Immunomediated Diseases Research Articles

DOP74 Short and long-term effectiveness and safety of ustekinumab in Ulcerative Colitis in real life: the ULISES study

Abstract Background Primary aim: To assess the durability of ustekinumab treatment in patients with ulcerative colitis (UC). Secondary aims: To assess the short-term effectiveness, the durability of response, and the tolerability of ustekinumab in clinical practice. Methods Retrospective, multicenter study including UC patients who had received the 1st ustekinumab dose at least 16 weeks before inclusion. Patients were followed-up from the 1st ustekinumab dose to treatment discontinuation or last visit. Only patients with active disease [Partial Mayo Score (PMS)>2] at ustekinumab start were considered in the effectiveness analysis. Clinical effectiveness was based on PMS. Patients who stopped ustekinumab before their last visit were considered not in remission at subsequent time points (negative imputation). Results 620 patients were included (table 1). 78% of patients who started ustekinumab maintenance treatment, did it with 90 mg every-8-weeks dose. 155 patients (25%) withdrew ustekinumab during follow-up [median=12 months (m)]. Incidence rate of ustekinumab discontinuation was 20% per patient-year of follow-up. The probability of maintaining ustekinumab is shown in figure 1A. Among patients who withdrew ustekinumab, the main reasons were primary non-response (39%) and loss of response (35%). Anaemia at baseline (HR=1.5, 95%CI=1.1-2.1), steroids at baseline (HR=1.5; 95%CI=1.06-2.08), and more severe clinical activity at baseline (HR=1.5; 95%CI=1.09-2.06) were associated with higher risk of ustekinumab discontinuation. Short and long-term effectiveness of ustekinumab is shown on figure 1B. Moderate-severe vs. mild disease activity at baseline (OR=0.3, 95%CI=0.2-0.5), male sex (OR=0.5; 95%CI=0.4-0.8), and increased number of previous biologics (OR=0.6, 95%CI=0.6-0.8) were associated with lower likelihood of steroid-free remission at week 16. A total of 57 (25%) patients among those with active disease at baseline and with steroid-free remission at week 16, lost response during a median follow-up of 8 m (IQR=3-16 m) (figure 1C). The dose was escalated in 72% of patients with loss of response, and 80% improved (67% remission); an intravenous reinduction was given in 3 patients, and none of them improved. A total of 176 patients (28%) had at least one adverse event, with infections being the most frequent (11%). No negative impact on extraintestinal manifestations and/or immunomediated diseases was seen. Conclusion Ustekinumab was effective in inducing remission even in highly refractory UC patients. A proportion of patients discontinue the treatment, mostly due to primary failure and loss of response. Dose escalation may be effective to regain response after loss of effectiveness. The safety profile was similar to previously reported.

Comprehensive analysis of mitochondrial DNA variants, mitochondrial DNA copy number and oxidative damage in psoriatic arthritis.

Growing evidence suggests that abnormalities in mitochondrial DNA (mtDNA) are involved in the pathogenesis of various inflammatory and immuno-mediated diseases. The present study analysed the entire mitochondrial genome by next-generation sequencing (NGS) in 23 patients with psoriatic arthritis (PsA) and 20 healthy controls to identify PsA-related variants. Changes in mtDNA copy number (mtDNAcn) were also evaluated by quantitative polymerase chain reaction (qPCR) and mtDNA oxidative damage was measured using an 8-hydroxy-2'-deoxyguanosine assay. NGS analysis revealed a total of 435 variants including 187 in patients with PsA only and 122 in controls only. Additionally, 126 common variants were found, of which 2 variants differed significantly in their frequencies among patients and controls (P<0.05), and may be associated with susceptibility to PsA. A total of 33 missense variants in mtDNA-encoded genes for complexes I, III, IV and V were identified only in patients with PsA. Of them, 25 variants were predicted to be deleterious by affecting the functions and structures of encoded proteins, and 13 variants were predicted to affect protein's stability. mtDNAcn analysis revealed decreased mtDNA content in patients with PsA compared with controls (P=0.0001) but the decrease in mtDNAcn was not correlated with patients' age or inflammatory biomarkers (P>0.05). Moreover, a higher level of oxidative damage was observed in patients with PsA compared with controls (P=0.03). The results of the present comprehensive analysis of mtDNA in PsA revealed that certain mtDNA variants may be implicated in the predisposition/pathogenesis of PsA, highlighting the importance of NGS in the identification of mtDNA variants in PsA. The current results also demonstrated that decreased mtDNAcn in PsA may be a consequence of increased oxidative stress. These data provide valuable insights into the contribution of mtDNA defects to the pathogenesis of PsA. Additional studies in larger cohorts are needed to elucidate the role of mtDNA defects in PsA.

Immune response after SARS-CoV-2 vaccination in patients with inflammatory immune-mediated diseases receiving immunosuppressive treatment

BackgroundReal world data on the response to the SARS-CoV-2 vaccine in patients with immunomediated diseases (IMIDs) treated with immunesuppressants is of great interest because vaccine response may be impaired. The main aim was to study the humoral and cellular immune response after SARS-CoV-2 vaccination in patients with IMIDs treated with immunosuppressants. The secondary aim was to describe the frequency of SARS-CoV-2 infections after vaccination in these patients.Material and methodsThis is an observational study including 86 patients with IMIDs. All patients were treated with biologic or targeted synthetic disease-modifying antirheumatic drugs [b/tsDMARDs: TNF inhibitors (TNFi), rituximab, anti-interleukin 6 receptor (anti-IL6R) or JAK inhibitors (JAKi)]. Demographic and clinical information were collected. After 4–6 weeks of 2nd and 3rd vaccine doses, humoral response was assessed using the Thermo Scientific ELiA SARS-CoV-2-Sp1 IgG Test. Also, in patients with serum SARS-CoV-2 antibody levels under 100UI/ml, cellular response was analyzed using the QuantiFERON SARS-CoV-2 Starter Pack.ResultsA total of 86 patients under b/tsDMARDs and 38 healthy controls were included. Most patients received TNFi (45 with TNFi, 31 with rituximab, 5 with anti-IL6R and 5 with JAKi). SARS-CoV-2 antibodies (Ab) were present in an 86% of patients with IMIDs and in 100% healthy controls (p = 0.017). However, 12 (14%) patients had undetectable SARS-CoV-2 Ab levels, all treated with rituximab. In addition, SARS-CoV-2 Ab (IU/ml) were statistically lower in patients (Mdn (IQR): 59.5 (17–163) in patients vs 625 (405–932) in controls, p < 0.001). Patients treated with rituximab had lower Ab levels than those treated with TNFi and controls (p < 0.001). The cellular response to SARS-CoV-2 vaccine was evaluated in 30 patients. Eleven patients had a positive cellular response, being more frequent in patients treated with rituximab (p = 0.03). SARS-CoV-2 infection was reported in 43% of patients and 34% of controls after vaccination. Only 6 (7%) patients required hospitalization, most of whom treated with rituximab (67%).ConclusionSARS-CoV-2 antibody levels were lower in patients than in controls, especially in patients treated with rituximab. A cellular response can be detected despite having a poor humoral response. Severe infections in vaccinated patients with IMIDs are rare, and are observed mainly in patients treated with rituximab.

S-100 Proteins: Basics and Applications as Biomarkers in Animals with Special Focus on Calgranulins (S100A8, A9, and A12).

S100 proteins are a group of calcium-binding proteins which received this name because of their solubility in a 100% saturated solution of ammonium sulphate. They have a similar molecular mass of 10-12 KDa and share 25-65% similarity in their amino acid sequence. They are expressed in many tissues, and to date 25 different types of S100 proteins have been identified. This review aims to provide updated information about S100 proteins and their use as biomarkers in veterinary science, with special emphasis on the family of calgranulins that includes S100A8 (calgranulin A; myeloid-related protein 8, MRP8), S100A9 (calgranulin B; MRP14), and S100A12 (calgranulin C). The proteins SA100A8 and S100A9 can be linked, forming a heterodimer which is known as calprotectin. Calgranulins are related to the activation of inflammation and the immune system and increase in gastrointestinal diseases, inflammation and sepsis, immunomediated diseases, and obesity and endocrine disorders in different animal species. This review reflects the current knowledge about calgranulins in veterinary science, which should increase in the future to clarify their role in different diseases and potential as biomarkers and therapeutic targets, as well as the practical use of their measurement in non-invasive samples such as saliva or feces.

Vaccines - beliefs and concerns: the voice of patients with inflammatory immunomediated diseases.

Vaccination is a key issue in patients with immunomodulated inflammatory diseases on immune-mediated therapy. Still, vaccination rates in these patients are low. This study aimed to assess the knowledge and fears of patients with immune-mediated inflammatory diseases (IMIDs) regarding vaccines, with the ultimate goal of increasing vaccination rates through the definition and implementation of more effective communication strategies with the patient. This study was conducted in a Portuguese hospital, between January 2019-December 2020, and included adult patients with an IMID. A questionnaire was developed and applied to evaluate knowledge and fears regarding vaccines. From the 275 included patients, more than 90% answered correctly to all questions on general knowledge, with an exception for the question related to protection from severe disease, without differences between age groups or education levels, except for the question about vaccine contraindications (P = 0.017). Regarding vaccines in immunocompromised hosts, the proportion of correct answers was lower and significantly different between education levels (P = 0.00-0.042),. More than 50% of the participants showed moderate to very high concern about several aspects of vaccines, with differences between age groups (P = 0.018). Our patients have general knowledge of vaccines but regarding vaccines in immunocompromised patients knowledge is lower and dependent on the education level. In addition, age influences the pattern of concerns related to vaccines. The information gathered in this study shall be considered to identify potential local interventions targeted to improve vaccination.

P675 Real world evidence of tofacinitib in ulcerative colitis: short and long-term effectiveness, safety and impact of extraintestinal manifestations and immunomediated diseases

Abstract Background Main aim: To assess the durability of tofacitinib treatment in patients with ulcerative colitis (UC). Secondary aims: To assess the short and long-term effectiveness; the tolerability of tofacitinib in clinical practice; and to evaluate the evolution of extraintestinal manifestations (EIMs) and immunomediated inflammatory diseases (IMIDs). Methods Retrospective, multicenter study including UC patients who had received the first tofacitinib dose at least 8 weeks before the inclusion. Patients were followed-up from the first tofacitinib dose to treatment discontinuation or last visit, whichever came first. Only patients with active disease [Partial Mayo Score (PMS)&amp;gt;2] at tofacitinib start were considered in the effectiveness analysis. Clinical effectiveness was based on PMS. In patients who stopped tofacitinib before their last visit, the last observation carried forward method was used to impute missing values at subsequent time points. Results 408 patients were included (figure 1). Incidence rate of tofacitinib discontinuation was 41% per patient-year of follow-up. The probability of maintaining tofacitinib is shown in figure 2a. Main reasons for tofacitinib withdrawal were primary non-response (44%) and loss of response (26%). Age at the start of tofacitinib (older) (HR=0.98, 95%CI=0.97-0.99) and the severity of clinical activity were associated with tofacitinib withdrawal (mild vs. remission: HR=1.5, 95%CI=0.5-4; and moderate-severe vs. remission: HR=3.0, 95%CI=1.2-7.4). Short-term effectiveness is shown in figure 3a. To have moderate-severe vs. mild disease activity at baseline (OR=0.2, 95%CI=0.1-0.4) and age at tofacitinib start (older) (OR=1.01, 95%CI=1.002-1.03) were associated with clinical remission at week 8. The probability of maintaining response in shown in figure 2b. Tofacitinib dose was escalated in 55 patients (66%) of those who had lost response, and 82% of them improved (60% regained remission). The proportion of patients on 10 mg b.i.d was over 40% in all timepoints during follow-up. The proportion of patients in clinical remission during follow-up in shown in figure 3b. Adverse events during tofacitinib treatment are summarized in figure 4. There was not any signal of negative impact of tofacitinib on EIM o IMIDs. Conclusion Tofacitinib is effective in inducing remission even in highly refractory UC patients. A relevant proportion of patients discontinue the treatment, mostly due to primary failure. Dose escalation is effective to regain response after loss of efficacy. The safety profile is similar to that previously reported

448 ACUTE IDIOPATHIC PERICARDITIS: THE IMPORTANCE OF GUIDELINE-BASED TREATMENT TO AVOID RECURRENCE

Abstract Background Acute pericarditis usually resolves with first-line treatment, but it may recur. Recurrences are usually attributed to a deranged immunity, but it is unclear whether they may also be related to inappropriate treatment. Purpose The aims of our study were to clarify the potential role of inappropriate treatment on relapse episodes in acute pericarditis. Methods Consecutive patients prospectively followed-up for over 20 years at Padua University Cardioimmunology outpatient clinic were included. Clinical and instrumental findings were recorded at diagnosis and at each follow-up. Spectrum, appropriateness, efficacy and side effects of therapies received by patients before and after referral to our centre were considered. The distribution of recurrence-free survival probability has been estimated using Kaplan-Meier method; impact of the covariates of interest on the outcome was assessed using Cox univariate analysis models. Results The cohort consisted of 144 patients (82 males, 62 females, mean age 50 years, 143 Caucasian and 1 African), 139 had acute pericarditis, which was recurrent in 63; 5 had constrictive pericarditis; aetiology was idiopathic/presumed-viral in 112, bacterial in 1, secondary to pericardial injury in 26, to Dressler syndrome in 2, and to a systemic immune-mediated disease in 3. At diagnosis, 68% were in NYHA class I, 22% in II, 5% in III, 5% in IV; 9% developed cardiac tamponade; 84% patients received non-steroidal-anti-inflammatory drugs, 54% colchicine and 19% corticosteroids. Treatment was not in line with ESC guidelines in 31% of patients for non-steroidal-anti-inflammatory drugs, in 12% for steroids and in 28% for colchicine, requiring readjustment. Patients with constrictive pericarditis underwent uncomplicated pericardiectomy. No patient was dead at last follow-up. Estimated recurrence-free-survival probability was 86% at 1st year, 58% at 5th, 52% at 10th. Variables which tended to be associated with a higher risk of recurrence were: cardiac tamponade at diagnosis, left heart failure, concomitant immuno-mediated diseases, specific etiology, history of recurrence, inappropriate treatment with colchicine, inappropriate treatment with non-steroidal anti-inflammatory-drugs, III or IV NYHA class at diagnosis. Treatment of acute/recurrent forms before referral did not appear in line with the international recommendations in terms of daily dosage and duration, or both, in 43 patients for anti-inflammatory drugs, in 17 for corticosteroids and in 39 for colchicine, which was omitted despite the absence of known contraindications (see attached Table). Following treatment adjustment to international guidelines, 107 patients with relapsing pericarditis obtained complete remission; only 13 (9%) of our AP patients showed a truly treatment-refractory form that required a second-line therapy. All patients (5) with constrictive pericarditis underwent uncomplicated pericardiectomy. Conclusion When treated according to international guidelines, pericarditis has usually a favourable evolution, even in its most adverse presentations. Treatment inaccuracies seems to account, at least in part, to disease recurrences.

Autoimmune gastritis: long-term natural history in naïve Helicobacter pylori-negative patients

ObjectiveAutoimmune gastritis (AIG) is an immunomediated disease targeting parietal cells, eventually resulting in oxyntic-restricted atrophy. This long-term follow-up study aimed at elucidating the natural history, histological phenotype(s), and associated cancer...

P373 Real world evidence of tofacinitib in ulcerative colitis: short and long-term effectiveness, impact of extraintestinal manifestations and immunomediated diseases and safety

Abstract Background Main aim: To assess the retention rate of tofacitinib treatment in patients with ulcerative colitis (UC). Secondary aims: To assess the short-term effectiveness and the durability of response; to evaluate the evolution of extraintestinal manifestations (EIMs) and immunomediated inflammatory diseases (IMIDs); to assess the tolerability of tofacitinib in clinical practice. Methods Retrospective, multicenter study. UC patients who had received the first tofacitinib dose at least, 8 weeks before the start date of recruitment. Patients were followed-up from the first tofacitinib dose to treatment discontinuation or last visit, whichever came first. Only patients with active disease [Partial Mayo Score (PMS)&amp;gt;2] were considered in the short-term effectiveness analysis. Clinical response was based on the PMS. Variables associated with short-term remission were identified by logistic regression analysis. Kaplan-Meier curves and Cox-regression analysis were used to evaluate the long-term effectiveness and durability of tofacitinib treatment. Results 335 patients have been included so far (recruitment still ongoing) (Table 1). A total of, 70 patients (21%) would have met the criteria for entering A3921133 trial. A total of, 155 patients interrupted tofacitinib during follow-up (Figure 1a), mainly due to primary non-response (46%) and loss of response (25%); predictive factors of tofacitinib discontinuation are shown in figure 1b. Short-term effectiveness and predictive factors of remission are shown on figure 2;, 16% of non-responders and, 35% with partial response at week, 4 reached remission at week, 8, and, 19% of non-responders and, 37% of partial responders at week, 8 reached remission at week, 16. Of, 151 patients in remission at week, 8, 68 (45%) lost response (Figure 3); tofacitinib dose was increased in, 27%, and, 71% of them reached remission again. Obvious blood with stool most of the time or blood alone passed at baseline was the only variable associated with losing response over time. There were, 86 adverse events related to tofacitinib treatment (Table 2). Fifty-seven patients (17%) had EIMs or IMIDs non-active at tofacitinib start; only, 2 out of, 12 patients with peripheral arthropathy worsened., 53 patients (16%) had active EIMs or IMIDs at the start of tofacitinib and some of them improved. A total of, 17 EIMs or IMIDs occurred after starting tofacitinib but only, 1 (vasculitis) caused tofacitinib withdrawal. Conclusion Tofacitinib is effective in inducing remission even in highly refractory UC patients. A relevant proportion of patients discontinue the treatment, mainly during the first months due to primary failure. The safety profile is similar to that previously reported for tofacitinib

Assessment of Stress Salivary Markers, Perceived Stress, and Shift Work in a Cohort of Fishermen: A Preliminary Work.

Due to work-related stress, today, work itself represents a daily challenge that must be faced in many occupations. While, in the past, the scientific community has focused on the helping professions, since, an increasing number of professions have since been investigated. Therefore, different approaches exist in order to assess this disorder, representing a scientific field wherein biological and psychological dimensions both need to be evaluated. In this paper, we consider three biological salivary markers: interleukin 1 beta (IL-1β), cortisol, and melatonin. The choice derives from recent contributions to the literature in which the interplay between these markers has been verified. Briefly, such interplay could explain how the central nervous, endocrine, and immune systems communicate with each other, supporting a holistic concept of person. In 30 marine fishermen from the Apulia region of Italy, perceived stress was measured using the Professional Stress Scale (PSS) and sleep disturbances were assessed through the Pittsburgh Sleep Quality Index (PSQI). Salivary markers were collected at 8:00 a.m. and 2:00 p.m. Those subjects reporting sleep disturbance and having altered scores in two PSS subclasses, home–work conflict and self-esteem, presented inverted salivary melatonin and cortisol nictemeral rhythms (with regard to melatonin levels at 8:00 a.m., those workers reporting values higher than the median showed 64.1% versus 48.6% home–work conflict with respect to cortisol levels, subjects having an inverted circadian rhythm showed 69.9% versus 52.5% home–work conflict, and these values resulted 47.7% versus 25.3% when the self-esteem was considered). As regards melatonin, PSQI score is statistically different in the two groups of subjects as identified by median melatonin at 8:00 a.m.; specifically, the subjects who had mean values higher than the median shared higher PSQI scores (10.8 versus 9.8). The same subjects reported more frequent home–work conflict and more sleep disorders. We found a negative correlation between IL-1β at 8:00 a.m. and Cortdiff (the difference between cortisol at 8:00 a.m.–cortisol at 2:00 p.m.), and that high IL-1β at 8:00 a.m. was associated with low Cortdiff. Based on our results we would like to propose this approach in health surveillance, in order to prevent mental and/or physical disorders, however our study is surely preliminary. The interesting perspectives and hypotheses cited in this paper, in which the roles of IL-1β and norepinephrine appear central and important, could remain hypothetical if not supported by more robust observation in order to produce, truly, new knowledge. In the future we will deepen this study with a larger sample, and if these results will be confirmed, this approach could allow preventing, not only mental and physical disorders, but also immuno-mediated diseases, and, perhaps, cancer.

Using Autoantibodies to Diagnose Systemic Autoimmune Diseases Triggered by Immune Checkpoint Inhibitors: A Clinical Perspective

Immunotherapies, such as immune checkpoint inhibitors (ICIs), have significantly advanced the treatment of cancer and other conditions. However, these therapies can also cause immune-related adverse events (irAEs), which are unintended side effects due to their effects on the immune system of the treated patient. These effects can be classified as organ-specific or systemic, with the latter being of particular interest due to their potential overlap with systemic autoimmune diseases (SADs). Autoantibodies, which are proteins produced by the immune system that react with self components, are often used to diagnose and classify SAD. However, the diagnostic value of autoantibodies in the context of systemic irAEs (sirAEs) triggered by ICIs is not well understood. This review aims to evaluate the diagnostic value of conventional autoantibodies in the identification and classification of sirAEs. A comprehensive search of the literature was conducted using the PubMed database, with a focus on articles published in the past 10 years. The results of the review suggest that, although autoantibodies can be useful in the diagnosis and classification of some SAD triggered by ICIs, there is a clear predominance of seronegative irAEs. The lack of traditional autoantibodies may suggest a unique mechanism for sirAEs and increases the already complex diagnostic approach of these manifestations, requiring evaluation by multidisciplinary teams with extensive experience in immunomediated diseases. Further research is needed to fully understand the diagnostic value of autoantibodies in this context and to determine the optimal approach for their detection and interpretation.

How to Tackle the Relationship between Autoimmune Diseases and Diet: Well Begun Is Half-Done.

Nutrition and immunity are closely related, and the immune system is composed of the most highly energy-consuming cells in the body. Much of the immune system is located within the GI tract, since it must deal with the huge antigenic load introduced with food. Moreover, the incidence of immune-mediated diseases is elevated in Westernized countries, where “transition nutrition” prevails, owing to the shift from traditional dietary patterns towards Westernized patterns. This ecological correlation has fostered increasing attempts to find evidence to support nutritional interventions aimed at managing and reducing the risk of immune-mediated diseases. Recent studies have described the impacts of single nutrients on markers of immune function, but the knowledge currently available is not sufficient to demonstrate the impact of specific dietary patterns on immune-mediated clinical disease endpoints. If nutritional scientists are to conduct quality research, one of many challenges facing them, in studying the complex interactions between the immune system and diet, is to develop improved tools for investigating eating habits in the context of immunomediated diseases.

Risk, Course, and Effect of SARS-CoV-2 Infection in Children and Adults with Chronic Inflammatory Bowel Diseases.

Susceptibility and disease course of COVID-19 among patients with inflammatory bowel diseases (IBD) are unclear and epidemiological data on the topic are still limited. There is some concern that patients with immuno-mediated diseases such as IBD, which are frequently treated with immunosuppressive therapies, may have an increased risk of SARS-CoV-2 infection with its related serious adverse outcomes, including intensive care unit (ICU) admission and death. Corticosteroids, immunomodulators, and biologic drugs, which are commonly prescribed to these patients, have been associated with higher rates of severe viral and bacterial infections including influenza and pneumonia. It is not known whether these drugs can be so harmful as to justify their interruption during COVID-19 infection or if, on the contrary, patients with IBD can benefit from them. As shown by recent reports, it cannot be excluded that drugs that suppress the immune system can block the characteristic cytokine storm of severe forms of COVID-19 and consequently reduce mortality. Another cause for concern is the up-regulation of angiotensin converting enzyme-2 (ACE2) receptors that has been noticed in these patients, which could facilitate the entry and replication of SARS-CoV-2. The aim of this narrative review is to clarify the susceptibility of SARS-CoV-2 infection in patients with IBD, the clinical characteristics of patients who contract the infection, and the relationship between the severity of COVID-19 and immunosuppressive treatment.

Anti-CD52 Therapy for Multiple Sclerosis: An Update in the COVID Era.

CD52 is a small surface glycoprotein composed of 12 amino acids. CD52 is found mostly on the surface of mature immune cells, such as lymphocytes, monocytes, eosinophils, and dendritic cells, as well as the male genital tract: within the epididymis and on the surface of mature sperm. Low CD52 expression is also found in neutrophils. CD52 function is not fully understood, although experiments with anti-CD52 antibodies have shown that CD52 is essential for lymphocyte transendothelial migration and may contribute to costimulation of CD4+ T cells and T-cell activation and proliferation. Although knowledge about exact CD52 function is still poor, CD52 presence on the surface of a broad spectrum of immune cells makes it a therapeutic target, especially in immunomediated diseases, such as multiple sclerosis. In multiple sclerosis, alemtuzumab is registered for adult patients with the relapsing–remitting form of the disease defined by clinical and imaging features. Despite the high efficacy of the drug, the main issue is its safety. The main adverse effects of alemtuzumab are associated with drug infusion due to cytokine release and cytotoxic effects of antibodies associated with lymphocyte depletion, which leads to immunosuppression, and secondary autoimmunity that may be the effect of excessive B-cell repopulation and cancer. This review presents current knowledge on the drug’s mechanism of action, efficacy and safety data from clinical trials, and real-world observations, including available though scarce data on using alemtuzumab in the COVID era.

Definitive pathognomonic signs and symptoms of paediatric neurological COVID-19 are still emerging.

Children with COVID‐19 tend to show milder symptoms than adults during the pandemic, but growing evidence of neurological involvement has emerged. Some studies have reported neurological symptoms in children with COVID‐19, which include multisystem inflammatory syndrome, a disease that shares some, but not all, of the characteristics of Kawasaki disease. This review presents, and discusses, the evidence to date. Our initial findings suggest that neurological manifestations can be considered to be the direct result of central nervous system viral invasion or post‐infection immuno‐mediated disease.

Hospitalization in Patients with Psoriasis: Impact of Biological Therapies on Temporal Evolution.

Psoriasis is an immunomediated disease mostly controlled at the outpatient level, although there is a low percentage of patients that require systemic drugs or even hospitalization for an adequate control. Biological drugs have represented a turning point in its treatment. So far, despite the growing interest in psoriasis and its management with biological therapies, there is a lack of studies focusing on their impact on hospitalization, a relevant issue to patients and to the sustainability of our healthcare system. In this study, we aimed to describe the temporal evolution of the hospitalizations of patients with psoriasis throughout the period between eight years before the commercialization of the first biological drugs and present, and secondly, whether this market irruption was related to a decrease in the number of admissions. Data was collected retrospectively from the Dermatology department of the Complexo Hospitalario Universitario de Ponte- vedra (CHUP) including patients of all ages with a diagnosis of psoriasis and at least one admission to the department of Dermatology along the study period. We established different time periods for comparing the average hospitalizations per 100,000 inhabitants-year and the average stay, considering that the first biologic drug marketed for the treatment of psoriasis was in 2004. Regression models indicated a significant change in the temporal trend of the hospitalization rate per 100,000 inhabitants-year starting in 2004. In all cases, a gradual and significant decrease in the number of admissions per 100,000 inhabitants-year and in the average hospitalization rate per psoriasis per 100,000 inhabitants-year along the study period were found. There was also a significant decrease in medical hospitalizations and medical hospitalizations excluding psoriasis throughout the study period. In our study population hospitalizations for psoriasis descended progressively and significantly from 2004. So far there are no extensive data on the impact of biological therapies on psoriasis hospitalization. J Drugs Dermatol. 2021;20(2):208-214. doi:10.36849/JDD.4931.

Management of patients with hidradenitis suppurativa during the COVID-19 pandemic: Risk and benefit of immunomodulatory therapy.

Coronavirus disease 2019 (COVID-19) is a clinical syndrome caused by a new coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Italy has been the first nation affected by the coronavirus pandemic and is the second in the number of reported deaths in the European Union. In the United Hospital of Ancona, a specialist outpatient clinic dealing with diagnosis and treatment of immunomediated skin diseases has been operating since 1985, and 291 patients with hidradenitis suppurativa (HS) are currently being treated. Several cutaneous immunomediated diseases, including HS, are treated with biologic and nonbiologic immunosuppressive and immunomodulatory drugs. Since the end of February 2020, when the SARS-CoV-2 pandemic had already spread in most of Italy, a task force comprised of seven specialists has been set up with the aim of addressing problems relating to the specific risk for this class of patients in relation to SARS-CoV-2 infection and immunosuppressive ongoing therapy. In this article, the management of HS disease during the COVID-19 pandemic is discussed. The main goal was to evaluate the risk/benefit in modulating treatment taking into consideration patients' risk of exposure to SARS-CoV-2 virus.

КЛИНИЧЕСКИЕ ПРОЯВЛЕНИЯ ПОРАЖЕНИЯ СЛИЗИСТОЙ ОБОЛОЧКИ РТА ПРИ РАЗЛИЧНЫХ ДЕРМАТОЗАХ

Subject. This review presents a modern literature review on the clinical manifestations of severe autoimmune disease — pemphigus vulgaris, chronic genetic determinate dermatosis — by the example of epidermolysis bullosa, dermatosis — lichen planus, acute immuno-mediated disease — multiforme exudative erythema.&#x0D; The goal is to conduct a systematic analysis of modern domestic and foreign literature to determine some features of the clinical manifestations of chronic dermatoses with lesions of the oral mucosa.&#x0D; Methodology. A review of the studies allows us to consider the etiology and pathogenesis of the development of these nosologies, approaches to modern classification, as well as an analysis of their clinical features with an emphasis on differential diagnosis.&#x0D; Results. It was noted that with combined damage to the skin and oral mucosa, the diagnosis of these dermatoses in patients does not present any particular difficulties. However, the significance of determining pathognomonic signs of damage to the oral mucosa with a particular dermatosis increases significantly with an isolated lesion of the oral mucosa, and when it is the primary and only manifestation of skin disease.&#x0D; Conclusions. Undoubtedly, the principle of continuity of the interested specialties among which are undoubted - dermatovenerologists, dentists, gastroenterologists, gynecologists, neuropsychiatrists, has great prospects in both diagnosis and complex treatment. Nevertheless, for their widespread use, the local and general treatment of these patients needs to be verified, solving urgent problems of introducing and adapting modern technologies for rapid prototyping them into practical healthcare, which together will allow significant progress in their diagnosis and prevention.

P306 Frequency and structure of extra-intestinal manifestations in IBD

Abstract Background IBD are immunomediated diseases that usually manifest at an early age, require lifelong pathogenetic therapy and significantly reduce the quality of life of a patient. Methods Since February 2017, the ‘North-West register of IBD patients’ has installed data of 1130 patients with an introduced diagnosis of UC or CD: 41.3% of them are patients with a diagnosis of CD and 58.7%—with a diagnosis of UC. Results Among patients with IBD the majority had mild (33.4%) and moderate activity (34%), a quarter was in remission and 7.65%—expressed activity. A population researches study using the University of Manitoba’s IBD epidemiology database (UMIBDED) reported that 6.2% of IBD patients had at least one extraintestinal manifestation, and 0.3% had several. The extraintestinal manifestations were observed in 43.4% of patients; meanwhile, 25% of them revealed mostly than one extraintestinal manifestation. System manifestations were more often registered in CD than in UC. The most frequent extraintestinal manifestations were signs of involvement of skeletal and muscular system. On the first place, it is peripheral arthropathy (73.6%), sacroiliitis (8.8%), ankylosing spondyloarthritis (8.8%), entezitis (10.3%) rheumatoid arthritis (1.5%), dactylitis (1.5%) were less frequent. Generally, articulate manifestations were noted by 17.5% of all included patients. In CD and UC, extra-intestinal manifestations were more often common in patients with a moderate attack (in 75.6 % and 51.6% of cases). In CD, extra-intestinal manifestations were more often frequent in patients with moderate attack −50.8%, in patients in remission there numbered to 32.8%, in severe attack-14.8%, in mild-1.6%. In UC, extra-intestinal manifestations were observed in severe attack in 2.6%, in moderate attack 35.9%, in mild attack 41%, in patients in remission 20.5%. Conclusion Among patients with IBD, extraintestinal manifestations, among which joint lesions prevail, are detected in 43.4% of the examined persons. The trend is noted to reduce the number of patients with severe attacks of the disease and extraintestinal manifestations, that can be related with improving the quality of diagnosis, reduction of terms of diagnosing and developing new methods of treatment for IBD. Peripheral arthropathy predominate among the extra-intestinal manifestations. We found no correlation between the severity of IBD and the presence of extra-intestinal manifestations. The spectrum of extra-intestinal manifestations includes more than 20 manifestations (diseases), which requires skills and experience in their diagnosis, as well as joint management of such patients by specialists of various profiles.

SYSTEMIC LUPUS ERYTHEMATOUS MIMETIZING BULLOUS PEMPHIGOID: A CASE REPORT

A 43-year-old woman was referred for evaluation of blister on the gingiva. Intraoral examination revealed erosion on the free marginal gingiva, bacterial plaque accumulation on the cervical and proximal teeth, and some destruction of interdental papilla with reddish coloration. Biopsy was performed after periodontal treatment, and histopathologic analysis evidenced bullous pemphigoid. The patient was treated with topical and systemic corticoid; however, there was no improvement in the clinical aspect. Therefore, complementary examination was done, and the positive ones were anti-nuclei factor and anti–double-stranded DNA. A new biopsy was performed, and histopathologic analysis evidenced systemic lupus erythematous. The patient was treated with systemic corticoid and hydroxychloroquine and showed regression of symptoms. Currently, the patient is without lesions and still continues the use of medication. Patients with immunomediated diseases with oral repercussions should be closely monitored because of the overlap of clinical and histopathologic findings.