Inflammatory bowel disease.2014

Clinical Case C.M., a 25-year-old female college student, has had episodic, watery diarrhea

and colicky abdominal pain relieved by defecation for the past 9 months. Eight weeks before, the diarrhea increased to 3 to 5 semi-formed stools

daily. The frequency of the stools gradually increased to 5 to 10 times a day 1 week ago.

At that time, C.M. noted bright red blood in the stools. She feels a great urgency to defecate, even though the volume is small. No H/O recent infection or travel to endemic area. C.M. complains of anorexia and a 10-lb weight loss over the past 2 months. For the past 4 months, she has had intermittent swelling, warmth, and

tenderness of the left knee, which is unassociated with trauma. C.M. appears to be a slightly anxious and tired young woman of normal body

habitus. Her temperature is 100°F; her pulse rate is 100 beats/minute and regular Physical examination is normal, except for evidence of acute arthritis of the left

knee and tenderness of the left lower abdomen to palpation. Stool examination shows a watery effluent that contains numerous red and

white cells with no trophozoites. Stool cultures and an amebiasis indirect hem-agglutination test are negative.

04/12/23 Dr Afzal Haq Asif 1

Clinical CaseLaboratory Data include hematocrit (HCT), 32% , hemoglobin

(Hgb), 8.5 g/dL ; white blood cell (WBC) count, 15,000/mm3

with 82% PMNs ; ESR, 70 mm/hour ; serum albumin, 2.4 g/dL and alanine aminotransferase (ALT), 55 U/mL

Sigmoidoscopy showed evidence of granular, edematous, and friable mucosa with continuous ulcerations extending from the anus throughout the colon.

What is the most likely cause of C.M.'s diarrheal illness, and what is the evidence for this?

How should the signs and symptoms be managed and

monitored?


Reference: Pharmacotherapy: Pathophysiologic approachApplied TherapeuticsAnn Gastroenterol 2011; 24 (3): 164 -172http://ocw.tufts.edu/Content/48/lecturenotes/571273

ILO’sDefine IBD and its typesDifferentiate between UC and CDDiscuss the proposed etiologies of inflammatory bowel

disease (IBD).Identify the common extra-intestinal manifestations

associated with IBD.Describe the typical clinical presentation of UC and CD, Describe the major complications of IBD and their

management.Formulate treatment goals for management of patients

with active IBD.Discuss the role of nutritional and surgical interventions

in the management of patients with IBD.


ILO’sExplain the pharmacologic options for

remission for patients with active UC or CD.

List the main adverse effects of drugs usedConstruct monitoring plan for evaluating

the efficacy and toxicity of Drugs used



Forms of IBD“The two clinically distinguished forms of

inflammatory bowel diseases (IBD), which are chronic remittent or progressive inflammatory diseasesCrohns disease (CD)

affect the gastrointestinal tractUlcerative colitis (UC)

only the colonic mucosa. Both genetic and environmental factors

contribute to the pathophysiology of IBD”


Two Forms of IBDUlcerative Colitis, a mucosal inflammatory

condition confined to the rectum and colon

Crohn's disease, a transmural inflammation of gastrointestinal (GI) mucosa that may occur in any part of the GI tract

The etiologies of both conditions are unknown, but may have a common pathogenetic mechanism.



Ulcerative colitis is categorized according to location: Proctitis involves

only the rectum Proctosigmoiditis

affects the rectum and sigmoid colon

Left-sided colitis encompasses the entire left side of the large intestine

Pancolitis inflames the entire colon


Crohn


Crohn’s Disease

EpidemiologyMost common in Westernized countries such as the United

States. UC affects up to 500,000 people and CD affects up to 480,000

people in USThe age of initial presentation of IBD is bimodal,

between the age ranges of 20 to 40 years or 60 to 80 years.5 The peak incidence of CD occurs in the second and third decades of

life, with a smaller peak in the fifth decade.2,5 Peak incidence of UC occurs between the ages of 15 and 25 years.6

Men and women are approximately equally affectedWhites are affected more often than blacks, Jewish have higher incidences of IBD. Greatest risk factors is a positive family history of the disease. The incidence of IBD is 10 to 40 times greater in patients with a

first-degree relative who has IBD compared to the general population




Etiological Factors for IBDInfectious agents

Viruses (e.g., measles) L-Forms of bacteria L form of bcteria Mycobacteria Chlamydia

Genetics Metabolic defects(Crohn’s disease in Galactosemia, glycogen storage disease) Connective tissue disorders

Environmental Factors Diet Smoking (Crohn's disease)

Immune defects Altered host susceptibility Immune-mediated mucosal damage

Psychologic factors Stress Emotional or physical trauma Occupation 04/12/23 Dr Afzal Haq Asif 15



Initiating events →

Perpetuating events →

Immunoregulatory abnormalities →

Tissue damage →

Clinical symptoms

Infections Toxins NSAIDs

Luminal bacteria Bacterial products Dietary antigens

Genetic susceptibility T lymphocytes ↑IL-1/IL-1ra TH1 vs. TH2 HLA-DR? Anitgen presentation

PMN Macrophage Tx, LT, PAF O2, NO Proteases Complement IFN-γ TNF-α

Diarrhea Bleeding Pain ↓Weight

Pathophysiology of IBD

Clinical Presentation: IBD: GeneralSigns and symptoms

Abdominal cramping Frequent bowel movements, often with blood in the stool Weight loss Fever and tachycardia in severe disease Blurred vision, eye pain, and photophobia with ocular involvement Arthritis Raised, red, tender nodules that vary in size from 1 cm to several

centimetersPhysical examination

Hemorrhoids, and fissures, or perirectal abscesses may be present Iritis, uveitis, episcleritis, and conjunctivitis with ocular

involvement Dermatologic findings with erythema nodosum, pyoderma

gangrenosum, or aphthous ulceration

Laboratory tests Decreased hematocrit/hemoglobin Increased erythrocyte sedimentation rate Leukocytosis and hypoalbuminemia with severe disease04/12/23 Dr Afzal Haq Asif 18

Extra-Intestinal Menifestation

Erythema Nodosum Pyoderma Gangrenosum

Aphthous ulceration



Comparison of the Clinical and Pathologic Features of Crohn and colitis

1.ULCERATIVE COLITIS Patholophysiology:

confined to the colon and rectum affects primarily the mucosa and the submucosa The primary lesion occurs in the crypts of the mucosa

(crypts of Lieberkuhn) in the form of a crypt abscess minor complications include hemorrhoids, anal

fissures, or perirectal abscesses.


Complications of UC Toxic Megacolon: a severe condition that

occurs in up to 7.9% of ulcerative colitis patients admitted to hospitals. High fever, tachycardia, distended

abdomen, elevated white blood cell count, and a dilated colon

Colonic Carcinoma: Risk is much greater in patients with

ulcerative colitis as compared with the general population

Hepato-biliary Complications: Approximately 11% of patients have fatty

liver, pericholangitis, chronic active hepatitis, cirrhosis, sclerosing cholangitis, cholangiocarcinoma, and gallstones04/12/23 Dr Afzal Haq Asif 23

Complications of UCArthritis:

Common, asymptomatic and migratory. involves one or a few large joints such as the knees, hips, ankles, wrists, and elbows.

Ocular Complications: iritis, epi-scleritis, and conjunctivitis)

occur in up to 10% of patients. Dermatologic or Mucosal

complications:5 to 10% of patients experience

(erythema nodosum, pyoderma ganrenosum, aphthous stomatitis


Grading of UC (Montreal classificationS0 Clinical

remissionAsymptomatic

S1 Mild UC Passage of four or fewer stools/day (with or without blood), absence of any systemic illness, and normal inflammatory markers (ESR)

S2 Moderate UC Passage of more than four stools per day but with minimal signs of systemic toxicity

S3 Severe UC Passage of at least six bloody stools daily, pulse rate of at least 90 beats per minute, temperature of at least 37.5°C, haemoglobin of less than 10.5 g/100 ml, and ESR of at least 30 mm/h


Fulminant UCSevere diarrhea with abdominal pain,

bleeding, fever, sepsis, electrolyte disturbances, and dehydration.



2. CROHN'S DISEASE: PathophysiologyTrans-mural inflammatory process. Terminal ileum is the most common site

but may occur in any part of the GI tract.Two thirds of patients have some colonic

involvement, 15% to 25% of patients have only colonic

disease.

Complications :May involve the intestinal tract or organs

unrelated to it. Small-bowel stricture and subsequent

obstruction: may require surgery. Fistula formation is common and occurs much

more frequently than with ulcerative colitis.04/12/23 Dr Afzal Haq Asif 28


Crohn’s disease:Clinical presentationHighly variableA single episode or continuous,disease. A patient may present with diarrhea and

abdominal pain or a perirectal or perianal lesion

Periods of remission and exacerbation. Some patients may be free of symptoms for

years, while others experience chronic problems in spite of medical therapy


Crohn’s Disease: Clinical presentationSigns and symptoms

Malaise and fever Abdominal pain Frequent bowel movements Hemotachezia (bright red blood per rectum: BRBPR) Fistula (an abnormal connection or passageway between two

epithelium-lined organs or vessels that normally do not connect)

Weight loss Arthritis

Physical examination Abdominal mass and tenderness Perianal fissure or fistula

Laboratory tests Increased white blood cell count and erythrocyte

sedimentation rate



Grading of Crohn's diseaseAsymptomatic remission : CDAI <150

Asymptomatic either spontaneously or after medical or surgical intervention. (but not on steroids)

Mild to moderate: Crohn disease CDAI 150-220 – Ambulatory patients able to tolerate an oral diet Have no dehydration, toxicity, abdominal tenderness,

mass, obstruction, or >10 percent weight loss.Moderate to severe Crohn disease : CDAI 220-45

Failed treatment for mild to moderate disease or Have prominent symptoms such as fever, weight loss, abdominal

pain and tenderness, intermittent nausea or vomiting, or anemia.Severe-fulminant disease : CDAI >450

Persisting symptoms despite conventional glucocorticoids or biologic agents as outpatients, or individuals presenting with high fevers, persistent vomiting, intestinal obstruction, significant peritoneal signs, cachexia, or evidence of an abscess



Patient reported stool patternAverage number of liquid or soft stools per day over seven days (14 points per stool)Using diphenoxylate or loperimide for diarrhea (30 points)

Average abdominal pain rating over seven daysNone (0 points)Mild pain (35 points)

Moderate pain (70 points)

Severe pain (105 points)General well being each day over seven days

Well (0 points)Slightly below average (49 points)Poor (98 points)Very poor (147 points)Terrible (196 points)

CDAI calculator

CDAI calculator


ComplicationsArthritis or arthralgia (20 points)

Iritis or uveitis (20 points)Erythema nodosum, pyoderma gangrenosum or aphthous stomatitis (20 points)Anal fissure, fistula or abcess (20 points)Other fistula (20 points)Temperature over 100 °F (37.8 °C) in the last week (20 points)

Finding of an abdominal massNo mass (0 points)Possible mass (20 points)Definite mass (50 points)

Anemia and weight changeAbsolute deviation of hematocrit from 47% in males or 42% in females (6 points per percent deviation)Percentage deviation from standard weight (1 point for each percent deviation)


Summary of differences in CD &UCClinical Feature Crohn's Disease Ulcerative Colitis

Malaise, fever Common Uncommon

Rectal bleeding Common Common

Abdominal tenderness Common May be present

Abdominal mass Common Absent

Abdominal pain Common Unusual

Abdominal wall and internal fistulas

Common Absent

Distribution Discontinuous Mouth to anus

Continuous(L.I and Rectum)

Aphthous or linear ulcers

Common Rare


Summary of differences in CD &UCPathologic Feature Crohn's Disease Ulcerative Colitis

Rectal involvement Rare Common

Ileal involvement Very common Rare

Strictures Common Rare

Fistulas Common Rare

Transmural involvement

Common Rare

Crypt abscesses Rare Very common

Granulomas Common Rare

Linear clefts Common Rare

Cobblestone appearance

Common Absent



Goals of Therapy1. Resolution of acute inflammatory

processes,2. Resolution of complications if present(e.g.,

fistulas, abscesses), 3. Relief in systemic manifestations (e.g.,

arthritis), 4. Maintenance of remission from acute

inflammation, 5. Surgical palliation or cure.


General MeasuresAlterations to diet

Some of the dietary changes that may be appropriate for a person with IBD include: Low fibre diet –

to ease diarrhoea and reduce abdominal cramping. Particularly when a narrowed small intestine

Low fat diet

Low lactose diet - the milk sugar lactose is broken down by the enzyme lactase, commonly found in the lining of the small intestine. Patient of Crohn's disease may lack this enzyme,

Liquid diet - a person with severe Crohn's disease may need a nutritionally balanced liquid diet.

Plenty of water - people with IBD need to drink plenty of fluids to prevent dehydration.


Vitamins and Mineral SupplementA patient on a low fibre diet may need

vitamin C and folic acid supplementation because they don't consume enough fruit and vegetables.

A patient with Crohn's disease who experiences steatorrhoea may need calcium and magnesium supplements.

Almost all children with IBD to take supplements to lower risk of impaired growth and development.


Drug T/M of U.C: To induce remissionMild to Moderate Disease

The first line of drug any one of the following Oral sulfasalazine or an oral mesalamine or, or topical

mesalamine or steroids for distal disease Dose 4 g/day, up to 8 g/day of sulfasalazine to control active

disease ( start with 500 mg/day and increase gradually Oral mesalamine alternative but not more effective than

Sulfazalazine If not responsive: STEROIDS:

Are equally effective as sulfasalazine, but effect appear sooner.

Prednisone up to 1 mg/kg/day or 40 to 60 mg dailyRectally administered steroids or mesalamine can be used as

initial therapy for patients with ulcerative proctitis or distal colitis.

Nicotine Transdermal improves symptoms of patients with mild to moderate active ulcerative colitis in daily doses of 15 to 25 mg.


T/M: Severe U.C.: Induce remissionHospitalizationSteroids: help to avoid colectomy in severe

UCHydrocortisone 100 mg iv 6-8 hourly till

remissionShift to oral prednisolone ( 1mg/kg/day)after

remission (prednisolone)All patients before surgery should be given trial of

SteroidsIf refractory to steroids, continuous IV

infusion of cyclosporine (4 mg/kg/day)If no response :Surgical procedures may be

required. 04/12/23 Dr Afzal Haq Asif 45

Maintenance of RemissionSulfasalazine : 2 g/day orallyMesalamine derivatives, can be used, but not as

effective as sulfasalazine.No role of steroids: withdraw gradually after

remission is induced (over 3 to 4 weeks)Azathioprine: effective in preventing relapse of

ulcerative colitis for periods exceeding 4 years. However, 3 to 6 months may be required for beneficial effect

Infliximab: continue if patient initially responded to it : 5 mg/kg every 8 weeks as maintenance therapy is an alternative for steroid dependent patients



Treatment Plan for Ulcerative Colitis


Treatment of Crohn’s Disease


Crohn’s Disease: Induce RemissionMain Drugs:

Sulfasalazine, mesalamine derivatives, or steroids,

Other choices, according to situationAzathioprine, mercaptopurine, methotrexate,

infliximab, Metronidazole, Ciprofloxacin??


Crohn’s Disease: Induce RemissionIf Colon is Involved:

Sulfasalazine is more effective Why??

If Ileal disease: Mesalamine derivatives (Pentasa or Asacol) more effective.

why??Steroids

When active and severe disease

Unresponsive to amino-salicylates. Budesonide first-line option for patients with mild to

moderate ileal or right-sided disease. Systemic steroids induce remission in up to 70% of

patients and should be reserved for patients with moderate to severe disease who have failed aminosalicylates or budesonide.


Metronidazole orally up to 20 mg/kg/day In patients with colonic or ileocolonic involvement The combination with ciprofloxacin is efficacious in some patients.

Immunosuppressive agents: azathioprine and mercaptopurineFor those not achieving adequate response to standard therapy,To reduce steroid doses when toxic doses are required. Dose: azathioprine is 2 to 3 mg/kg/day and mercaptopurin: 1 to 1.5

mg/kg/day for Duration: Up to 3 to 4 months may be required to observe a

response. Starting doses are typically 50 mg/day and increased at 2-week

intervals while Monitoring:

Complete blood count Determine TPMT or TPMT before start of therapy Patients

deficient in thiopurine S-methyltransferase (TPMT) are at greater risk of bone marrow suppression


Crohn’s Disease: Induce remission

Cyclosporine Symptomatic and severe perianal or cutaneous fistulas. An oral dose of 7.9 mg/kg/day. However, toxicMonitor dose by whole-blood concentrations.

Methotrexate, 5 to 25 mg iv/week, for induction of remission and maintenance

therapy. The risks bone marrow suppression, hepatotoxicity,

and pulmonary toxicityInfliximab moderate to severe active disease

failing immunosuppressive therapy, Corticosteroid dependent, Treatment of fistulizing disease. Dose: 5 mg/kg infusion every day for 8 weeks. Additional doses at2 and 6 weeks following the initial dose results


Crohn’s Disease: Induce remission

Crohn’s Disease: Induce remissionAdalimumab

effective in 54% of patients with moderate to severe disease who have lost response to infliximab.

Dosage is 160 mg subcutaneously initially, followed by 80 mg subcutaneously at week 2, with subsequent doses of 40 mg subcutaneously every other week


Maintain RemissionDifficult than that in U.C.

Sulfasalazine and oral mesalamine derivatives are effective

Steroids have no place Azathioprine, mercaptopurine, methotrexate, infliximab, and adalimumab are effective in maintaining remission in selected patients Crohn’s disease.



Treatment Plan for Crohn’s Disease

Rationale of AntibacterialsBased upon a large body of evidence

demonstrating that luminal bacteria have an important role in the pathogenesis of IBDDecreasing the concentrations of bacteria and

fungi in the gut lumenAltering the composition of the intestinal

microbiota to favor beneficial bacteriaDecreasing bacterial tissue invasion and

treating microabscessesDecreasing bacterial translocation and

systemic dissemination


Fulminant Colitis and Toxic MegacolonAcute fulminant colitis : severe diarrhea with

abdominal pain, bleeding, fever, sepsis, electrolyte disturbances, and dehydration.

Toxic mega colon: in 1%-2% of patients with UC; the colon becomes atonic and modestly dilates, systemic toxicity is the dominant feature.

Treatment Keep NPO, with NG suction if there is evidence of small-

bowel ileus.Treat dehydration and electrolyte disturbancesAnticholinergic and opioid medication should be

discontinued. Intensive therapy with IV corticosteroids (hydrocortisone,

100 mg IV q6h or equivalent) Broad-spectrum antimicrobials: Metro+CiprofloxacinSurgery: Urgent total colectomy

Clinical deterioration/lack of improvement despite 7-10 days of management,

Evidence of bowel perforation, or peritoneal signs


Pregnancy & IBDPregnancies are well managed in patients

with these diseases. Same indications for medical and surgical

treatmentFirst attack:

standard treatment with sulfasalazine or steroids

Folic acid supplementation, 1 mg twice daily, Metronidazole or methotrexate should not be

used during pregnancy.Azathioprine and mercaptopurine may be

associated with fetal deformities.


Evaluation of Therapeutic Outcomes:C.DCrohn Disease Activity Index

EIGHT parameters:The Crohn’s Disease Activity Index is used for evaluation of patients during clinical trials. 1) number of stools in the past 7 days 2) sum of abdominal pain ratings from the past 7 days 3) rating of general well-being in the past 7 days 4) use of antidiarrheals 5) body weight 6) hematocrit 7) finding of abdominal mass 8) a sum of symptoms present in the past week.

Elements of this index provide a guide to assess the effectiveness of treatment regimens.


Evaluation of Therapeutic Outcomes: U.CLook for:

Stool frequencyPresence of blood in the stoolMucosal appearance (from endoscopy)Physician’s global assessment based on

physical examination, endoscopy, and laboratory data.


Surgery in IBD


Surgery in IBDFor ulcerative colitis, colectomy may be

performed:If disease uncontrolled by maximum medical

therapy Complications of the disease such as colonic

perforation, toxic dilatation (megacolon), uncontrolled colonic hemorrhage, or colonic strictures.

In Crohn’s disease surgery is reserved for The complicated disease. But there is a high recurrence rate of Crohn’s

disease after surgery.04/12/23 Dr Afzal Haq Asif 63

• Objectives for this section:• After completion of this section, the student will be able to

• Select rationalizd therapy• Know the adverse effect for follow up evaluation


Drug used in Treatment of IBD5-Aminosalicylic acid

(ASA) compoundsSulfasalazineNewer 5-ASA

preparations lack the sulfa moiety Mesalamine (5-ASA) Olsalazine

Glucocorticoids PrednisoneBudesonideHydrocortisone

AntibioticsMetronidazole. Ciprofloxacin Sulfamethoxazole-

trimethoprimImmunomodulating

agents 6-MercaptopurineAzathioprineMethotrexate cyclosporine

Infliximab Sargramostim recombinant granulocyte-macrophage colony-

stimulating factor 04/12/23 Dr Afzal Haq Asif 65

SulfasalazineReaches the colon intact, where it is metabolized into 5-ASA

and a sulfa-pyridine. Used for colonic disease (UC and Crohn's disease limited to

the colon), either as initial therapy (0.5 g PO bid, increased as tolerated to 0.5--1.5 g PO qid) or to maintain remission (1 g PO bid to qid).

Adverse effects: Mainly caused by the sulfa pyridine moiety

Headache, nausea, vomiting, and abdominal pain; a reduction in dose may be beneficial.

Can cause drug induced pancreatitis

Hypersensitivity reactions are less common and include skin rash, fever, agranulocytosis, hepatotoxicity, and aplastic anemia. Reversible reduction in sperm counts can be seen in males. Paradoxic exacerbation of colitis is a rare adverse effect.

Folic acid supplementation is recommended, as sulfasalazine impairs folate absorption.

STUDY ASSIGNEMENT: Mechanism of action of ASA’s (Ref:Katzung Pharmacology,,


Newer 5-ASA preparations Mesalamine (5-ASA) is available in several formulations.

An oral preparation released at pH >7 (Asacol, 800 to 1,600 mg PO tid) is useful in UC as well as ileocecal/colonic Crohn's disease.

Balsalazide (2.25 g PO tid for active disease, 1.5 g PO bid for maintenance), is cleaved by colonic bacteria to mesalamine and an inert carrier molecule and is useful for colonic inflammation

Olsalazine is a 5-ASA dimer that is cleaved by bacteria in the colon and can be used in UC and Crohn's colitis. Diarrhea is a major side effect and can limit its use

Adverse effectsRare hypersensitivity reactions occur and include pneumonitis, pancreatitis, hepatitis, and nephritis.

.


Glucocorticoids-1Beneficial in inducing remission of active UC

and Crohn's disease. Can be used concurrently with other anti-inflammatory agents in

moderate to severe disease, In exacerbations of the disease Extra colonic manifestations of inflammatory bowel disease

ocular lesions, skin disease, peripheral arthritis

Not recommended for mild diseaseNot recommended for maintenance therapy Dose:

Prednisone is 40-60 mg orally, once a day in the morning. can be reduced by 10 mg every 5-10 days and tapered off in 3-6 weeks

Methylprednisolone, 20-40 mg INTRAVENOUS daily to bid, up to 1 mg/kg/d) In severe disease in Patients who cannot tolerate oral medication brief periods;

higher doses are used in refractory disease Budesonide (9 mg/d) may have less systemic side effects compared to

glucocorticoids when used for mild to moderate ileocolonic Crohn's disease


Immunosuppressive agents 6-Mercaptopurine, and Azathioprine,

Cause preferential suppression of T-cell activation and antigen recognition.

Are used orally in doses of 1-1.5 mg/kg body weight dailyMore favorable side effect profiles than do glucocorticoids Are used as steroid-sparing agents in severe or refractory

inflammatory bowel disease (IBD). Response after up to 1-2 months. Adverse effects

Reversible bone marrow suppression, Pancreatitis, Allergic reactions

Methotrexate (15-25 mg IM or PO weekly) used as a steroid-sparing agent in Crohn's disease. Adverse effects

hepatic fibrosis, bone marrow suppression, alopecia, pneumonitis, allergic

reactions, and teratogenicity


Immunosuppressive agentsCyclosporine has been used INTRAVENOUSLY

in refractory cases of UC. The benefit is temporary.

Adverse effects nephrotoxicity, hepatotoxicity, hypertrichosis, seizures, lymphoproliferative disorders


InfliximabMonoclonal antibody against tumor necrosis factor-Î induces inflammatory cell lysis by binding to tumor

necrosis factor receptors on the cell surface. Infliximab is used for

fistulous Crohn's disease, refractory inflammatory-type Crohn's disease

unresponsive to conventional therapy, severe ulcerative colitis.

Dose: IV infusions of 5 mg/kg) Induction regimens typically consist of doses at 0, 2, and 6

weeks, with maintenance doses every 8 weeks.Adverse Effects:

Congestive heart failure may worsen after therapy. Sepsis and reactivation of latent tuberculosis or histoplasmosis

may occur; a tuberculin test may be indicated to evaluate for latent tuberculosis.

Serious infusion reactions may occur, and constant monitoring is essential during infusion.


Antibacterial AgentsMetronidazole (250-500 mg PO tid)

first-line agent or adjunctive therapy in mild to moderate Crohn's disease.

Peripheral neuropathy is a concern with long-term use.

Ciprofloxacin (500 mg PO bid) has also been used in

Crohn's disease.

The two agents can be used concurrently in perianal Crohn's disease for prolonged periods with good results.

An alternative agent is Co-trimoxazole



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Inflammatory bowel disease.2014