Methylated miRNAs may serve as potential biomarkers and therapeutic targets for hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disease influenced by genetics, non-genetic and environmental factors that modulate miRNA expression. Currently, no miRNA data are available for HS. In this study, we profiled DNA methylation patterns of miRNA genes associated with HS susceptibility. OBJECTIVES: Identify miRNA gene methylation profiles associated with HS susceptibility. This study examined the methylation patterns of DNAs from 24 healthy controls and 24 patients with HS using Illumina Infinium MethylationEPIC BeadChip array analysis. Methylation patterns of miRNA genes were analysed using KEGG pathway analysis to explore the inversely correlated pathways regulated by miRNAs. RESULTS: We identified 60 CpG sites representing 65 unique microRNA genes including 54 hypomethylated and 6 hypermethylated CpGs as potentially associated with HS. Some of these CpGs were found to be critical for skin function, such as miR-29, miR-200, miR-205, miR-548 and miR-132. The miR-192 is implicated in non-alcoholic fatty liver disease. The miR-200c gene was identified as a vital determinant in regulating skin repair after injury and may contribute to age-associated alterations in wound repair. miR-132 was significantly upregulated during the inflammation phase of wound repair, enhancing the activity of STAT3 and ERK pathways that promote keratinocyte proliferation. CONCLUSIONS: Epigenetically altered microRNA genes are implicated in wound healing, inflammation, keratinocyte proliferation and wound modulation. This is the first study to analyse methylation profiles of miRNA genes in the HS population, highlighting the unique role that miRNAs might play in diagnosing and treating HS.

The association between patient activation and healthcare resources utilization: a systematic review and meta-analysis.

OBJECTIVES: To measure the association between patient activation and hospitalization or emergency department (ED) visits among adults with chronic diseases. STUDY DESIGN: Systematic review and meta-analysis. METHODS: A systematic review of English articles was performed using the following databases: PubMed, Cochrane Library, Web of Science, PsycINFO, and Embase. Articles were searched from 2005 until July 2021. Observational studies that measured the association between patient activation, measured by the Patient Activation Measure (PAM), and hospitalization or ED visits among adults with chronic or multichronic diseases were included. Pairs of reviewers independently screened the studies and extracted data for qualitative and quantitative synthesis. The methodological quality was assessed using the Quality in Prognostic Studies (QUIPS) tool. RESULTS: A total of nine observational studies (153,121 participants) were included in the qualitative synthesis, whereas six were pooled in the quantitative synthesis (151,359 participants). High levels of patient activation were significantly associated with a reduced risk for both hospitalizations (RR [95% CI] = 0.69 [0.61; 0.77], I2 = 78%) and ED visits (RR [95% CI] = 0.76 [0.70; 0.84], I2 = 72%). CONCLUSIONS: Our findings suggest the existence of an inverse association between patient activation and healthcare resources utilization. Further observational studies are needed to fully comprehend the magnitude of this association.

Hospital networks in Italy: state of the art and future pespectives. Insights from a qualitative research study.

Background Hospitals have undergone important that changes that have led, in recent decades at the international level, to the need for greater integration between hospitals and local healthcare services. The main institutional networks that have been developed in Italy are, as commended by the institutional levels, of 4 main types: the Emergency-Urgency Network, the Time-Dependent Networks, the Oncological Networks, and the Networks with primary care settings. It was important to assess the state of the art and analyze it in relation to possible future developments. Objective The aim of the study was to collect insights from both evidence-based knowledge and personal experience gained by experts in the field regarding the current condition and possible future developments of hospital networks. Material and methods A qualitative research methodology was chosen. Four mini-focus group meetings were organized among participants with proven expertise on the subject. Discussions were guided by four open-ended questions corresponding to the four areas of interest. Directed content analysis was chosen as the methodology for data analysis and final reporting of results. Results Four main categories were explored: "hospital networks and complexity", "hospital networks complexity and the need for integration", "levers for hospital networks governance" and "the COVID-19 challenge and future developments for hospital networks". In particular, the participants found that it is important to understand healthcare systems as complex systems and, therefore, to study the properties of complex systems. In this way it is possible to achieve value-based healthcare in complex contexts. It is also necessary to keep in mind that complexity represents a challenge for coordination/ integration in hospital networks. Mintzberg identified specific mechanisms to achieve it. Of them, mutual adaptation is the key to self-organization. Valentijn showed the organizational levels on which coordination/integration has to be obtained. Hospital network governance should include both hierarchy and self-determination logic to achieve integration in each of the four levels. The participants identified three key levers for governing complex organizations: "education", which consists of multi-professional and multi-level training in governance in complex systems; "information" consisting in considering the data registering as an integral part of the clinical care process to informative value; "leadership", which consists in convincing actors, directed towards personal gains, to achieve valuable goals. Finally, the challenge that COVID-19 served as an incentive for future developments of hospital networks. Discussion Various common points between the definitions of network and complex systems can be found. It is important to study the properties of complex systems in order to achieve value-based healthcare in the hospital networks context. The insights gained should be useful for all professionals from and across all levels of healthcare organizational responsibility, being able to orient roles and actions to achieve coordination/integration inside hospital networks. Conclusions Complexity literature can help understand how to achieve coordination/integration in healthcare settings and find levers for effective governance. It is important to study the current situation to anticipate and, possibly govern, future developments. In conclusion, governance of hospital networks should be interpreted as coordination/integration inside and across multiple organizational levels of co-responsibility.

Geographic tongue clinical response in moderate-to-severe psoriatic patients undergoing secukinumab: a real-life, multicenter retrospective observational study.

Geographic tongue (GT), a form of inverse psoriasis, is frequently linked to plaque psoriasis. The objective of the study is to evaluate IL-17 blocker (secukinumab) effect on GT severity. This reallife, multicenter, retrospective observational pilot study evaluated patients with plaque psoriasis and concomitant GT that started in label treatment with secukinumab. Patients were evaluated twice (T0=baseline and T1=after 16 weeks) by a dentist and a dermatologist collecting data on cutaneous Psoriasis Area Severity Index (PASI) and oral statuses using Hume's classification of the Geographic Tongue Severity Index (GTASI). Twenty-nine psoriatic patients with GT treated with secukinumab were enrolled for the study. Seventeen patients display type I GT, 6 type II and 6 type III with an overall GTASI of 25.52±9.57 at the baseline (T0). No correlation was found between delta GTASI and delta PASI (r=-0.27, p=0.1551). GTASI decrement from T0 to T1 was statistically significant ([95%CI -26.64 to -19.56], t=-13.36, p<0.0001). Secukinumab may enter in GT therapeutic armamentarium as the first biologic IL-17 blocker in patients with concomitant moderate-to-severe plaque psoriasis.

Cutaneous and oral comorbidities in patients with geographic tongue: a multicenter multidisciplinary cross-sectional observational study.

Geographic tongue (GT) represents a localized type of psoriasis inversa and its burden of dermatological and oral comorbidities frequently conditions its severity and diagnosis. Currently, no epidemiological studies have evaluated GT muco-cutaneous comorbidities. We aimed to study oral and dermatological comorbidities in a large sample of GT patients. In this multicenter, cross-sectional study, involving 4 primary referral centers in Italy, we evaluated adult GT patients, who were assessed by board certified dermatologists and dentists for 5 months and collected demographics and medical history. GT was evaluated using Hume's classification together with Geographic tongue severity index (GTASI) to score its severity. The prevalence of oral and dermatological comorbidities was recorded. In the sample we enrolled 137 GT patients (M/F= 5:1) with a mean age of 48,2 ± 14,7 yoa and 33.6% had GT family history. The clinical evaluation found 96 (70.1%) GT type I, 7 (5.1%) type II, 13 (9.5%) type IIIa, 19 (13.9%) type IIIb, 2 (1.5%) type IV, following Hume's classification. The mean GTASI score was 23,7 ± 14,2 and the vast majority displayed a severe form of GT. Eighty-nine patients had oral comorbidities (burning mouth syndrome, caries, parulid and lichen planus) and 80 had dermatological concurrent conditions (plaque psoriasis, inverse psoriasis and atopic dermatitis). In GT patients, both dermatological and dental evaluation should be mandatory to identify previously undiagnosed mucocutaneous comorbidities.

Hidradenitis suppurativa: an update on epidemiology, phenotypes, diagnosis, pathogenesis, comorbidities and quality of life.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that severely impairs patients' quality of life. It is characterized by recurrent painful nodules, abscesses and draining sinus tracts in primarily intertriginous areas. We aimed to review the most up-to-date information regarding the epidemiology, clinical presentation, diagnostic studies, pathogenesis, comorbidities and quality of life of patients with hidradenitis suppurativa. We performed a systematic search of Medline, Embase database (from inception to September 2019) and review of bibliographies without restrictions on year or language. HS has an estimated global prevalence of 0.00033-4.1% (but most likely 0.7-1.2% in the European-US population). Patients still experience a significant diagnostic delay, up to several years. In the absence of pathognomonic tests, the diagnosis of HS is made from clinical observation and the disease narrative. Phenotypic variation renders diagnosis and severity assessment difficult. Ultrasound imaging is an emerging assessment tool for deep-seated lesions. The Hurley Staging System is still widely used in severity rating. Follicular hyperkeratosis and dilatation, follicular rupture and chronic inflammation with architectural tissue changes have been implicated in the pathogenesis of HS. HS has been associated with metabolic syndrome and other risk factors for cardiovascular disease, diabetes mellitus type II, polycystic ovarian syndrome, depression, suicide and substance use disorders. It has been linked to other immune-mediated diseases such as inflammatory bowel disease and spondyloarthropathy. Pain, pruritus, malodour, low self-esteem, sleep and sexual dysfunctions, and poor mental health are chronic symptoms or consequences of uncontrolled disease. HS is an under-diagnosed and under-treated disease with a profound negative impact on patients' quality of life. In the light of its associated comorbidities, an interdisciplinary management approach may be needed to ensure the best outcomes.

L'emergenza COVID-19 nell'ottica del finanziamento del Servizio Sanitario Nazionale: analisi e proposte.

The COVID-19 pandemic crisis has strongly stressed national health systems and resulted in a global economic crisis. This paper aims to frame and evaluate the funding disbursed and the costs incurred by the National Health Service, in relation to the COVID-19 emergency. It also intends to assess current monetary policies. It aims also to suggest and provide proposals in the context of strengthening the NHS. A narrative review of the grey literature was conducted querying OpenGray, WONDER e Pro-quest's Digital Dissertations e Conference Papers Index and the major institutional websites. The ALTEMS COVID-19 Instant Reports and reports published by regional, national and European institutional bodies were used as main information sources. The discussion begins with the presentation of the economic-health and epidemiological situation, and ends with the proposal of possible initiatives aimed at economic and financial reinforcement of the NHS.

[Fragility in a Public Health perspective: principles and tools for a "life course" approach prevention- oriented]. / La Fragilità in una prospettiva di Sanità Pubblica: principi e strumenti per un approccio "life course" orientato alla prevenzione.

The Covid-19 pandemic significantly increased the workload for the Italian Health Service. There is few information in the literature on the pediatric population and on the management of pediatric hospitals. The aim of this article is to describe the management of healthcare services during Covid-19 emergency in Regina Margherita Children's Hospital. The Regina Margherita Children's Hospital is specialized in the prevention, diagnosis and treatment of pediatric diseases. About 1000 health worker work in this Hospital and 278 hospitalization places are available.

Celocentesis for early prenatal diagnosis of hemoglobinopathy.

OBJECTIVE: Celocentesis is an invasive technique that can provide prenatal diagnosis of single-gene disorders, from as early as 7 weeks' gestation. The objective of this study was to examine the safety of celocentesis. METHODS: In this prospective study, celocentesis was performed for prenatal diagnosis of hemoglobinopathy in 402 singleton pregnancies in which both parents were carriers of ß-thalassemia or sickle cell disease trait. We assessed procedure-related maternal discomfort or pain, success of sampling and obtaining results, pregnancy outcome and postnatal follow-up. RESULTS: First, celocentesis was carried out at a median gestational age of 8.6 (range, 6.9-9.9) weeks and celomic fluid was successfully aspirated in 99.8% of cases. Second, 67% of women had no or only mild discomfort, 18% had moderate discomfort, 12% had mild-to-moderate pain and 3% had severe pain. Third, prenatal diagnosis from analysis of the celomic fluid was successful in 93.8% cases, and in the last 121 cases, it was always successful. Fourth, in all cases of successful sampling and analysis of celomic fluid, the diagnosis was concordant with results obtained from additional prenatal or postnatal testing. Fifth, in addition to diagnosis of hemoglobinopathy, quantitative fluorescence polymerase chain reaction analysis, which was performed to evaluate maternal contamination using several markers for chromosomes X, Y, 21, 18 and 13, led to the accurate diagnosis of chromosomal aneuploidy. Sixth, in all cases of an affected fetus diagnosed by celocentesis in which the parents chose termination of pregnancy, this was carried out < 10 weeks' gestation. Seventh, in 97.1% (298/307) of the continuing pregnancies there was live birth, in seven (2.3%) there was miscarriage and in two (0.7%) there was loss to follow-up. Eighth, fetal abnormalities were diagnosed in three (1%) cases, including unilateral transverse amputation of the forearm, unilateral moderate hydronephrosis and small-bowel duplication. All neonates were examined by a pediatrician and were found to be phenotypically normal, except for the three cases with a prenatally diagnosed defect. CONCLUSIONS: Celocentesis can be used for early prenatal diagnosis of genetic abnormalities, and the procedure-related risk of pregnancy complications appears to be low. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Epidemiology of odontogenic sinusitis: an old, underestimated disease, even today. A narrative literature review.

Odontogenic sinusitis is an inflammatory condition of the paranasal sinuses resulting from dental pathology. The aim of this study is to provide an overview of the current literature on the dimensions of the phenomenon, quality of life, economic considerations, and approaches to odontogenic sinusitis. A narrative review was conducted following the methodology proposed by Green et al. (2006). There appears to have been an increase in the incidence over the last decade. Nowadays, evidence in the literature reports that 10-12% up to 40% of all sinusitis cases are associated with odontogenic infections. The iatrogenia was by far the leading cause of odontogenic sinusitis (55.97%) while the first and second molars were the most affected teeth with an incidence of 35.6% and 22%. If not properly diagnosed and treated, these infections may lead to a rapid spread, giving rise to potentially life-threatening complications with a significant general health-related Quality of Life detriment. The proper management of patients in a pre-implant logical setting leads to substantial savings, ranging from €38 million to €152 million, for the Italian National Health Service. Odontogenic sinusitis management should involve shared decisionmaking between the otolaryngologist, dental provider, and patient, where the benefits and risks of dental treatment and endoscopic sinus surgery are discussed.

Comorbidities in pediatric alopecia areata.

BACKGROUND: Comorbidities are associated with higher health care costs, complex management, and poorer health outcomes. Identification and treatment of comorbid conditions in paediatric alopecia areata (AA) patients could provide an opportunity to improve health outcomes. OBJECTIVES: To determine the prevalence of comorbidities among paediatric patients with AA using a large de-identified aggregated patient database. METHODS: This is a cross-sectional study using aggregated health record data through April 1, 2019. Patients ≤18 years of age, with alopecia areata (n = 3510) and without alopecia areata (n = 8 310 710) were identified. The primary outcome was the prevalence of comorbidities among AA patients. RESULTS: Of the 8 314 220 paediatric patients, 3510 (1570 males and 1940 females) had a diagnosis of alopecia areata. The most common comorbidities included atopic dermatitis (17.4% vs. 2.2% controls, OR 9.2, 95% CI 8.55-10.18, P < 0.001), anaemia (7.7% vs. 2.4% controls, OR 3.4, 95% CI 3.06-3.92, P < 0.001), obesity (5.7% vs. 1.1% controls, OR 5.6, 95% CI 4.76-6.34, P < 0.001), vitamin D deficiency (5.1% vs. 0.4% controls, OR 14.7, 95% CI 13.5-18.1, P < 0.001), hypothyroidism (2.6% vs. 0.2% controls, OR 12, 95% CI 10.73-15.9, P < 0.001), vitiligo (1.4% vs. 0.04% controls, OR 32.2, 95% CI 24.01-42.1, P < 0.001), psoriasis (1.4% vs. 0.07% controls, OR 20.6, 95% CI 15.55-27.2, P < 0.001), hyperlipidemia (1.4% vs. 0.2% controls, OR 5.9, 95% CI 4.4-7.7, P < 0.001), and depression (2.6% vs. 0.6% controls, OR 4.8, 95% CI 5.09-9.45, P < 0.001). CONCLUSIONS: Findings from this study suggest that children with AA are more likely to have certain autoimmune and metabolic disorders than the general paediatric population. Paediatric AA patients display a severe burden of autoimmune and metabolic diseases, thus in daily practice, dermatologists might consider multidisciplinary management in these patients.

Artificial neural networks allow response prediction in squamous cell carcinoma of the scalp treated with radiotherapy.

BACKGROUND: Epithelial neoplasms of the scalp account for approximately 2% of all skin cancers and for about 10-20% of the tumours affecting the head and neck area. Radiotherapy is suggested for localized cutaneous squamous cell carcinomas (cSCC) without lymph node involvement, multiple or extensive lesions, for patients refusing surgery, for patients with a poor general medical status, as adjuvant for incompletely excised lesions and/or as a palliative treatment. To date, prognostic risk factors in scalp cSCC patients are poorly characterized. OBJECTIVE: To identify patterns of patients with higher risk of postradiotherapy recurrence. METHODS: A retrospective observational study was performed on scalp cSCC patients with histological diagnosis who underwent conventional radiotherapy (50-120 kV) (between 1996 and 2008, follow-up from 1 to 140 months, median 14 months). Out of the 79 enrolled patients, 22 (27.8%) had previously undergone a surgery. Two months after radiotherapy, 66 (83.5%) patients achieved a complete remission, 6 (7.6%) a partial remission, whereas 2 (2.5%) proved non-responsive to the treatment and 5 cases were lost to follow-up. Demographical and clinical data were preliminarily analysed with classical descriptive statistics and with principal component analysis. All data were then re-evaluated with a machine learning-based approach using a 4th generation artificial neural networks (ANNs)-based algorithm. RESULTS: Artificial neural networks analysis revealed four scalp cSCC profiles among radiotherapy responsive patients, not previously described: namely, (i) stage T2 cSCC type, aged 70-80 years; (ii) frontal cSCC type, aged <70 years; (iii) non-recurrent nodular or nodulo-ulcerated, stage T3 cSCC type, of the vertex and treated with >60 Grays (Gy); and (iv) flat, occipital, stage T1 cSCC type, treated with 50-59 Gy. The model uncovering these four predictive profiles displayed 85.7% sensitivity, 97.6% specificity and 91.7% overall accuracy. CONCLUSIONS: Patient profiling/phenotyping with machine learning may be a new, helpful method to stratify patients with scalp cSCCs who may benefit from a RT-treatment.

Photoadaptation to ultraviolet B TL01 in psoriatic patients.

BACKGROUND: In the biologic era, narrow-band ultraviolet B (NB-UVB) phototherapy still remains a valuable, effective, inexpensive, safe anti-psoriatic treatment. Patients can lose response to NB-UVB over time due to photoadaptation. This phenomenon is the tendency of the skin to respond to ultraviolet (UV) exposure by undergoing changes that may result in a decreased future response to an equivalent dose of radiation, thus leading to the need for an increased exposure during phototherapy course. AIM: To characterize and quantify the determinants of photoadaptation in NB-UVB treated psoriatic patients. METHODS: We enrolled 57 adult patients with moderate plaque psoriasis. Patients underwent 24 sessions of NB-UVB phototherapy delivered thrice a week. Dosing was started with 70% of the minimal erythema dose (MED) with percentage-based dose increments every two treatments. MED as well as change in the erythema and melanin index (MI) were measured at baseline and at the end of phototherapy course. Moreover, an adaptation factor (AF) was calculated for each patient. RESULTS: Adaptation factor was not influenced by both baseline MED and skin type. We found a weak correlation between higher cumulative dosages and the initial MED (Spearman's rho = 0.32, P = 0.0154) as well as with the mean initial MI (Spearman's rho = 0.25, P = 0.0624, statistically borderline). Clearance and mean number of treatments were correlated (Spearman's rho = 0.48, P < 0.001). CONCLUSION: Photoadaptation is a physiological skin response that negatively influences NB-UVB responsiveness and is not predictable by the baseline MED and skin type. Thus, starting with more aggressive protocols and increasing rapidly dosage progression to prevent AF may increase NB-UVB response.

'High dose' vs. 'medium dose' UVA1 phototherapy in italian patients with severe atopic dermatitis.

BACKGROUND: The current evidences attest UVA1 phototherapy as effective in the treatment of severe atopic dermatitis (AD). Furthermore, in this indication, 'medium dose' is as effective as 'high dose' regimen. To date, a randomized comparison study evaluating the effectiveness as well as safety of different UVA1 protocols in different skin types in the treatment of adult patients with severe AD is still lacking. OBJECTIVE: The aim of the present study was to compare the safety and the efficacy of medium and high dose UVA1 either in fair or in dark skin types. METHODS: Twenty-seven adult patients with severe AD were consecutively included in a randomized, controlled, open, two arms trial Severity of AD was determined by means of SCORAD index and clinical improvement was also monitored. A total of 13 out of 27 patients were treated with high dose (130 J/cm2 ) UVA1 protocol while 14 out of 27 patients received medium dose (60 J/cm2 ) UVA1 protocol. Phototherapy was performed five times weekly up to 3 weeks. Before and after UVA1 treatment each patient was evaluated for skin pigmentation through Melanin Index (MI) quantitative evaluation. RESULTS: Skin status improved in all patients resulting in a reduction of SCORAD index in all groups. Our results demonstrated that among patients with darker skin types and higher MI, high dose UVA1 was significantly more effective than medium dose (P < 0.0001) while within the groups with skin type II, no significant differences between high and medium dose protocols were observed. CONCLUSION: Our study, confirms previous observations that UVA1 phototherapy should be considered among the first approaches in the treatment of patients with severe generalized AD and also demonstrates that in darker skin types, high dose UVA1 phototherapy is more effective than medium dose in the treatment of adult patients with severe AD.

An Italian pilot study of a psycho-social intervention to support family caregivers' engagement in taking care of patients with complex care needs: the Engage-in-Caring project.

BACKGROUND: The raising of disability and chronic illness burden among European population is calling for a new paradigm of care, focused on primary health care interventions. Engage-In-Caring is a novel multicomponent intervention clearly dedicated to improve family caregiver engagement in the care of patients with complex care needs, by supporting them to develop a stronger consciousness of their role, needs and skills. METHOD: Engage-In-Caring intervention's efficacy and feasibility have been evaluated through a single arm pre-post observational pilot study settled in Rome. A qualitative phase, consisting of literature analysis of caregivers' unmet needs and a final revision from an experts' group, led to the structuration of the intervention, following the Caregiver Health Engagement Model (CHE-Model). Afterwards, a quantitative phase allowed understanding the feasibility of the intervention through Kruskal-Wallis test on a sample of 47 caregivers. RESULTS: Results showed a reduction of the physical burden (Chi Squared = 6,483; p = .01) perceived by the caregivers and increase of the health literacy (Chi Squared = 3,560; p = .059) after the intervention. CONCLUSIONS: Feasibility tests on caregivers of patients with complex care needs are promising: this pilot study suggests a first effectiveness evidence, particularly concerning aspects related to burden perception and improvements in health literacy. Randomised controlled trials on larger samples are needed.

Validation of a visual-aided questionnaire for the self-assessment of hidradenitits suppurativa.

BACKGROUND: Hidradenitis Suppurativa (HS) is a chronic, highly debilitating disease. Few questionnaires have been developed to identify potential HS cases based on simple questions. A visual representation may help in characterising these lesions. OBJECTIVE: To develop and validate a visually assisted questionnaire for HS detection. METHODS: This was an observational diagnostic study on a series of patients with a first diagnosis of HS and a corresponding series of age and gender-matched controls consecutively observed in two Italian centres. The questionnaire was developed based on a critical appraisal of the relevant literature and on expert consensus. Measures of accuracy and reproducibility were assessed. RESULTS: 57 patients with HS and 57 controls were included in the study (mean age 32.9 ± 12.3 years). Based on at least one affirmative answer to the proposed questionnaire items, the accuracy was 95.6%, with a sensitivity of 98.2% and a specificity of 93.0%. Reproducibility was almost perfect on all the tested items (Cohen's kappa ≥ 0.85). LIMITATIONS: The questionnaire was tested only in experimental conditions. CONCLUSION: The questionnaire could be a useful tool for HS screening in the general population. Further studies are needed to confirm its performance in a real-world setting.

Autoinflammation in pyoderma gangrenosum and its syndromic form (pyoderma gangrenosum, acne and suppurative hidradenitis).

BACKGROUND: Pyoderma gangrenosum (PG) is a rare skin disease characterized clinically by ulcers with undermined borders, and histologically by neutrophil-rich infiltrates. PG may occur alone, in syndromic forms or associated with systemic diseases, such as inflammatory bowel disease and haematological or rheumatological disorders. OBJECTIVES: To determine a specific genetic background related to autoinflammation for PG. METHODS: We assessed autoinflammation by evaluating the cytokine profile and genes involved in classic autoinflammatory diseases in 13 patients with PG and in seven patients with the syndromic form, known as PASH (pyoderma gangrenosum, acne and suppurative hidradenitis). RESULTS: In skin samples, the expression of interleukin (IL)-1ß and its receptors, IL-17 and its receptor, and tumour necrosis factor-α and its receptors were significantly higher in both PG (P = 0·001) and in PASH (P < 0·001) than in controls. The chemokines IL-8; chemokine (C-X-C motif) ligand 1/2/3; chemokine (C-X-C motif) ligand 16; and RANTES (regulated on activation, normal T-cell-expressed and secreted) were also overexpressed. Cases of PG and PASH showed mutations in the autoinflammatory genes MEFV, NLRP3, NLRP12, NOD2, LPIN2 and PSTPIP1. CONCLUSIONS: Overexpression of cytokines/chemokines, along with genetic changes, supports the hypothesis that PG and its syndromic form, PASH, are a spectrum of polygenic autoinflammatory conditions.