Common Approach to Metabolic-Associated Fatty Liver Disease in Patients With Psoriasis: Consensus-Based Recommendations From a Multidisciplinary Group of Experts. / Abordaje común del paciente con psoriasis y riesgo de esteatosis hepática metabólica: recomendaciones de un grupo de expertos multidisciplinar.

Recent years have seen concerted efforts to understand the relation between psoriasis and metabolic-associated fatty liver disease (MAFLD). Not only is MALFD diagnosed more often in patients with psoriasis, but its clinical course is also more aggressive. A common approach is therefore needed to enable early detection of liver disease coincident with psoriasis. Especially important is an analysis of risks and benefits of potentially hepatotoxic treatments. This consensus paper presents the recommendations of a group of experts in dermatology and hepatology regarding screening for MALFD as well as criteria for monitoring patients and referring them to hepatologists when liver disease is suspected.

Tralokinumab for moderate-to-severe atopic dermatitis: results from two 52-week, randomized, double-blind, multicentre, placebo-controlled phase III trials (ECZTRA 1 and ECZTRA 2).

BACKGROUND: Tralokinumab, a fully human monoclonal antibody, specifically neutralizes interleukin-13, a key cytokine driving peripheral inflammation in atopic dermatitis (AD). In phase II studies, tralokinumab combined with topical corticosteroids provided early and sustained improvements in AD signs and symptoms. OBJECTIVES: To evaluate the efficacy and safety of tralokinumab monotherapy in adults with moderate-to-severe AD who had an inadequate response to topical treatments. METHODS: In two 52-week, randomized, double-blind, placebo-controlled, phase III trials, ECZTRA 1 and ECZTRA 2, adults with moderate-to-severe AD were randomized (3 : 1) to subcutaneous tralokinumab 300 mg every 2 weeks (Q2W) or placebo. Primary endpoints were Investigator's Global Assessment (IGA) score of 0 or 1 at week 16 and ≥ 75% improvement in Eczema Area and Severity Index (EASI 75) at week 16. Patients achieving an IGA score of 0 or 1 and/or EASI 75 with tralokinumab at week 16 were rerandomized to tralokinumab Q2W or every 4 weeks or placebo, for 36 weeks. The trials were registered with ClinicalTrials.gov: NCT03131648 and NCT03160885. RESULTS: At week 16, more patients who received tralokinumab vs. placebo achieved an IGA score of 0 or 1: 15·8% vs. 7·1% in ECZTRA 1 [difference 8·6%, 95% confidence interval (CI) 4·1-13·1; P = 0·002] and 22·2% vs. 10·9% in ECZTRA 2 (11·1%, 95% CI 5·8-16·4; P < 0·001) and EASI 75: 25·0% vs. 12·7% (12·1%, 95% CI 6·5-17·7; P < 0·001) and 33·2% vs. 11·4% (21·6%, 95% CI 15·8-27·3; P < 0·001). Early improvements in pruritus, sleep interference, Dermatology Life Quality Index, SCORing Atopic Dermatitis and Patient-Oriented Eczema Measure were observed from the first postbaseline measurements. The majority of week 16 tralokinumab responders maintained response at week 52 with continued tralokinumab treatment without any rescue medication (including topical corticosteroids). Adverse events were reported in 76·4% and 61·5% of patients receiving tralokinumab in ECZTRA 1 and ECZTRA 2, respectively, and in 77·0% and 66·0% of patients receiving placebo in ECZTRA 1 and ECZTRA 2, respectively, in the 16-week initial period. CONCLUSIONS: Tralokinumab monotherapy was superior to placebo at 16 weeks of treatment and was well tolerated up to 52 weeks of treatment.

Real-world effectiveness and safety of apremilast in psoriasis at 52 weeks: a retrospective, observational, multicentre study by the Spanish Psoriasis Group.

BACKGROUND: Little has been published on the real-world effectiveness and safety of apremilast in psoriasis. OBJECTIVES: To evaluate the effectiveness, safety and drug survival of apremilast at 52 weeks in patients with moderate to severe plaque psoriasis or palmoplantar psoriasis in routine clinical practice. METHODS: Retrospective, multicentre study of adult patients with moderate to severe plaque psoriasis or palmoplantar psoriasis treated with apremilast from March 2016 to March 2018. RESULTS: We studied 292 patients with plaque psoriasis and 85 patients with palmoplantar psoriasis. The mean (SD) Psoriasis Area and Severity Index (PASI) score was 10.7 (7.0) at baseline and 3.0 (4.2) at 52 weeks. After 12 months of treatment, 73.6% of patients had a PASI score of 3 or less. In terms of relative improvement by week 52, 49.7% of patients achieved PASI-75 (≥75% reduction in PASI score) and 26.5% achieved PASI-90. The mean physician global assessment score for palmoplantar psoriasis fell from 4.2 (5.2) at baseline to 1.3 (1.3) at week 52. Overall drug survival after 1 year of treatment with apremilast was 54.9 %. The main reasons for treatment discontinuation were loss of efficacy (23.9%) and adverse events (15.9%). Almost half of the patients in our series (47%) experienced at least one adverse event. The most common events were gastrointestinal problems. CONCLUSIONS: Apremilast may be a suitable alternative for the treatment of moderate to severe psoriasis and palmoplantar psoriasis. Although the drug has a good safety profile, adverse gastrointestinal effects are common.

Sensitivity and specificity of the lymphocyte transformation test in drug reaction with eosinophilia and systemic symptoms causality assessment.

BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe delayed hypersensitivity reaction. The determination of drug causality is complex. The lymphocyte transformation test (LTT) has been reported positive in more than 50% of DRESS cases. Nevertheless, the sensitivity and specificity of LTT specifically in DRESS have not yet been established. Rechallenge with the culprit drug is contraindicated and cannot be used as gold standard for sensitivity and specificity determination. OBJECTIVE: To estimate the sensitivity and specificity of LTT in a clinically defined series of patients with DRESS. METHODS: Some 41 patients diagnosed with DRESS were included in the study. The results of the algorithm of the Spanish Pharmacovigilance System were used as the standard for a correct diagnosis of drug causality. A standard LTT was performed with involved drugs in acute or recovery samples. A stimulation index (SI) ≥2 in at least one concentration except for beta-lactams (SI ≥3) and contrast media (SI ≥4) was considered positive. Contingency tables and ROC curves were used for analysis. RESULTS: Sensitivity and specificity of LTT in the recovery phase of DRESS were 73% and 82%, respectively, whereas in the acute phase, they were only 40% and 30%, respectively. Comparison of skin tests and LTT confirmed a higher sensitivity and specificity of LTT in DRESS. LTT showed high sensitivity (S) and specificity (Sp) for anticonvulsants (S 100%, Sp 100%; P = .008), anti-TB drugs (S 87.5%, Sp 100%; P = .004), and beta-lactams (S 73%, Sp 100%; P = .001). ROC curves revealed that the best criteria for LTT positivity for all drugs are SI ≥2 in at least one concentration, increasing overall sensitivity to 80%, and for beta-lactams from 73% to 92%. CONCLUSIONS AND CLINICAL RELEVANCE: LTT is a good diagnostic tool for drug causality in DRESS, mainly when performed in the recovery phase.

Methotrexate in Moderate to Severe Psoriasis: Review of the Literature and Expert Recommendations.

Methotrexate (MTX) is the most frequently used conventional systemic drug in the treatment of psoriasis. Despite over 50years of experience in this setting, certain aspects of the use of this drug in clinical practice are still little standardized and poorly understood. For this reason, a group of 15 experts took part in a consensus development conference to achieve consensus on a series of recommendations on the use of MTX in psoriasis. The guidelines, which were developed on the basis of a systematic review of the literature, were validated by 2 rounds of voting and categorized by level of evidence and grade of recommendation. Before MTX can be used to treat moderate to severe psoriasis, the patient must be evaluated to assess the suitability of the treatment, including consideration of vaccination status and screening for tuberculosis and pregnancy. The recommended starting dose for a patient with no risk factors is 10 to 20mg/wk, the therapeutic dose for most patients is 15mg/wk, and the maximum dose is 20mg/wk. Most patients who respond to treatment will show improvement within 8weeks. Parenteral administration of MTX is desirable when there is a risk of erroroneous dosing, nonadherence, gastrointestinal intolerance, or inadequate response to the therapeutic dose taken orally. Noninvasive methods are preferred for monitoring hepatotoxicity. MTX is a good treatment option for patients with a history of cancer, but is not recommended in patients with chronic hepatitisB infection or individuals who are seropositive for human immunodeficiency virus.

Osteochondromas in fibrodysplasia ossificans progressiva: a widespread trait with a streaking but overlooked appearance when arising at femoral bone end.

Metaphyseal bony outgrowths are a well-recognized feature of fibrodysplasia ossificans progressiva (FOP) phenotype, but its genuine frequency, topographic distribution, morphological aspect, and potential implications are not fully established. To better ascertain the frequency and characteristics of osteocartilaginous exostoses in FOP disease, we conducted a cross-sectional radiological study based on all the traceable cases identified in a previous comprehensive national research. Metaphyseal exostoses were present in all the 17 cases of FOP studied. Although most often arising from the distal femoral (where metaphyseal exostoses adopt a peculiar not yet reported appearance) and proximal tibial bones, we have found that they are not restricted to these areas, but rather can be seen scattered at a variety of other skeletal sites. Using nuclear magnetic resonance imaging, we show that these exophytic outgrowths are true osteochondromas. As a whole, these results are in agreement with data coming from the literature review. Our study confirms the presence of metaphyseal osteochondromas as a very frequent trait of FOP phenotype and an outstanding feature of its anomalous skeletal developmental component. In line with recent evidences, this might imply that dysregulation of BMP signaling, in addition to promoting exuberant heterotopic ossification, could induce aberrant chondrogenesis and osteochondroma formation. Unveiling the molecular links between these physiopathological pathways could help to illuminate the mechanisms that govern bone morphogenesis.

Routine abdominal X-rays in the emergency department: a thing of the past?

The large number of abdominal X-ray examinations done in the emergency department is striking considering the scant diagnostic yield of this imaging test in urgent disease. Most of these examinations have normal or nonspecific findings, bringing into question the appropriateness of these examinations. Abdominal X-ray examinations are usually considered a routine procedure or even a "defensive" screening tool, whose real usefulness is unknown. For more than 30 years, the scientific literature has been recommending a reduction in both the number of examinations and the number of projections obtained in each examination to reduce the dose of radiation, unnecessary inconvenience for patients, and costs. Radiologists and clinicians need to know the important limitations of abdominal X-rays in the diagnostic management of acute abdomen and restrict the use of this technique accordingly. This requires the correct clinical selection of patients that can benefit from this examination, which would allow better use of alternative techniques with better diagnostic yield, such as ultrasonography or computed tomography.

Piperacillin-induced DRESS: distinguishing features observed in a clinical and allergy study of 8 patients.

BACKGROUND: DRESS (drug reaction with eosinophilia and systemic symptoms) syndrome is characterized by fever, rash, eosinophilia, and multiorgan failure. Previous reports have described differences in clinical and laboratory findings of DRESS syndrome depending on the inducing drug. Piperacillin has been reported as the drug responsible for this syndrome in 3 patients. OBJECTIVE: To analyze and describe the clinical, laboratory, and allergy study findings of piperacillin-induced DRESS. PATIENTS AND METHODS: Retrospective case series of patients diagnosed with DRESS associated with piperacillin-tazobactam (Pip/Taz) according to the Kardaun diagnostic score criteria. Assessment of causality was established using the Spanish Pharmacovigilance System and the lymphocyte transformation test (LTT). The allergy study included skin and epicutaneous tests. RESULTS: Eight patients were diagnosed with DRESS due to Pip/Taz (3 probable and 5 definite cases). Skin rash was observed in all cases and facial edema in 50%; the mean latency period was 18 days. Fever was present in 7 patients. Liver and kidney injuries were detected in 6 and 3 patients, respectively. All patients had eosinophilia and a full recovery. The LTT to Pip/Taz was strongly positive in all patients, with a stimulation index of over 6. Three of 3 patients had a positive intradermal test to Pip/Taz, and 1 of 4 had a positive patch test. All patients had a negative LTT to carbapenems. CONCLUSIONS: We have reported on the first case series of piperacillin-induced DRESS. A latency period of 18 days, skin rash, eosinophilia, fever, liver injury, and good prognosis were the most common features. The allergy study, and the LTT in particular, was highly useful for identifying Pip/Taz as the culprit drug and piperacillin as the responsible active ingredient.

Safety and effectiveness of ustekinumab and antitumour necrosis factor therapy in patients with psoriasis and chronic viral hepatitis B or C: a retrospective, multicentre study in a clinical setting.

BACKGROUND: Both the safety and efficacy of biologic therapy may be affected in the presence of highly prevalent chronic viral hepatitis. OBJECTIVE: To evaluate the safety and effectiveness of ustekinumab and antitumour necrosis factor therapy in patients with psoriasis and concomitant chronic viral hepatitis. METHODS: This was a retrospective, multicentre study. Twenty-five patients with psoriasis and concurrent hepatitis C virus (HCV) (20 patients) or hepatitis B virus (HBV) (five patients) infection who had received at least one biologic agent (etanercept, 21 treatments; adalimumab, four; ustekinumab, four; infliximab, two) were included. Clinical, imaging and laboratory data were recorded. RESULTS: In the case of HCV infection, the majority of the patients did not exhibit increases in their viral load or serum liver tests. Aspartate aminotransferase, alanine aminotransferase and gamma glutamyl transpeptidase were doubled from the baseline measurement in only one patient treated with etanercept. Two other cases exhibited viral load increases during the follow-up period. In total, 18 of the 26 treatments achieved a 75% improvement in their Psoriasis Area and Severity Index (PASI 75) score during the follow-up period. Two patients treated with etanercept were diagnosed with hepatocellular carcinoma. In the case of HBV infection, all of the patients were being treated with antiviral therapy, and none presented significant variations in viral load or serum liver enzymes. All patients achieved a PASI 75 during follow-up. CONCLUSIONS: Biologic therapy was effective and safe for the majority of our patients with HCV and HBV infection, although there may be a risk of reactivation or aggravation. We describe the first cases to receive ustekinumab. The use of biologics should be limited to those cases in which the risk-benefit ratio is justified.

[Early reconstruction of congenital pseudoarthrosis of the tibia with free vascularized fibular grafts]. / Reconstrucción precoz de pseudoartrosis congénita de tibia con injerto libre vascularizado de peroné.

Congenital pseudoarthrosis of the tibia (CPT) is an uncommon disease presenting a tibial nonunion since birth and frequently associated to neurofibromatosis type 1. Surgical management by wide excision of the pseudoarthrosis and sustitution of the defect with vascularized bone in an early stage has proven to be the most effective technique in terms of bone consolidation. We present a clinical case of a 22-month-old patient with CPT treated successfully by reconstruction with a free vascularized fibula graft with an excellent functional result.

[Translated article] Bone lengthening with magnetic nails. Experience in patients younger than 18.

BACKGROUND AND GOAL: Bone elongation with magnetic endomedullary nails (MEN) has been proposed as an advantageous alternative to other techniques, by eliminating the drawbacks of external fixation. The aim of this work is to analyse the results and assess the complications in a series of patients under the age of 18. MATERIAL AND METHODS: From 2014 to 2019, 31 elongations (23 femurs, 8 tibias) using MEN (Precice2®) have been performed in 28 patients younger than 18 (15 males and 13 females). In this observational retrospective study, only patients with follow-up longer than 18 months have been included. The average age has been 14.4 years (8-18). The most relevant aspects analysed have been: previous shortening/deformity, elongation/correction achieved and time to full weight bearing. Complications and re-interventions have also been assessed. RESULTS: The elongation achieved has been 5.5cm on average (3-8). In 28 elongations (90.3%) the planned goal of lengthening was achieved. The mean healing index (HI) was 1.1months/cm. More than half of elongations (55%) presented complications. Although they produced permanent sequelae in only two patients (7.1%), a total of 9 patients required re-intervention (13 operations). No infections were detected. CONCLUSIONS: Bone lengthening with MEN in individuals younger than 18 has achieved its goal in more than 90% of patients in an effective, accurate and safe manner. The use of MEN in this series has eliminated the need for external fixators and has successfully tutorized the operated segment. The high number of complications detected in this study remains a concern.

Bone lengthening with magnetic nails. Experience in patients younger than 18. / Alargamiento óseo con clavos magnéticos. Experiencia en pacientes menores de 18 años.

BACKGROUND AND GOAL: Bone elongation with magnetic endomedullary nails (MEN) has been proposed as an advantageous alternative to other techniques, by eliminating the drawbacks of external fixation. The aim of this work is to analyze the results and assess the complications in a series of patients under the age of 18. MATERIAL AND METHODS: From 2014 to 2019, 31 elongations (23 femurs, 8 tibias) using MEN (Precice2™) have been performed in 28 patients younger than 18 (15 males and 13 females). In this observational retrospective study, only patients with follow-up longer than 18 months have been included. The average age has been 14.4 years (8-18). The most relevant aspects analyzed have been: previous shortening/deformity, elongation/correction achieved and time to full weight bearing. Complications and re-interventions have also been assessed. RESULTS: The elongation achieved has been 5.5cm on average (3-8). In 28 elongations (90.3%) the planned goal of lengthening was achieved. The mean healing index was 1.1months/cm. More than half of elongations (55%) presented complications. Although they produced permanent sequelae in only two patients (7.1%), a total of 9 patients required re-intervention (13 operations). No infections were detected. CONCLUSIONS: Bone lengthening with MEN in individuals younger than 18 has achieved its goal in more than 90% of patients in an effective, accurate and safe manner. The use of MEN in this series has eliminated the need for external fixators and has successfully tutorized the operated segment. The high number of complications detected in this study remains a concern.

Mid-follicular LH supplementation in women aged 35-39 years undergoing ICSI cycles: a randomized controlled study.

This single-centre, randomized, parallel group, comparative study aimed to identify potential benefits of mid-follicular recombinant human LH (r-HLH) supplementation in women aged 35-39 years undergoing ovarian stimulation for intracytoplasmic sperm injection (ICSI). The main endpoint was the number of metaphase II oocytes retrieved. After pituitary suppression with a gonadotrophin-releasing hormone agonist, ovarian stimulation was initiated with recombinant human FSH (r-HFSH; 300-450 IU/day). On stimulation day 6, patients were randomized to receive r-HFSH alone or r-HFSH + r-HLH (r-HLH 150 IU/day) for the remainder of the stimulation period. Final follicular maturation was triggered with 250 µg of recombinant human chorionic gonadotrophin. After assessing oocyte nuclear maturity, oocyte were fertilized by ICSI and afterwards embryo quality was analyzed. Of the 131 women enrolled, 68 were allocated to r-HFSH alone and 63 to r-HFSH + r-HLH. No significant differences were observed in markers of either oocyte or embryo quality or quantity. However, higher rates of implantation and live birth per started cycle were observed with r-HLH supplementation than with r-HFSH alone. Although additional large studies are required to further investigate these findings, r-HLH supplementation for women aged 35-39 years undergoing ICSI is recommended as it may have a beneficial action on implantation.

[Early detection of anal intraepithelial neoplasia in high-risk patients]. / Detección precoz de la neoplasia intraepitelial anal en pacientes de alto riesgo.

The incidence of anal squamous cell carcinoma has increased alarmingly, particularly in high-risk groups such as men who have sex with men and immunosuppressed patients. Infection with an oncogenic strain of the human papillomavirus in the anal canal or perianal skin leads to anal intraepithelial neoplasias (AIN), progressive dysplastic intraepithelial lesions that are the precursors of anal squamous cell carcinoma. AIN can be diagnosed through cytological screening and biopsy guided by high-resolution anoscopy and can be treated using a range of procedures in an effort to prevent progression to invasive anal carcinoma. Given the recent advances in the understanding of this disease, and the increasing calls from experts for the establishment of screening programs to identify AIN, we review current knowledge on the condition, its diagnosis, and treatment from the point of view of dermatology.

Direct-to-Patient Teledermatology During COVID-19 Lockdown in a Health District in Madrid, Spain: The EVIDE-19 Pilot Study. / Estudio piloto de la teledermatología directa durante el estado de alarma por la pandemia COVID-19 en un área sanitaria de Madrid (Estudio EVIDE-19).

BACKGROUND: Dermatologic care was halted because of the coronavirus disease 2019 pandemic, prompting us to study the usefulness of direct-to-patient teledermatology via a mobile application. We aimed to evaluate the service as a tool for avoiding face-to-face consultations, describe the main conditions diagnosed, and assess levels of patient and physician satisfaction. MATERIAL AND METHOD: Prospective descriptive study of new patients who met the inclusion criteria. Descriptive statistics for all variables were analyzed with SPSS. RESULTS: Of the 1,497 patients who agreed to participate in the study, 25% (n=374) sent an image to a consultant dermatologist through the mobile application. Sixty-four patients (17%) were discharged directly and referred to primary care for follow-up. A face-to-face consultation was avoided for at least 3 months in 85% of patients (n=318); 87.1% (n=325) received a diagnosis and the dermatologist's level of confidence in this diagnosis was 7 or higher in 77.5% of cases (n=290). The quality of the images sent was considered sufficient in 52.1% of cases. Patients rated their satisfaction with a score of 4.5 out of 5. Eleven of the 16 dermatologists rated their satisfaction as good overall. The most common conditions were inflammatory and melanocytic lesions. The main diagnoses were nevi, acne, and eczema. DISCUSSION: Direct-to-patient store-and-forward teledermatology is an effective means of evaluating new patients. Both clinicians and patients expressed high levels of satisfaction with the service. Systems enabling the addition of digital images to patient records are necessary to ensure the efficiency of teledermatology.

Posteromedial tibial deformity: Radiological evolution and treatment of the discrepancy. / Deformidad posteromedial de la tibia: evolución radiológica y tratamiento de la discrepancia.

INTRODUCTION: Postero-medial deformity (DMPT), unlike other congenital forms that affect the tibia, presents a good evolution spontaneously correcting the important misalignments that present at birth based on the classic orthopedic laws of Wolff and Hueter-Volkmann, leaving slight residual angulations and variable limb length discrepancy. MATERIAL AND METHODS: Authors carry out a retrospective review of cases diagnosed with DPMT, the evolution of the tibial angulation and the discrepancy in the length of fourteen patients (11 males and 3 females) followed and treated between the years 2003 and 2018. Seven of these were treated by callus distraction. We have considered: PA and lateral of the tibia and stand-up entire limbs x-ray during age growth, along with the clinical records of the patients. RESULTS: The medial diaphyseal radiological deformity of the newborn or neonatal period was 34° and the final 10°. The posterior deformity evolved from 46° to a final angulation of 11°. The physeal angulation in the initial AP projection was 34° and the end view was 8° and in the lateral projection from 44 to 6°. The mechanical axis of the limb was correcting towards a neutral axis in relation to the aforementioned physeal and diaphyseal correction in all cases except two. In five of the cases, although the mechanical axis was normal-aligned, at the tibial level it ran eccentrically and externally to the tibial cortex. The length relationship between the short tibia and the healthy tibia maintains a constant proportion throughout the growth of 89%, that is, the inhibition of growth is 11%. We observe that 80% of the discrepancy is found in the tibia and that the remaining 20% ??was exposed from the height of the tarsus. Two patients presented a traumatic and accidental diaphyseal fracture of the tibia. The difference in the length of the tibia was compensated to seven patients by callus distraction of 5.4cm using the callotasis method with a Healing Index of 34.5 days/cm. CONCLUSIONS: DPMT improves substantially during the first years of life. Joint alignment of the knee and ankle is achieved before the correction of diaphyseal deformity. The tibia length discrepancy increases with the growth of the child since there is an 11% growth inhibition that will cause a skeletal maturity discrepancy between 4-7cm. Callus distraction before skeletal maturity is the method chosen to compensate this discrepancy.