Causal relationship between inflammatory bowel disease and erythema nodosum: A two-sample bidirectional Mendelian randomization study.

BACKGROUND: Previous studies have demonstrated the coexistence of erythema nodosum (EN) and inflammatory bowel disease (IBD), while the exact etiology of the co-occurrence of the two disorders remains uncertain. METHODS: A bidirectional two-sample Mendelian randomization (MR) design was employed to determine the causal link between EN and IBD. Genetic variations associated with Crohn's disease (CD) and ulcerative colitis (UC) were derived from accessible genome-wide association studies pertaining to European ancestry. The FinnGen database was used to find the genetic variations containing EN. In the forward model, IBD was identified as the exposure, whereas in the reverse model, EN was identified as the exposure. The causal link between IBD and EN was examined using a range of different analysis techniques, the primary one being the inverse variance weighted (IVW) method, including inverse variance weighted-fixed effects (IVW-FE) and inverse-variance weighted-multiplicative random effects (IVW-MRE). To strengthen the results, assessments of sensitivity, heterogeneity, and pleiotropy were also conducted. RESULTS: MR results showed that IBD increased the risk of EN (IVW-MRE: OR = 1.242, 95% CI = 1.068-1.443, p = 0.005). Furthermore, there was a strong correlation found between CD and a higher risk of EN (IVW-FE: OR = 1.250, 95% CI = 1.119-1.396, p = 8.036 × 10-5 ). However, UC did not appear to be linked to EN (IVW-FE: OR = 1.104, 95% CI = 0.868-1.405, p = 0.421). The reverse MR analysis findings did not imply that EN was linked to IBD. Horizontal pleiotropy did not appear to exist, and the robustness of these findings was confirmed. CONCLUSION: The current investigation found that in European populations, IBD and its subtype CD could raise the incidence of EN.

The Distinct Pattern of Granulomatous Lobular Mastitis with Erythema Nodosum: More Severe Conditions and Extensive Lesions.

PURPOSE: Granulomatous lobular mastitis (GLM) is a benign inflammatory disease of the mammary gland with unknown etiology. Erythema nodosum (EN) is a rare, extramammary symptom of GLM. The purpose of this article was to investigate the clinical features of EN associated with GLM. METHODS: We recruited 102 GLM patients diagnosed between December 2018 and December 2021 at Renmin Hospital of Wuhan University. The clinical characteristics and laboratory indices of the EN group (n = 12) and the non-EN group (n = 90) were compared. RESULTS: The proportion of GLM patients with lesions involving ≥2 quadrants and high peripheral white blood cell count, absolute neutrophil count and neutrophil-to-lymphocyte ratio (NLR) was larger in the EN group than in the non-EN group (p = 0.002, 0.025, 0.014, 0.002, respectively). The duration of EN was longer in GLM patients with EN than in GLM patients without EN (p = 0.005). GLM patients with EN had more abscesses and sinus tracts than those without EN (p = 0.003, 0.038). Lesions involving ≥2 quadrants and the NLR were positively associated with the occurrence of EN (R = 0.304, 0.0302, p = 0.002, 0.002). Receiver operating characteristic curve analysis revealed that the area under the curve of the NLR was 0.770. When NLR > 5.73, the sensitivity and specificity of predicting EN were 66.67% and 87.78%, respectively. CONCLUSION: Our findings suggest that GLM concomitant with EN suggests the presence of a more severe condition and extensive lesions.

Erythema nodosum in children: a cohort study from a tertiary pediatric hospital in Italy.

Erythema nodosum (EN), although relatively uncommon in the pediatric population, is the most frequent type of panniculitis in children. The present study aimed to report all the cases of children admitted to our tertiary pediatric hospital with the diagnosis of EN to evaluate the epidemiology, clinical manifestations, etiology, treatment, and the course of this disease in the pediatric age. This observational study retrospectively considered all children evaluated to the emergency room (ER) of Meyer Children's University Hospital, Florence, Italy, discharged with a diagnosis of EN over a 12-year period (from January 2009 to December 2021). Clinical and laboratory data were recorded using a standardized report form. Sixty-eight patients with EN were included. The etiologic diagnosis of EN was made in 38 children (55.9%): 29 (42.6%) had infection-related EN (in particular EBV and ß-hemolytic streptococcus), 6 (8.8%) had Crohn's disease, 1 celiac disease, 1 Sjogren syndrome, and 1 Hodgkin lymphoma. In 30 patients (45%), no definitive diagnosis was reached, and they were defined as having idiopathic EN. Most of the laboratory tests were nonspecific. No statistical differences were found in the demographic and clinical data, and the main diagnostic laboratory parameters between patients with idiopathic EN versus those with secondary EN.  Conclusion: Since EN can be isolated or the first manifestation of heterogeneous underlying pathologies, some of which can be severe and life-threatening, it is important to recognize it and carry out all the necessary etiological diagnostic investigations to understand its etiology and start the specific treatment. What is Known: • Erythema nodosum (EN) is the most frequent type of panniculitis in children. • It has been associated with a wide spectrum of disorders, such as different types of infection, malignancies, chronic inflammations, and drugs. What is New: • No statistical differences can be found in clinical features as well as laboratory data, between patients with idiopathic EN versus those with secondary EN. • A broad spectrum of investigations and a proper follow-up should be taken into account in order to prevent a delayed or missed secondary EN diagnosis.

Predictive Factors of Severe Behçet's disease: A Longitudinal, Prospective Cohort Followed Between 1981-2020.

INTRODUCTION: Behçet's disease (BD) is a systemic vasculitis of unknown cause. The spectrum of the disease ranges from mucocutaneous manifestations to other organ diseases with relevant morbidity. Associations between disease severity and male sex, earlier age at onset, and the presence of erythema nodosum have been described. OBJECTIVES: To evaluate clinical factors associated with manifestations of severe disease in a single-center cohort. METHODS: A longitudinal, prospective, unicentric cohort study with patients followed in a specialized outpatient clinic between 1981 and 2020. Severe BD was defined as a Krause total clinical severity score >4 points. RESULTS: We included 243 patients, of whom 31% were male, with an average follow-up time of 14.6 years. Regarding organ manifestations, all patients had mucous manifestations (N=243, 100%), 133 (55%) skin, 104 (43%) joint, 71 (29%) ocular, 48 (20%) vascular, 47 (19%) neurological, 22 (9%) gastrointestinal and 1 (0.4%) cardiac involvement by BD. One hundred fifty-six (64%) patients were classified as having severe BD. Severe BD was more frequent in men (OR=2.004, p=0.024), increasing with age (OR=1.021 per year, p=0.037), in the presence of skin manifestations (OR=4.711, p<0.001), specifically erythema nodosum (OR=8.381, p<0.001), and pseudofolliculitis (OR=2.910, p<0.001). In the multivariate model, variables independently associated with severe BD were male gender (Adjusted OR=1.961, p=0.047), erythema nodosum (Adjusted OR=8.561, p<0.001) and pseudofolliculitis (Adjusted OR=2.372, p=0.007). DISCUSSION: Male gender, erythema nodosum, and pseudofolliculitis were independently associated with severe BD forms and therefore should serve as warning signs to the clinician.

Understanding leprosy reactions and the impact on the lives of people affected: An exploration in two leprosy endemic countries.

BACKGROUND: Leprosy reactions, Type-1 and erythema nodosum leprosum, are immune-mediated complications of leprosy, which play a significant role in the morbidity associated with the disease. A considerable amount of literature has been published on the impact of leprosy in general but few studies focus specifically on leprosy reactions. This study aimed to investigate the impact of leprosy reactions on physical, psychological, and social aspects of the lives of people affected by analysing their life experiences and perspectives about leprosy reactions. METHODS/PRINCIPAL FINDINGS: This qualitative study involved people affected by leprosy reactions and their family members in two leprosy endemic countries. The data were collected through 66 interviews and 9 focus group discussions (4-6 participants each) in Surabaya, Indonesia, and Purulia, India. Content analysis and conversational analysis were performed. This study found that both types of leprosy reactions were perceived as an unpredictable and painful condition. Leprosy reactions restricted physical activities of the participants, such as going to bathroom, sleeping, eating, and cooking. In the interviews, the respondents expressed a range of emotions and feelings including confusion, sadness, anxiety, and anger. Some recounted that they felt stigmatized and lost opportunities to socialise and earn money. Differences between the two settings were identified. The majority of Indonesian participants preferred to stay at home, and some concealed the diagnosis of leprosy, while most of the Indian respondents continued working up to the time of hospitalization. CONCLUSION: Leprosy reactions are a distressing complication of leprosy and adversely affect the lives of those affected. Individuals reported physical discomfort, distress, anxiety, stigma, and financial hardship and these negative impacts in the physical, psychological, and social spheres reinforced each other. These findings provide important information about a need for early detection and sustained commitment to follow-up care for people with a history of leprosy reactions. More research on new drugs for reactional episodes, tools to measure knowledge, attitude, and practice, and costing study on leprosy reactions treatment are needed. We recommend the development and testing of holistic strategies to improve the management of leprosy reactions.

A United States expert consensus to standardise definitions, follow-up, and treatment targets for extra-intestinal manifestations in inflammatory bowel disease.

BACKGROUND AND AIMS: Extra-intestinal manifestations (EIMs) are a common complication of inflammatory bowel diseases (IBD), affecting up to half of the patients. Despite their high prevalence, information on standardised definitions, diagnostic strategies, and treatment targets is limited. METHODS: As a starting point for a national EIM study network, an interdisciplinary expert panel of 12 gastroenterologists, 4 rheumatologists, 3 ophthalmologists, 6 dermatologists, and 4 patient representatives was assembled. Modified Delphi consensus methodology was used. Fifty-four candidate items were derived from the literature review and expert opinion focusing on five major EIMs (erythema nodosum, pyoderma gangrenosum, uveitis, peripheral arthritis, and axial arthritis) were rated in three voting rounds. RESULTS: For use in a clinical practice setting and as part of the creation of a prospective registry of patients with EIMs, the panel developed definitions for erythema nodosum, pyoderma gangrenosum, uveitis, peripheral arthritis, and axial arthritis; identified the appropriate and optimal subspecialists to diagnose and manage each; provided methods to monitor disease course; offered guidance regarding monitoring intervals; and defined resolution and recurrence. CONCLUSIONS: Consensus criteria for appropriate and optimal means of diagnosing and monitoring five EIMs have been developed as a starting point to inform clinical practice and future trial design. Key findings include straightforward diagnostic criteria, guidance regarding who can appropriately and optimally diagnose each, and monitoring options that include patient and physician-reported outcomes. These findings will be used in a national multicenter study network to optimise the management of EIMs.

Comportamiento clínico-epidemiológico del eritema nudoso en el Hospital Provincial Docente Clínico Quirúrgico León Cuervo Rubio / Epidemiological clinical behavior of erythema nodosum at the Provincial Teaching Clinical Surgical Hospital Leon Cuervo Rubio

RESUMEN Introducción: el eritema nudoso es la variante clínico-patológica más frecuente de la paniculitis. Es una reacción cutánea inmunológica en respuesta a un amplio espectro de agentes etiológicos. Objetivo: caracterizar el comportamiento clínico-epidemiológico del eritema nudoso. Materiales y métodos: se realizó un estudio descriptivo, prospectivo y longitudinal en pacientes con diagnóstico de eritema nudoso, ingresados en el Hospital Provincial Docente Clínico Quirúrgico León Cuervo Rubio, de Pinar del Río, en el período de enero de 2017 a diciembre de 2018. El universo estuvo constituido por 34 pacientes con diagnóstico clínico de eritema nudoso, hospitalizados en los servicios de Medicina Interna y Dermatología. Para la recogida de la información se utilizaron la historia clínica, el examen físico y los exámenes de laboratorio. Se utilizaron métodos teóricos, empíricos y estadísticos; de los últimos se empleó la estadística descriptiva a través de frecuencias absolutas y porcentaje. Resultados: el mayor grupo de pacientes estuvo entre 30 y 39 años, y fue del sexo femenino. Las lesiones fueron más frecuentes en los meses de invierno. El tipo de eritema nudoso idiopático prevaleció. Predominó el tiempo de evolución de 1 a 3 meses. Como causa secundaria predominaron las infecciones, y los tratamientos más usado fueron los antiinflamatorios no esteroideos. Conclusiones: se trata de una importante enfermedad de salud, cuyo un diagnóstico etiológico temprano permite un tratamiento adecuado. Resulta difícil su identificación y manejo tanto en la atención primaria como en la secundaria (AU).

ABSTRACT Introduction: erythema nodosum is the most common clinical-pathological variant of panniculitis. It is an immunological skin reaction in response to a wide spectrum of etiologic agents. Objective: to characterize the clinical-epidemiological behavior of erythema nodosum. Materials and methods: a descriptive, prospective and longitudinal study was carried out in patients with diagnosis of erythema nodosum, admitted to the Provincial Teaching Clinical Surgical Hospital León Cuervo Rubio, of Pinar del Río, in the period January 2017 to December 2018. The universe was formed by 34 patients with clinical diagnosis of erythema nodosum, hospitalized in the services of Internal Medicine and Dermatology. Medical records, physical examination and laboratory tests were used for the collection of information. Theoretical, empirical and statistical methods were used; descriptive statistics was used through absolute frequencies and percentage. Results: the largest group of patients was between 30 and 39 years, and they were female. Injuries were more frequent in the winter months. The type of idiopathic erythema nodosum prevailed. The time of evolution prevailed from 1 to 3 months. Infections predominated as a secondary cause, and the most commonly used treatments were non-steroidal anti-inflammatory drugs. Conclusions: it is an important health condition, whose early etiological diagnosis allows the proper treatment. Its identification and management in both primary and secondary care is difficult (AU).

The Risk of Later Diagnosis of Inflammatory Bowel Disease in Patients With Dermatological Disorders Associated With Inflammatory Bowel Disease.

BACKGROUND: Dermatological conditions such as erythema nodosum (EN), pyoderma gangrenosum, Sweet's syndrome, and aphthous stomatitis can occur with inflammatory bowel disease (IBD) and are considered dermatological extraintestinal manifestations (D-EIMs). Rarely, they may precede IBD. Other common conditions such as psoriasis have also been associated with IBD. This study examined the risk of a subsequent IBD diagnosis in patients presenting with a D-EIM. METHODS: A retrospective cohort study compared patients with D-EIMs and age-/sex-matched patients without D-EIMs. Hazard ratios (HRs) were adjusted for age, sex, body mass index, deprivation, comorbidity, smoking, loperamide use, anemia, and lower gastrointestinal symptoms. Logistic regression was used to produce a prediction model for the diagnosis of IBD within 3 years of EN diagnosis. RESULTS: We matched 7447 patients with D-EIMs (74% female; median age 38 years (interquartile ratio [IQR], 24-65 years) to 29,297 patients without D-EIMs. We observed 131 (1.8%) subsequent IBD diagnoses in patients with D-EIMs compared with 65 (0.2%) in those without D-EIMs. Median time to IBD diagnosis was 205 days (IQR, 44-661 days) in those with D-EIMs and 1594 days (IQR, 693-2841 days) in those without D-EIMs. The adjusted HR for a later diagnosis of IBD was 6.16 (95% confidence interval [CI], 4.53-8.37; P < 0.001), for ulcerative colitis the HR was 3.30 (95% CI, 1.98-5.53; P < 0.001), and for Crohn's disease the HR was 8.54 (95% CI, 5.74-12.70; P < 0.001). Patients with psoriasis had a 34% increased risk of a subsequent IBD diagnosis compared with the matched control patients (HR, 1.34; 95% CI, 1.20-1.51; P < 0.001). We included 4043 patients with an incident EN diagnosis in the prediction model cohort, with 87 patients (2.2%) diagnosed with IBD within 3 years. The model had a bias-corrected c-statistic of 0.82 (95% CI, 0.78-0.86). CONCLUSIONS: Patients with D-EIMs have a 6-fold increased risk of a later diagnosis of IBD. Younger age, smoking, low body mass index, anemia, and lower gastrointestinal symptoms were associated with an increased risk of diagnosis of IBD within 3 years in patients with EN.

Erythema Nodosum: A Practical Approach and Diagnostic Algorithm.

Erythema nodosum is the most common form of panniculitis and is characterized by tender erythematous nodules mainly in the lower limbs on the pretibial area. The exact cause of erythema nodosum is unknown, although it appears to be a hypersensitivity response to a variety of antigenic stimuli. Although the etiology is mostly idiopathic, ruling out an underlying disease is imperative before diagnosing primary erythema nodosum. Erythema nodosum can be the first sign of a systemic disease that is triggered by a large group of processes, such as infections, inflammatory diseases, neoplasia, and/or drugs. The most common identifiable causes are streptococcal infections, primary tuberculosis, sarcoidosis, Behçet disease, inflammatory bowel disease, drugs, and pregnancy. We propose a diagnostic algorithm to optimize the initial work-up, hence initiating prompt and accurate management of the underlying disease. The algorithm includes an initial assessment of core symptoms, diagnostic work-up, differential diagnosis, and recommended therapies. Several treatment options for the erythema nodosum lesions have been previously reported; nevertheless, these options treat the symptoms, but not the triggering cause. Making an accurate diagnosis will allow the physician to treat the underlying cause and determine an optimal therapeutic strategy.

Various skin manifestations related to inflammatory bowel disease: A nationwide cross-sectional study on the Korean population.

Inflammatory bowel disease (IBD) presents with various extraintestinal manifestations. As part of them, various skin diseases are suggested to be related to IBD. We aimed to identify the epidemiology and risk of developing skin manifestations in patients with IBD. We used Korean insurance claims data and selected patients with IBD and age/sex-matched non-IBD subjects between 2013 and 2017 using the diagnosis code and prescription records of IBD-specific medications. The prevalence and risk of concurrent skin diseases were estimated. We identified 64 837 patients with IBD. Reactive skin eruptions including pyoderma gangrenosum and erythema nodosum were associated with IBD with highest odds ratios among three categories of reactive, inflammatory, and autoimmune skin diseases. Inflammatory skin diseases including rosacea, psoriasis, atopic dermatitis, hidradenitis suppurativa, and acne conglobata were significantly associated with IBD, but the association was less marked compared to reactive skin eruptions. The patients with IBD also had a higher risk of autoimmune skin diseases including vitiligo and alopecia areata than non-IBD subjects. We determined that IBD was related to various skin diseases including reactive, inflammatory, and autoimmune skin diseases. Considering these relationships can allow better management of patients with IBD and comorbid skin diseases.

Characterization and prevalence of extraintestinal manifestations in a cohort of patients with inflammatory intestinal disease in Medellin, Colombia. / Caracterización y prevalencia de manifestaciones extraintestinales en una cohorte de pacientes con enfermedad inflamatoria intestinal en Medellín (Colombia).

INTRODUCTION: Extraintestinal manifestations (EIMs) are frequent in patients with inflammatory bowel disease (IBD). Our objective is to characterize and determine the prevalence of MEIs in our cohort of patients with IBD. PATIENTS AND METHODS: A retrospective study was carried out in adult patients with IBD at the Pablo Tobón Uribe Hospital in Medellín. Colombia. Articular MEIs, primary sclerosing cholangitis (PSC), both ophthalmological and dermatological, were considered. Absolute and relative frequencies were used. The Chi square test of independence was used to compare 2proportions and the odds ratio (OR) was estimated. RESULTS: Our registry has 759 patients with IBD, 544 present UC (71.6%), 200 CD (26.3%) and 15 unclassifiable IBD (1.9%); 177 patients with IBD (23.3%) presented EIMs, 123 of 544 (22.6%) with UC and 53 of 200 (26.5%) with CD (OR: 0.81, 95% CI: 0.55-1.17, P=0.31). Regarding the type of EIMs, the articular ones were the most frequent (13.5%), more in CD than in UC (20.0 vs. 11.3%, OR 1.94, 95% CI: 1.25-3.00, P=0.0037). Patients with IBD and EIMs used more antibodies against tumor necrosis factor (anti-TNFs), compared to those without EIMs (43.5 vs. 18.5%, OR 3.38, 95% CI: 2.31-4.90, P=0.0001). CONCLUSIONS: The prevalence of EIMs in our cohort is high (23.3%) and the most frequent type is joint. Anti-TNFs are most used when IBD and EIMs coexist. Our study provides valuable information on the association of EIMs and IBD in Latin America.

Causas de eritema nudoso en pacientes ingresados en un hospital español de tercer nivel / Causes of Erythema Nodosum in Patients Admitted to a Tertiary Care Hospital in Spain

El eritema nudoso (EN) es la paniculitis más frecuente y aunque puede ser idiopático, presenta múltiples procesos causales. Elaboramos un estudio retrospectivo, observacional y descriptivo de las causas de EN en pacientes ingresados en un hospital español de tercer nivel durante un período de 11 años, y comparamos los resultados obtenidos con los publicados en otros trabajos. Comparamos los marcadores analíticos de inflamación entre causas inflamatorias y no inflamatorias de EN. La cohorte final quedó compuesta por 52 pacientes, con un 20% de casos idiopáticos, un 34% de casos secundarios a infecciones y otro 34% de casos secundarios a enfermedades autoinmunes. No hubo casos secundarios a fármacos o linfomas. No observamos diferencias significativas en los parámetros analíticos de inflamación en función de causa inflamatoria o no inflamatoria de EN

Erythema nodosum (EN) is the most frequent panniculitis, and although it can be idiopathic, it presents multiple causal processes. We made a retrospective, observational and descriptive study about causes of EN in patients admitted to a third-level Spanish hospital over a period of 11 years, and we compared the results obtained with those published in other studies. We compared the analytical markers of inflammation between inflammatory and non-inflammatory causes of EN. The final cohort was composed by 52 patients, with 20% of idiopathic cases, 34% of cases secondary to infections and another 34% of cases secondary to autoimmune diseases. There were no cases secondary to drugs or lymphomas. We did not observe significant differences in the analytical parameters of inflammation between inflammatory or non-inflammatory cause of EN

Clinical management of the most common extra-intestinal manifestations in patients with inflammatory bowel disease focused on the joints, skin and eyes.

Extra-intestinal manifestations (EIMs) of inflammatory bowel disease (IBD) occur frequently and contribute to morbidity and reduced quality of life. The musculoskeletal, ocular and cutaneous organ systems are frequently involved in IBD-related EIMs. By focusing on manifestations involving the joints, skin and eyes, this review will discuss the most common clinically relevant and burdensome EIMs that affect IBD patients, and strives for early recognition, adequate treatment and timely referral. For this purpose, we aimed to create a comprehensive overview on this topic, with the main focus on the treatment of reactive and associated EIMs, including spondyloarthropathies, pyoderma gangrenosum, erythema nodosum, psoriasis and anterior uveitis. The recently developed biologicals enable simultaneous treatment of inflammatory disorders. This review can be used as a helpful guide in daily clinical practice for physicians who are involved in the treatment of IBD patients.

Causes of Erythema Nodosum in Patients Admitted to a Tertiary Care Hospital in Spain. / Causas de eritema nudoso en pacientes ingresados en un hospital español de tercer nivel.

Erythema nodosum (EN) is the most frequent panniculitis, and although it can be idiopathic, it presents multiple causal processes. We made a retrospective, observational and descriptive study about causes of EN in patients admitted to a third-level Spanish hospital over a period of 11 years, and we compared the results obtained with those published in other studies. We compared the analytical markers of inflammation between inflammatory and non-inflammatory causes of EN. The final cohort was composed by 52 patients, with 20% of idiopathic cases, 34% of cases secondary to infections and another 34% of cases secondary to autoimmune diseases. There were no cases secondary to drugs or lymphomas. We did not observe significant differences in the analytical parameters of inflammation between inflammatory or non-inflammatory cause of EN.

Epidemiological profile and severity of erythema nodosum leprosum in Brazil: a cross-sectional study.

BACKGROUND: Leprosy can cause acute reactions, which may be type 1 (reverse reaction) or type 2 (erythema nodosum leprosum - ENL). ENL has been classified as mild, moderate, or severe. In order to standardize the classification, the Erythema Nodosum Leprosum International Study (ENLIST) Group has developed an objective scale, the ENLIST ENL Severity Scale (EESS), which was the first validated severity scale of ENL in the world. The goal of the study was to describe the sociodemographic and clinical characteristics of patients with ENL attending a tertiary hospital in Piauí, Brazil, classifying them according to the EESS. METHODS: A descriptive cross-sectional observational study was conducted on 26 patients recruited sequentially from May 2017 to February 2018. Their data were statistically analyzed and compared against each other through a structured questionnaire. RESULTS: According to the score obtained in the scale, the patients were divided into two groups: mild ENL and moderate/severe ENL. The extent and number of nodules were related to the severity of the cases, and these data were statistically significant. The majority of the patients were male, between the ages of 31 and 49 years old, with low educational level, and residents in the urban area. CONCLUSIONS: This was the first study to use EESS in Brazil. This scale is easy to apply and allows for the enhancement of treatment protocols. The study also showed a correlation between the number and extension of nodules and the severity of the condition.

Sarcoidosis presenting with and without Löfgren's syndrome: Clinical, radiological and behavioral differences observed in a group of 691patients.

OBJECTIVES: Just a few series of Löfgren's syndrome have been reported. Our aim was to describe the epidemiology and clinical profile of sarcoidosis patients presenting with Löfgren's syndrome vs. non-Löfgren's syndrome. METHODS: Retrospective cohort study of 691consecutive patients with sarcoidosis diagnosed at the Bellvitge University Hospital in Barcelona, Spain, between 1976 and 2018. RESULTS: Three hundred and nine patients (44.7%) were diagnosed with Löfgren's syndrome and 382with non-Löfgren's syndrome (55.3%). The mean age at diagnosis was 39.8years-old (SD 11.7) vs. 46.6 (SD 14.5) (P<0.001). 249 patients (80.6%) vs. 218 (57.1%) were female (P<0.001), and mostly Caucasians (304, 98.4% vs. 351, 91.9%, P=0.002). Out of the total 309, Löfgren's syndrome patients developed more frequently fever and articular involvement, and 45 (14.6%) presented with isolated periarticular ankle inflammation. When compared, radiological stages at diagnosis were more advanced in non-Löfgren's syndrome patients: stage 0 (2.9% vs. 14.7%), stage I (82.5% vs. 41.4%), stage II (14.6% vs. 29.3%), and stage III/IV (0 vs. 14.7%) (P<0.001). Chronic trend>2years was more prevalent in non-Löfgren's syndrome (66, 22.6% vs. 233, 67.4%; P<0.001), as well as the proportion of patients in whom treatment was needed (58, 18.8% vs. 224, 58.6%; P<0.001). Risk factors related to chronic trend>2 years were older age, stage II at diagnosis and the need of treatment. CONCLUSIONS: Löfgren's syndrome is a well-differentiated form of sarcoidosis with persuasive different epidemiological, clinical, radiological and prognostic features.

Chronic nonbacterial osteomyelitis in children: a multicenter case series.

Chronic nonbacterial osteomyelitis (CNO) is a primary autoinflammatory bone disease that presents more frequently in children and is characterized by inflammatory bone lesions in the absence of an infectious etiology. There is little information of this disease in Latin America. The objective of the study was to evaluate demographic, clinical, laboratory, imaging, histopathology characteristics, and treatment responses of pediatric CNO patients. The clinical records of 19 patients with CNO diagnosed between 2007 and 2019 at three tertiary centers in Santiago, Chile were reviewed. The median age of onset was 10 years and 47% were female. Median delay in diagnosis was 12 months. All patients had a pattern of recurrent multifocal disease. 37% of patients had positive antinuclear antibodies and 16% HLA-B27 positivity. 21% of patients presented arthritis or other rheumatologic comorbidity, although no association with psoriasis, inflammatory bowel disease (IBD) or palmoplantar pustulosis (PPP) was observed. Eighteen patients received treatment with nonsteroidal anti-inflammatory drugs with partial response. Twelve patients received methotrexate, and half of them received steroids at the same time reaching remission in 50%. Of the five patients who received bisphosphonates, 60% achieved remission. All four patients who received adalimumab had comorbid arthritis and 75% achieved remission. In a series of Chilean children with CNO, all patients presented with multifocal lesions. Comorbid autoimmune diseases including arthritis were frequent, but no association was observed with psoriasis, IBD, or PPP.

Differential Expression of IFN-γ, IL-10, TLR1, and TLR2 and Their Potential Effects on Downgrading Leprosy Reaction and Erythema Nodosum Leprosum.

Leprosy reactions are acute immunological events that occur during the evolution of chronic infectious disease causing neural damage and disabilities. A study using blood samples of 17 leprosy reaction patients and 17 reaction-free was carried out by means of associations between antigens, receptors, and expression of cytokines, using path analysis providing new insights into the immunological mechanisms involved in triggering leprosy reactions. Toll-like receptors (TLR) such as TLR1 and TLR2, presented balanced expression in the reaction-free multibacillary (MB) group (TLR1: 1.01 ± 0.23, TLR2: 1.22 ± 0.18; p = 0.267). On the other hand, downgrading type 1 reaction (T1R) (TLR1: 1.24 ± 0.17, TLR2: 2.88 ± 0.37; p = 0.002) and erythema nodosum leprosum (ENL) (TLR1: 1.93 ± 0.17, TLR2: 2.81 ± 0.15; p = 0.004) revealed an unbalance in relation to the expression of these receptors. When the path analysis was approached, it was noted that interleukin 10 (IL-10) expression showed a dependence relation with phenolic glycolipid I (PGL-I) in downgrading T1R (direct effect = 0.503 > residual effect = 0.364), whereas in ENL, such relationship occurred with lipoarabinomannan (LAM) (direct effect = 0.778 > residual effect = 0.280). On the contrary, in the reaction-free leprosy group, interferon-gamma (IFN-γ) levels were dependent on the association between TLR2 and TLR1 (0.8735). The high TLR2 expression associated with IL-10 levels, in the leprosy reaction groups, may be hypothetically related to the formation of TLR2/2 homodimers and/or TLR2/6 heterodimers linked to evasion mechanisms in downgrading reactions and pathophysiology of ENL.