Introduction frequent diarrhea are the main symptoms that

Introduction

Inflammatory bowel disorder has two main components which include ulcerative colitis and Crohn’s disease (Baumgart & Sandborn, 2012). Crohn’s disease is a condition that is featured by chronic gastrointestinal (GI) inflammation. The inflammation can occur anywhere along the gastrointestinal tract and mostly occurs at the terminal of the small intestine, ileum terminalis, in small patches or stenotic presentation. Approximately seven hundred thousand people, both men and women, are affected by Crohn’s disorder in the U.S and studies indicate that a large percentage of these people have at least one relapse in every 5 years after treatment (Baumgart & Sandborn, 2012). Crohn’s disease can occur any time throughout a person lifetime but most often it starts between ages fifteen and thirty-five. There has been an increasing incidence of the disease globally (Baumgart & Sandborn, 2012) as witnessed in various countries that are undergoing urbanization (Torres, Mehandru, Colombel, & Peyrin-Biroulet, 2017). Even though the exact causes of the disease are unknown, studies indicate that a combination of factors that involve a disturbed immune system, the environment and genetics play an important role in its aetiology.

Evidence based diagnosis methods for a patient with the disease show that it is characterized by symptoms such as mucus or blood in stool, frequent diarrhea, severe abdominal pain, intestinal infections and inconsistent cramps among other symptoms. There are several diagnostic approaches for detection of the disease that combines both the physical findings and medical history to obtain a purposeful data from experiments and imaging studies (Baumgart & Sandborn, 2012).

 

Pathogenesis

Since Crohn’s disease is a progressive disorder of the gastrointestinal (GI) tract and affects all the parts from mouth to colon, the condition is classified as a chronic disease and needs immediate, interdisciplinary and integral medical attention. Abdominal pains and frequent diarrhea are the main symptoms that characterize the disease and help to its characterization by Dr. Burrill Crohn (Mazal, 2014). There have been several sub-types of the disease that have been identified according to the morphological area that has been affected the most. Globally, it has been embraced that the disorder is due to disturbed mucosal immune function to the normal flora along the GI tract as well as other antigens present (Mazal, 2014; Torres et al., 2017). The main cause of Crohn’s disease is not well understood but there are related combinatorial factors in the gastrointestinal tract that demonstrate the cause of the disorder(Torres, Mehandru, Colombel, & Peyrin-Biroulet, 2016). 

Causes of Crohn’s Disease

Breakdown of balance between the native micro flora and an individual’s mucosal immunity is one of the major causes of the disorder(Schreiber, Rosenstiel, Albrecht, Hampe, & Krawczak, 2005). The epithelial wall along the GI tract acts as a barrier acting as one of the most critical areas that mucosal malfunction is likely to occur (Mazal, 2014). The intestinal wall has five layers where by individuals who are likely to be diagnosed of the disease usually have an epithelial layer that has enhanced permeability, thus,  allowing foreign pathogens to pass through to the other four layers which are highly permeable (Baumgart & Sandborn, 2012). Immune response might later be triggered due to the intrusion of these microbes to the mucosal layer and therefore the inflammatory system activated (Lewis & Bleier, 2013). Toll-like pattern recognition receptors (TLRs) are found throughout the GI epithelium wall and their role is to identify the antigens present. Disruption of this layer hereafter can lead to immune malfunction as the receptors will experience a variation in their concentration in the affected region(Baumgart & Sandborn, 2012). TLR-5 and TLR-3 are usually present in high numbers in a healthy individuals while fewer in patients with Crohn’s disease. An uncontrolled inflammatory response later occurs in such a situation due to the hypersensitivity to the sudden exposure to foreign antigens (Torres et al., 2016). Another complication also arises when the mucosa layer is incapable of suppressing the reinforced immune response. Immune cells such as the white blood cells undergo uncontrolled active replication and are not cleared properly from the body as they resist the programmed cell death (Baumgart & Sandborn, 2012; Mazal, 2014). These cells play a crucial role in cell-mediated immunity and as such, the malfunctioning of the mucosa membrane and disruption of the immune system leads to other associated primary risk factors (Mazal, 2014).

Studies have identified genetics as one of the major risk factors for the disease. Identical studies in twins in northern Europe indicated the role of familial aggregation as a major indicator of a genetic component of the disorder (Schreiber et al., 2005). A smaller percentage of dizygotic twins as compared to monozygotic pairs were linked to Crohn’s disease. It is estimated that twelve percent of the patients have a history of the disease within their family (Torres et al., 2017). The disease has also been highly linked to particular ethnic groups such as the Ashkenazi Jews where studies indicate that there is a high prevalence on individuals with a Jewish decent (Baumgart & Sandborn, 2012). The susceptibility loci on 17 chromosomes have been observed through genome wide analysis which have described the disease as polygenic (Schreiber et al., 2005). Non-synonymous  single nucleotide polymorphisms (SNPs) have been  used to identify the substantial linkage of rs2241880 gene and Crohn’s disease (Hampe et al., 2007).

           Another example is the expression product of IBD1 gene in chromosome 16, NOD2 that is associated with the unsuppressed inflammatory response as well as the control of macrophages production (Hugot, Chamaillard, & Zouali, 2001; Nakamura, 2002).  The identification of these genes in 71 positions within these chromosomes has opened ways for further research in the critical and disrupted pathways of the immune system in the intestine (Nabhani, Dietrich, Hugot, & Barreau, 2017).  The discovery of these crucial genes has enabled further understanding the underlying mechanisms of the disease has given rise to development of new therapeutics (Nabhani et al., 2017; Schreiber et al., 2005). Genetic polymorphisms on the TLRs along the affected gastrointestinal tract have also been identified as primary risk factors of the disease. Other genes associated with the innate immunity such as IRGM and NOD2 linked to the function of Th17-cell have also been discovered and have given rise to major insights on the etiology of the disease (Nabhani et al., 2017).

          There exist several environmental factors of Crohn’s disorder and have been identified to be highly involved as a trigger for the manifestation of genetic mutations along the gastrointestinal tract. According to Mazal et al., the incidence rates of the disease vary from one region to the other all over the world (Mazal, 2014). Study reports have indicated an increase in the diagnosis cases in low-prevalence areas while the incidence rates in the regions with high-prevalence are stable (Baumgart & Sandborn, 2012). Countries that have a high occurrence rate include the United States and those in the northern part of Europe while those in the southern hemisphere such as China and Argentina have a low prevalence rate. However new studies have indicated that the incidence rates on the southern hemisphere countries and those in the northern hemisphere are similar as such indication no major gradient between the two regions (Baumgart & Sandborn, 2012; Mazal, 2014; Torres et al., 2017).

          The socioeconomic status of a defined population is also one of the environmental risk factors involved. Some rural communities in countries like China lack access to good healthcare facilities as well as standard sanitation. Crowded living conditions and intake of contaminated water and foods are some of the situations that are highly associated with the disease (Gent, Hellier, Grace, Swarbrick, & Coggon, 1994). Another potential factor linked to Crohn’s condition is a diet majorly composed of excessive protein from milk and meat as well as a reduction in fiber consumption. Polyunsaturated fatty acids have a positive correlation with the disease (Baumgart & Sandborn, 2012). The best studied environmental factor that has proven to have a positive correlation to the disease is cigarette smoking. Studies have indicated that individuals who consume tobacco excessively are at a double risk of developing the disease. Children exposed to strong antibiotics at an early age are prone to developing the disease. Several drugs have also been linked as potential factors in increasing the risk which include; aspirin and other birth control pills (Baumgart & Sandborn, 2012; Torres et al., 2017).

 

Complications of Crohn’s Disease

          The Vienna Classification was developed to display all the physical manifestations of the Crohn’s disease according to the area affected as well as the effect it brings about (Louis et al., 2001). A complication that occurs at the end of the small intestine is referred to as Crohn Ileitis and is the most frequent among patients with a percentage of forty seven percent (Torres et al., 2017). Manifestation in the colon is known as Crohn’s colitis while an affected upper GI tract is known as Crohn’s disease of the esophagus which occurs at a percentage of 28% and 3% respectively of the patient cases. Studies also categorized the disease as penetrating, non-penetrating and stricturing (Baumgart & Sandborn, 2012).

          Since the disorder is progressive and chronic, patients with Crohn’s disease often experience major complications as the inflammatory response is triggered on other parts of the bowel. The immune system of the body is activated when bacteria reaches the mucosa layer. Due to this action, the inflammatory cascade migrates to the mucosal layer in the intestine from the vascular system. Tissue damage then occurs as a result of presence of metabolites such as histamines released at the location of inflammation (Hugot et al., 2001; Nabhani et al., 2017). The intestinal pathway blocks for patients who develop a narrower lumen as such developing a mechanical obstruction that needs an emergency medical attention. In other situations, the colon becomes excessively dilated such that the bowel perforation increases causing septic shock(Lewis & Bleier, 2013). Another effect is aggressive inflammation in the deep layers of the intestinal surface. The inflammation starts from the epithelial layer to the serosa layer which forms the base of progression of Crohn’s disorder and later causing a disorder called serotosis (Baumgart & Sandborn, 2012).

          During the early stages of the disease, ulcers may develop and as the disease develops, the sores form a longitudinal linear feature that resembles a fissure filling the entire surface of the affected organ tissue. Fistulae can develop as well leading to excessive blood loss that can result to anemic conditions. It is estimated that approximately 29% of Crohn’s disease patients develop fistulae as the disease progresses (Bass et al., 2012) Several comorbidities along the GI tract are associated with the disease and patients are at a higher risk of contracting related diseases. Since a patient develops complications in digestion and disruption of absorption at the epithelial layer, he /she may suffer from malnutrition as a result of reduced food consumption(Bass et al., 2012).

 

 

Diagnosis

The clinical manifestation of the disease is based on the area affected along the gastrointestinal tract as well as the intense of the inflammatory reaction on the mucosal layer (Louis et al., 2001). Physical examination is performed so as to check on any signs of malnutrition, anemia or dehydration (Baumgart & Sandborn, 2012).  Body temperatures are also checked to assess presence of high fever since it is a way of detecting a bowel complication (Torres et al., 2017). Perianal region of a patient exhibiting suspected symptoms of Crohn’s disease should be examined carefully since the region can display skin sores that are as a result of fistulae and ulcers (Panés et al., 2011). A clinician should listen to the patient’s abdominal sounds since percussion can disrupt the pattern and frequency of the sounds made by the abdomen (Panés et al., 2011). Body mass index, heart rate and weight are also examined for clinical record purposes. Both the physical examinations and other laboratory tests provide an objective data that is useful in the diagnosis of the disease.

Laboratory tests are conducted after yielding information from the physical examination and the patient’s history determination. The most essential and routine laboratory test is the total white blood cell (WBC) count (Stein, Hartmann, & Dignass, 2010). This test has two goals where one is to measure the concentration of leukocytes in the blood while the other is to measure the amount of each type of these cells within the same blood sample. An increase in the leukocytes concentration in the blood indicates presence of an infection of unsuppressed inflammation. However, the test should be done serially at different times of the day due to variations in concentration so as to give an average count.  C-reactive protein (CRP) is another laboratory examination done to check on the concentration of the protein that is usually produced in low amounts within the hepatocytes of healthy individuals. Inflammatory diseases and abdominal infections are confirmed by a clinician through the presence of elevated levels of these proteins(Mazal, 2014). Erythrocyte sedimentary rate (ESR) is also an examination method where a blood sample of a suspected patient is placed is placed in a saline solution and the rate of settling of the red blood cells over a certain period is determined. Inflammatory diseases and infections along the GI tract increase the fibrinogen content within the red blood cells as such, the cell aggregate together and with the higher density, they move to the bottom of the saline water or plasma faster (Mazal, 2014).

Various imagine methods are required to confirm the presence of the disease in a suspected patient. Radiography is one of the imaging methods used to confirm the presence of Crohn’s disease (Panés et al., 2011). Radiographs of abdominal region are obtained using an x-ray, whereby large amounts of stools in the colon and a dilated bowel can be observed in patients with symptoms such as diarrhea, vomiting or abdominal pains (Mazal, 2014; Panés et al., 2011). Computed tomography (CT) scan is also a useful technique in the diagnosis of Crohn’s disease. CT gives multiple images that show the entire abdominal cavity, the bowel size, as well as capturing the presence of any lesions on the intestinal wall. However, the CT scan procedure has its own disadvantages in that during the patient’s examination, he/she is exposed to some sort of radiation making other forms of imaging that use less radiation more applicable. Another disadvantage is that the method creates diagnostic indications even in the presence of loops of the abdomen as such giving a wrong diagnosis or a wrong pathology (Mazal, 2014; Panés et al., 2011).

Magnetic resonance imaging (MRI) gives several images of the pelvic region as well as the abdomen. Peristalsis and Crohn’s disease can be differentiated using this technique unlike when using the CT scan that artifacts from breathing. Furthermore, the method can display all the lesions and cysts that characterize abnormalities as well as reducing exposure of radiation to the patient. Ultrasonography is also a radiation-free imaging technique that uses sound waves to detect the presence of Crohn’s disease that is associated with liver diseases (Panés et al., 2011). However, the method has its limitation such as the inability to detect the lesions and infections  along the GI tract especially for obese patients (Mazal, 2014).   Endoscopy is a standard procedure for all patients with Crohn’s disease. Each patient is required to undergo a full ileocolonoscopy (Baumgart & Sandborn, 2012). Operative enteroscopy is applicable in cases where a further examination of the small intestine is needed in areas that are not feasible by the fiber-optic camera through the anus. This is done by an incision being made on the surface of the patient’s abdomen to examine the serosal surface(Lewis & Bleier, 2013).

Conclusion

Despite the major complications caused by the disease, there are remedies both modern and traditional put in place to help patients who suffer from the disease.  Drugs are prescribed according to the progress of the disease or the level reached shown through diagnosis. Sulfasalazine and corticosteroids are inflammatory drugs used to control the aggressive inflammation response. Other drugs include immunomodulators and antibiotics such as ciprofloxacin which prevent bacteria from penetrating thought the intestinal wall(Torres et al., 2017). Surgical procedures in severe cases is recommended such as anal fistula plug and fistulotomy (Lewis & Bleier, 2013). Surgical intervention for treating Crohn’s disease is perfumed at least once in every patient and is usually common to those who do not respond positively to the pharmacological therapeutics available (Mazal, 2014).