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Segmental stiff skin syndrome (SSSS) is a rare genetic connective tissue disease, which is often misdiagnosed. High-frequency ultrasonography can represent a useful clinical adjunct in the differential diagnosis of this condition, in conjunction with the clinical and histopathological findings. Treatment options are limited and evidence is scarce. We present the clinical, sonographic and histological features of 5 paediatric patients diagnosed at our institution and we discuss their response to treatment.

Background Adalimumab (ADA) intensification is recommended for inadequate or loss of response in inflammatory bowel disease (IBD) patients. A new presentation of ADA 80mg administered every other week (eow) has been approved as an alternative to ADA 40mg every week (ew). Data regarding impact of ADA 80mg eow in clinical practice is still scarce. The aim of this study was to assess long-term durability, safety and cost-effectiveness of treatment with ADA 80mg eow in patients with IBD. Methods A retrospective cohort study in a tertiary hospital that included all IBD patients under intensified maintenance therapy with ADA 80mg eow was performed. Durability was calculated considering the time from the first dose to treatment withdrawn or to the end of follow-up. Biological remission (BR) was defined as CR together with fecal calprotectin (FC) Results Sixty-three patients (52 CD and 11 CU) were included; median age 47 (IQR 39–59), 54% male; median duration of the disease before ADA of 11 years (IQR 6–20); 30% were active smokers. Among CD patients, 56% had ileal disease, 17% colonic and 27% ileocolonic. The inflammatory behavior was the most frequent (52%) and 31% had perianal disease. In UC, 55% had extensive colitis. 44 patients (70%) were bio-naïve and 36 (57%) received immunosuppressants at baseline. At the time of escalation, 48 patients (76%) were symptomatic. After intensification, 52 (83%) patients (CD 42 and UC 10) achieved CR and 46 (73%) BR. The changes in the levels of FC, CRP and ADA were significant (p 22 patients (35%) discontinued treatment after a median of 6.5 (IQR 5–10) months due to: 11 no clinical response (50%), 4 loss of response (18%), 3 adverse events (14%) (psoriasis) and 4 endoscopic progression (18%). 44 patients (70%) remained under treatment and in CR (median follow-up 17 months, IQR 13–24) (Graph 4) and with a median ADA levels of 10.46 mg/l (IQR 7.34–15.25). Use of ADA 80 eow regimen saved 223500€ in patients who maintained treatment. In the multivariate analysis, being in CR when intensifying reduced the risk of treatment discontinuation by 87% (HR 0.13, 95%CI 0.02–0.99; p Conclusion ADA intensification to 80mg eow in IBD patients is safe, effective and may reduce costs in real life clinical practice. Early intensification, even in CR, may enhance ADA treatment durability.

Summary Background Recessive dystrophic epidermolysis bullosa (RDEB), Kindler syndrome (KS) and xeroderma pigmentosum complementation group C (XPC) are three cancer‐prone genodermatoses whose causal genetic mutations cannot fully explain, on their own, the array of associated phenotypic manifestations. Recent evidence highlights the role of the stromal microenvironment in the pathology of these disorders. Objectives To investigate, by means of comparative gene expression analysis, the role played by dermal fibroblasts in the pathogenesis of RDEB, KS and XPC. Methods We conducted RNA‐Seq analysis, which included a thorough examination of the differentially expressed genes, a functional enrichment analysis and a description of affected signalling circuits. Transcriptomic data were validated at the protein level in cell cultures, serum samples and skin biopsies. Results Interdisease comparisons against control fibroblasts revealed a unifying signature of 186 differentially expressed genes and four signalling pathways in the three genodermatoses. Remarkably, some of the uncovered expression changes suggest a synthetic fibroblast phenotype characterized by the aberrant expression of extracellular matrix (ECM) proteins. Western blot and immunofluorescence in situ analyses validated the RNA‐Seq data. In addition, enzyme‐linked immunosorbent assay revealed increased circulating levels of periostin in patients with RDEB. Conclusions Our results suggest that the different causal genetic defects converge into common changes in gene expression, possibly due to injury‐sensitive events. These, in turn, trigger a cascade of reactions involving abnormal ECM deposition and underexpression of antioxidant enzymes. The elucidated expression signature provides new potential biomarkers and common therapeutic targets in RDEB, XPC and KS. What's already known about this topic? Recessive dystrophic epidermolysis bullosa (RDEB), Kindler syndrome (KS) and xeroderma pigmentosum complementation group C (XPC) are three genodermatoses with high predisposition to cancer development.Although their causal genetic mutations mainly affect epithelia, the dermal microenvironment likely contributes to the physiopathology of these disorders. What does this study add? We disclose a large overlapping transcription profile between XPC, KS and RDEB fibroblasts that points towards an activated phenotype with high matrix‐synthetic capacity.This common signature seems to be independent of the primary causal deficiency, but reflects an underlying derangement of the extracellular matrix via transforming growth factor‐β signalling activation and oxidative state imbalance. What is the translational message? This study broadens the current knowledge about the pathology of these diseases and highlights new targets and biomarkers for effective therapeutic intervention.It is suggested that high levels of circulating periostin could represent a potential biomarker in RDEB., Linked Comment: https://doi.org/10.1111/bjd.18104. https://doi.org/10.1111/bjd.18271 available online

Background Current therapeutic goals in Crohn’s disease (CD) include not only the mere absence of symptoms but also the objective resolution of macroscopic lesions, so-called deep remission (DR), which has been related to better outcomes. DR is usually acknowledged by endoscopy, although magnetic resonance (MR) or intestinal ultrasound (IUS) are also reliable, provide extramucosal information and may be more appropriate in certain clinical scenarios. Data regarding the achievement of DR with ustekinumab in real-life clinical practice is still scarce. Methods Retrospective cohort study carried out in a tertiary hospital between April 2017 and April 2019 including patients who had clinically active CD (Harvey–Bradshaw index [HBI] ≥ 4) objectively assessed by either endoscopy, MR or IUS; received intravenous induction with ustekinumab, had achieved clinical remission and had treatment response assessed by either endoscopy, MR or IUS. DR was defined by SES-CD 0–3 or Rutgeerts index i0 if endoscopically assessed, or by complete normalisation of inflammatory parameters on cross-sectional imaging. Endoscopic response was defined by the decrease of SES-CD of 50% compared with baseline. Radiographic response was defined by improvement in bowel wall thickness, inflammatory fat, mural blood flow and hyperenhancement compared with baseline imaging by physician global assessment. Demographics, clinical data and information regarding ustekinumab treatment were collected. Results 90 patients treated with ustekinumab at our centre were analyzed, but only 28 met inclusion criteria (14(50%) female; median age 45 (43–50)) with a median follow-up of 19 (IQR: 15–23) months. All of them had previously failed to antiTNFα and 20 (71%) failed to ≥2 biologics. Treatment response assessment was made by endoscopy (22 cases; 79%) or cross-sectional imaging technique (6 cases; 21%) in a median time of 10 months (IQR: 7–13) from the start of treatment. Deep remission was achieved in 18 (64%) patients. Endoscopic response was achieved in 5 (18%) additional patients. Five (18%) remaining patients obtained no objective response to ustekinumab despite being in clinical remission. Patients who had received prior treatment with ≥2 biologics or those classified as B2 or B3 according to Montreal Classification were less likely to achieve deep remission, although those associations did not reach statistical significance. Conclusion In our experience, a majority of refractory CD patients who achieved clinical remission with ustekinumab also reached deep remission assessed by either endoscopy, MR or IUS.

Background Current therapeutic goals in inflammatory bowel disease (IBD) include not only the mere absence of symptoms but also the resolution of endoscopic lesions, so-called mucosal healing (MH), which has been related to better outcomes. Data regarding the achievement of MH with vedolizumab (VDZ) in real-life clinical practice is still scarce. Methods Retrospective cohort study was carried out in a tertiary hospital between January 2015 and April 2019 including patients with a basal colonoscopy showing activity and who achieved clinical remission under treatment with VDZ, defined by partial Mayo score Results In total, 118 patients treated with VDZ were analysed, but only 45 met inclusion criteria with a median follow-up of 21 (IQR: 14–19) months. Surveillance colonoscopy was performed after a median time of 12 months (IQR:9–17) of treatment. MH achieved in 33/45 patients (73%): 17/23 CD patients (74%) and 16/22 UC patients (73%). The endoscopic response was achieved in 9 of the remaining 12 patients: 3/6 CD patients and 6/6 UC patients. Only 3 (7%) of patients included showed no endoscopic benefit at the time of surveillance endoscopy. In multivariate analysis, probability of not achieving MH was 75% in patients previously treated with immunosuppressants (ISS) (HR 0.25, 0.11–0.55 IC95; p = 0.001) and 60% in patients previously treated with anti-TNFα (HR 0.40, 0.18–0.90 95% CI; p = 0.026). Type of IBD, concomitant ISS, corticosteroid use at induction, baseline endoscopy score or duration of disease before VDZ treatment were not associated with the achievement of MH. Conclusion In our experience, most of the patients who achieve clinical remission with VDZ also achieve MH. Refractory patients were less likely to achieve MH despite having achieved clinical remission.

Summary Background Basal epidermolysis bullosa simplex (EBS) is a group of blistering geno-dermatoses mostly caused by mutations in the keratin genes, KRT5 and KRT14.Recessive mutations represent about 5% of all EBS mutations, being common andspecific in populations with high consanguinity, where affected patients showsevere phenotypes.Objectives To accomplish the first mutational analysis in patients of Spanish originwith EBS and to delineate a comprehensive genotype–phenotype correlation.Methods Twenty-one EBS families were analysed. Immunofluorescence mapping atthe dermoepidermal junction level was performed on skin biopsies from patients.Mutation screening of the entire coding sequences of KRT5 and KRT14 in genomicDNA was assessed by polymerase chain reaction and direct sequencing.Results KRT5 or KRT14 causative mutations were identified in 18 of the 21 EBSfamilies. A total of 14 different mutations were disclosed, of which 12 weredominant missense mutations and two truncating recessive mutations. Five of the14 mutations were novel including three dominant in KRT5 (p.V186E, p.T321Pand p.A428T) and two recessive in KRT14 (p.K116X and p.K250RfsX8). The twopatients with EBS carrying homozygous recessive mutations were affected bysevere phenotypes and belonged to consanguineous families. All five familieswith the EBS Dowling–Meara subtype carried recurrent mutations affecting thehighly conserved ends of the a-helical rod domain of K5 and K14. The sevenmutations associated with the localized EBS subtype were widely distributedalong the KRT5 and KRT14 genes. Two families with mottled pigmentation carriedthe P25L mutation in KRT5, commonly associated with this subtype.Conclusions This study further confirms the genotype–phenotype correlation estab-lished for EBS in other ethnic groups, and is the first in a Mediterranean country(excluding Israel). This study adds two novel recessive mutations to the worldwiderecord to date, which includes a total of 14 mutations. As in previous reports, therecessive mutations resulted in a lack of keratin K14, giving rise to a generalizedand severe presentation.

Immunosuppression is a well-documented precipitant of porokeratosis (PK). However, PK is not considered among the most common cutaneous disorders in immunosuppressed patients. We studied prospectively a series of 103 renal transplant patients and found 11 cases (10.68%) of PK. Our series represents the highest incidence of PK in transplant patients reported so far. Our findings suggest that PK in transplant recipients may be more frequent than previously thought.