Abstract
Inflammatory bowel disease (IBD) is a chronic immune-mediated inflammatory condition primarily involving the gastrointestinal tract. It includes Crohn’s disease (CD), ulcerative colitis (UC), and a less common phenotype—indeterminate colitis. It is thought to result from a complex interplay of environmental, microbial, and host factors including genetic factors, although the exact mechanism is not known. Dietary factors have been shown to play a role in the pathogenesis of IBD and can potentially alter the intestinal microbiota as well as disrupt the immune function in the gut. CD is characterized by transmural inflammation, sometimes associated with granulomatous lesions, and involves the entire gastrointestinal tract but often spares the rectum. UC is characterized by mucosal inflammation typically confined to the colon and rectum. Although IBD is mostly seen in western world, recent data suggests that the incidence and prevalence are increasing worldwide. Enteral nutrition has been shown to be effective in inducing remission in pediatric population with CD; however, there is mixed data in adult population. Nutritional deficiencies such as vitamin D and zinc deficiency are often noted in IBD patients. Several extraintestinal manifestations are noted in patients with IBD. Some of them parallel with the disease activity and others are independent of the disease course. Assessment of IBD disease activity clinically, radiologically, if indicated, biochemically and endoscopically is important to guide therapy in IBD. To ensure comprehensive care, it is important to assess associated conditions such as nutritional and psychological well-being, as well as age appropriate health maintenance status prior to starting treatment for IBD. Several biologic agents including anti-tumor necrosis factor alpha (anti-TNF-α) drugs, anti-integrins, and antibodies to the p40 subunit of IL12/23 are approved for induction and maintenance of remission of IBD. Steroids are also often used for induction. Anti-metabolites and thiopurines are also useful either as monotherapy or in combination regimens. Potential side effects of anti-TNF-α drugs such as serious infections, malignancy, worsening of heart failure, and infusion-related reactions should be considered prior to starting these drugs. Anti-TNF-α drugs with or without immunomodulators (azathioprine, 6-mercaptopurine, methotrexate) are often used for the induction and maintenance of remission. Treating to target of endoscopic and clinical remission provides the best long-term outcomes. Our knowledge and understanding of IBD has grown significantly. However, there are several unanswered questions on pathogenesis, disease behavior, and drivers of inflammation in various patient subgroups which require further research.
Similar content being viewed by others
References
Baumgart DC, Carding SR (2007) Inflammatory bowel disease: cause and immunobiology. Lancet 369:1627–1640
Molodecky NA, Soon IS, Rabi DM, Ghali WA, Ferris M, Chernoff G, Benchimol EI, Panaccione R, Ghosh S, Barkema HW, Kaplan GG (2012) Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology 142:46–54
Anderson CA, Massey DC, Barrett JC et al (2009) Investigation of Crohn’s disease risk loci in ulcerative colitis further defines their molecular relationship. Gastroenterology 136:523–529
Franke A, McGovern DP, Barrett JC et al (2010) Genome-wide meta-analysis increases to 71 the number of confirmed Crohn’s disease susceptibility loci. Nat Genet 42:1118–1125
Fukata M, Abreu MT (2009) Pathogen recognition receptors, cancer and inflammation in the gut. Curr Opin Pharmacol 9:680–687
Lakatos PL (2009) Environmental factors affecting inflammatory bowel disease: have we made progress? Dig Dis 27:215–225
de Lange KM, Moutsianas L, Lee JC et al (2017) Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease. Nat Genet 49:256–261
Molodecky NA et al (2012) Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology 142:46–54. e42
Kaplan GG et al (2015) The global burden of IBD: from 2015 to 2025. Nat Rev Gastroenterol Hepatol 12:720–727
Shivashankar R, Tremaine WJ, Harmsen WS, Loftus EV Jr (2017) Incidence and prevalence of Crohn’s disease and ulcerative colitis in Olmsted County, Minnesota from 1970 through 2010. Clin Gastroenterol Hepatol 15(6):857–863
Nerich V et al (2006) Geographical variations of inflammatory bowel disease in France: a study based on national health insurance data. Inflamm Bowel Dis 12:218–226
Freeman HJ (2007) Application of the Montreal classification for Crohn’s disease to a single clinician database of 1015 patients. Can J Gastroenterol 21:363–366
Farmer RG, Hawk WA, Turnbull RB Jr (1975) Clinical patterns in Crohn’s disease: a statistical study of 615 cases. Gastroenterology 68(4 Pt 1):627
Pimentel M, Chang M, Chow EJ, Tabibzadeh S, Kirit-Kiriak V, Targan SR, Lin HC (2000) Identification of a prodromal period in Crohn’s disease but not ulcerative colitis. Am J Gastroenterol 95(12):3458
Mekhjian HS, Switz DM, Melnyk CS, Rankin GB, Brooks RK (1979) Clinical features and natural history of Crohn’s disease. Gastroenterology. 77(4 Pt 2):898
Thoreson R, Cullen JJ (2007 Jun.) Pathophysiology of inflammatory bowel disease: an overview. Surg Clin North Am 87(3):575–585
A. M. C. Faria, D. Mucida, D.-M. McCafferty, N. M. Tsuji, and V. Verhasselt (2012) “Tolerance and inflammation at the gut mucosa,” Clinical and Developmental Immunology, vol. 2012, Article ID 738475, pages, 3
van der Flier LG, Clevers H (2009) Stem cells, self-renewal, and differentiation in the intestinal epithelium. Annu Rev Physiol 71:241–260
Geremia A, Biancheri P, Allan P, Corazza GR, Di SA (2014) Innate and adaptive immunity in inflammatory bowel disease. Autoimmun Rev 13:3–10
Geremia A, Biancheri P, Allan P et al (2014) Innate and adaptive immunity in inflammatory bowel disease. Autoimmun Rev 13(1):3–10
Kaser A, Blumberg RS (2010) Endoplasmic reticulum stress and intestinal inflammation. Mucosal Immunol 3:11–16
Salim SY, Soderholm JD (2011) Importance of disrupted intestinal barrier in inflammatory bowel diseases. Inflamm Bowel Dis 17:362–381
Turner JR (2006) Molecular basis of epithelial barrier regulation: from basic mechanisms to clinical application. Am J Pathol 169(6):1901–1909
Salzman NH, Hung K, Haribhai D, Chu H, Karlsson-Sjöberg J, Amir E, Teggatz P, Barman M, Hayward M, Eastwood D, Stoel M, Zhou Y, Sodergren E, Weinstock GM, Bevins CL, Williams CB, Bos NA (2010) Enteric defensins are essential regulators of intestinal microbial ecology. Nat Immunol 11(1):76
Hermiston ML, Gordon JI (1995) Inflammatory bowel disease and adenomas in mice expressing a dominant negative N-cadherin. Science. 270(5239):1203
Barrett JC, Lee JC, Lees CW et al (2009) Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A region. Nat Genet 41:1330–1334
Anderson CA, Boucher G, Lees CW et al (2011) Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47. Nat Genet 43:246–252
Uehara A, Fujimoto Y, Fukase K, Takada H (2007) Various human epithelial cells express functional Toll-like receptors, NOD1 and NOD2 to produce anti-microbial peptides, but not proinflammatory cytokines. Mol Immunol 44:3100–3111
Wehkamp J, Harder J, Weichenthal M et al (2003) Inducible and constitutive betadefensins are differentially expressed in Crohn's disease and ulcerative colitis. Inflamm Bowel Dis 9:215–223
Ogura Y, Bonen DK, Inohara N, Nicolae DL, Chen FF, Ramos R, Britton H, Moran T, Karaliuskas R, Duerr RH, Achkar JP, Brant SR, Bayless TM, Kirschner BS, Hanauer SB, Nuñez G, Cho JH (2001) A frameshift mutation in NOD2 associated with susceptibility to Crohn’s disease. Nature 411(6837):603
Hugot JP, Chamaillard M, Zouali H, Lesage S, Cézard JP, Belaiche J, Almer S, Tysk C, O’Morain CA, Gassull M, Binder V, Finkel Y, Cortot A, Modigliani R, Laurent-Puig P, Gower-Rousseau C, Macry J, Colombel JF, Sahbatou M, Thomas G (2001) Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn’s disease. Nature 411(6837):599
Glick D, Barth S, Macleaod KF (2010) Autophagy: cellular and molecular mechanisms. J Pathol 221(1):3–12
Deretic V, Saitoh T, Akira S (2013) Autophagy in infection, inflammation and immunity. Nat Rev Immunol 13(10):722–737
Hampe J, Franke A, Rosenstiel P et al (2007) A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1. Nat Genet 3(9):207–211
Parkes M, Barrett JC, Prescott NJ et al (2007) Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn’s disease susceptibility. Nat Genet 39:830–832
Reinecker HC, Steffen M, Witthoeft T, Pflueger I, Schreiber S, MacDermott RP, Raedler A (1993) Enhanced secretion of tumour necrosis factor-alpha, IL-6, and IL-1 beta by isolated lamina propria mononuclear cells from patients with ulcerative colitis and Crohn's disease. Clin Exp Immunol 94(1):174
Reimund JM, Wittersheim C, Dumont S, Muller CD, Kenney JS, Baumann R, Poindron P, Duclos B (1996) Increased production of tumour necrosis factor-alpha interleukin-1 beta, and interleukin-6 by morphologically normal intestinal biopsies from patients with Crohn’s disease. Gut 39(5):684–689
Kamada N, Hisamatsu T, Okamoto S, Chinen H, Kobayashi T, Sato T, Sakuraba A, Kitazume MT, Sugita A, Koganei K, Akagawa KS, Hibi T (2008) Unique CD14 intestinal macrophages contribute to the pathogenesis of Crohn disease via IL-23/IFN-gamma axis. J Clin Invest 118(6):2269–2280
Romagnani S (1994) Lymphokine production by human T cells in disease states. Annu Rev Immunol 12:227–257
Korn T, Bettelli E, Oukka M, Kuchroo VK (2009) IL-17 and Th17 cells. Annu Rev Immunol 27:485–517
Flammer JR, Rogatsky I (2011) Minireview: glucocorticoids in autoimmunity: unexpected targets and mechanisms. Mol Endocrinol 25:1075–1086
Kühn R, Löhler J, Rennick D, Rajewsky K, Müller W (1993) Interleukin-10-deficient mice develop chronic enterocolitis. Cell 75(2):263
Fuss IJ, Marth T, Neurath MF, Pearlstein GR, Jain A, Strober W (1999) Anti-interleukin 12 treatment regulates apoptosis of Th1 T cells in experimental colitis in mice. Gastroenterology 117(5):1078
Powrie F, Leach MW, Mauze S, Menon S, Caddle LB, Coffman RL (1994) Inhibition of Th1 responses prevents inflammatory bowel disease in scid mice reconstituted with CD45RBhi CD4+ T cells. Immunity 1(7):553
Targan SR, Hanauer SB, van Deventer SJ, Mayer L, Present DH, Braakman T, DeWoody KL, Schaible TF, Rutgeerts PJ, Crohn’s Disease cA2 Study Group (1997) A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn’s disease. N Engl J Med 337(15):1029
Podolsky DK (2002) Inflammatory bowel disease. N Engl J Med 347:417–429
Monteleone G, Trapasso F, Parrello T et al (1999) Bioactive IL-18 expression is up-regulated in Crohn’s disease. J Immunol 163:143–147
Zhou L, Ivanov II, Spolski R et al (2007) IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nat Immunol 8:967–974
Monteleone G, Monteleone I, Fina D et al (2005) Interleukin-21 enhances T-helper cell type I signaling and interferon-gamma production in Crohn’s disease. Gastroenterology 128:687–694
Sarra M, Monteleone I, Stolfi C et al (2010) Interferon-gamma-expressing cells are a major source of interleukin-21 in inflammatory bowel diseases. Inflamm Bowel Dis 16:1332–1339
Dore J, Corthier G (2010) The human intestinal microbiota. Gastroenterol Clin Biol 34(Suppl. 1):S7–S15
Lozupone CA, Stombaugh JI, Gordon JI, Jansson JK, Knight R (2012) Diversity, stability and resilience of the human gut microbiota. Nature 489(7415):220–230
Hildebrandt MA, Hoffmann C, Sherrill-Mix SA, Keilbaugh SA, Hamady M, Chen YY, Knight R, Ahima RS, Bushman F, Wu GD (2009) High-fat diet determines the composition of the murine gut microbiome independently of obesity. Gastroenterology 137(5):1716–1724 e1–2
Weinstock JV (2006) Helminths and mucosal immune modulation. Ann N Y Acad Sci 1072:356–364
Margolis DJ, Fanelli M, Hoffstad O, Lewis JD (2010) Potential association between the oral tetracycline class of antimicrobials used to treat acne and inflammatory bowel disease. Am J Gastroenterol 105(12):2610
Elson CO, Cong Y, McCracken VJ, Dimmitt RA, Lorenz RG, Weaver CT (2005) Experimental models of inflammatory bowel disease reveal innate, adaptive, and regulatory mechanisms of host dialogue with the microbiota. Immunol Rev 206:260–276
Garrett WS, Lord GM, Punit S, Lugo-Villarino G, Mazmanian SK, Ito S, Glickman JN, Glimcher LH (2007) Communicable ulcerative colitis induced by T-bet deficiency in the innate immune system. Cell 131(1):33–45
Frank DN, St Amand AL, Feldman RA, Boedeker EC, Harpaz N, Pace NR (2007) Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci U S A 104(34):13780–13785
Manichanh C, Rigottier-Gois L, Bonnaud E, Gloux K, Pelletier E, Frangeul L, Nalin R, Jarrin C, Chardon P, Marteau P, Roca J, Dore J (2006) Reduced diversity of faecal microbiota in Crohn’s disease revealed by a metagenomic approach. Gut 55(2):205–211
Hansen R, Russell RK, Reiff C et al (2012) Microbiota of de-novo pediatric IBD: increased Faecalibacterium prausnitzii and reduced bacterial diversity in Crohn’s but not in ulcerative colitis. Am J Gastroenterol 107:1913–1922
Morgan XC, Tickle TL, Sokol H et al (2012) Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment. Genome Biol 13:R79
Moustafa A, Li W, Anderson EL, Wong EHM, Dulai PS, Sandborn WJ et al (2018) Genetic risk, dysbiosis, and treatment stratification using host genome and gut microbiome in inflammatory bowel disease. Clin Transl Gastroenterol 18:9(1)
Marteau P (2009) Bacterial flora in inflammatory bowel disease. Dig Dis 27(Suppl. 1):99–103
Reshef L, Kovacs A, Ofer A, Yahav L, Maharshak N, Keren N, Konikoff FM, Tulchinsky H, Gophna U, Dotan I (2015) Pouch inflammation is associated with a decrease in specific bacterial taxa. Gastroenterology 149(3):718–727
Morgan XC, Kabakchiev B, Waldron L, Tyler AD, Tickle TL, Milgrom R, Stempak JM, Gevers D, Xavier RJ, Silverberg MS, Huttenhower C (2015) Associations between host gene expression, the mucosal microbiome, and clinical outcome in the pelvic pouch of patients with inflammatory bowel disease. Genome Biol 16:67
Zachos M, Tondeur M, Griffiths AM (2007) Enteral nutritional therapy for induction of remission in Crohn’s disease. Cochrane Database Syst Rev 1:CD000542
Brestoff JR, Artis D (2013) Commensal bacteria at the interface of host metabolism and the immune system. Nat Immunol 14:676–684
Han PD, Burke A, Baldassano RN, Rombeau JL, Lichtenstein GR (1999) Nutrition and inflammatory bowel disease. Gastroenterol Clin N Am 28(2):423e43
Klement E, Cohen RV, Boxman J, Joseph A, Reif S (2004) Breastfeeding and risk of inflammatory bowel disease: a systematic review with meta-analysis. Am J Clin Nutr 80:1342–1352
Zachos M, Tondeur M, Griffiths AM (2001) Enteral nutritional therapy for inducing remission of Crohn’s disease. Cochrane Database Syst Rev 3:CD000542
Racine A, Carbonnel F, Chan SS, Hart AR et al (2016) Dietary patterns and risk of inflammatory bowel disease in Europe: results from the EPIC study. Inflamm Bowel Dis 22(2):345–354
Chan SSM, Luben R, Olsen A, Tjonneland A, Kaaks R, Lindgren S et al (2014) Association between high dietary intake of the n-3 polyunsaturated fatty acid docosahexaenoic acid and reduced risk of Crohn’s disease. Aliment Pharmacol Ther 39:834e42
Jantchou P, Morois S, Clavel-Chapelon F et al (2010) Animal protein intake and risk of inflammatory bowel disease: the E3N prospective study. Am J Gastroenterol 105:2195–2201
Ananthakrishnan AN, Khalili H, Konijeti GG, Higuchi LM, de Silva P, Fuchs CS et al (2014) Long-term intake of dietary fat and risk of ulcerative colitis and Crohn’s disease. Gut 6:776e84
Vagianos K, Bector S, McConnell J, Bernstein CN (2007) Nutrition assessment of patients with inflammatory bowel disease. JPEN J Parenter Enteral Nutr 31(4):311
Phelip JM, Ducros V, Faucheron JL, Flourie B, Roblin X (2008) Association of hyperhomocysteinemia and folate deficiency with colon tumors in patients with inflammatory bowel disease. Inflamm Bowel Dis 14(2):242
Del Pinto R, Peitrapaoli D, Chadar AK et al (2015) Association between inflammatory bowel disease and vitamin D deficiency: a systematic review and meta-analysis. Inflamm Bowel Dis 21(11):2708–2717
White JH (2008) Vitamin D signaling, infectious diseases, and regulation of innate immunity. Infect Immun 76(9):3837–3843
Baeke F, van Etten E, Gysemans C, Overbergh L, Mathieu C (2008) Vitamin D signaling in immune-mediated disorders: evolving insights and therapeutic opportunities. Mol Asp Med 29(6):376–387
Ardesia M, Ferlazzo G, Fries W. Vitamin D and inflammatory bowel disease. Biomed Res In. 2015
Garg M, Rosella O, Lubel JS, Gibson PR (2013) Association of circulating vitamin D concentrations with intestinal but not systemic inflammation in inflammatory bowel disease. Inflamm Bowel Dis 19(12):2634–2643
Kabbani TA, Koutroubakis IE et al. Association of vitamin D level with clinical status in inflammatory bowel disease: a 5-year longitudinal study
Prasad AS (2000) Effects of zinc deficiency on Th1 and Th2 cytokine shifts. J Infect Dis 182(Suppl 1):S62–S68
Ojuawo A, Keith L (2002) The serum concentrations of zinc, copper and selenium in children with inflammatory bowel disease. Cent Afr J Med 48:116–119
Alkhouri RH, Hashmi H, Baker RD et al (2013) Vitamin and mineral status in patients with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 56:89–92
Siva S, Rubin DT, Gulotta G, Wroblewski K, Pekow J (2017) Zinc deficiency is associated with poor clinical outcomes in patients with inflammatory bowel disease. Inflamm Bowel Dis 23(1):152–157
Ananthakrishnan AN, Khalili H, Song M, Higuchi LM, Richter JM, Chan AT (2015) Zinc intake and risk of Crohn’s disease and ulcerative colitis: a prospective cohort study. Int J Epidemiol 44:1995–2005
Dziechciarz P, Horvath A, Shamir R, Szajewska H (2007) Meta-analysis: enteral nutrition in active Crohn’s disease in children. Aliment Pharmacol Ther 26(6):795–806
Akobeng AK, Thomas AG (2007) Enteral nutrition for maintenance of remission in Crohn’s disease. Cochrane Database Syst Rev 3:CD005984
Nakahigashi M, Yamamoto T, Sacco R, Hanai H, Kobayashi F (2016) Enteral nutrition for maintaining remission in patients with quiescent Crohn’s disease: current status and future perspectives. Int J Color Dis 31:1–7
Travis SP, Stange EF, Lémann M, Oresland T, Chowers Y, Forbes A et al (2006) European evidence based consensus on the diagnosis and management of Crohn’s disease: current management. Gut 55(Suppl 1):i16–i35
Konno M, Takahashi M, Toita N, Fujiwara S, Nojima M (2015) Long-term therapeutic effectiveness of maintenance enteral nutrition for Crohn’s disease. Pediatr Int 57(2):276–280
Frivolt K, Schwerd T, Werkstetter KJ, Schwarzer A, Schatz SB, Bufler P, Koletzko S (2014) Repeated exclusive enteral nutrition in the treatment of paediatric Crohn’s disease: predictors of efficacy and outcome. Aliment Pharmacol Ther 39(12):1398–1407
Wall CL, Day AS, Gearry RB (2013) Use of exclusive enteral nutrition in adults with Crohn’s disease: a review. World J Gastroenterol 19(43):7652–7660
Yang Q, Gao X, Chen H, Li M, Wu X, Zhi M, Lan P, Hu P (2017) Efficacy of exclusive enteral nutrition in complicated Crohn’s disease. Scand J Gastroenterol 52(9):995–1001
Bernstein CN, Blanchard JF, Rawsthorne P, Yu N (2001) The prevalence of extraintestinal diseases in inflammatory bowel disease: a population-based study. Am J Gastroenterol 96(4):1116
Das KM, Vecchi M, Sakamaki S (1990) A shared and unique epitope(s) on human colon, skin, and biliary epithelium detected by a monoclonal antibody. Gastroenterology 98(2):464
Orchard TR, Chua CN, Ahmad T, Cheng H, Welsh KI, Jewell DP (2002) Uveitis and erythema nodosum in inflammatory bowel disease: clinical features and the role of HLA genes. Gastroenterology 123(3):714
Ruocco E, Sangiuliano S, Gravina AG, Miranda A, Nicoletti G (2009) Pyoderma gangrenosum: an updated review. J Eur Acad Dermatol Venereol 23(9):1008–1017
Sasor SE, Soleimani T, Chu MW, Cook JA, Nicksic PJ, Tholpady SS (2018) Pyoderma gangrenosum demographics, treatments, and outcomes: an analysis of 2,273 cases. J Wound Care 27(Sup1):S4–S8
Powell FC, Hackett BC, Wallach D. Pyoderma gangrenosum. In: Fitzpatrick’s dermatology in general medicine, 8th ed, Goldsmith LA, Katz SI, Gilchrest BA, et al (Eds), McGraw-Hill Companies, Inc., New York 2012. Vol 1, p.371
Wise CA, Gillum JD, Seidman CE, Lindor NM, Veile R, Bashiardes S, Lovett M (2002) Mutations in CD2BP1 disrupt binding to PTP PEST and are responsible for PAPA syndrome, an autoinflammatory disorder. Hum Mol Genet 11(8):961
Marzano AV, Trevisan V, Gattorno M, Ceccherini I, De Simone C, Crosti C (2013) Pyogenic arthritis, pyoderma gangrenosum, acne, and hidradenitis suppurativa (PAPASH): a new autoinflammatory syndrome associated with a novel mutation of the PSTPIP1 gene. JAMA Dermatol 149(6):762
Binus AM, Qureshi AA, Li VW, Winterfield LS (2011) Pyoderma gangrenosum: a retrospective review of patient characteristics, comorbidities and therapy in 103 patients. Br J Dermatol 165(6):1244
Xia FD, Liu K, Lockwood S, Butler D, Tsiaras WG, Joyce C, Mostaghimi A (2018) Risk of developing pyoderma gangrenosum after procedures in patients with a known history of pyoderma gangrenosum—a retrospective analysis. J Am Acad Dermatol 78(2):310–314 e1
Jockenhöfer F, Wollina U, Salva KA, Benson S, Dissemond J. The PARACELSUS score: a novel diagnostic tool for pyoderma gangrenosum. Br J Dermatol 2018. doi: https://doi.org/10.1111/bjd.16401
Leiphart PA, Lam CC, Foulke GT (2017) Suppression of pathergy in pyoderma gangrenosum with infliximab allowing for successful tendon debridement. JAAD Case Rep. 4(1):98–100
Le Cleach L, Moguelet P, Perrin P, Chosidow O (2011) Is topical monotherapy effective for localized pyoderma gangrenosum? Arch Dermatol 147(1):101–103
Reichrath J, Bens G, Bonowitz A, Tilgen W (2005) Treatment recommendations for pyoderma gangrenosum: an evidence-based review of the literature based on more than 350 patients. J Am Acad Dermatol 53(2):273–283
Brooklyn TN, Dunnill MG, Shetty A, Bowden JJ, Williams JD, Griffiths CE, Forbes A, Greenwood R, Probert CS (2006) Infliximab for the treatment of pyoderma gangrenosum: a randomised, double blind, placebo controlled trial. Gut 55(4):505
Song H, Lahood N, Mostaghimi A (2017) Intravenous immunoglobulin as adjunct therapy for refractory pyoderma gangrenosum: systematic review of cases and case series. Br J Dermatol. 5
Van Hale HM, Rogers RS, Zone JJ, Philip R, Greipp R (1985) Pyostomatitis vegetans—a reactive mucosal marker for inflammatory disease of the gut. Arch Dermatol 121:94–98
Clark LG, Tolkachjov SN, Bridges AG, Camilleri MJ (2016) Pyostomatitis vegetans (PSV)-pyodermatitis vegetans (PDV): a clinicopathologic study of 7 cases at a tertiary referral center. J Am Acad Dermatol 75(3):578–584
NIgen S, Poulin Y, Rochette L, Levesque MH, Gagne E (2003) Pyodermatitis-pyostomatitis vegetans: two cases and a review of the literature. J Cutan Med Surg 7(3):250–255
Hegarty AM, Barett AW, Scully C (2004) Pyostomatitis vegetans. Clin Exp Dermatol 29(1):1–7
Thornhill MH, Zakrzewska JM, Gilkes JJH (1992) Pyostomatitis vegetans: report of three cases and review of the literature. J Oral Pathol Med 21:128–133
Soriano ML, Martinez N, Grilli R, Farina MC, Martin L, Requena L (1999) Pyodermatitis-pyostomatitis vegetans. Report of a case and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 87:322–326
Storwick GS, Prihoda MB, Fulton RJ, Wood WS (1994) Pyodermatitis-pyostomatitis vegetans: a specific marker for inflammatory bowel disease. J Am Acad Dermatol 31:336–341
Ballo FS, Camisa C, Allen CM (1989) Pyostomatitis vegetans: report of a case and review of the literature. J Am Acad Dermatol 21:381–387
Lopes Caçola R, Soares M, Cardoso C, Furtado A (2016) Sweet’s syndrome complicating ulcerative colitis: a rare association. BMJ Case Rep 20:2016
Cohen PR, Hongsmann H, Kurzrock R (2012) Acute febrile neutrophilic dermatosis (Sweet syndrome). In: Fitzpatrick’s dermatology in general medicine, 8th ed, Goldsmith LA, Katz SI, Gilchrest BA, et al. (Eds), McGraw Hill, Vol 1, p.362
Yang CS, Teeple M, Muglia J, Robinson-Bostom L (2016) Inflammatory and glandular skin disease in pregnancy. Clin Dermatol 34(3):335–343
Cohen PR, Kurzrock R (1993) Sweet’s syndrome and cancer. Clin Dermatol 11(1):149–157
Rochet NM, Chavan RN, Cappel MA, Wada DA, Gibson LE (2013) Sweet syndrome: clinical presentation, associations, and response to treatment in 77 patients. J Am Acad Dermatol 69(4):557
Casarin Costa JR, Virgens AR, de Oliveira ML, Dias NF, Samorano LP, Valente NYS, Festa NC (2017) Sweet syndrome: clinical features, histopathology, and associations of 83 cases. J Cutan Med Surg 21(3):211–216
Amouri M, Masmoudi A, Ammar M, Boudaya S, Khabir A, Boudawara T, Turki H (2016) Sweet’s syndrome: a retrospective study of 90 cases from a tertiary care center. Int J Dermatol 55(9):1033–1039
Giasuddin AS, El-Orfi AH, Ziu MM, El-Barnawi NY (1998) Sweet’s syndrome: is the pathogenesis mediated by helper T cell type 1 cytokines? J Am Acad Dermatol 39(6):940
Voelter-Mahlknecht S, Bauer J, Metzler G, Fierlbeck G, Rassner G (2005) Bullous variant of Sweet’s syndrome. Int J Dermatol 44(11):946–947
Mijovic A, Novak A, Medenica L (1992) Sweet’s syndrome associated with inversion of chromosome 3q in a patient with refractory anemia. Eur J Haematol 49(3):156–157
Takahama H, Kanbe T (2010) Neutrophilic dermatosis of the dorsal hands: a case showing HLA B54, the marker of Sweet’s syndrome. Int J Dermatol 49(9):1079–1080
Jo T, Horio K, Migita K (2015) Sweet’s syndrome in patients with MDS and MEFV mutations. N Engl J Med 372(7):686
Cohen PR, Kurzrock R (2002) Sweet’s syndrome: a review of current treatment options. Am J Clin Dermatol 3(2):117–131
Seminario-Vidal L, Guerrero C, Sami N (2015]) Refractory Sweet’s syndrome successfully treated with rituximab. JAAD Case Rep 1(3):123–125
Hashemi SM, Fazeli SA, Vahedi A, Golabchifard R (2016) Rituximab for refractory subcutaneous Sweet’s syndrome in chronic lymphocytic leukemia: a case report. Mol Clin Oncol 4(3):436–440
Agarwal A, Barrow W, Selim MA, Nicholas MW (2016) Refractory subcutaneous sweet syndrome treated with adalimumab. JAMA Dermatol. 152(7):842
Muhammed K, Nandakumar G, Thomas S (2004) Granulomatous cheilitis evolving into Melkersson-Rosenthal syndrome with bilateral facial palsy. Indian J Dermatol Venereol Leprol 70(5):313–314
Dummer W, Lurz C, Jeschke R, Meissner N et al (1999) Granulomatous cheilitis and Crohn’s disease in a 3-year-old boy. Pediatr Dermatol 16(1):39–42
Oliveira AM, Martins M, Martins A, Ramos de Deus J (2016) Granulomatous cheilitis associated with Crohn’s disease. Am J Gastroenterol 111(4):456
White A, Nunes C, Escudier M, Lomer MC, Barnard K, Shirlaw P et al (2006) Improvement in orofacial granulomatosis on a cinnamon- and benzoate-free diet. Inflamm Bowel Dis 12(6):508–514
Inui S, Itami S, Katayama I (2008) Granulomatous cheilitis successfully treated with roxithromycin. J Dermatol 35:244–245
Williams PM, Greenberg MS (1991) Management of cheilitis granulomatosa. Oral Surg Oral Med Oral Pathol 72(4):436–439
Fdez-Freire LR, Serrano Gotarredona A, Bernabeu Wittel J, Pulpillo Ruiz A, Cabrera R, Navarrete Ortega M et al (2005) Clofazimine as elective treatment for granulomatous cheilitis. J Drugs Dermatol 4(3):374–377
Hindryckx P, Novak G, Bonovas S, Peyrin-Biroulet L, Danese S (2017) Infection risk with biologic therapy in patients with inflammatory bowel disease. Clin Pharmacol Ther 102:633–641
Shah ED, Farida JP, Siegel CA et al (2017) Risk for overall infection with anti-TNF and anti-integrin agents used in IBD: a systematic review and meta-analysis. Inflamm Bowel Dis 357:570–577
Thayu M, Markowitz JE, Mamula P et al (2005) Hepatosplenic T-cell lymphoma in an adolescent patient after immunomodulator and biologic therapy for Crohn disease. J Pediatr Gastroenterol Nutr 40(2):220–222
Beaugerie L, Brousse N, Bouvier AM et al (2009) Lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study. Lancet 357:1617–1625
Seror R, Mariette X (2017) Malignancy and the risks of biologic therapies: current status. Rheum Dis Clin North Am 357:43–64
Axelrad J, Bernheim O, Colombel JF et al (2016) Risk of new or recurrent cancer in patients with inflammatory bowel disease and previous cancer exposed to immunosuppressive and anti-tumor necrosis factor agents. Clin Gastroenterol Hepatol 357:58–64
Shovman O, Tamar S et al (2018) Diverse patterns of anti-TNF-α-induced lupus: case series and review of the literature. Clin Rheumatol 37(2):563–568
Kemanetzoglou E, Andreadou E (2017) CNS demyelination with TNF-α blockers. Curr Neurol Neurosci Rep 17(4):36
Cleynen I, Van Moerkercke W, Billiet T et al (2016) Characteristics of skin lesions associated with anti-tumor necrosis factor therapy in patients with inflammatory bowel disease: a cohort study. Ann Intern Med 357:10–22
Guerra I, Pérez-Jeldres T, Iborra M et al (2016) Incidence, clinical characteristics, and management of psoriasis induced by anti-TNF therapy in patients with inflammatory bowel disease: a nationwide cohort study. Inflamm Bowel Dis 357:894–901
Mourad AA, Boktor MN, Yilmaz-Demirdag Y, Bahna SL (2015) Adverse reactions to infliximab and the outcome of desensitization. Ann Allergy Asthma Immunol 115(2):143–146
Rutgeerts P, Schreiber S, Feagan B et al (2008) Certolizumab pegol, a monthly subcutaneously administered Fc-free anti-TNFalpha, improves health-related quality of life in patients with moderate to severe Crohn’s disease. Int J Color Dis 23(3):289–296
Clowse ME, Wolf DC, Förger F, Cush JJ, Golembesky A, Shaughnessy L, De Cuyper D, Mahadevan U (2015) Pregnancy outcomes in subjects exposed to certolizumab pegol. J Rheumatol 42(12):2270–2278
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of Interest
There are no conflicts of interest relevant to this manuscript. However, for full disclosure, Dr. Clarke is on the speakers’ bureau for AbbVie, Takeda, and Janssen. In addition, he has served on an Ad Board for Pfizer.
Ethical Approval and Informed Consent
This is a review article; no patients were involved, and informed consent was not required. Permission was obtained for all images used and appropriate attribution/acknowledgement stated.
Disclosures
Speakers Bureau for Abbvie, Janssen and Takeda; Ad Board for Pfizer.
Rights and permissions
About this article
Cite this article
Clarke, K., Chintanaboina, J. Allergic and Immunologic Perspectives of Inflammatory Bowel Disease. Clinic Rev Allerg Immunol 57, 179–193 (2019). https://doi.org/10.1007/s12016-018-8690-3
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12016-018-8690-3