Kembara Xtra - Medicine - Crohn Disease

Kembara Xtra - Medicine - Crohn Disease 
​A condition of the gastrointestinal tract that is chronic and gets progressively worse over time. It most frequently affects the terminal ileum (80% of the time).
Characteristics that are unique to people with Crohn disease (CD)
- Inflammation that spreads throughout the mucous membranes and can lead to fibrotic strictures, fistulas, fissures, or abscesses
- Granulomas that are not caseating (30%)
- Skip lesions are characterized by diseased mucosa that is alternated with normal mucosa. These lesions can be continuous and provide the appearance of ulcerative colitis (UC).
– Variable clinical manifestations, include ileitis (1/3) and ileocolitis (1/3) as well as colitis (1/3) on its own.


Epidemiology (Incidence and Prevalence) 
Bimodal age distribution: the predominant age range is 15 to 30 years, with a second, lesser peak at 50 to 80 years. Incidence: 3 to 20 instances per 100,000 person-years in North America; incidence is rising globally.
• Women are somewhat more likely to be affected than males; the frequency of the disease is higher in northern climates • The risk of the disease is two to five times higher in whites than in nonwhites
Prevalence 247 cases per 100,000 individuals


Causes and effects: etiology and pathophysiology 

 In a general sense, clinical manifestations are the end result of the activation of inflammatory cells, which is followed by tissue damage.
Inflammation and tissue injury are caused by a combination of multiple factors, including genetics, environmental stimuli, commensal microbial antigens, and immunologic disorders.

A first-degree relative of a person who has inflammatory bowel disease (IBD) has a three- to thirtyfold greater chance of having IBD by the age of 28 years. Genetics Fifteen percent of people who have Crohn's disease have a first-degree family who has IBD.
The Turner syndrome, the Hermansky-Pudlak syndrome, and glycogen storage disease type 1b are associated genetic syndromes.

factors of danger 
Environmental factors
Quitting smoking can lessen the severity of CD symptoms and symptoms of flare-ups and relapses. Cigarette smoking more than doubles the risk of developing CD.
Dietary factors: greater prevalence if diet high in processed or ultraprocessed foods, animal fat or protein, or refined carbohydrates

Conditions That Often Occur Together 

 Arthritis (20%): seronegative, small and big joints (ankylosing spondylitis [AS] or sacroiliitis [SI], related with HLA-B27); extraintestinal symptoms
- Skin problems (10%): erythema nodosum, pyoderma gangrenosum, psoriasis
— Diseases of the eye (five percent), including uveitis (related with HLA-B27), iritis, and episcleritis
- The most common types of kidney stones are calcium oxalate stones (caused by steatorrhea and diarrhea) and uric acid stones (caused by dehydration and metabolic acidosis).
- Low calcium levels (hypocalcemia), osteopenia, and osteoporosis
- Hypercoagulability: It is crucial for hospitalized patients to get prophylaxis against venous thromboembolism
- Gallstones are cholesterol stones that develop when bile acid reabsorption in the gallbladder is hindered.
- Primary sclerosing cholangitis (PSC), which accounts for 5% of cases
Peripheral arthropathy, not SI and AS, is one of the conditions linked to higher disease activity.
- Episcleritis (not uveitis)
- Aphthous ulcers of the mouth as well as erythema nodosum
GI bleed, toxic megacolon, bowel blockage, bowel perforation, peritonitis, malignancy, intra-abdominal fistula, and perianal disease are some of the complications that can arise.
DIAGNOSIS HISTORY
Symptoms include crampy abdominal pain (which may or may not be accompanied by bleeding), persistent diarrhea, exhaustion, loss of weight, fever, and perianal illness. Children could show symptoms of not growing or developing normally.
● Concurrent infections, smoking, nonsteroidal anti-inflammatory drugs (NSAIDs), antibiotics, and stress can all make CD symptoms worse.

Clinical Examination 

The manifestation of the disease differs depending on its location.
Abdominal: focal or diffuse tenderness, distension, rebound/guarding, rectal bleeding, palpable mass Perianal: fistulae, fissures, abscess Skin: erythema nodosum, pyderma gangrenosum; psoriasis

Differential Diagnosis Acute and severe stomach pain: ruptured viscus, pancreatitis, appendicitis, diverticulitis, intestinal blockage, kidney stones, and ovarian torsion ovarian torsion
Diarrhea that lasts for an extended period of time and is accompanied by cramping discomfort (colitis-like): UC, radiation colitis, infection, medications, ischemia, microscopic colitis, inflammatory bowel disease (IBD), celiac disease, malignancy (lymphoma, carcinoma), carcinoid, segmental colitis linked with diverticulosis.
● Wasting illness: malabsorption, malignancy


Results From the Laboratory Initial Examinations (lab, imaging)
CBC, serum chemistries, LFTs, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), serum iron, vitamin B12, vitamin D-25 OH, and stool calprotectin If diarrhea, a stool specimen for routine culture, Clostridium difficile, and ova and parasites in at-risk populations With severe flares, a KUB to rule out toxic megacolon.
Ileocolonoscopy has the highest diagnostic sensitivity and specificity; mucosal biopsies can be taken from both normal and diseased tissue.
Upper endoscopy for patients who have signs or symptoms related to the upper gastrointestinal tract- Upper gastrointestinal tract CD symptoms include antral constriction, segmental constriction, and inflammatory mucosa
sensitivity of CT or magnetic resonance enterography (MRE) better than small bowel follow through for the small bowel. MRE does not expose patients to radiation, which is especially significant for younger patients. Capsule endoscopy permits sight of the small bowel but does not allow for biopsy.
Symptoms of small bowel disease include a constricted lumen with nodularity (the string sign), a separation of the bowel loops (indicating transmural inflammation), and an enhanced enhancement or thickness of the intestinal wall that signals inflammation.
● Perianal disease: endoscopic ultrasound (EUS) or MRI
pelvis, exam under anesthesia
● Contraindications to endoscopy: perforated viscus, recent
myocardial infarction, severe diverticulitis, toxic
megacolon

● In some cases, unprepared limited sigmoidoscopy allows
adequate visualization to assess severity, extent, aspirate
stool for C. difficile, obtain biopsies to assess histologic
severity, and exclude other disorders (e.g.,
cytomegalovirus) in CD.

Additional Assessments, as well as Other Important Factors
Indications of the existence of problems
- Constriction: obstructive symptoms such as nausea, vomiting, pain, decreased body weight, diarrhea, or an inability to pass gas or feces
– Abscess or inflammatory mass: localized abdominal peritonitis with fever and abdominal discomfort; generalized peritonitis suggests perforation or abscess rupture (may be masked by steroids or opiates). – Peritonitis of the peritoneum (peritonitis of the peritoneum) with or without fever.
– Fistula:
 Enteroenteric: characterized by the absence of symptoms or the presence of a palpable, though typically subdued, abdominal mass
○ Enterovesicular: pneumaturia, recurrent UTI
○ Retroperitoneal: psoas abscess, ureteral blockage
 Enterovaginal: the passage of gas or feces into the vaginal canal; drainage from an ileal fistula that is clear and nonfeculent (which can be mistaken as a primary vaginal infection).
The goals of treatment are to achieve steroid-free clinical remission as well as biochemical (CRP and ESR), as well as biologic (calprotectin), remission.
— Radiologic reaction as determined by ultrasonic imaging or cross-sectional imaging
– The endoscopic response and remission rate (2) – Symptoms may not correlate with the activity of the disease; therefore, objective testing (biomarkers, imaging, endoscopy) is essential.

Diagnostic Methods and Other Procedures
How to differentiate between CD and UC:
Crohn's disease: illness of the small bowel or colon, rectal sparing; skip lesions; granulomas, perianal fistula or abscess; RLQ discomfort; rectal bleeding is rare.
UC is characterized by continuous colonic involvement, including the rectum; pain in the lower right quadrant; and frequent rectal bleeding.
The symptoms of ALERT CD can be quite similar to those of UC, and in 10–15% of instances, the two conditions are difficult to separate.

Disease activity can be measured using the Harvey Bradshaw Index or the Crohn Disease Activity Index (CDAI). Management

 Disease severity: risk stratification for rapidly progressive disease – Risk factors for high-risk disease: age at diagnosis 30, extensive anatomic involvement, perianal or severe rectal disease, deep ulcers/severe endoscopic disease, prior surgical resection, stricturing/penetrating behavior, extraintestinal manifestation Disease severity: risk stratification for slowly progressive disease
Disease severity takes into account longitudinal factors and prognosis, whereas disease activity is a one-time assessment of symptoms. Decisions about therapy should be driven by disease severity and risk assessment.
Budesonide or prednisone taper, with or without immunomodulator, for patients with low-risk diseases
For patients with a moderate to high risk illness, either biologic monotherapy or biologic combination therapy with an immunomodulator is recommended.


Medication 
CD ranging from mild to moderate
Asymptomatic patients with minor endoscopic illness are treated with observation alone. Mesalamine has no place in the treatment of CD.
Antibiotics are not advised in this case.
– Induction: Controlled ileal release budesonide (9 mg/day for 8 weeks, followed by discontinuation over a 2-week taper) for involvement of the distal ileum and/or right colon OR prednisone taper
- During maintenance, you should stop the treatment and either study the patient or think about immunomodulator or biological therapy.
CD ranging from moderate to severe
- The beginning:
 The use of biologics as the primary induction agent in order to avoid the use of corticosteroids
 It is possible that budesonide or prednisone at a dosage of 40 to 60 mg per day will be required in the near term to alleviate symptoms.- Maintenance: ○ No role for mesalamine
If steroids are necessary for the induction process, you may want to explore using a biologic and/or immunomodulator.
● Immunomodulators:
– Thiopurines: azathioprine or 6-mercaptopurine for maintenance, but none of them for induction (1) [C]
– Methotrexate (intramuscular or subcutaneous) is a successful treatment for the induction and maintenance of steroid-dependent CD (1)[C]. It should be taken in conjunction with folic acid at a dosage of 1 mg per day.
● Anti–tumor necrosis factor (anti-TNF): infliximab, adalimumab, certolizumab pegol for induction and maintenance (1)[A],(3)[A]
Before beginning anti-TNF treatment, it is important to get a TB test and an HBV test.
Combination therapy with anti-TNF and an immunomodulator — Compared to either of these treatments alone, combination therapy with an immunomodulator at a standard dose is more effective.
Combining anti-TNF with a low dose of an immunomodulator lowers the risk of developing an immune response to anti-TNF.
Hepatosplenic T-cell lymphoma is a deadly complication that can occur in young males after receiving anti-TNF and thiopurine treatment.

vedolizumab for the induction and maintenance of antileukocyte trafficking— Selective for the gastrointestinal tract; does not pose a threat of progressive multifocal leukoencephalopathy (PML).
Anti–IL-12/IL-23: ustekinumab for induction and maintenance of remission

First Line
Patients with moderate to severe CD who have never taken biologic medicines before:
● Infliximab, adalimumab, or ustekinumab recommended over certolizumab to produce remission
It is recommended that vedolizumab be used rather than certolizumab in order to promote remission.
Two-Thirds Line
Patients with moderate to severe CD who have never responded to anti-TNF therapy and are considered to have primary nonresponse:
It is recommended to use ustekinumab in order to induce remission.
It is suggested that vedolizumab be used rather than no therapy in order to induce remission.
Patients with moderate to severe CD who had previously reacted to anti-TNF but have not responded this time (secondary nonresponse):
It is recommended to use adalimumab or ustekinumab in order to induce remission.
It is suggested that vedolizumab be used rather than no therapy in order to induce remission.

Extra Medical Interventions 
Oral lesions can be treated with triamcinolone acetonide with benzocaine and carboxymethyl cellulose or topical sucralfate for cheilitis and aphthous ulcers.
Gastroduodenal CD: Case reports demonstrate that anti-TNF medication is successful; symptomatic alleviation may be attained with the use of proton pump inhibitors, H2 receptor blockers, and/or sucralfate.
Follow-up Be sure to check your CBC, BMP, and LFT levels every three to four months.
Perform active monitoring of the disease every six months using CRP and/or calprotectin.
Before beginning treatment with azathioprine or 6-mercaptopurine, it is important to monitor the TPMT/NUDT15 genotype and activity, as well as the levels of thiopurine metabolites one month later.
Monitoring of the Patient
● Vaccinations – Check titers; avoid live vaccines (MMR, varicella, Zostavax) in patients on immunosuppressive medication.
– The COVID-19 vaccine is suggested for all inflammatory bowel disease (IBD) patients, regardless of immunosuppression, in addition to the following vaccinations: HPV, influenza, pneumococcal, meningococcal, hepatitis A and B, Tdap, and varicella zoster for individuals younger than 18 years old.
Bone health – Calcium and vitamin D supplementation with each course of corticosteroids or if vitamin D deficient – Bone density assessment if previous steroid use, maternal histor Cancer prevention – Colonoscopy with targeted biopsies every 1 to 5 years after 8 to 10 years of CD with colonic involvement; consider chromoendoscopy if available (4)[C]; in PSC patients, annual screening colonoscopy recommended – Annual

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