2018, to determine whether sex influences prescription, effectiveness of therapy, and the risk of adverse events. The results show that women are more likely than men to be prescribed biologics. There were no differences between men and women in effectiveness of therapy, measured in terms of drug survival. Women were more likely to develop adverse events, but the difference in risk was small and does not justify different management. Study limitations include residual confounding and the use of drug survival as a proxy for effectiveness.

Long-term safety of nine systemic medications for psoriasis: A cohort study using the Spanish Registry of Adverse Events for Biological Therapy in Dermatological Diseases (BIOBADADERM) Registry.

BACKGROUND: Registry studies broadly describing the safety of systemic drugs in psoriasis are needed. OBJECTIVE: To describe the safety findings of the systemic drugs acitretin, adalimumab, apremilast, cyclosporine, etanercept, infliximab, methotrexate, secukinumab, and ustekinumab used for the treatment of moderate to severe psoriasis in patients included in the Spanish Registry of Adverse Events for Biological Therapy in Dermatological Diseases (BIOBADADERM) Registry. METHODS: The incidence rate ratio (IRR) and adjusted IRR (including propensity scores) of identified adverse events for each drug, using methotrexate as reference, were determined by means of a prospective cohort. RESULTS: Our study included 2845 patients (8954 treatment cycles; 9642 patient-years). Ustekinumab and secukinumab had the lowest rate of adverse events for several of the system organ classes, with a statistically significant decreased rate ratio (IRR of <1), whereas cyclosporine and infliximab had the highest, with an increased rate ratio (IRR of ≥5). LIMITATIONS: Observational study, drug allocation not randomized, depletion of susceptibles, and prescribed doses not registered. CONCLUSION: Our data provide comparative safety information in the real-life setting that could help clinicians selecting between available products.

Nevus-associated melanoma: An observational retrospective study of 22 patients evaluated with dermoscopy and reflectance confocal microscopy.

BACKGROUND: The frequency of nevus-associated melanoma (NAM) has been estimated to be 29% of diagnosed melanomas. MATERIALS AND METHODS: This is an observational retrospective study of 22 cases of NAM diagnosed in the Universitary Hospital Alcorcón between September 2011 and 2018. The main objective was to analyze dermoscopic and RCM features of NAM. We also studied if there was an association between any dermoscopic or RCM parameter and Breslow depth. RESULTS: The most frequent dermoscopic characteristics were multicomponent pattern (50%), multifocal pigmentation (45.5%), atypical network (59.1%), and blue-gray regression structures (77.3%). RCM evidenced pagetoid cells in 95.5% melanomas (abundant in 59.1%), non-edged dermal papillae in 86.4%, atypical cells at the dermal-epidermal junction in 90.9%, and atypical junctional nesting in 81.8%. Deeper Breslow index was associated with red color (mean Breslow 0.65 vs 0.37 in melanomas without red, P = 0.035), shiny white streaks (0.85 vs 0.38, P = 0.041), abundant pagetoid cells (0.68 vs 0.26, P = 0.017), and non-edged papillae (0.59 vs 0.00, P = 0.014). CONCLUSION: RCM is a valuable tool for diagnosing NAM. Even it is very difficult to differentiate NAM from DNM both with dermoscopy and RCM, RCM can help us to detect remnants of a preexisting nevus and estimate Breslow depth.

Delphi-based recommendations for the management of cardiovascular comorbidities in patients with psoriatic arthritis and moderate-to-severe psoriasis.

The aim of this study was to generate practical recommendations to assist rheumatologists and dermatologists in the management of cardiovascular (CV) comorbidities in patients with moderate-to-severe psoriasis (MS-PSO) and psoriatic arthritis (PsA). A two-round Delphi study was conducted. A panel of experts rated their agreement with a set of statements (n = 52) on a nine-point Likert scale (1 = totally disagree; 9 = totally agree). Statements were classified as inappropriate (median 1-3), irrelevant (median 4-6) or appropriate (median 7-9). Consensus was established when at least two-thirds of the panel responded with a score within any one range. A total of 25 experts, 60% rheumatologists and 40% dermatologists, participated in two consultation rounds. There was overall unanimity on the appropriateness of an initial assessment for CV risk factors in all patients with MS-PSO and PsA. Most panelists (88.0%) also supported the evaluation of patients' psychological and physical status. Additionally, most panelists (72.2%) agreed on a novel sequential approach for the management of CV comorbidities. This sequence starts with the assessment of hypertension, diabetes and dyslipidemia along with the identification of depression and anxiety disorders. Once these factors are under control, smoking cessation programs might be initiated. Finally, if patients have not met weight loss goals with lifestyle modifications, they should receive specialized treatment for obesity. This study has drawn up a set of practical recommendations that will facilitate the management of CV comorbidities in patients with MS-PSO and PsA.

Genetic variation at the glycosaminoglycan metabolism pathway contributes to the risk of psoriatic arthritis but not psoriasis.

OBJECTIVE: Psoriatic arthritis (PsA) is a chronic inflammatory arthritis affecting up to 30% of patients with psoriasis (Ps). To date, most of the known risk loci for PsA are shared with Ps, and identifying disease-specific variation has proven very challenging. The objective of the present study was to identify genetic variation specific for PsA. METHODS: We performed a genome-wide association study in a cohort of 835 patients with PsA and 1558 controls from Spain. Genetic association was tested at the single marker level and at the pathway level. Meta-analysis was performed with a case-control cohort of 2847 individuals from North America. To confirm the specificity of the genetic associations with PsA, we tested the associated variation using a purely cutaneous psoriasis cohort (PsC, n=614) and a rheumatoid arthritis cohort (RA, n=1191). Using network and drug-repurposing analyses, we further investigated the potential of the PsA-specific associations to guide the development of new drugs in PsA. RESULTS: We identified a new PsA risk single-nucleotide polymorphism at B3GNT2 locus (p=1.10e-08). At the pathway level, we found 14 genetic pathways significantly associated with PsA (pFDR<0.05). From these, the glycosaminoglycan (GAG) metabolism pathway was confirmed to be disease-specific after comparing the PsA cohort with the cohorts of patients with PsC and RA. Finally, we identified candidate drug targets in the GAG metabolism pathway as well as new PsA indications for approved drugs. CONCLUSION: These findings provide insights into the biological mechanisms that are specific for PsA and could contribute to develop more effective therapies.

Laser therapy for hair removal on grafts and flaps.

The diversity and utility of laser procedures have increased over the recent years and nowadays, applications for medical and cosmetic reasons have increased considerably. Problematic intraoral and cutaneous hirsutisms have been described as a consequence of complex reconstruction usually after oncology surgery. We present three patients in whom hair removal laser was performed on grafts and flaps in different compromised anatomical areas: oral cavity, penis, and auricular pavilion. All three patients were men; in two of them the hairy graft was a consequence after oncologic surgery reconstruction whereas the third patient presented hair in his auricular pavilion after cochlear implant due to a congenital ear malformation. In all the patients, neodymium:yttrium, aluminum, garnet laser (Nd:YAG) (1,064 nm) laser was performed with excellent aesthetic and functional outcomes with only three sessions. Hair removal laser is a well-accepted and effective method of achieving permanent decrease in hair density. Several lasers have been used successfully, including the long-pulse Alexandrite (755 nm), the long-pulse diode (810 nm), and the Nd:YAG laser (1,064 nm). There is currently no standard protocol for laser use on hairy grafts or flaps and there is limited published data regarding skin graft revision to enhance aesthetics and function.

Key dermoscopic signs in the diagnosis and progression of extrafacial lentigo maligna: Evaluation of a series of 41 cases.

BACKGROUND/OBJECTIVES: Lentigo maligna is usually located on the face. Extrafacial lentigo maligna is less common, and diagnosis of early forms is very difficult. Confocal microscopy of facial and extrafacial lentigo maligna shares the same features (abundant dendritic cells and generalised atypical junctional thickenings) and helps us to identify the dermoscopic features of extrafacial lentigo maligna. METHODS: We analysed dermoscopic and clinical features of 41 lesions diagnosed by confocal microscopy of extrafacial lentigo maligna confirmed on histology to identify dermoscopic signs of early lesions. RESULTS: Erased areas on dermoscopy were the clue to diagnose early lesions. At the borders of these areas, very small, round or triangular structures were found. At the lesion periphery, dermoscopy revealed a fine reticular pattern that helped to identify them as a melanocytic lesion. A progressive increase of the number and size of erased areas was accompanied by the appearance of various angulated structures around them (angulated lines, zig-zag structures or polygonal structures). Analysis of invasive lesions revealed very large erased areas containing white lines and atypical vascularisation. CONCLUSIONS: We have identified the dermoscopic early features and signs of progression by examining the dermoscopic and reflectance confocal microscopy findings of early and invasive extrafacial lentigo maligna.

Practical management of acne for clinicians: An international consensus from the Global Alliance to Improve Outcomes in Acne.

Scientific advances are continually improving the knowledge of acne and contributing to the refinement of treatment options; it is important for clinicians to regularly update their practice patterns to reflect current standards. The Global Alliance to Improve Outcomes in Acne is an international group of dermatologists with an interest in acne research and education that has been meeting regularly since 2001. As a group, we have continuously evaluated the literature on acne. This supplement focuses on providing relevant clinical guidance to health care practitioners managing patients with acne, with an emphasis on areas where the evidence base may be sparse or need interpretation for daily practice.

The Use of a Self-Occluding Topical Anasthetic in Daily Practice: A Non-Interventional Study.

INTRODUCTION: A variety of topical anesthetic creams are available to reduce pain associated with dermatological procedures. Pliaglis is a self-occluding eutectic mixture of lidocaine and tetracaine. STUDY OBJECTIVES: To evaluate the post-marketing safety profile of Pliaglis and efficacy in terms of pain reduction, product satisfaction, and daily practice use prior to pre-defined dermatological procedures. METHODS: A prospective, non-interventional study conducted at 44 sites in four European countries; 581 patients were treated prior to dermatological procedures such as pulsed-dye laser therapy, laser-assisted hair removal, non-ablative laser resurfacing, dermal filler injections, and vascular access. Efficacy was assessed by patients and investigators and included pain intensity (visual analogue scale [VAS]), satisfaction, and adequacy of pain relief. Safety was evaluated by adverse event (AE) reporting. RESULTS: In 75% of the performed procedures, patients scored the pain experienced during the procedure as ≤30 mm on the VAS and most were very satisfied or satisfied with the pain reduction. The investigators assessed the product as providing adequate anesthesia in 97% of the performed procedures and were mostly very satisfied or satisfied with the convenience of use (79%) and tolerability (95%). Twenty-four AEs were reported in 18 (3%) patients. DISCUSSION: Most patients experienced mild pain only as evident by the ≤ 30 mm VAS scores. Patients and investigators were aligned with regards to both product satisfaction and their opinion on adequacy of pain reduction. The AE frequency was low compared to previous studies, possibly relating to different ways of collecting AEs. CONCLUSION: Pliaglis was well-tolerated and provided adequate pain reduction prior to dermatological procedures. www.clinicaltrials.gov (NCT01800474).

J Drugs Dermatol. 2018;17(4):413-418.

Partial study data have been presented at the Anti-Aging Medicine European Congress (AMEC), Paris; October, 24-25, 2014, and the European Academy of Dermatology and Venereology (EADV), Istanbul; October 2-6, 2013.

Reaccion acneiforme noduloquistica secundaria a vemurafenib con buena respuesta a isotretinoina oralSevere acneiform eruption associated with vemurafenib with response to isotretinoin.

Vemurafenib, a kinase inhibitor that targets tumors with the BRAF V600E mutation, is a promising option for unresectable or metastatic melanoma. Cutaneous side-effects have been reported including alopecia, photosensitivity, squamous cell carcinoma, keratoacanthomas, keratosis pilaris-like eruption, and palmoplantar hyperkeratosis. Acneiform eruptions have been reported in 3%-6% of the patients treated with BRAF inhibitors,and 5 cases are described in the literature. Although they responded well to topical therapies, oral antibiotics, or observation, one case required oral etretinate and the withdrawal of vemurafenib because the adverse event reached grade 3. We report one case of a severe acneiform eruption associated with vemurafenib with a good response to isotretinoin allowing continuation of the BRAF inhibitor.

Cutaneous infection due to Mycobacterium immunogenum: an European case report and review of the literature.

(no more than 200 words): In the last few years, the incidence of cutaneous infections caused by nontuberculous mycobacteria is increasing. Since Mycobacterium immunogenum was first described in 2001, few case reports have been described, all of them in the American continent. We report a case with cutaneous infection caused by this newly discovered NTB in Europe.A 65-year-old woman presented with a 3-months history of pruritic lesions on abdomen. Examination revealed erythematous inflammatory papules, pustules, and crusts. Three weeks later, mycobacteria were cultured from the biopsy specimen. Mycobacterium immunogenum was identified based on susceptibility test results and polymerase chain reaction (PCR) restriction enzyme analysis. Treatment with clarithromycin was started. M. immunogenum is a nontuberculous mycobacterium that was first described by Wilson et al. in 2001 as a rapidly growing variety and new species in the Mycobacterium chelonae-Mycobacterium abscessus group. PCR-restriction analysis of a 439-bp segment of the hsp65 gene and/or sequencing the species-specific region of the 16S rDNA can confirm this new species. Since the description of M. immunogenum, 8 clinical case reports have been published, most involving cutaneous infections and all of them in the American continent. We present a case of cutaneous infection caused by M. immunogenum in a Spanish woman.

A case of de novo palmoplantar psoriasis with psoriatic arthritis and autoimmune hypothyroidism after receiving nivolumab therapy.

Nivolumab, a monoclonal antibody against the programmed cell death protein 1 (PD-1), has shown promising results in patients with advanced malignancies, including melanoma, lung cancer, and renal cancer. Immune-related adverse events (irAEs) have been reported, including both organ-specific toxicities and skin toxicities. Herein, we report a case of predominantly palmoplantar psoriasis with severe nail involvement, psoriatic arthritis, and autoimmune hypothyroidism after receiving nivolumab treatment for lung cancer. We also summarize the case reports that have been published previously. The knowledge of these irAEs in patients undergoing anti-PD1 therapy is important since it will enable earlier recognition and appropriate management, with the aim of maintaining effective dose without disruption.