Multiple-choice questions · Multiple-choice questions Multiple-choice questions in thoracic transplantation medicine S W Dubrey, C Melikian, N R Banner Are the statements listed

Multiple-choice questions

Multiple-choice questions in thoracictransplantation medicine

S W Dubrey, C Melikian, N R Banner

Are the statements listed beneath each question true or false? Answers are given on pages 122−4.

Question 1

In the selection of donors and recipientsfor heart transplantation:A HIV positive status in the recipient is an

absolute contraindicationB Pulmonary hypertension in the donor is a

relative contraindicationC Body size is an important consideration in

matching donor and recipientD Medical history of tuberculosis in the

recipient is a contraindicationE Cytomegalovirus (CMV) positive status in

the donor is a contraindication

Question 2

In transplant patients on immunosup-pressive therapy, the following agents arecorrectly paired with their recognisedpotential side-eVect profile:A Azathioprine: nephrotoxicity, hypertension

and neurotoxicityB Corticosteroids: leucocytosis, aVective dis-

orders and osteoporosisC Cyclosporin: bone marrow suppression,

pancreatitis and hepatitisD Antithymocyte globulin: anaphylaxis, leuco-

penia and haemolysisE Mycophenolate: bone marrow suppression

and haemorrhagic cystitis

Question 3

Immunosuppressed transplant recipientsshould not have the following:A BCG vaccineB Camembert cheeseC Varicella immune globulinD Influenza vaccineE Malaria prophylaxis

Question 4

The following drugs have important inter-actions with either cyclosporin or azathio-prineA AllopurinolB Non-steroidal anti-inflammatory drugs

(NSAIDs)C ErythromycinD MetforminE Warfarin

Question 5

In the diagnosis of acute rejection of atransplanted organ:A Cardiac rejection is usually accompanied by

an increase in ECG voltage amplitudeB Obliterative bronchiolitis is characteristic of

acute pulmonary rejectionC Cardiac rejection may cause left ventricular

systolic dysfunctionD Rejection is excluded by the findings of a

pyrexial patient with flu-like symptomsE An asymptomatic patient may have sig-

nificant histological rejection on cardiacbiopsy

Question 6

In the selection of recipient candidates forthoracic organ transplantation:A Irreversible pulmonary hypertension is a

contraindication to orthotopic heart trans-plantation

B A prior history of hepatitis C is an absolutecontraindication to transplantation

C Matching of body size is less critical forheart than for lung transplantation

D Insulin-dependent diabetes in the recipientis an absolute contraindication

E Creatinine clearance of <50 ml/min andproteinuria of >0.5 g/24 h would prohibittransplantation

Question 7

In patients transplanted and on conven-tional immunosuppression:A Pneumocystis carinii is the commonest cause

of pneumonia in lung transplant patientsB A pre-transplant history of tuberculous lym-

phadenitis would not require prophylactictherapy

C Angina can never be appreciated in theheart transplant recipient due to denerva-tion

D Coronary artery disease develops more rap-idly in the transplanted heart than in anative heart

E Lymphoproliferative disease is frequentlycaused by CMV infection

Postgrad Med J 2000;76:120–124 © The Fellowship of Postgraduate Medicine, 2000

Department ofTransplant Medicine,Harefield Hospital,Harefield, Middlesex,UKS W DubreyC MelikianN R Banner

Correspondence to DrSimon Dubrey, Departmentof Cardiology, HillingdonHospital, Pield Heath Road,Uxbridge, MiddlesexUB8 3NN, UK

Submitted 26 January 1999Accepted 13 August 1999

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Question 8

In patients being assessed for transplanta-tion:A Patients with pulmonary histiocytosis X are

at risk of recurrent disease after lungtransplantation

B Amyloid heart disease is an absolute con-traindication to cardiac transplantation

C Current cigarette smoking should be anabsolute contraindication to thoracic organtransplantation

D A lack of social and domestic support is nota contraindication to transplantation

E Ventricular arrhythmia resistant to treat-ment with drugs or automatic implantablecardioverter defibrillators is an indicationfor heart transplantation

Question 9

In patients who have undergone thoracicorgan transplantation:A One year mortality for adult heart transplan-

tation is 10%B Detection of aspergillus on broncho-alveolar

lavage indicates invasive diseaseC The dose and number of immunosuppres-

sive agents may be reduced as time elapsesfollowing transplantation.

D The commonest indication for heart trans-plantation in adults is ischaemic cardiomy-opathy

E The commonest indication for heart trans-plantation in children is congenital heartdisease

Question 10

The following malignancies are a particu-lar problem in patients on immunosup-pressive therapy:A MelanomaB Non-Hodgkins lymphomaC Sunlight-related skin malignancies.D Kaposi’s sarcomaE Bronchogenic carcinoma

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ANSWERS

Question 1

A TrueB FalseC TrueD FalseE False

Absolute contraindications to the use of adonor heart for transplantation include coron-ary artery disease, previous myocardial infarc-tion, ventricular arrhythmias, severe hypokine-sis, HIV positive status, death due to carbonmonoxide poisoning and metastatic cancer.

Relative contraindications include prolongedinotropic support, sepsis, prolonged hypoten-sion, a long ischaemic time and a history ofintravenous drug abuse. All potentially causecomplications but the benefits must beweighed against the potential recipient’s imme-diate prognosis. A history of tuberculosis in therecipient is not an absolute contraindicationbut it would have required appropriate treat-ment at the time and would necessitateisoniazid prophylaxis after transplantation. If ahigh-risk donor is proposed then it must bewith the recipient patient’s prior informed con-sent. CMV positive status is not a contraindica-tion to transplantation in either the donor orrecipient although reactivation of latent infec-tions after immunosuppression may causeactive infection.

Question 2

A FalseB TrueC FalseD TrueE False

Azathioprine, corticosteroids and cyclosporinare often used in maintenance immunosuppres-sion. The major side-eVects of cyclosporin arenephrotoxicity (acute and chronic), neurotoxic-ity (headaches, tremor and convulsions), hyper-tension and cosmetic problems (gum hyperpla-sia and hirsutism). These side-eVects are sharedby the newer immunosuppressant tacrolimuswhich can be used in place of cyclosporin.

Azathioprine may cause bone marrow sup-pression, pancreatitis, hepatitis and gastro-intestinal upset. In the event of any of the abovethen cyclophosphamide may be a reasonablealternative agent. Antithymocyte globulin iscommonly used as an immunosuppressiveinduction agent to cover the early postoperativeperiod and occasionally to treat acute severerejection episodes. It is produced by immunis-ing rabbits or horses with human lymphoidcells. The most frequent side-eVect of thesepreparations are chills, rigors, flu-like symp-toms and less commonly serum sickness oranaphylaxis. Patients are hence often pre-medicated with paracetamol, antihistaminesand corticosteroids. A major consideration isalso the increased risk of infection, particularlyCMV, with the use of such preparations.Mycophenolate can cause gastrointestinal side-eVects, including nausea and diarrhoea, in

addition to bone marrow suppression. Haem-orrhagic cystitis is a side-eVect associated withcyclophosphamide.

Question 3

A TrueB TrueC FalseD FalseE False

Immunosuppressed patients in general shouldnot receive live vaccines such as BCG, MMR,oral polio, oral typhoid or rubella vaccine. Inac-tivated vaccines, such as influenza, hepatitis A orB, pneumococcal and adsorbed tetanus vaccineare permitted, although these are likely to be lesseVective than in an immunocompetent indi-vidual. Varicella immune globulin is used inimmunosuppressed patients who have comeinto contact with chicken pox or varicella zostercases. Patients are advised to avoid eating foodsliable to be contaminated with listeria, such assoft ripened cheeses, for example Brie, Camem-bert, blue-veined cheeses and all pates.

Question 4

A TrueB TrueC TrueD FalseE False

Many drugs interact with the standard immu-nosuppressive agents used. Cyclosporin isnephrotoxic and therefore combinations whichincrease the risk of nephrotoxicity, eg,NSAIDs, aminoglycoside antibiotics and van-comycin should be avoided. Allopurinol canonly be used with careful monitoring as itinhibits the metabolism of azathioprine (usu-ally a reduction in dose of azathioprine to 1/4the original dose is required). The combinationcan cause dangerous bone marrow suppres-sion. Metformin is excreted via the kidneys andshould be avoided when renal function isimpaired. In addition, metformin has beenshown to interact with contrast agents used inangiography, a procedure often performedannually in the follow-up of heart transplantpatients. Thus, whilst not contraindicated intransplantation or with immunosuppressivemedications per se, metformin should be usedwith caution when radiographic contrastagents are used.

Question 5

A FalseB FalseC TrueD FalseE True

Fever in a transplant recipient will most oftenbe due to infection. A minority of patients withrejection can present with fever and generalisedflu-like symptoms, reflecting the presence of an‘inflammatory’ process. Most sinister is thepresence of significant rejection with few or nosymptoms and therefore surveillance right ven-

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tricular endocardial biopsy is utilised. Cardiacrejection is indicated by symptoms of dys-pnoea, palpitations or loss of appetite and signsof heart failure including dependent oedema, athird heart sound and raised jugular venouspressure. The ECG will often show a reductionin voltage with significant rejection. In acuterejection diastolic dysfunction of the leftventricle appears to occur early; once systolicimpairment is evident then urgent therapy isrequired. Echocardiography will usually show aglobal reduction in ventricular function; aregional abnormality being more suggestive ofischaemic damage from graft vascular disease(chronic rejection). Pulmonary rejection isindicated by symptoms of dyspnoea and byreduction in both air flow and lung volume onspirometry. Possible rejection is investigated bybronchoscopy, broncho-alveolar lavage andtransbronchial biopsy to exclude infection as adiVerential diagnosis. Rejection can often beconfirmed histologically from the transbron-chial biopsy. Obliterative bronchiolitis is a fea-ture of chronic rejection and not usually seenacutely or in the immediate time period aftertransplantation.

Question 6

A TrueB FalseC FalseD FalseE True

Whilst irreversible pulmonary hypertension is acontraindication to conventional orthotopicheart transplantation, the problem can be tack-led by the use of a ‘pressure primed’ heart froma donor with primary pulmonary hypertension.Patients with cystic fibrosis who receive a heartand lung block may also donate their heart in a‘domino’ donor programme to a recipient withpulmonary hypertension. A second procedureoccasionally used is that of heterotopic trans-plantation, in which the donor heart isimplanted in the right side of the chest,attached in parallel to the patient’s native heartand vascular circuit, to act in eVect as a physi-ologic assist mechanism. In this way the donorheart, with right ventricle attached via the pul-monary artery to the native heart’s rightatrium, or superior vena cava, is not exposed tothe high pulmonary artery pressures.

The majority of individuals infected withhepatitis C have persistent infection which maybe aggravated by immunosuppressant drugtherapy. Patients with pre-existing liver dys-function or cirrhosis would be excluded but inother cases transplantation could be possible,albeit at an increased risk. Body size isparamount to the selection and matching ofrecipients to donor organs for both hearts,lungs and heart lung transplants. In the case ofhearts, a 20% mismatch on body size is themaximum advisable. Insulin-dependentdiabetes is a systemic disease but providedthere is not significant end-organ damage(retinopathy, peripheral or cerebral vasculardisease and renal impairment particularly), itdoes not represent an absolute contraindica-

tion. Evidence of significant renal impairment(creatinine clearance <50 ml/min), of whateveraetiology, is a serious consideration usuallyresulting in the rejection of a candidate. Some-times the renal dysfunction can be secondaryto heart failure and may be improved with ino-trope therapy or mechanical circulatory sup-port prior to transplantation. The considera-tion is that with the obligatory introduction ofcyclosporin and the peri-operative stress therewill be further reduction in renal performancethat could result in the need for dialysis.

Question 7

A FalseB FalseC FalseD TrueE False

The commonest opportunistic infection inboth heart and lung transplant patients is CMVinfection. This usually responds to treatmentwith intravenous ganciclovir. Tuberculosis maybe reactivated by steroids and chronic immu-nosuppressive therapy. Angina may be appreci-ated in heart transplant patients several yearsafter their surgery; the mechanism presumablydue to re-innervation of the donor heart. Lym-phoproliferative disease resulting from immu-nosuppressive therapy is associated with theEpstein Barr virus in most cases and willfrequently respond to a reduction in immuno-suppression and/or treatment with aciclovir.

Question 8

A TrueB FalseC TrueD FalseE True

Amyloid heart disease is usually part of asystemic process and recurrence of amyloiddeposition in the transplanted organ is welldocumented. However, if the primary diseaseprocess of amyloidosis is also treated then hearttransplantation should not be considered anabsolute contraindication. Continued cigarettesmoking should be considered an absolute con-traindication, particularly with the added risk ofaccelerated coronary artery disease. Social,domestic and family support are essential com-ponents to recovery from organ transplantation;these components form an essential part of apotential transplant recipients evaluation.

Question 9

A FalseB FalseC TrueD FalseE True

Current estimates from the International Soci-ety of Heart & Lung Transplantation show aone-year mortality for heart transplantation of20%, with an approximate 4% mortality peryear thereafter. Isolation of Aspergillus frompulmonary secretions does not necessarily

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imply invasive disease. The mainstay of diagno-sis of invasive aspergillosis is its detection intissue where branched septate hyphae are seenon histology of lung biopsies. The commonestindication for heart transplantation in adults iscurrently dilated cardiomyopathy of non-ischaemic origin.

Question 10

A FalseB TrueC TrueD FalseE False

An unfortunate consequence of chronic immu-nosuppression is an increased risk of a numberof malignancies due to a loss of T-cell immunesurveillance. In general, the risk of malignancyis three times that of an age-matched non-transplant population; some malignancies areparticularly common. Lymphoproliferative tu-mours, often in younger recipients, are perhapsthe most important and can occur early aftertransplantation. As the risk of most malig-nancies increases with age and the addition ofimmunosuppressive therapy may accelerate theprogression of occult malignancy, age and/orsymptom driven screening tests should be per-formed in all candidates for transplantation.

Images in medicine

Skull osteomyelitis and multiple brain abscesses

A 52-year-old diabetic Indian man presentedwith a 2-week history of headache and fever.He had no evidence of meningism. There wasmild polymorph leucocytosis and raised eryth-rocyte sedimentation rate of 113 mm/h. Otherinvestigations, including tests for humanimmunodeficiency virus and immunoglobu-lins, yielded negative or normal results. Initialskull X-ray and brain computed tomography(CT) scan were normal. Three days later, hewas found to have subcutaneous swelling overthe left frontoparietal region of the scalp. Inci-sion drainage revealed a subaponeurotic ab-scess in direct contact with the bone. Pseu-domonas cepacia was grown from pus andtreated with appropriate antibiotics. Fever andheadache settled and he became asymptomaticafter few days. Two weeks later, a dischargingsinus with serosanguinous material from thescalp wound was noted. At this point, osteomy-elitis of the cranial vault was clearly seen onplain skull X-ray (figure 1). A follow-up brainCT scan showed left-sided soft tissue swellingand multiple ring-enhancing frontal lobe ab-scesses (figure 2). Surprisingly, apart from thescalp discharge, he remained asymptomatic. Pcepacia was again grown from the wound andtreated with a combination of piperacillin andceftazidime. Three weeks later, a repeat CTscan showed marked improvement of hisintracerebral and scalp lesions. The antibioticswere continued for another 3 weeks. This casedemonstrates that even a minor superficialsuppurative lesion has the potential to becomesinister in an immunocompromised subject, asit may rapidly extend to deeper tissues. Moreo-ver, the diagnosis of these multiple and appar-ently silent cerebral abscesses would have beendelayed if repeated radiological imaging hadnot been undertaken.

HAIDER M AL ATTIARAHEEL A QURESHI

IDRIS A EL HAGMedical Department, Mafraq Hospital,

POBox 2951, Abu Dhabi, United Arab Emirates

Figure 1 Skull X-ray

Figure 2 Cranial CTscan

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