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      Leukocytoclastic vasculitis as a rare dermatologic manifestation of Crohn’s disease mimicking cellulitis: a case report

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          Abstract

          Background

          Leukocytoclastic vasculitis (LCV) is an immune-complex mediated vasculitis characterized by neutrophilic inflammation and nuclear debris in post capillary venules. LCV is a rare dermatologic manifestation of Crohn’s disease (CD) and may occur with the onset of the disease or any time after the diagnosis including the period of exacerbation.

          Case presentation

          We present a 70 year old woman with history of psoriasis and treatment refractory CD requiring monoclonal antibody therapy with ustekinumab. One month prior to the current admission, she developed abdominal pain, worsening diarrhea and was diagnosed with CD exacerbation for which she was given ustekinumab. While her abdominal symptoms mildly improved with ustekinumab, she developed new bilateral lower extremity rash initially treated with levofloxacin for presumed cellulitis. The rash consisted of mild erythematous, non-scaling patches with scattered non-palpable petechiae on the lower extremities with subsequent involvement of abdomen, lower back and buttocks. Abdominal exam showed diffuse tenderness without mass, guarding or rebound while reminder of physical exam was unremarkable. Following the failure of antimicrobial therapy, she was diagnosed with LCV by skin biopsy. Complete work up was negative for infectious, malignant and inflammatory etiologies of LCV. Patient improved with increased dose of budesonide and subsequently continued to tolerate ustekinumab without recurrence of LCV.

          Discussion and conclusion

          LCV is a rare form of vasculitis and one of the rarest dermatologic manifestations of CD, appearing at any stage of the disease. LCV has been associated with autoimmune diseases, infections, specific drugs (levofloxacin, ustekinumab), and malignancy. Clinical presentation of LCV is variable and frequently mistaken for cellulitis. LCV should be considered in differential diagnosis of bilateral lower extremity rash in patients with CD after infectious, malignant and auto-immune/inflammatory etiologies are excluded. Unlike erythema nodosum (EN) and pyoderma gangrenosum (PG), LCV requires biopsy for diagnosis. Most patients respond well to steroids without scarring.

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          Most cited references22

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          Frequency and risk factors for extraintestinal manifestations in the Swiss inflammatory bowel disease cohort.

          Data on the frequency of extraintestinal manifestations (EIMs) in Crohn's disease (CD) and ulcerative colitis (UC) and analyses of their risk factors are scarce. We evaluated their prevalence and risk factors in a large nationwide cohort of inflammatory bowel disease (IBD) patients. IBD patients from an adult clinical cohort in Switzerland (Swiss IBD cohort study) were prospectively included. Data from validated physician enrolment questionnaires were analyzed. A total of 950 patients were included, 580 (61%) with CD (mean age 41 years) and 370 (39%) with UC (mean age 42 years). Of these, 249 (43%) of CD and 113 (31%) of UC patients had one to five EIMs. The following EIMs were found: arthritis (CD 33%, UC 21%), aphthous stomatitis (CD 10%, UC 4%), uveitis (CD 6%, UC 4%), erythema nodosum (CD 6%, UC 3%), ankylosing spondylitis (CD 6%, UC 2%), psoriasis (CD 2%, UC 1%), pyoderma gangrenosum (CD and UC each 2%), and primary sclerosing cholangitis (CD 1%, UC 4%). Multiple logistic regression identified the following risk factors for ongoing EIM in CD: active disease (odds ratio (OR)=1.95, 95% confidence interval (CI)=1.17-3.23, P=0.01), and positive IBD family history (OR=1.77, 95% CI=1.07-2.92, P=0.025). No risk factors were identified in UC patients. EIMs are a frequent problem in CD and UC patients. Active disease and positive IBD family history are associated with ongoing EIM in CD patients. Identification of EIM prevalence and associated risk factors may result in increased awareness for this problem and thereby facilitating their diagnosis and therapeutic management.
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            Skin Manifestations of Inflammatory Bowel Disease

            Inflammatory bowel disease (IBD) is a disease that affects the intestinal tract via an inflammatory process. Patients who suffer from IBD often have diseases that affect multiple other organ systems as well. These are called extraintestinal manifestations and can be just as, if not more debilitating than the intestinal inflammation itself. The skin is one of the most commonly affected organ systems in patients who suffer from IBD. The scientific literature suggests that a disturbance of the equilibrium between host defense and tolerance, and the subsequent over-activity of certain immune pathways are responsible for the cutaneous disorders seen so frequently in IBD patients. The purpose of this review article is to give an overview of the types of skin diseases that are typically seen with IBD and their respective pathogenesis, proposed mechanisms, and treatments. These cutaneous disorders can manifest as metastatic lesions, reactive processes to the intestinal inflammation, complications of IBD itself, or side effects from IBD treatments; these can be associated with IBD via genetic linkage, common autoimmune processes, or other mechanisms that will be discussed in this article. Ultimately, it is important for healthcare providers to understand that skin manifestations should always be checked and evaluated for in patients with IBD. Furthermore, skin disorders can predate gastrointestinal symptoms and thus may serve as important clinical indicators leading physicians to earlier diagnosis of IBD.
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              Extraintestinal manifestations in inflammatory bowel disease - epidemiology, genetics, and pathogenesis.

              Inflammatory bowel disease (IBD) is a chronic inflammatory disorder, primarily of, but not restricted to the gut. Extraintestinal manifestations (EIMs) are frequently observed and involve the joints, eyes, hepatobiliary tract, and skin. Areas covered: In this review, we discuss classical EIM focusing on epidemiology, genetics, and pathogenesis, highlighting recent advances in the understanding of EIM. We further discuss treatment-induced immunological phenomena, which are increasingly recognized and might challenge IBD-treating physicians in the era of biological treatment. Expert opinion: EIM considerably contributes to morbidity and mortality. Genetic studies have revealed a common genetic background between EIM and IBD and among specific EIM. Identified protein interactions have been shown to cluster in shared biological pathways. However - despite these recent advances - pathogenesis of EIM is at best partially understood. Several pathogenic mechanisms have been proposed such as upregulation of tumor necrosis factor, aberrant lymphocyte homing, and cross-reactive antigen presentation. It still remains unclear whether EIM is a direct result of the inflammatory process in the gut or rather a consequence of a shared genetic background leading to dysfunctional immune responses to environmental stimuli. Exploration and understanding of EIM genetics and pathophysiology will pave the road for better and more efficacious treatment options in the future.
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                Author and article information

                Contributors
                Dumic.Igor@mayo.edu
                Journal
                BMC Gastroenterol
                BMC Gastroenterol
                BMC Gastroenterology
                BioMed Central (London )
                1471-230X
                29 July 2020
                29 July 2020
                2020
                : 20
                : 240
                Affiliations
                [1 ]Mayo Clinic Family Medicine Residency – Eau Claire Program, Eau Claire, WI USA
                [2 ]GRID grid.66875.3a, ISNI 0000 0004 0459 167X, Mayo Clinic Alix College of Medicine and Science, ; Rochester, MN USA
                [3 ]GRID grid.414713.4, ISNI 0000 0004 0444 0900, Division of Hospital Medicine, , Mayo Clinic Health System, ; Eau Claire, WI USA
                [4 ]GRID grid.59734.3c, ISNI 0000 0001 0670 2351, Icahn School of Medicine at Mount Sinai, ; New York City, NY USA
                [5 ]GRID grid.414713.4, ISNI 0000 0004 0444 0900, Department of Pathology, , Mayo Clinic Health System, ; Eau Claire, WI USA
                [6 ]GRID grid.418577.8, ISNI 0000 0000 8743 1110, Department of Gastroenterology, , Clinical Center of Serbia, ; Belgrade, Serbia
                [7 ]GRID grid.414713.4, ISNI 0000 0004 0444 0900, Department of Family Medicine, , Mayo Clinic Health System, ; Eau Claire, WI USA
                Author information
                http://orcid.org/0000-0002-5312-8812
                Article
                1371
                10.1186/s12876-020-01371-3
                7389435
                32727390
                87089566-6176-4ec8-b2b0-c7a9da29c389
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 3 November 2019
                : 9 June 2020
                Categories
                Case Report
                Custom metadata
                © The Author(s) 2020

                Gastroenterology & Hepatology
                leukocytoclastic vasculitis,crohn’s disease,dermatologic manifestation,cellulitis,inflammatory bowel disease,ustekinumab,levofloxacin,case report

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