Crohn’s Disease: Etiology, Incidence, Precipitating Factors, Complications, Prognosis, Iatrogenic, Sequalae

This article provides an overview of Crohn’s Disease, including its etiology, incidence, precipitating factors, complications, prognosis, iatrogenic, and sequalae. It discusses the role of environmental factors, genetic predisposition, and microbiota in the development of Crohn’s Disease. The article also explores the various complications, risk factors, and long-term outcomes associated with this inflammatory bowel disease.

Crohn’s Disease
Etiology
The complete etiology of Crohn’s disease is grossly unidentified. However, intestinal
microbiota’s immune dysregulation response and its consistent interaction with environmental risk
factors and genetic predisposition lead to the development of Crohn’s disease (Ha & Khalil, 2015).
The environmental factors responsible for Crohn’s disease development include intestinal infections,
toxins, and drugs. The phenotypes’ genetic associations are also responsible for Crohn’s disease
onset in predisposed individuals. Crohn’s disease phenotypes in many clinical scenarios are related
to CARD15/NOD2 mutations that impact young patients and lead to the development of ileal
complications (Ranasinghe & Ronald, 2019). The stimulation of gut responses in Crohn’s disease is
based on gut microbiota’s disbalance under the impact of mucosal barrier’s perturbance. Microbial
stimulation under the impact of environmental factors not only triggers dysbiosis but also
deteriorates the T-cell function, antigen presenting cells, and normal epithelial physiology of the
intestine (Boyapati, Satsangi, & Ho, 2015). The impairment of antimicrobial peptide and mucous is
followed by pro-inflammatory epithelial outcomes, immunogenic triggering, and endogenous
damage-associated molecular pattern release. The episodes are followed by defective bacterial
killing, bacterial intolerance, inappropriate bacterial handling, innate-adaptive immune crosstalk
deterioration, unrestricted Th17 activation, and immunoregulatory response deterioration (Boyapati
et al., 2015).
Incidence
The greatest incidence of Crohn’s disease is reported in northern Europe, North America,
and the United Kingdom. A 4.6-6.2 times elevation in incidence rates of Crohn’s disease in women as
compared to men is reported in various developed nations. Crohn’s disease predominantly impacts
women and men of age group 15-29 years at the incident rates of 9.1 and 5.3 respectively. The
incidence rate of Crohn’s disease across the United States, Minnesota, and Olmsted County is

reported to be 5.7 patients (for every 100, 000 person-years). Evidence-based findings reveal a
substantial elevation in Crohn’s disease’s incident rates during the past several years (Hovde &
Moum, 2012). However, the reported differences in Crohn’s disease incidence rates are based on
reported variations/inconsistencies in epidemiological studies types, study design, and diagnostic
tools.
Precipitating Factors
The precipitating factors of Crohn’s disease include exercise, smoking, infections,
environment, hygiene, diet, drugs, and stress (Boyapati, Satsangi, & Ho, 2015). Other risk factors
include oral contraceptive utilization, depression, psychosocial stress, NSAID use, dietary animal
protein consumption, appendectomy status, and cigarette smoking. Smoking substantially
deteriorates the configuration of the intestinal microbiome in a manner that elevates the production
of free radicals (Ananthakrishnan, 2013). The eventual development of oxidative stress and intestinal
immunity reduction induces the onset of Crohn’s disease in the affected patients.
Complications
Crohn’s disease complications are based on several comorbidities including bowel
obstruction, digestive tract ulcers, fistulas, anal fissure, malnutrition, colon cancer, liver disease,
arthritis, osteoporosis, skin disorders, abscesses, intra-abdominal inflammatory masses, and anemia
(Thia, Sandborn, Harmsen, Zinsmeister, & Loftus-Jr, 2010). One-fifth of the patients affected with
Crohn’s disease vitamin B12 deficiency as a result of a reduction in the absorptive capacity of their
terminal ileum (Donnellan, Yann, & Lal, 2013). Similarly, vitamin A deficiency in Crohn’s disease
patients increases their risk for night blindness. Mucosal inflammatory mediators’ immune
responses, epigenetic alterations, and genetic instability include some of the significant factors that
elevate the prevalence and incidence of colorectal cancer in Crohn’s disease patients (Kim & Chang,
2014). Biliary tract disorders prove to be Crohn’s disease’s extraintestinal complications (Rojas-Feria,
Castro, Suarez, Ampuero, & Romero-Gómez, 2013). The cutaneous manifestations of Crohn’s

disease include pyoderma gangrenosum and erythema nodosum (Peluso, Manguso, Vitiello,
Iervolino, & Minno, 2015). Other extraarticular complications include cardiac symptoms,
genitourinary inflammation, eye problems, and mucous membrane lesions. Furthermore, iron
deficiency anemia is a predominant outcome in most of Crohn’s cases and develops under the
impact of tissue inflammation-related iron absorption impairment and chronic blood loss (Kaitha,
Bashir, & Ali, 2015).
Prognosis
The gastrointestinal tract’s transmural inflammation under the impact of Crohn’s disease
leads to the development of various intestinal or colonic complications (Peppercorn & Kane, 2019).
For example, small bowel engagement in Crohn’s disease predominantly impacts the distal ileum of
the affected patients. However, 50% of Crohn’s disease patients exclusively develop ileitis, ileocolitis,
and related complications (Peppercorn & Kane, 2019). 20% of Crohn’s disease patients do not
experience any clinical manifestation outside their colonic region. Approximately, half of Crohn’s
disease patients rarely experience any rectal complication or related comorbidity. However, perianal
disease impacts more than one-third of the patients affected with Crohn’s disease.
Iatrogenic
Iatrogenic perforations are reportedly tracked in 3% of Crohn’s disease cases (Bessissow,
Reinglas, Aruljothy, Lakatos, & Assche, 2018). The administration of immunosuppressants
substantially elevates the risk of iatrogenic complications in Crohn’s disease patients (Feuerstein &
Cheifetz, 2017). Iatrogenic and intercurrent infections in many clinical scenarios barricade the
differentiation of Crohn’s disease from ulcerative colitis (Hanauer, 2019).
Sequalae
Crohn’s disease sequelae are based on acute flare-ups (of chronic disease) or the
development of mild gastrointestinal symptoms (Cosnes et al., 2012). Immunosuppressant therapy,

prior intestinal surgery, rectal disease, intestinal ulcers, the patients’ education level, and other
maintenance therapies variably lead to the development of sequelae in Crohn’s disease cases. Other
recurrent and long-term sequelae include bile duct carcinoma, cirrhosis, chronic active hepatitis,
cholelithiasis, primary sclerosing cholangitis, pericholangitis, hypercoagulable state, and aphthous
ulcers.

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