crohn’s disease and its associated disorders · theinformedpatient 5 terminal...

Crohn’s disease andits associated disorders

The informed patient

13th edition 2008© 2008 Falk Foundation e.V.All rights reserved.

Publisher

www.falkfoundation.com


Prof. Dr. Volker Gross

Crohn’s disease andits associated disorders

AuthorProf. Dr. Volker GrossKlinikum St. MarienMedizinische Klinik IIMariahilfbergweg 7D-92224 AmbergGermanyE-mail: [email protected]


Contents

Diagnosis: Crohn’s disease – what does it mean? 4

The symptoms of Crohn’s disease 7

Crohn’s disease and disorders of other organs 8

The role of the immune system 10

Crohn’s disease can affect the nervous system 12

Effects on the joints 14

Osteoporosis 16

Disorders of the eyes 17

Skin changes in Crohn’s disease 18

Liver, gallbladder and pancreas in Crohn’s disease 20

Crohn’s disease and renal disorders 22

The respiratory tract in Crohn’s disease 24

Psychic factors in Crohn’s disease 25

The risk of cancer in Crohn’s disease 28

Living with Crohn’s disease 29

Crohn’s disease and pregnancy 31

Nutritional requirements in Crohn’s disease 32

Medical treatment of Crohn’s disease 34

Glossary 37

3

4

Diagnosis: Crohn’s disease –what does it mean?

Crohn’s disease takes it name from Dr. Burrill B. Crohn,a physician in New York, who in 1932 first described aninflammation of the small intestine that is chronic andresults in formation of scar tissue in the bowel. Thepreferred site of this inflammation is the terminal (final)segment of the small bowel, which is also known asthe ileum; hence, the disease has also been termed

Esophagus

Stomach

Colon

Small intestineTerminal ileum

Rectum

The organs ofdigestion fromthe mouth to therectum


5

terminal ileitis. Crohn’s disease can strike at any age,even in infants and small children. Usually, however, thedisease makes its first appearance in young adulthood(20–40 years of age).Children affected by Crohn’s disease should be carefullytreated as soon as the diagnosis is confirmed. If the dis-ease is not recognized early, the untreated inflammationof the bowel can lead to growth retardation, delayedpuberty and decreased levels of performance at school.In principle, practically the entire gastrointestinal tractcan be affected by Crohn’s disease. Inflammatorychanges affecting individual bowel segments are char-acteristic: these segments are separated by segmentsthat are essentially normal.The inflammation can affect all layers of the bowel wall,including the mucosal layer, the longitudinal (length-wise) and annular (ring-shaped) muscles of the bowelwall and even the connective tissue that envelopesthe bowel. The inflammatory changes in these tissuesalso affect the glandular structures of the bowel withthe result that the digestive functions of the bowel areincreasingly affected. The absorption of nutrients in thefood and the secretion into the lumen of the bowel ofsubstances necessary for normal digestion may bothbe compromised.Once the acute inflammation has passed, scars andthickening of the bowel wall may remain in the affectedbowel segments. The bowel lumen becomes more nar-row and transport of food through the bowel is impeded.

6

Intestinal villi

Blood andlymphaticvessels

Mucosal folds, schematic

Normalintestinal villus

Inflammation Fistula

Intestinal mucosa affected byCrohn’s disease


The symptoms of Crohn’s disease

In many cases, Crohn’s disease develops slowly andcauses uncharacteristic symptoms. Patients usuallycomplain of unclear abdominal pain and increaseddiarrhea. A more dramatic first presentation is, however,also possible, with very severe abdominal pain.Beside colicky abdominal pain, most patients withCrohn’s disease report recurrent diarrhea. There mayalso be irregular bouts of fever and persons affectedby Crohn’s disease report unintended weight loss anddepressed appetite.The often unclear symptoms early in the course of thedisease do not point directly to Crohn’s disease and itmay sometimes take several years before the correctdiagnosis is made. Laboratory evidence of inflammatorybowel disease include the unspecific signs of inflamma-tion (accelerated erythrocyte sedimentation rate, anincrease in the number of white blood cells and C-reac-tive protein and, in some cases, a decrease in the num-ber of red blood cells). In other cases, the simultaneousoccurrence of abdominal pain, diarrhea, fever, jointcomplaints, dermatitis (skin inflammation) and/or re-peated inflammation of the eyes may be considereda sign of Crohn’s disease. Anal fistulae also point toCrohn’s disease.The course of the disease is not continuous. Instead,Crohn’s disease occurs episodically in flares, separatedby symptom-free intervals of varying length.

7

Crohn’s disease and disorders ofother organs

The effects of Crohn’s disease are not confined to thebowel. In a high percentage of patients other organsand organ systems are affected, sometimes to such anextent that the underlying disease may actually be ob-scured. And, because Crohn’s disease is usually treatedby the patient’s family physician, internist or gastroen-terologist, changes in other organs can easily be missed.

8

Central nervoussystem

Eye

Lung

Liver

Biliary tract

Joints

Pancreas

Kidney

Skin

Organs that maybe affected bydisorders accom-panying Crohn’sdisease


It is clearly in the patient’s own interest to pay specialattention to changes in the skin, joints or eyes and askhis physician about the potential connection of changesin these organs to his bowel disease.

In rare cases, patients with Crohn’s disease may alsoexhibit changes in the pancreas, a gland in the abdomenresponsible for providing the bowel with enzymes andother secretions necessary for normal digestion. Otherpatients may develop disorders of the respiratory tract,of the kidneys or even of the nervous system. It is evenpossible for more than one organ or organ system tobe involved in the disease process. In some patients, adisorder affecting some organ or organ system maybecome so prominent that it obscures the symptomsof the underlying disease. Possibly, the work-up of thissymptom will provide the detour necessary to identifythe patient’s underlying inflammatory bowel disease.Clinical experience suggests that these accompanyingdisorders all have a common cause. This cause, how-ever, is to be sought, not in the bowel, but in a disorderof the immune system. Certain arguments suggest thatsome of the disorders associated with Crohn’s diseasemay actually be due to the medical treatment of thisdisease. Researchers, however, are in agreement thatthe commonly encountered findings in various organsystems in patients with Crohn’s disease are caused bydisturbances in the interplay of the various componentsof the immune system, the psyche, organic changesand drug treatment.

9

The role of the immune system

Researchers still cannot answer the question of whycertain people develop Crohn’s disease. Evidence ismounting, however, that genetic predisposition, environ-mental factors and the immune system are involved inits development. About 25% of Crohn’s cases in Europeappear to be related to a defect in the so-called NOD2gene.Were one to spread it out flat, the entire surface area ofthe human digestive system would cover 200 to 300 m2.This fact becomes even more important when oneconsiders the enormous number and amount of sub-stances with which it comes into contact on a dailybasis through the food, many of which have the poten-tial for causing serious disease. The digestive systemserves as an interface between the body’s own environ-ment and the outer world around it: to help protect thisboundary, the digestive organs are furnished with alarge number of different immunologically active cells.These belong to a group of cells that actively preventthe penetration of foreign proteins and other substancesinto the organism. In patients with Crohn’s disease,these immune cells are present in unusually large num-bers and are activated. In this state, they produce anexcess of pro-inflammatory substances (e.g. cytokines,chemical messengers). This can be corrected, at leastin part, by drugs such as the corticosteroids or 5-amino-salicylic acid.Immunoglobulin A (IgA) also plays an important role inthe immune defences of the bowel; its function differs inseveral important ways from the more well-known im-munoglobulin G (IgG), which is present predominantlyin the blood. Studies have shown that, in patients in anactive flare of inflammatory bowel disease, the relation-ship between IgA and IgG is shifted in favor of IgG.While IgA is primarily involved in keeping antigens away

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from the bowel wall and preventing their entry into thebody, IgG does not possess this capacity. Instead, itactually binds antigens to the bowel wall and this cancontribute to inflammation and destruction of tissue.

Immunoglobulins of the G-class forming together withantigens and antibodies the so-called immune com-plexes may also be important for the development ofdisorders of other organs observed in patients withCrohn’s disease. These protein conglomerates passthrough the body and leave behind damage of varioustypes in many different organs.

11

Formation of an immune complex

Antibodies Antigen

Antigen determinants

Antigen binding site(each antibody has 2)

Crohn’s disease can affect thenervous system

Some patients with Crohn’s disease and with ulcerativecolitis, which is another type of inflammatory bowel dis-ease, have suffered disturbances of circulation and evenocclusion of small blood vessels affecting the centralnervous system. Possible causes include changes inthe viscosity or ability of the blood to flow, which maybe due to fluid losses or to the presence of end prod-ucts of inflammation in the blood, or to a local inflam-mation of the blood vessels in the brain. Because pa-tients with Crohn’s disease often fail to absorb B vita-mins in sufficient quantities, they may experience avitamin deficiency, which, in turn, can cause damage tothe nerves. An inflamed bowel segment or a surgicallyshortened bowel may not be able to absorb adequateamounts of vitamins and other nutrients from the food

12

Nerve cells

Synapse

Dendrites Cell body withcell nucleus

Axon withmyelin sheath


and provide them to the organism. Especially affectedare the fat-soluble vitamins (A, D, E and K) and water-soluble vitamins of the B group (B6 and B12).Some Crohn’s patients suffer from so-called polyneu-ropathies. This term indicates abnormal function ofseveral nerves resulting in changes in sensitivity in theareas served by the affected nerves. Patients may noticereduced sensitivity or even stabbing pain, together withreduced activity of normal reflexes.Patients with Crohn’s disease, who, due to the pro-nounced nature of their disease require treatment withmetronidazole, may also suffer from nerve damage.Metronidazole fights bacteria in the bowel and cansometimes prevent worsening of the disease. The drug,however, also binds B vitamins and this may result inpolyneuropathy with unpleasant sensations in the handsand feet or loss of reflexes. These symptoms usuallyresolve once metronidazole is discontinued.

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Effects on the joints

Arthritis and Crohn’s disease can affect eachother.Arthritic joint inflammation may occur in association withCrohn’s disease. The use of anti-inflammatory medica-tions or analgesics (pain medication), such as aspirin,however, may make the symptoms of Crohn’s diseaseworse or provoke a flare. In such cases, the coopera-tion of two physicians from different areas of specializa-tion may be necessary.The causes for this simultaneous occurrence of inflam-mation in the joints and the bowel are believed to beimmunological in nature. In some cases, antibodiesdirected at the body’s own tissues (autoantibodies,autoaggression) may be produced or may be inducedby an inflammatory process due to infection. Suchantibodies may damage tissue at any place they maybe deposited.

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Lower spinal column


Recent research has shown that the permeability (extentto which the bowel wall allows substances to pass) ofthe bowel in Crohn’s disease is increased, permittingabnormally large amounts of foreign substances to passinto the body and potentially stimulate the immune sys-tem. Pain in the large joints of the arms and legs and/orin the spinal column is reported by 25% of patients withCrohn’s disease. In some cases, the tendons and liga-ments throughout the skeletal system may be painfullyaffected.The close association between inflammation of thebowel and the joints is very apparent during treatment.Improvement in arthritic complaints may occur parallelto successful treatment and resolution of inflammatoryactivity in the bowel. One must not forget, however, thatthe severity of the joint inflammation does not alwayscorrelate to the intensity of the bowel inflammation.Similarly, the findings of endoscopy and a patient’s re-ported general condition may be highly contradictory.

15

Hip joint

Osteoporosis

Often, patients with Crohn’s disease exhibit a reductionin bone density. This condition is known as osteoporo-sis and can lead to fractures, especially in the spine.Particularly at risk are patients with chronic disease ac-tivity, poor nutritional condition, patients who have takencortisone for extended periods, and those in whom sig-nificant sections of the small bowel have been surgicallyremoved. Patients at risk for osteoporosis are advisedto take calcium and vitamin D in order to stop furtherbone loss. In cases of very extensive osteoporosis,patients may benefit from bisphosphonates, whichare drugs that inhibit bone destruction.

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Disorders of the eyes

Inflammation of the eyes is reported in a much higherpercentage of patients with Crohn’s disease than in thegeneral population. Types of inflammation include con-junctivitis, an inflammation of the membrane surround-ing the eyes; scleritis, an inflammation of the white ofthe eyes; iridocyclitis, an inflammation of the iris; uveitis,an inflammation of the middle layer of the bulb of theeye; and retinitis, an inflammation of the inner layer ofthe eye, which is immediately involved in vision. Mostcommonly associated with Crohn’s disease are inflam-mations of the sclera or iris and occur at first diseasemanifestation or in association with an acute flare. Pa-tients complain of feeling a foreign body in the eye, andreport pain, sensitivity to light and loss of visual acuity.These symptoms can be isolated or occur together.Therapy consists of cortisone eye drops and adequatetreatment of the underlying bowel inflammation.It is very probable that these disorders of the eyesoccurring in association to Crohn’s disease are due toan antigen-antibody reaction. It is important for boththe patient and physician to consider an associationbetween disorders of the eyes and Crohn’s diseasein order that prompt referral to an ophthalmologist canbe made at the first appearance of symptoms.

17

Skin changes in Crohn’s disease

Patients with Crohn’s disease not infrequently experi-ence changes of the skin and the mucous membranesof the mouth and other areas. The mucous membraneof the mouth or the anal region may develop painful,reddened lesions, which, in some cases, are seen priorto the manifestation of the bowel disease and present ahelpful clue pointing toward Crohn’s disease. Skin ormucosal lesions occur in up to 40% of patients withCrohn’s disease.Dermatologists call these changes “granulomatousinflammation” because these nodular (knot-like) skinchanges consist of characteristic cells of the immunesystem, including granulocytes, lymphocytes andmonocytes. These more or less sharply demarcated,brownish to bluish red areas may in some cases becovered by a flaking crust. They are particularly com-mon in the vicinity of fistulae or may be found whereskin rubs against skin, such as under the breasts or inthe groin.Although they have no direct contact with the intestinaltract, such granulomatous lesions may occur on theinner sides of the lips or cheeks. In these areas, theremay be characteristic cobble-stone-like thickening orpainful fissures of the edge of the tongue.Patients may sometimes develop painful, reddish nod-ules on the front side of their legs. This condition iscalled erythema nodosum. In some cases, purulent skinulcerations may develop (pyoderma gangraenosum).These vary in size from millimeters to several centimetersand are not due to infection by pathological organisms.Here, too, scientists believe that immunological damageto the skin and blood vessels in the skin underlies theselesions.

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Some of the skin changes appear to be associatedwith the inadequate absorption of vitamins and traceelements caused by patients’ frequent diarrhea and lossof blood and fluid. For example, anemia may be associ-ated with glossitis, an inflammation of the tongue, whichmanifests itself as a reddened and smooth tongue.Eczema-like changes around the mouth are due to zincdeficiency. Zinc is an important trace element crucial forthe body’s immune defenses. Deficiencies in zinc mayalso result in prolonged healing of skin injuries.Similarly, skin fungi can more easily spread in personswhose immune systems have become weaker.

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Liver, gallbladder and pancreas inCrohn’s disease

In rare cases, inflammation involving the liver and biliarysystem may also be observed. Such disorders areidentified using blood tests to measure the levels ofenzymes specific to the liver.In some cases, nodular conglomerations of cells (granu-lomas) may develop in the liver tissue. This condition isknown as granulomatous hepatitis. These granulomasare similar to lesions seen in the mucosal membrane ofthe bowel in patients with Crohn’s disease.The bile ducts may also be affected by a non-infectiousinflammation (primary sclerosing cholangitis). The tissuethat makes up the bile ducts may, as a result of inflam-mation, become hardened, while the ducts themselvesmay become narrowed (stenosis). This acts to impedethe flow of bile and this back-up can, on one hand,damage the liver, while, on the other, patients are at ahigher risk of developing gallstones. These stones havea tendency to form or become trapped at narrow pointsin the bile ducts, resulting in an increase in the symp-toms of biliary stasis, or can cause patients to experi-ence biliary colic.Patients with Crohn’s disease can also develop differenttypes of problems with the pancreas. For example, invery rare cases, drugs used to treat Crohn’s disease(sulfasalazine, mesalazine, azathioprine) have beenknown to cause acute pancreatitis, or inflammation ofthe pancreas.Acute pancreatitis, however, may also occur as one ofthe so-called extraintestinal manifestations (effects ofthe disease occurring outside the bowel) of Crohn’sdisease. This may be due to changes in the duodenum,the first segment of the small bowel after the stomach.The pancreas produces important digestive enzymes


and secretes these through a small duct into the duo-denum. Inflammatory narrowing or occlusion of thisduct may result in a back-up of secretions in the pan-creas.

The altered secretion of digestive enzymes seen insome patients with Crohn’s disease is thought to bedue to the general disturbance of digestion in the affect-ed bowel segments or to an immunological cause. Theoccurrence of elevated pancreatic enzyme levels in theserum, especially of α-amylase (which may often beindependent of acute bowel inflammation and withoutany other complaints) is, by itself, no sign of acute pan-creatitis. Acute pancreatitis manifests itself as severeupper abdominal pain associated with elevation of allpancreatic enzymes (amylase, lipase) in the blood.

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Bile and pancreatic juice secretedinto the duodenum

Liver

Gall-bladder

Duodenum

Digestiveenzyme

Pancreas

22

Crohn’s disease and renal disorders

Crohn’s patients have an increased risk of nephrolithia-sis (development of kidney stones). An important causeof this phenomenon is believed to be the increased ab-sorption of oxalic acid in the damaged bowel segments.Kidney function, however, may also be reduced by thedevelopment of amyloidosis, which is a condition inwhich a certain type of protein (amyloid) is deposited inthe kidneys. The increased precipitation of immunecomplexes in the renal tubules has also been discussedas a cause for damage to the kidneys and the resultingloss of renal function. Patients experience the increasedloss of protein in the urine, probably due to damageto the membrane of the renal tubules caused by sub-stances related to inflammation, such as tumor necrosisfactor (TNF). This damage permits large protein mole-cules to pass from the blood into the urine.Because of the losses of large amounts of fluid throughthe bowel, the body loses important molecules knownas electrolytes (sodium, bicarbonate). This causes a

Kidney

Renal pelvis

Ureter

Renalmedulla

Renalcortex


shift in the balance of the electrolytes. This mechanismmay also be responsible for the development of kidneystones.A very rare complication of the treatment of Crohn’s dis-ease is the development of nephritis, or inflammation ofthe kidneys. The cause of this is believed to be an intol-erance or allergy to the anti-inflammatory medication.

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The respiratory tract inCrohn’s disease

It is highly probable that immunological processes,such as those believed to occur in Crohn’s disease,also cause changes in the respiratory tract. In fact,many Crohn’s patients do exhibit mildly reduced pul-monary function, but the effects can be quite variable.For example, in some patients, the trachea and bronchimay be inflamed or reduced in caliber. Other patientsmay experience an allergy-like disorder of the lung tis-sue (alveolitis), in which the alveoli (the tiny sacs in thelungs where gas exchange take place) are inflamed; orthe pleural membrane, which envelops the lungs, maybe affected. Because these disorders are extremely rareconcomitants of Crohn’s disease, it has not yet beenpossible to demonstrate a clear association with diseaseactivity or with the duration of the disease. To complicatematters further, the drugs used to treat Crohn’s diseasecan also cause allergic or inflammatory reactions in thelungs. Especially at risk are patients in whom pulmonaryfunction has already been compromised by the inflam-matory bowel disease.

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Psychic factors in Crohn’s disease

It has only been in the last few years that researchershave identified an association between changes in thenerves and psychic reactions. It has been shown, forexample, that the so-called vegetative nervous system(comprised of the sympathetic and parasympatheticnervous systems) can exert both stimulating and in-hibitory effects on the immune system. Of interest tothe researchers was the observation that not only dothe nerve cells of the brain (the central nervous system)possess regulatory influences over the immune systembut that information from the immune system reachesthe nerves and the brain.The brain regulates the production of important hor-mones, including the corticosteroids, growth hormonesand the sex hormones. An antigen-antibody reaction asa response of the immune system is also affected bythis system through the increased production of gluco-corticoids. This is the basis of the body’s own counter-reaction to self-immunization. Also involved in thisprocess are the cytokines, substances involved in thetransfer of information between inflammatory cells(lymphocytes, monocytes). Feedback control of thebody’s own immune response regulates the extent andduration of each individual immune reaction.

Of high scientific interest are the reactions of the humanimmune system to psychic stress. Information in thisregard has been collected from patients who suffer fromdepression, people who have recently lost their spouses,and others exposed to significant psychic stress.The association of psychic and immunological processesrepresents a complex network of biochemical, neuro-hormonal and immunological components, each ofwhich exerts an effect on the psychological state andon the immune system of patients with Crohn’s disease.

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To this category belong the many cases in which expo-sure to psychic stress has been followed by a worsen-ing of patients’ inflammatory bowel disease. Conversely,however, solving a psychic problem may be associatedwith improvement in patients’ inflammatory bowelsymptoms.

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Psychic stress

Stress factors

Physical stress,inflammation

Hypothalamusand

pituitary gland

Adrenal cortexand

adrenal medulla

CortisolAdrenalineNoradrenaline


Psychotherapy can be an important tool for solvingpsychic conflicts and may at the same time help in re-ducing the symptoms of inflammatory bowel disease.Psychotherapeutic counseling, autogenic training, deeprelaxation and physiotherapy in either individual orgroup setting can in many cases result in improvementin physical symptoms when instituted as an adjuvantpsychological therapy.

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The risk of cancer inCrohn’s disease

Patients with Crohn’s disease affecting the colon (largebowel) have an increased risk of developing cancer ofthe colon when the duration of their disease exceeds10 years. The risk continues to rise in proportion to theduration of the disease. For this reason, patients withextensive Crohn’s disease for more than eight yearsshould undergo colonoscopy every one to two years.This allows for early detection of any developing coloncarcinoma and increases the prospects for curativesurgical therapy.There is evidence that consequent treatment with sul-fasalazine or 5-aminosalicylic acid significantly reducesthe risk of developing cancer of the colon.

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Living with Crohn’s disease

Inflammatory bowel diseases – this includes Crohn’sdisease and ulcerative colitis – are disorders that havenot yet been fully understood. For this reason, there isno therapy which can truly be said to address the causeof these diseases. The therapeutic alliance betweenphysician and patient is characterized by the subjectiveexperience of the patient and the knowledge and expe-rience of the treating physician. Not infrequently, theremay be a difference between the objective assessmentof the physician and the patient’s subjective experienceof his disease. And each patient has experienced phas-es of life when he has the strength to more fully tolerateand accept his disease, as well as more stressful phases,when the ability to master the situation may be com-pletely lost.As long as there are no reliable methods of cure, thera-py must remain limited to improving the symptoms andpreventing or managing any complications of the dis-ease that may occur. Changes in diet, a large number ofdrugs of varying efficacy, and psychological and surgicaltreatments represent the spectrum of possible therapies.Whether conservative methods are instituted singly orto complement one another, and whether surgery willever be required must be decided in close cooperationbetween physician and patient.Of especial assistance to the patient are the many self-help groups that have been formed in many areas.These groups provide a setting for people with similarproblems to meet and exchange experiences, expresstheir feelings, pass on recommendations on correctbehavior, diet, and much more. Most importantly, theydeal with the problems of the disease from a positionof understanding and support.

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Physician, family and self-help group belong to theclose social environment of patients with Crohn’s dis-ease. Frank discussions and cooperation in developingcoping strategies not only assist the Crohn’s patient toaccept the fact that he suffers from a chronic diseasebut also help persons in the patient’s social environmentto better understand both the patient and his specificissues.

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Crohn’s disease and pregnancy

Crohn’s disease can manifest itself at any age; hence,women of childbearing age may also be affected. Con-cerns that the disease may have a negative impact onthe course of pregnancy, however, have not been con-firmed. Long-term observations of pregnant womenwith Crohn’s disease, in fact, suggest that the severityof the disease may actually improve during pregnancy.This may be related to the fact that the hormonal envi-ronment changes so profoundly during pregnancy. Thisobservation is also supported by the fact that, in manypatients, the dose of medications used to treat Crohn’sdisease can be reduced. Should it happen, however,that the activity of the disease increases despite co-existing pregnancy, there are today a number of veryeffective drugs for reducing the inflammation of Crohn’sdisease that are not associated with increased risks forthe unborn child. Use of mesalazine (5-aminosalicylicacid), salazosulfapyridine and corticosteroids is notcontraindicated in pregnancy. There is also much evi-dence that azathioprine does not negatively affectpregnancy.

A comparison of pregnant Crohn’s patients and preg-nant women in the general population has shown thatthe probability of giving birth to a healthy baby is identi-cal for both groups. In addition, the risk of Crohn’s pa-tients for miscarriage or birth defects in the baby doesnot differ from that of the general population.Of particular importance is a close cooperation betweenthe patient’s gynecologist and the internist or gastroen-terologist who is managing the patient’s Crohn’s disease.This will help assure that any complications can bedetected early and promptly treated.

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Nutritional requirements inCrohn’s disease

There is no uniform diet that can be prescribed for allCrohn’s patients. However, some guidelines for propernutrition have been proposed, which should help patientsavoid mistakes in planning their nutrition. Cakes andfoods with a high sugar content have been implicated ina worsening of Crohn’s symptoms in some patients.Foods that have the potential for causing large amountsof gas should also be avoided by Crohn’s patients. So-called dietary fiber plays an important role in supportingregular bowel function. Special care, however, is neces-sary in patients with scar tissue formation or inflamma-tion, which has resulted in a narrowing of the bowel(stenoses). These patients must consume a diet low indietary fiber.It should be clear to both the physician and patient thatnutritional deficits in the sense of a deficiency situationcan occur during an acute flare of an inflammatory boweldisease. In particular, deficiency syndromes can arisefor protein, lipids (fats), electrolytes, vitamins and traceelements. Depending on the acute or chronic course ofthe disease, these may have various causes:

A protein deficiency may occur if:– The diet is too one-sided or if the patient fasts due

to fear of symptoms.– Nutrients are not adequately absorbed in bowel

segments affected by inflammation.– Inflammatory secretions with high protein content

are lost through the bowel.– Loss of protein through the kidneys if these are

affected by the disease.

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Iron deficiency is usually due to a loss of blood. How-ever, chronic inflammation may also be characterized bya disorder of iron metabolism in which the transport of,and binding capacity for iron is reduced. Iron is an im-portant element for blood production and is crucial foroxygen transport. Therefore, all patients with inflamma-tory bowel disease should have their iron levels checkedon a yearly basis.

Vitamin deficiencies, especially deficiencies of fat-soluble vitamins (vitamins A, D, E and K), may be dueto extensive inflammation affecting the small bowel orresection of significant portions of the small bowel, butalso to inadequate diet, especially when the diseaseactivity has become chronic. Especially important is adeficiency of vitamin D (risk of osteoporosis) and/orvitamin B12 (anemia).

Disturbances of water and electrolyte metabolismare due to the high losses of fluid associated with wa-tery diarrhea. Sodium, potassium, calcium and chlorideare dissolved in every body fluid and are lost togetherwith any loss of fluid. These losses, however, can becompensated by a supplementation of electrolytes withthe diet or in the form of tablets or electrolyte drinks.

Trace elements such as magnesium, copper, seleniumand zinc play important roles in different organs. Defi-ciencies of these substances can be determined at ayearly routine check of laboratory values and supple-mented, if needed.

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Medical treatment ofCrohn’s disease

Drugs can be used both to treat an acute flare ofCrohn’s disease (acute phase therapy) and to preventrecurrence of inflammation (remission maintenance).

“Cortisone” or better corticosteroids“Cortisone” or, more correctly, corticosteroids representa group of agents (prednisone, prednisolone, methyl-prednisolone etc.) that are among the most importantdrugs used to treat Crohn’s disease. Patients whosedisease manifests itself as an isolated inflammation ofthe small bowel or as a combination of disease affectingboth the small bowel and colon usually respond well tocorticosteroids. In Crohn’s disease limited to the colon,however, their efficacy is often poorer. In acute diseaseflares, corticosteroids must be administered at a suffi-ciently high dose (e.g. prednisolone, 60 mg per day).If disease activity is reduced by this treatment, the dosecan be slowly tapered. As disease activity decreases,the dose can be slowly reduced and the agent can becompletely discontinued after about three months.

BudesonideIn an effort to find agents that preserve the high efficacyof corticosteroids but are not associated with the samedegree of side effects, new kinds of corticosteroidshave been developed. Among these new corticosteroidsare some which are known as topical corticosteroids:these are drugs that work locally at the site of applica-tion. One of these, budesonide, has become an accept-ed treatment for patients with Crohn’s disease.Budesonide is effective after administration as a capsule,enema or rectal foam directly on the inflammation ofthe intestinal mucosa. The drug is also absorbed in the

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bowel and carried by the circulation to the liver. Unlikeother corticosteroids, however, about 90% of the ab-sorbed budesonide is broken down in the liver to inac-tive substances: hence, only a tiny portion of the admin-istered dose can be distributed in the body and causeside effects. Several large studies have shown that theefficacy of budesonide is only slightly less than that ofconventional corticosteroids but is associated with asignificantly lower rate of side effects. Budesonide,however, should not be used in patients with verysevere disease activity, in those with extensive extrain-testinal disease affecting other organs, or when Crohn’slesions are present in the esophagus, stomach or duo-denum, since the drug is not sufficiently effective atthese sites.

SalazosulfapyridineSalazosulfapyridine no longer plays a meaningful role inthe treatment of Crohn’s disease. It is mostly used only incases of joint disease associated with Crohn’s disease.

Mesalazine/5-aminosalicylic acid (5-ASA)Mesalazine has replaced salazosulfapyridine in thetreatment of Crohn’s disease. Mesalazine is particularlyuseful in treating a mild flare of Crohn’s disease, espe-cially in the terminal ileum and colon. Mesalazine canalso help prevent the occurrence of recurrent flares ofCrohn’s disease. An advantage of the substance is itsgood tolerability. It is available in the form of tablets,enemas and suppositories.

AzathioprineThe most effective medication for long-term manage-ment of Crohn’s disease is azathioprine, which is espe-cially useful in patients who are dependent on, or resis-tant to corticosteroids. Azathioprine, however, can alsobe successfully used to prevent disease recurrence (re-

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mission maintenance). It is more potent than mesalazine,but, because of its greater strength, requires closermonitoring of the patient.

Anti-TNF-α antibodyTumor necrosis factor-α (TNF-α) is a substance producedin the body that plays an important role in the inflammato-ry process associated with inflammatory bowel disease.The anti-TNF-α antibody, infliximab, causes the destruc-tion of activated immune cells and, therefore, has im-munosuppressive and anti-inflammatory effects. Theantibody is administered as an intravenous infusion. Itcan be used in patients with Crohn’s disease that hasproven resistant to conventional therapeutic measures.In some patients, administration of this antibody leadsto rapid reduction in disease activity. This is also true forpatients whose disease has been complicated by thedevelopment of fistulae. Administration of the antibodyat eight-week intervals has also been shown to preventdisease recurrence in some patients. Factors limitingthe feasibility of this method include infusion reactionsand the occurrence of infections, including tuberculosis,as well as its high costs.The objective of any treatment of Crohn’s disease is torelieve inflammation as effectively as possible. In addi-tion, a combination of medical treatment, appropriatediet and, when necessary, psychological support,should result in postponing the recurrence of diseaseas long as possible, making acute disease flares lessfrequent.Close cooperation between the physician and patientcan help to get the disease activity of Crohn’s diseaseunder control. By controlling symptoms, the patient canexpect a fairly normal life with only a moderate restric-tion in quality of life.

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Glossary

Absorption: process by which substances are takenin through the skin or mucous membranes or othertissues into the blood or lymphatic system

5-Aminosalicylic acid (5-ASA): active ingredient insalazosulfapyridine

Amyloidosis: deposition of a certain protein in thetissue and the resulting disorder of metabolism

Arthritis: inflammatory disorder of the joints

Causal therapy: therapy, which targets the actualcause of a disease

Cholangitis: inflammation of the bile ducts

Conjunctivitis: inflammation of the membraneconnecting the eye to the socket

Conservative therapy: any non-surgical form oftreatment (drugs, diet, physiotherapy etc.)

Cortisone: a drug used to treat Crohn’s disease withhigh disease activity and which has an anti-inflamma-tory effect

Crohn: Burril B. Crohn (born 1884), the first physicianto describe regional ileitis as an independent diseaseentity

CRP: C-reactive protein: a marker of inflammation inthe blood

Cytokine: messenger substance associated withinflammation

Enzymes: biocatalysts, which accelerate chemicalreactions

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Episcleritis: inflammation of the connective tissuebetween the sclera and conjunctiva of the eye

Erythema nodosum: acute inflammatory skin diseaseof the subcutaneous adipose (fatty) tissue

Erythrocyte sedimentation rate (ESR): rate at whichred blood cells settle in blood that has been treated soas not to coagulate

Fistula: abnormal tubular tract between one diseasedhollow organ and another or between such an organand the body surface

Granuloma: typical nodular structure that develops asa response of the tissue to an inflammatory or otherprocess

Ileitis, terminal: inflammation of the end portion of thesmall bowel; another term for regional Crohn’s disease

Immune system: complex system in higher animalswhich defends the body from foreign proteins andother substances

Iridocyclitis: inflammation of the iris and ciliary body ofthe eye

Lesion: site of damage or injury

Lumen, bowel: the interior of the bowel

Muscle reflex: contraction of a muscle in response tobrief extension

Nephrolithiasis: kidney stone disease

Oligoarthritis: simultaneous inflammation of 2–4 largejoints

Polyneuropathy: disorder of more than one peripheralnerve

Psyche: soul, mood

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Retinitis: inflammation of the inner layer of the bulb ofthe eye

Salazosulfapyridine: compound consisting of5-aminosalicylic acid and sulfapyridine

Secretion: release of fluid or of molecules from cells

Scleritis: inflammation of the sclera (the white) of the eye

Uveitis: inflammation of the middle layer of the bulb ofthe eye

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Further information for patientswith inflammatory bowel diseases:

– Ulcerative colitis andCrohn’s diseaseAn overview of the diseases and their treatment68 pages (S80e)

– Diet and Nutrition in Crohn’s Diseaseand Ulcerative Colitis20 Questions – 20 Answers60 pages (S84e)

– Crohn’s Disease, Ulcerative Colitisand Pregnancy57 pages (S82e)Revised edition 2008

– Corticosteroid therapy in inflammatorybowel diseases32 pages (Bu80e)Revised edition 2008

These brochures can be ordered free of chargefrom Falk Foundation e.V. or the local Falk partner.

www.falkfoundation.com

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