The causal relationship between inflammatory bowel diseases and erythema nodosum: a bidirectional two-sample mendelian randomization study.

BACKGROUND: Individuals with inflammatory bowel disease (IBD) exhibit a heightened likelihood of developing erythema nodosum (EN), but the presence of causal link is unknown. The purpose of the present research was to investigate this connection using a bidirectional two-sample Mendelian randomization (MR) analysis. METHODS: Summarized statistics for EN were sourced from the FinnGen consortium of European ancestry. The International Inflammatory Bowel Disease Genetic Consortium (IBDGC) was used to extract summary data for IBD. The inverse variance weighted (IVW) technique was the major method used to determine the causative link between them. RESULTS: The study evaluated the reciprocal causal link between IBD and EN. The IVW technique confirmed a positive causal link between IBD and EN (OR = 1.237, 95% CI: 1.109-1.37, p = 1.43 × 10- 8), as well as a strong causality connection between Crohn's disease (CD) and EN (OR = 1.248, 95% CI: 1.156-1.348, p = 1.00 × 10- 4). Nevertheless, a causal connection between ulcerative colitis (UC) and EN could not be established by the data. The reverse MR research findings indicated that analysis indicated that an increase in EN risks decreased the likelihood of UC (OR = 0.927, 95% CI: 0.861-0.997, p = 0.041), but the causal association of EN to IBD and CD could not be established. CONCLUSION: This investigation confirmed that IBD and CD had a causal connection with EN, whereas UC did not. In addition, EN may decrease the likelihood of UC. Further study must be performed to uncover the underlying pathophysiological mechanisms producing that connection.

The impact of vedolizumab therapy on extraintestinal manifestations in patients with inflammatory bowel disease: A systematic review and meta-analysis.

BACKGROUND AND AIM: Extraintestinal manifestations (EIMs) pose a significant threat in inflammatory bowel disease (IBD) patients. Vedolizumab (VDZ) primarily affects the gastrointestinal tract. However, its impact on EIMs remains uncertain. Therefore, we conducted this meta-analysis to examine the effects of VDZ on EIMs during treatment. METHODS: Relevant studies were identified by conducting thorough searches across electronic databases, including PubMed, Ovid Embase, Medline, and Cochrane CENTRAL. Primary outcomes focused on the proportion of patients with resolution for pre-existing EIMs in IBD patients receiving VDZ. Secondary outcomes included the proportion of patients with EIM exacerbations and new onset EIMs during VDZ treatment. RESULTS: Our meta-analysis encompassed 21 studies. The proportion of patients with resolution of pre-existing EIMs in VDZ-treated IBD patients was 39% (150/386; 95% confidence interval [CI] 0.31-0.48). The proportion of patients with EIM exacerbations occurred at a rate of 28% (113/376; 95% CI 0.05-0.50), while new onset EIMs had a rate of 15% (397/2541; 95% CI 0.10-0.20). Subgroup analysis revealed a 40% (136/337) proportion of patients with resolution for articular-related EIMs and a 50% (9/18) rate for erythema nodosum. Exacerbation rates for arthritis/arthralgia, erythema nodosum/pyoderma gangrenosum, and aphthous stomatitis during VDZ use were 28% (102/328), 18% (7/38), and 11% (3/28), respectively. The incidence rate of newly developed EIMs during treatment was 11% (564/4839) for articular-related EIMs, with other EIMs below 2%. CONCLUSION: VDZ demonstrates efficacy in skin-related EIMs like erythema nodosum and joint-related EIMs including arthritis, arthralgia, spondyloarthritis, and peripheral joint diseases. Some joint and skin-related EIMs may experience exacerbation during VDZ therapy.

Atypical and Typical Presentation of Erythema Nodosum: Clinical Differences in Treatment and Outcome.

INTRODUCTION: Erythema nodosum (EN) is the most common form of panniculitis that predominantly affects the shins. While EN in atypical sites has been described by many authors, there are currently only case studies published on this topic. This study aimed to evaluate clinical differences between patients suffering from EN on the shins, compared to patients with EN in atypical locations. METHODS: We analyzed 105 patients in a retrospective, single-center study at a university hospital in Switzerland. Typical EN was defined as lesions, found only on the lower legs, while atypical EN as lesions on the upper legs, trunk, arms, or face, only or in addition to lesions on the lower legs. The patients were assessed for age, gender, dermatologic history, time until first medical consultation, time to diagnosis, and time until remission. Further, etiology, symptoms, and applied therapies were investigated. Findings were then compared between the typical and atypical EN cohorts. RESULTS: Overall, we included 70 patients (37.99 ± 15.67 [3-81] years) with EN solely on the shins and 35 patients (41.27 ± 16.85 [9-76] years) with EN on other locations. Interestingly, time until diagnosis was significantly shorter in atypical EN (p = 0.034, 1.14 ± 4.68 vs. 0.46 ± 1.14 months). Time to remission was similar in both groups (3.61 ± 2.73 vs. 3.05 ± 2.86 months, respectively). Sarcoidosis was the only etiologic factor significantly more frequent in atypical EN compared to typical EN (23% vs. 9%, p = 0.042). Besides that, solely subtle differences were seen regarding etiology, gender, age at onset, course of the disease, and symptoms. CONCLUSIONS: Our study suggests that only minor alterations between both study populations exist. Significant differences were found in time to diagnosis (shorter for atypical EN), as well as in sarcoidosis as an etiologic factor (more frequent in atypical EN). While adalimumab was only prescribed in atypical EN cases, prognosis seems to be similar for typical and atypical EN (similar time to remission, similar amount of reoccurring cases). Due to the limited sample size, however, our study population may have been too small to detect the relevant differences, and bigger studies may be needed.

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.

Granulomatous mastitis during pregnancy with sudden onset of gait difficulty and erythema nodosum: A case report and review of the literature.

Granulomatous mastitis (GM), a benign inflammatory disease of the breast, often mimics breast cancer on presentation. We present a case of GM during pregnancy manifesting as a breast mass, sudden onset of plantar pain, and erythema nodosum (EN). A 31-year-old pregnant Japanese woman, gravida 2, para 1, was referred to our hospital with severe plantar pain on both soles, causing difficulty walking. This pain worsened and EN appeared on both lower legs, followed by a left breast mass. Ultrasound findings suggested malignancy; however, aspiration biopsy confirmed GM. Her arthritis and EN resolved 2 days after commencing oral prednisolone and her walking improved. EN with/without arthritis is commonly associated with GM, especially during pregnancy. The described manifestations with a breast mass are suggestive of this diagnosis.

To ASLO or Not to ASLO: Utility of the ASLO Test in Dermatology.

BACKGROUND: Group A Streptococcus (GAS) causes a wide spectrum of acute infections and immune-related diseases, most of which include a dermatological presentation. However, dermatological findings have a wide range of other possible etiologies. The diagnosis of GAS-related disease requires an indication of preceding GAS infection by direct culture or by measuring antistreptolysin O (ASLO) titer. OBJECTIVES: To explore the correlation between ASLO positivity and dermatological diseases. METHODS: We analyzed clinical data from all cases of patients over 18 years of age who underwent ASLO testing between the years 2016 and 2020 in the Department of Dermatology at Rambam Health Care Campus. RESULTS: Of 152 adult patients with ASLO tests, 100 had diagnoses that were potentially related to streptococcal infection. Vasculitis and psoriasis were the most suspected diagnoses. Positive ASLO test was found in 44 (29%) patients. The diagnoses showing the highest ratio of positive ASLO were psoriasis (60%), erythema nodosum (46%), skin infections (43%), Sweet syndrome (33%), and vasculitis (15%). Psoriasis types included plaque psoriasis (8 patients), guttate psoriasis (3 patients), and palmoplantar pustulosis and erythroderma (2 patients each). CONCLUSIONS: Although the applicability of ASLO for the spectrum of dermatological diseases remains unclear, our results enhance the practical relevance of the test. We showed a higher prevalence of positive ASLO tests in psoriasis and erythema nodosum cases and a lower prevalence in vasculitis. Notably, ASLO was positive in all psoriasis subtypes, suggesting high utility of the test for psoriasis.

Mucocutaneous manifestations of inflammatory bowel disease.

Mucocutaneous manifestations can be indicative of a variety of gastrointestinal diseases, and the dermatologist needs to know how to recognize them to refer the right patients to the gastroenterologist. Conversely, the gastroenterologist is often confronted with mucocutaneous lesions that raise the question of a possible association with a known digestive disease. Among the extra-intestinal manifestations of inflammatory bowel disease (IBD), mucocutaneous manifestations are the most common. This review will provide a breakdown by classifying them into 4 groups: 1) reactive manifestations, which include neutrophilic dermatoses, aphthous stomatitis, erythema nodosum, and vasculitis; 2) Crohn's disease-specific granulomatous skin lesions, which are histologically characterized by tuberculoid granulomas similar to those found in the gastrointestinal tract; 3) nutritional deficiency manifestations secondary to anorexia, malabsorption, loss, and drug interactions; and 3) a variety of autonomous autoimmune or inflammatory skin diseases. Dermatologists may also be involved in the management of the adverse effects of IBD treatments, especially the so-called "paradoxical" psoriatic eruptions.

Erythema nodosum induced by Covid-19 Pfizer-BioNTech mRNA vaccine: A case report and brief literature review.

Erythema nodosum (EN), the most common form of panniculitis, is a reactive inflammation of the subcutaneous fat clinically presented with a sudden onset of painful, erythematous, nodular, subcutaneous lesions, typically localized to the pretibial area. EN is commonly caused by numerous infections (especially beta-haemolytic streptococcal infections), autoimmune diseases (sarcoidosis), inflammatory bowel conditions and drugs. EN induced by Covid-19 vaccines is rarely reported. We describe an original clinical observation of a 75-year-old woman who presented with EN after receiving the second dose of BNT162b2, an mRNA vaccine.

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.

Panniculitis as a manifestation of metal-associated autoimmune/inflammatory syndrome induced by adjuvants: a case-based review.

Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) is associated with a hyperergic response of the immune system. The spectrum of clinical changes in ASIA is extensive and difficult to diagnose. Panniculitis is a heterogeneous group of diseases characterized by lesions of the adipose tissue. Panniculitis may become one of the signs of ASIA progress.To describe the clinical signs and morphological changes in the subcutaneous fat as a manifestation of ASIA, developing after osteosynthesis with metal structures.In this case-based review, were searched for all articles published in PubMed and Scopus databases until March, 2021 using the following keywords "panniculitis", "erythema nodosum", "Weber-Christian Disease", "idiopathic lobular panniculitis", "Autoimmune/inflammatory syndrome induced by adjuvants", "Shoenfeld's syndrome", "metal allergy" "metal implants", "metal hypersensitivity" and reviewed them. Irrelevant items and duplicates were excluded.We report a case of an adult female patient presenting with a non-healing uninfected surgical wound following implantation of metal osteosynthesis construction and panniculitis developed after surgery. A comprehensive examination of the patient to check for ASIA was conducted. Considering the medical history of exposure to metals, tissue lesions, arthralgia, myalgia, low-grade fever, the disappearance of symptoms on the background of immunosuppressive therapy suggested the diagnosis of ASIA.Report affords clinicians and pathologists additional insight into the clinical and morphological picture of ASIA-associated panniculitis which, if remain unidentified, may cause severe complications. We recommend the removal of constructions with adjuvant activity in patients with suspected ASIA-associated manifestations.

Autoimmune rheumatic diseases associated with granulomatous mastitis.

Granulomatous mastitis (GM) is a benign, inflammatory condition of the breast that mainly affects women of reproductive age. Although its pathogenesis remains unknown, previous studies revealed an association between autoimmune rheumatic diseases (ARDs) and GM in a subset of patients implicating immune-mediated mechanisms. The aim of this narrative review was to identify and describe the ARDs associated with GM to shed further light on disease pathogenesis. We conducted a comprehensive literature search of patients presenting with GM and coexisting ARDs using electronic databases. An association between GM and various ARDs has been reported, including sarcoidosis, systematic lupus erythematosus, granulomatosis with polyangiitis, psoriasis/psoriatic arthritis, familial Mediterranean fever, ankylosing spondylitis, Sjogren's syndrome, rheumatoid arthritis, and erythema nodosum, with the most common being granulomatous mastitis-erythema nodosum-arthritis syndrome (GMENA), granulomatosis with polyangiitis (Wegener's) and sarcoidosis. In addition, clinical characteristics, diagnostic and therapeutic approaches were recorded. Further research is warranted to better understand the association between GM and ARDs and raise awareness amongst rheumatologists.

Superficial (nodular) thrombophlebitis as a heterogeneous entity with distinctive clinico-pathological aspects: Correlation with the underlying conditions.

BACKGROUND: Superficial (nodular) thrombophlebitis, referring to a thrombo-inflammatory disorder of dermal-subcutaneous veins, encompass a spectrum of nodular lesions often associated with inflammatory, infectious, neoplastic or thrombophilic diseases. OBJECTIVE: We postulate that distinct clinico-pathological features may correlate with the underlying conditions. METHODS: We conducted a retrospective monocentric study of all patients seen in our dermatology department for a superficial thrombophlebitis, completed with a literature review. Clinical and pathological data were extracted from the patient files and articles. RESULTS: A total of 108 cases of superficial thrombophlebitis was analysed. Forty-five percent manifested as elongated nodules clearly evoking vascular involvement, while the other 55% were presenting as nodules or plaques. The elongated phenotype was strongly associated with malignancy or thrombophilia if a pure thrombosis was demonstrated histopathologically, while tuberculosis was the main underlying condition if a granulomatous vasculitis was present. Panniculitis-like lesions were mainly corresponding to erythema-nodosum-like lesions of Behçet's disease, characterized by the distinctive feature of thrombotic veins with an associated leukocytoclastic vasculitis. LIMITATIONS: Retrospective design and risk of publication bias. CONCLUSION: Superficial (nodular) thrombophlebitis is a heterogeneous entity with a distinct clinico-pathological presentation that strongly points to the nature of the underlying medical condition, thus guiding the medical workup.

Erythema nodosum after azacitidine in a patient with acute myeloid leukemia.

INTRODUCTION: Nodular skin lesions in patients with acute myeloid leukemia (AML) raise clinical suspicion for leukemia cutis versus fungal infections. Here, we report a rare case of treatment-related erythema nodosum (EN) in a patient with AML. CASE REPORT: Approximately 5 weeks after the initiation of sorafenib and one week after azacitidine initiation, a 32-year-old man with primary refractory AML presented with several painful red nodules on the lower extremities. Histological examination established a diagnosis of EN. MANAGEMENT AND OUTCOME: Treatment with topical and oral steroids led to complete resolution of the nodules. However, once the dose of steroids was reduced, the lesions rapidly recurred. Higher dose steroids were reinitiated, again with a resolution of the nodules, confirming steroid responsiveness of the underlying process. DISCUSSION: Given the onset of lesions one week after the initiation of azacitidine and 5 weeks after the initiation of sorafenib, azacitidine was considered the more likely culprit. Only 2 cases of EN-like eruption after azacitidine and 1 case after sorafenib have been reported. Although fungal infections and leukemia cutis are the top differentials considered for skin nodules in a patient with AML, EN should be considered as an alternative diagnosis. Correct diagnosis is critical because it will guide treatment.

Erythema nodosum associated with COVID19 infection: A pediatric case report and review of the literature.

Erythema nodosum (EN) is a common panniculitis characterized by tender erythematous nodules predominantly on the pretibial area and represents a hypersensitivity reaction to multiple triggers. COVID19 infection and vaccination have been associated with EN in the adult population. We report a pediatric case of EN following COVID19 infection and review the literature on COVID19 infection and COVID19 immunization-related EN.

Erythema nodosum after COVID-19 vaccine: Report of two pediatric cases.

With the introduction of large-scale COVID-19 vaccination programs, a variety of cutaneous manifestations have been described. We present two girls (ages 12 and 5 years) who developed erythema nodosum (EN) 3 and 14 days after Pfizer-BioNTech COVID-19 vaccination, respectively. While EN after COVID-19 vaccination has been reported in adults, it is can also occur in children.

The 2021 European Alliance of Associations for Rheumatology/American College of Rheumatology points to consider for diagnosis and management of autoinflammatory type I interferonopathies: CANDLE/PRAAS, SAVI and AGS.

OBJECTIVE: Autoinflammatory type I interferonopathies, chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature/proteasome-associated autoinflammatory syndrome (CANDLE/PRAAS), stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI) and Aicardi-Goutières syndrome (AGS) are rare and clinically complex immunodysregulatory diseases. With emerging knowledge of genetic causes and targeted treatments, a Task Force was charged with the development of 'points to consider' to improve diagnosis, treatment and long-term monitoring of patients with these rare diseases. METHODS: Members of a Task Force consisting of rheumatologists, neurologists, an immunologist, geneticists, patient advocates and an allied healthcare professional formulated research questions for a systematic literature review. Then, based on literature, Delphi questionnaires and consensus methodology, 'points to consider' to guide patient management were developed. RESULTS: The Task Force devised consensus and evidence-based guidance of 4 overarching principles and 17 points to consider regarding the diagnosis, treatment and long-term monitoring of patients with the autoinflammatory interferonopathies, CANDLE/PRAAS, SAVI and AGS. CONCLUSION: These points to consider represent state-of-the-art knowledge to guide diagnostic evaluation, treatment and management of patients with CANDLE/PRAAS, SAVI and AGS and aim to standardise and improve care, quality of life and disease outcomes.

Immunological profile of erythema nodosum and their relationship of C-reactive protein level and erythrocyte sedimentation rate: A retrospective analysis of 61 patients.

This experiment was carried out to investigate changes in lymphocyte subpopulation, immunoglobulins (Igs), and complements, and also to explore the relationship between these immune indices and C-reactive protein and erythrocyte sedimentation rate in 61 patients with erythema nodosum. For this aim, a 4-year, retrospective study contained 61 patients with erythema nodosum, and 61 healthy control subjects were included from the out-patient clinic. The subpopulation of the T, B and natural killer lymphocytes and levels of IgA, IgG, IgM, complement C3, complement C4, C-reactive protein, and erythrocyte sedimentation rate from peripheral blood of them were detected. A correlation analysis was done between lymphocyte subpopulation, levels of IgA, IgG, and IgM, complement C3, complement C4 and C-reactive protein level and erythrocyte sedimentation rate in the patient group. Results showed that the percentage of CD4+ cells, CD4+/CD8+ ratio, the level of C-reactive protein and the erythrocyte sedimentation rate in the patients were higher than in controls (P<0.05). While the percentage of CD8+ cells and the serum levels of complement C3 were lower than in controls (P<0.05). There were no differences in the percentages of CD3+, B and natural killer cells and the serum levels of IgA, IgG and IgM, and complement C4 between the patients and the controls (P>0.05). IgM level was positively correlated with C-reactive protein (P<0.05) but did not correlate with an erythrocyte sedimentation rate (P>0.05). There was no correlation between lymphocyte subpopulation, levels of IgA, IgG, complement C3, complement C4 and C-reactive protein level and erythrocyte sedimentation rate (P>0.05). In conclusion, there was dysregulation of both cellular immunity and humoral immunity in patients with erythema nodosum. IgM level has a positive correlation with C-reactive protein.

A case report of COVID-19-associated erythema nodosum: a classic presentation with a new trigger.

BACKGROUND: Over the course of the pandemic, cutaneous manifestations of SARS-CoV-2 infections have been increasingly characterized, yet only a few cases of erythema nodosum (EN) are reported in the literature and international registries. CASE PRESENTATION: In this report, we describe a case of tender, erythematous nodules that appeared acutely on the distal legs in a 48-year-old female with renal transplant following SARSs-CoV-2 infection complicated by prolonged fevers and pneumonia. The patient was diagnosed with a classic presentation of EN arising from a new and emerging trigger-COVID-19 infection. The cutaneous lesions resolved with conservative management. CONCLUSIONS: This report highlights the importance of clinician awareness of the potential association of COVID-19 with a classic clinical presentation of EN and underscores that these cases can be managed with the same therapeutic repertoire as EN due to other aetiologies. Of note, use of systemic agents was not employed in this case, as our patient improved with conservative therapy alone.

Etonogestrel-releasing contraceptive implant in a patient using thalidomide for the treatment of erythema nodosum leprosum: a case report.

INTRODUCTION: Thalidomide is an immunomodulatory drug and first choice in the treatment of erythema nodosum leprosum. Given its teratogenic potential, it is essential that an effective contraceptive method is used, especially a long-acting reversible contraceptive (LARC) method. The subdermal etonogestrel (ENG)-releasing implant is an adequate method due to the high effectiveness and long-term use. However, interaction between thalidomide and ENG has not been well documented. Concern arises because thalidomide interacts with cytochrome P450 (CYP450) enzymes that metabolize sexual steroids. AIM: We aimed to study the effectiveness and safety of the ENG-implant in a thalidomide user. METHODS: Case report of a sexually active 21-year-old patient with both Hansen's disease and leprosy reaction type 2 treated with thalidomide requiring effective contraception. Follow-up was up to 36 months after implant placement. RESULTS: Contraception with ENG-implant was effective and safe, based on clinical parameters (reduction of menstrual flow and cervical mucus thickening) and laboratory parameters (gonadotropins and sexual steroids). CONCLUSION: To the best of our knowledge, this is the first case reported which presents a patient in simultaneous use of thalidomide and ENG-implant. Although this case report preliminary supports effectiveness and safety of ENG-implant as a contraceptive option in women using thalidomide, rigorous drug-drug interaction research is needed to better characterize the interaction between thalidomide and the ENG-implant.

Evaluation of the influence of genetic variants in Cereblon gene on the response to the treatment of erythema nodosum leprosum with thalidomide.

BACKGROUND: Erythema nodosum leprosum (ENL) is an acute and systemic inflammatory reaction of leprosy characterised by painful nodules and involvement of various organs. Thalidomide is an immunomodulatory and anti-inflammatory drug currently used to treat this condition. Cereblon (CRBN) protein is the primary target of thalidomide, and it has been pointed out as necessary for the efficacy of this drug in others therapeutics settings. OBJECTIVES: In this study, we aimed to evaluate the influence of CRBN gene variants on the dose of thalidomide as well as its adverse effects during treatment of ENL. METHODS: A total of 103 ENL patients in treatment with thalidomide were included in this study. DNA samples were obtained from saliva and molecular analysis of CRBN gene were performed to investigate the variants rs1620675, rs1672770 and rs4183. Different genotypes of CRBN variants were evaluated in relation to their influence on the dose of thalidomide and on the occurrence of adverse effects. FINDINGS: No association was found between CRBN variants and thalidomide dose variation. However, the genotypes of rs1672770 showed association with gastrointestinal effects (p = 0.040). Moreover, the haplotype DEL/C/T (rs4183/rs1672770/rs1620675) was also associated with gastrointestinal adverse effects (p = 0.015). MAIN CONCLUSIONS: Our results show that CRBN variants affect the treatment of ENH with thalidomide, especially on the adverse effects related to the drug.