Inflammatory Bowel Disease
Intermittent bouts of diarrhoea, low-grade fever, and right lower quadrant pain...
Diagnostic
summary
Crohn’s disease
Intermittent bouts of diarrhoea, low-grade fever, and right lower quadrant pain.
Anorexia, weight loss,
flatulence, and malaise.
Abdominal tenderness, especially right lower quadrant, with signs of peritoneal irritation and an abdominal
or pelvic mass.
X-rays how abnormality of terminal ileum.
Ulcerative Colitis
Bloody diarrhoea with cramps in lower
abdomen.
Mild abdominal tenderness, weight loss, and fever.
Rectal exam may show perianal irritation, fissures, haemorrhoids, fistulas,
and abscesses.
Diagnosis confirmed by X-ray and sigmoidoscopy.
Definition
Inflammatory bowel disease (IBD) is a general term for
a group of chronic inflammatory disorders of the bowel; two major categories; Crohn’s disease and ulcerative colitis; IBD is characterized
by recurrent inflammatory involvement of specific intestinal segments, resulting in diverse clinical manifestations.
• Crohn’s
disease (CD): granulomatous inflammatory reaction throughout entire thickness of bowel wall; 40% of cases, granulomas either poorly
developed or totally absent; may involve buccal mucosa, oesophagus, stomach, duodenum, jejunum, ileum, and colon’ Crohn’s disease
of small intestine is called ‘regional enteritis’; colon involvement is called ‘Crohn’s disease of the colon’ or ‘granulomatous colitis’
(only a portion of patients develop granulomatous lesions).
• Ulcerative Colitis (UC): non-specific inflammatory response limited
to colonic muscosa: well-developed granuloma formation does not occur.
Common features shared by Crohn’s disease and ulcerative colitis:
-
- Although rare, patients with UC and total
colon involvement may develop ‘backwash ileitis’ – both conditions may cause changes in the small intestine.
- Patients with CD
often have close relatives with UC, and vice versa.
- When no granuloma in CD of the colon, the two lesions may resemble each
other clinically and pathologically.
- There are epidemiological similarities between CD and UC – age, race, sex, and geographical
distribution.
- Both conditions are associated with similar extraintestinal manifestations.
- There are etiological parallels
between the two conditions.
- Both conditions are associated with increased frequency of colonic carcinoma.
Etiology
- Genetic
predisposition: supported by ethnic distribution of incidence, and multiple members of a
family have CD or UC in 15-40% of cases.
- Infectious
etiology: idea that transmissible agent is responsible for IBD (inflammatory bowel disease) is a hotly debated subject: viruses (rotavirus,
Epstein-Barr virus, cytomegalovirus, and an uncharacterised RNA intestinal cytopathic virus) and mycobateria continue to be favoured
candidates.
- Antibiotic exposure: prior to 1950’s, CD found in selected groups with strong genetic component; rapid climb in
developed countries and countries that previously had virtually no reported cases; CD has spread like epidemic; wherever antibiotics
used early and in large quantities, incidence of CD is now quite high; infectious agent may be a normal intestinal florum suddenly
producing immunostimulatory toxins or becoming invasive via sublethal doses of antibiotics making flora stronger in virility and numbers.
- Immune
mechanisms: immunologic derangements are found in IBD, but whether causal of IBD or secondary to it remains unclear; current evidence
indicates that derangements are secondary to disease process.
- Dietary factors:
Therapeutic considerations
Control of causative factors
- Natural history of Crohn’s disease: many patients will undergo spontaneous remission, 20% at 1 year and
12% at 2 years; ‘success’ of placebo therapy rises dramatically – in patients having no history of steroid therapy, 41% remitted after
17 weeks; 23% of this group continued in remission after 2 years, compared with 4% of group with history of steroid use; once remission
is achieved, 75% of patients will continue in remission at end of 1 year and up to 63% by 2 years, regardless of maintenance therapy
used; key="achieving" remission, which, once attained, can be maintained by conservative non-drug therapy.
- Eicosanoid metabolism:
prostaglandins are greatly increased in colonic mucosa, serum, and stools of IBD patients; increased synthesis of lipoxygenase products,
leukotrienes, and mono HETEs – produced by neutrophils and amplify inflammation and cause smooth muscle contraction; release of lipoxygenase
products promoted by activation of alternative complement pathway; sulfasalazine inhibits cyclooxygenase and neutrophil lipoxygenase
and inhibits degranulation of mast cells; corticosteroids inhibit phospholipase A2, blocking release of arachidonic acid from membrane
phospholipids; natural flavonoid quercetin interacts with these enzymes; formation of inflammatory compounds is decreased by reducing
dietary meat and daily while increasing omega-3 fatty acids (cold-water ocean fish)-eicosapentaenoic acid (EPA) and docosahexanoic
acid (
- Mucin defects in ulcerative colitis: mucins
are high-molecular weight, carbohydrate-rich glycoproteins responsible for viscous/elastic characteristics of secreted mucous; alterations
in mucin composition and content in colonic mucosa noted in UC: dramatic decrease in mucous content of goblet cells (proportional
to severity of disease) and decrease in major sulfomucin subfraction: these abnormalities are not found in CD: mucin content of goblet
cells returns to normal during remission but sulfomucin deficiency does not; specific components of sulfomucin can cause of its lower
level are unknown; mucin abnormalities are a major factor in increased risk of colon cancer in these patients.
- Intestinal
microflora: 400 distinct species; fecal flora of patients with IBD contain higher numbers of Gram-positive anaerobic coccoid rods
and Bacteroides vulgatus, a Gram-negative rod; these alterations in fecal flora are not secondary to disease, and alterations in metabolic
activity of bacteria are more important than alterations in number of bacteria; specific bacterial cell components may be responsible
for promoting lymphocyte cytotoxic activity against colonic epithelial cells.
- Carrageenans: sulphated polymers of galactose
and D-anhydrogalactose extracted from red seaweeds (Eucheuma spinosum or Chondrus crispus) have been used to induce IBD in animals;
used by food industry as stabilizing and suspending agents (ice cream, cottage cheese, milk chocolate, etc.) due to ability to stabilize
milk proteins, no correlation between human consumption of carrageen and development of UC; differences in intestinal bacterial flora
are probably responsible for discrepancy – germ-free animals do not display carrageen-induced damage; bacteria linked to facilitating
carrageen-induced damage in animals in strain of Bacteroides vulgatus- found in much higher concentrations (six times as high) in
fecal cultures of patients with IBD; carrageenan is metabolised into non-damaging components in most humans, and people with overgrowth
of Bacteroides vulgatus may be at risk; avoid carrageens.
- Aspirin and intestinal permeability: first degree relatives of CD
patients had 110% increase in intestinal permeability after acetylsalicylic acid vs. increase of 57% in controls; 35% were hyper-responders;
familial permeability defect is a significant predisposing factor for CD – leaky gut linked to increased incidence of food allergy
and absorption of intestinal toxins.
- Endotoxemia and alternative complement pathway: endotoxemia is linked to CD and UC; endotoxemia-induced
activation of alternative complement pathway could explain extra-GI manifestations of IBD; whole gut irrigation significantly reduces
endotoxin pool in gut and has a very beneficial anti-endotoxinemia effect; colonic irrigation may offer similar benefit; colon irrigation
during acute inflammatory flare contraindicated.
Extra-gastrointestinal manifestations
Over 100 disorders are systemic complications
of IBD; most common extraintestinal lesion (
• Skin manifestations seen in 15% of patients; lesions – erythema nodosum, pyoderma gangrenosum, and aphthous ulcerations; recurrent aphthous stomatitis in 10% of patients; serious liver disease (sclerosing cholangitis, chronic active hepatitis, cirrhosis) affects 3-7% of patients with IBD from increased endotoxin load; liver enzyme abnormalities indicate need for hepatoprotection from Glycyrrhiza glabra, Silybum marianum, catechin and curcumin.
• Other common Eils: thrombophlebitis, finger clubbing, ocular manifestations (episcleritis, iritis, and uveitis),
nephrolithasis, and, in children, failure to grow, thrive, and mature normally.
Malnutrition
Nutritional complications of IBD
have great influence on morbidity (and mortality).
Causes of malnutrition in inflammatory bowel disease
• Decreased oral
intake
o disease-induced (pain, diarrhoea, nausea, anorexia)
o iatrogenic (restrictive diets without supplementation)
• Malabsorption
o decreased
absorptive surface due to disease or resection
o bile salt deficiency after resection
o bacterial overgrowth
o drugs (e.g.
corticosteroids, sulfasalazine, cholestyramine)
• Increased secretion and nutrient loss
o protein-losing enteropathy
o Electrolyte,
mineral, and trace mineral loss in diarrhoea
• Increased utilization and increased requirements
o inflammation, fever, infection
o increased
intestinal cell turnover
Weight loss prevalent in 65-75% of IBD patients; malabsorption-from extensive mucosal involvement of
small intestine and resection of segments of small intestine; fat malabsorption – loss of calories and fat-soluble vitamins and minerals;
ileum involvement or resection causes bile acid malabsorption – cathartic effect of bile acids on colon, causes chronic watery diarrhoea;
expect electrolyte and trace mineral deficiency from chronic diarrhoea, plus Ca and Mg deficiency from chronic steatorrhea; loss of
plasma proteins across damaged/inflamed mucosa – may exceed ability of liver to replace plasma proteins; chronic blood loss causes
Fe depletion anaemia; drugs used to treat IBD (corticosteroids and sulfasalazine) increase nutritional needs.
Corticosteroids
are knows to:
• stimulate protein catabolism
• depress protein synthesis
• decrease the absorption of calcium and phosphorous
• increase
the urinary excretion of ascorbic acid, calcium, potassium, and zinc
• increase blood glucose, serum triglycerides, and serum
cholesterol
• increase the requirements for vitamin B6, ascorbic acid, folate, and vitamin D
• decrease bone formation
• impair
wound healing
Sulfasalazine has been shown to:
• inhibit the absorption and transport of folate
• decrease serum folate
and iron
• increase the urinary excretion of ascorbic acid.
Nutritional consequences of chronic inflammatory and/or infectious
disease – protein requirement may be increased; elevated sedimentation rate signifies increased protein breakdown and synthesis; IBD
requires 25% more protein than usual recommended allowance.
Prevalence of nutritional deficiencies
Nutritional deficiencies quite
high in hospitalised patients with IBD; greater prevalence of nutritional deficiencies in hospitalised patients than in outpatients
(more severe condition); ambulatory CD patients also display deficiencies – Fe, B12, folate, Mg, K, retinal, ascorbate, vitamin D,
Zn, vitamin K, Cu, niacin, and vitamin E; assume that most patients suffer from micronutrient deficiency; often deficiency is subclinical
and only detected by lab investigation; use therapeutic vitamin supplements of at least five times
• Elemental diet: effective non-toxic alternative to corticosteroids at primary treatment of acute of acute IBD; contains all essential nutrients; protein as pre-digested or free-form amino acids; provides nutritional improvement, alters fecal flora, and serves allergy elimination diet; main drawback is unpalatability, hyperosmolality (causing diarrhoea); hospitalisation often required for satisfactory administration, and relapse is common when patients resume normal eating; elimination diet may be acceptable alternative for acute IBD, especially for chronic IBD.
• Elimination (oligoantigenic) diet: elimination is the primary therapy for chronic IBD; most common offending foods are
wheat and dairy; alternative approach – determine actual allergens by lab methods – measure IgG- and IgE-mediated reactions; allergens
are avoided or rotary diversified diet.
• High-complex carbohydrate, high-fiber (HFC) diet: favourable effect on course of CD,
in direct contrast to allopathic dietary treatment: low-fiber diet; some foods are too ‘rough’ to handle, but use an unrefined carbohydrate,
fiber-rich diet with allergen avoidance or rotary-diversified diet; fiber has profound effect on intestinal environment and promotes
optimal intestinal flora; avoid supplemental wheat bran.
Minerals
• Zinc: deficiency in 45% of CD patients; due to low dietary
intake, poor absorption, and excess fecal losses; many complications of CD may result from Zn deficiency; poor healing of fissures
and fistulas, skin lesions (acrodermatitis), hypogonalism, growth retardation, retinal dysfunction, depressed cell-mediated immunity,
anorexia; many patients unresponsive to oral or i.v. Zn due to defect in tissue transport; no improvement in patients with intestinal
absorption and tissue transport; no improvement in patients with pancreatic insufficiency; zinc citrate may also be appropriate alternative;
make every attempt to ensure adequate tissue stores – disease activity correlated with zinc deficiency; use parenteral administration
as needed.
• Magnesium: deficiency prevalent in IBD; poor correlation between serum levels (frequently normal) and intracellular
levels (commonly decreased); low intracellular Mg causes; weakness, anorexia, hypotension, confusion, hyperirritability, tetany, convulsions,
ECG or EEG abnormalities – responsive to parenteral Mg supplementation; daily i.v. dose of 200-400mg elemental Mg if patient unresponsive
to oral supplements; IBD may require i.v. route due to cathartic action of Mg and poor absorption in patients with short bowel; oral
supplement – Mg chelates (citrate, aspartate, etc.) rather than inorganic magnesium salts (i.e. carbonate).
• Iron: deficiency
anaemia frequent in IBD from chronic gut blood loss; serum ferritin is the most useful index of Fe status; ferritin > 55ng/ml indicates
adequate Fe reserves; ferritin < 18ng/ml indicates Fe deficiency; improve absorption with supplemental vitamin C rather than direct
Fe supplements – Fe promotes intestinal infection.
• Calcium: risk of Ca deficiency due to loss of absorptive surfaces,
steatorrhea, corticosteroids, vitamin D deficiency.
• Potassium: diarrhoea linked to K+ and other electrolyte deficiencies; symptoms
of K+ deficiency rare in IBD patients, but levels below optimum; correcting K+ deficiency reduces rates of surgical complications.
Vitamins
• Vitamin
A: low serum retinal in 20% of CD patients, correlated with activity of disease; vitamin A affects metabolism and differentiation
of intestinal epithelial mucosa – increases number of goblet cells, production of mucins, secretion of mucus, and restores normal
barrier function; vitamin A may be useful in CD, but long-term trials have (50,000 IU b.i.d.) found no benefit in majority of CD cases;
certain patients may respond to vitamin A; zinc supplements often normalized vitamin A metabolism – zinc is a component of retinal-binding
protein (RBP).
• Vitamin D: deficiency common in IBD, particularly patients with other signs of nutritional deficiency;
result of decreased absorption of 25-hydroxy-vitamin D; increased risk of metabolic bone diseases (osteoporosis and osteomalacia).
• Vitamin E: deficiency can occur in IBD with presenting symptoms; bilateral visual field scotomata, generalized motor weakness,
broad-based gait with marked ataxia, brisk reflexes, bilateral Babinski response; inhibits leukotriene formation and reduces free
radical damage.
• Vitamin K: deficiency results in formation of abnormal prothrombin (deficient in gamma-carboxyglutamic acid),
common in patients with IBD.
• Folic acid: low serum levels in 25-64% of cases; sulfasalazine interferes with folate-dependent
enzymes and intestinal folate transport system; deficiency promotes malabsorption from altered structure of intestinal mucosa – cells
have rapid turnover (1-4 days) vs. RBCs (3-4 months); deficiency affects these cells earlier than
• Vitamin B12: significant
correlation between B12 absorption and terminal ileal disease and/or resection; abnormal Schilling tests in 48% of CD patients; when
ileal resection exceeds 90cm, Schilling test is abnormal in all patients and never improved; length of resection <60cm, or extent
of inflammatory lesion <60cm; adequate absorption may occur.
• Ascorbic acid: low vitamin C intake common in IBD patients,
particularly those on low-fiber diet; serum and leukocyte ascorbic acid much lower in CD patients than in matched controls; vitamin
C important to prevent fistulas – patients with fistulas have lower ascorbic acid levels than those without.
Recommend a high-potency
multiple vitamin and mineral formula: absolutely essential in IBD; additional antioxidants to manage increased oxidative stress and
decreased antioxidant defences in mucosa; two primary antioxidants in human body are vitamins C (‘aqueous phase’) and E (‘lipid phase’).
• vitamin
E (D-alpha-tocopherol)
• vitamin C (ascorbic acid)
Botanical medicines
• Quercetin: plant flavonoids are natural biological
response modifiers; quercetin is the most pharmacologically active flavonoid; many enzymes affected by quercetin are involved in release
of histamine and other inflammatory mediators from mast cells, basophils, neutrophils, and macrophages, in the migration and infiltration
of leukocytes, and in smooth muscle contraction; action of quercetin antagonises calmodulin; when Ca bound to calmodulin, it activates
enzymes involved in cyclic nucleotide metabolism, protein phosphorylation, secretary function, muscle contraction, microtubule assembly,
glycogen metabolism, and Ca flux; quercetin interacts directly with calmodulin and Ca channels; potent inhibitor of mast cell and
basophil degranulation; inhibits receptor-mediated Ca influx, inhibiting primary signal for degranulation; also active when Ca-channel
mechanism not operative – other mechanisms also involved; inhibits inflammatory processes of activated neutrophils via membrane stabilization,
antioxidant effect (prevents production of free radicals and inflammatory leukotrienes), and inhibition of hyaluronidase (preventing
breakdown of collagen); membrane stabilizing effect – prevents mast cell and basophil degranulation and decreases neutrophil lysosomal
enzyme secretion; inhibits eicosanoid metabolism-inhibits phospholipase A2 and lipoxygenase; net results is the reduction in formation
of leukotrienes; excess leukotrienes linked to asthma, psoriasis, atopic dermatitis, gout, possible cancer, and IBD; leukotrienes
C4, D4, and E4 (in slow-reacting substances of anaphylaxis,
Irish Centre of Integrated Medicine (ICIM) formula
• Althea
officinalis (marshmallow root) – demulcent, soothing to mucous membranes
• Baptisia tinctora (wild indigo) – used for gastrointestinal
infections
• Echinacea angustifolia (purple coneflower) – antibacterial that normalises immune system
• Geranium maculatum
– a GI haemostatic
• Hydrastis Canadensis (goldenseal) – inhibits growth of many enteropathic bacteria.
• Phytolacca Americana
(poke root) used for healing ulcerations of intestinal mucosa.
• Symphytum offinale (comfrey) – anti-inflammatory; promotes tissue
growth and wound healing.
• Ulmus fulva (slippery elm) – demulcent.
Other ingredients: cabbage powder heals GI ulcers; pancreatin
assists digestive process; niacinamide has anti-inflammatory effects; and duodenal substances heals GI ulcers.
Butyrate enemas
in ulcerative colitis
• Short-chain fatty acids and colon function: SCFAs (acetate, propionate, and butyrate) are colon end-products
of bacterial carbohydrate fermentation; function as primary energy sources for luminal colon cells, especially distal segments; decreased
levels or utilization of SCFA’s impair cellular energetics – major role in ulcerative colitis; enemas providing SCFA’s (butyrate only
at 80-100 mmol/L, or SCFA combinations with acetate 60mmol/L, propionate 25mmol/L, and butyrate 40mmol/L) – excellent preliminary
results in well-designed double-blind study; butyrate and SCFA enemas may prove useful adjuncts for UC.
Irish Centre of Integrated
Medicine (ICIM) Therapeutic Approach
• IBD is life-threatening, requiring emergency treatment in some patients; small percentage
of patients with severe colitis may have severe exacerbations requiring hospitalisation – more common in patients with UC – fever
of 101 degrees F or higher, profuse, constant, loose, bloody stools, anorexia, apathy and prostration; abdominal signs normal, but
physical exam reveals distended abdomen, tympany, absent bowel sounds, and even rebound tenderness:
o IBD is a chronic disease
requiring long-term therapy and follow-up; identify and remove all factors initiating/aggravating inflammation (food allergens, carrageenan,
etc.)
o Use diet maximising macro- and micronutrients and minimizing aggravating foods/non-foods.
o Broad-based individualized
nutritional supplement plan; critical – Zn, Mg, folate, and vitamin A; use nutritional supplements to correct deficiencies.
o Normalise
inflammatory process and promote healing of damaged mucosa.
o Botanical medicines to promote healing and normalise intestinal
flora.
• Diet: eliminate all allergens, wheat, corn, dairy, carrageenan-containing foods; high in complex carbohydrates and fiber,
low in sugar and refined carbohydrates.
• Supplements:
o Multivitamin and mineral supplement
o Magnesium
o Zinc picolinate
o Vitamin
A
o Vitamin E
o Fish Oil
• Botanical medicines:
o Quercetin
o ICIM formula
This article is to be used for information and guide line purpose. Any advice and/or suggestions from this article should be supervised by your health professional. ICIM can offer a medical professional at the centre to guide you through your health complaints. Contact ICIM for more information.
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ICIM Medics, St. Johns Grove, Johnstown, Naas, Co. Kildare, Ireland.
Tel: 00353 (0)45 844 819 - www.icim.ie - info@icim.ie
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