Burket, ch. 19 Falace, ch. 22

Transcription

1 Burket, ch. 19 Falace, ch. 22

2 transplantation has become the treatment of choice for the restoration of function in end-stage organ disease. Heart, liver, kidney, pancreas, heart/lung, bone marrow, and other transplants may be available for the appropriate recipient. The ideal combination involves transplantation of an organ from an identical twin to the other twin (syngeneic). The next best match for organ survival is transplantation of an organ from one living relative to another (allogeneic). This is followed by transplantation of an organ between living nonrelated individuals (xenograft).

3 Laboratory findings of particular importance to the dentist include bleeding time, differential white blood cell count, prothrombin time, hematocrit, partial thromboplastin time, blood urea nitrogen, aspartate aminotransaminase, serum creatinine, specific gravity of urine, platelet count, white blood cell (WBC) count, serum bilirubin, alkaline phosphatase, and testing of urine for proteins. Elevations in aspartate aminotransaminase, alkaline phosphatase, prothrombin time, and serum bilirubin would suggest advanced liver disease. Increased bleeding time, low platelet count, decreased WBC count, and decreased hematocrit are associated with many of the blood dyscrasias.

4 Elevations in serum creatinine and blood urea nitrogen and increased specific gravity of urine and proteinuria are associated with advanced renal disease. In addition, a low hematocrit value, prolonged partial thromboplastin time, and decreased WBC count may be found inpatients with advanced renal disease. The immunosuppressive agents now used for most heart, liver, kidney, and pancreas transplantations are cyclosporine, azathioprine, mycophenolate mofetil, prednisone, tacrolimus, sirolimus, everolimus, and an antilymphocyte agent. Total body irradiation (1000 cgy) has been the most effective means of conditioning a bone marrow graft recipient.

5 The best clinical results are attained with triple-drug immunosuppressive therapy cyclosporine, prednisone, and azathioprine or mycophenolate mofetil (MMF). After transplantation, doses of the immunosuppressive agents are reduced as much as possible to prevent rejection of the graft. Heart Transplantation: Heart transplantation involves surgical removal of the heart from the donor and removal of the recipient s diseased heart and attachment of the donor s heart to the major vessels of the recipient s heart. In addition to the immunosuppressive agents given to the recipient, other medications are given at the time of transplantation. These include agents such as dipyridamole (for platelet suppression), trimethoprimsulfamethoxazole (to prevent infection), and nystatin (Mycostatin) (Candida prophylaxis).

6 Heart/Lung Transplantation: In addition to the surgical protocol for cardiac transplantation, the lungs are generally combined in patients with primary pulmonary hypertension, pulmonary fibrosis, cystic fibrosis, certain congenital heart conditions, and primary cardiac disease accompanied by secondary pulmonary hypertension. Anastomotic sites: trachea, the right atrium, and the aorta. Liver Transplantation: Liver transplantation involves excision of the diseased recipient s liver, along with reconstruction of the vena cava, portal vein, and biliary tree. Small-Bowel Transplantation: SBT currently is performed only in patients with end-stage intestinal failure for whom conventional treatment has been unsuccessful. Intestinal failure is characterized by the inability to maintain a balance between nutrition and intestinal fluids and electrolytes.

7 Massive small-bowel resection and the short gut syndrome(rapid intestinal transit without proper absorption of nutrients). The small bowel is unique among solid organ transplant grafts because of the large amount of lymphoid tissue contained in the mesenteric lymph nodes, Peyer s patches, and the lamina propria, and the heavy colonization that occurs with microorganisms and large quantities of antigens on the surface of the intestinal epithelium. These factors contribute to high rates of GVHD, graft rejection, and sepsis. Kidney Transplantation. Patients who have a living related donor who is available for kidney transplantation usually are admitted to the hospital 2 days before transplantation.

8 Indications for renal transplantation generally include chronic renal disease and end-stage renal disease (ESRD). ESRD is a progressive, bilateral deterioration of kidney nephrons that results inuremia and, ultimately, death. Accompanying hypertension, diabetes, congestive heart failure, infection, volume depletion, urinary tract obstruction, hypercalcemia, and hyperuricemia must be constantly managed. Pancreas Transplantation: Simultaneously with kidney transplantation After kidney transplantation As a separate procedure

9 In most grafts, the pancreatic duct is drained into the bladder. Urine amylase levels (25% reduction) are used in bladder-drained patients to monitor for rejection. Decreased urinary amylase activity precedes hyperglycemia as a manifestation of rejection. In patients who simultaneously receive kidney and pancreas transplants, an increase in serum creatinine indicates the possible onset of rejection before changes in urinary amylase are detected. Bone Marrow Transplantation: The greatest chance for successful BMT occurs in patients with chronic myelogenous leukemia. Cyclophosphamide and total body irradiation or busulfan may be used for patients with leukemia.

10 The recipient of a syngeneic marrow graft (from an identical twin) requires no immunosuppressive preparation. Similarly, the patient with severe immunologic deficiency requires no immunosuppressive preparation. Intensive chemotherapy or total body irradiation kills the cancer. However, these treatments also may kill the patient, so BMT may be used to rescue the patient from the lethal effects of chemoradiation therapy. Marrow is harvested from the donor s iliac bones through numerous needle aspirations with the patient under spinal anesthesia inan operating room environment. Histocompatibility: Matching of blood type and human lymphocyte antigens (HLAs) with tissue compatibility tests usually results in longer graft and patient survival.

11 The best matching occurs in identical twins. Syngeneic or isogeneic human marrow transplantation involves donors and recipients who carry the same tissue antigens, as occurs in identical twins. An autologous marrow graft refers to transplantation of the patient s own marrow,. An allogeneic marrow graft involves a donor and a recipient of different genetic origin within the same species. Siblings are the best candidates for a partial match (haploidentical), or parents may donate the marrow (they provide usually 30% to 50% of BMTs). The recipient may react adversely to the donated marrow and reject it, or infused marrow cells from the donor transplant, which contain immunologically competent cells, may react against the host to produce GVHD.

12 Complications associated with organ transplantation generally consist of technical problems involving the surgical procedure, problems related to immunosuppression, and special problems specific to the organ transplanted. Major Medical Complications Associated With Transplantation: Excessive immunosuppression Infection Tumors Delayed healing Rejection of allograft Graft failure heart, kidney, liver, pancreas Increased risk for excessive bleeding liver, kidney, bone marrow

13 Overdosage if drugs are metabolized or excreted by kidney or liver, they are administered in normal amounts Death or retransplantation heart, liver, bone marrow Insulin, hemodialysis, or retransplantation kidney, pancreas Adverse effects caused by immunosuppressive agents Hypertension Diabetes mellitus Infection Excessive bleeding Anemia Osteoporosis Adrenal crisis (significant stress from surgery, trauma) Special organ complications Heart transplants accelerated coronary artery atherosclerosis, cardiac valvulopathy Bone marrow transplants graft-versus-host disease

14 Signs of Overimmunosuppression in Posttransplantation Patients: Viral infections (HSV, CMV, HBV, HIV) Bacterial infections (respiratory, wound, etc.) Fungal infections (candidiasis, pulmonary, etc.) Delayed healing Excessive bleeding Hypertension Cushingoid reaction (edema, ascites, etc.) Addison s reaction (adverse reaction to stress, etc.) Diabetes mellitus Anemia Osteoporosis Tumors

15 Rejection of the transplanted organ is apparent when signs and symptoms of organ failure begin to occur. Organ biopsies are used to confirm the rejection reaction. When evidence of acute rejection is found, dosages of immunosuppressive agents usually are increased. Chronic rejection occurs insidiously and is progressive. It cannot be reversed through intensified therapy. Agents used for immunosuppression have several important adverse effects. A major adverse effect of azathioprine is bone marrow suppression with resultant leukopenia, thrombocytopenia, and anemia. Cyclosporine has replaced azathioprine as the key agent for immunosuppression in transplant patients because it does not suppress the bone marrow.

16 Cyclosporine may cause severe kidney and liver changes, which can lead to hypertension, bleeding problems, and anemia; it also may potentiate renal injury caused by other agents. Cyclosporine also is related to an increased incidence of gingival hyperplasia, hirsutism, gynecomastia, and cancer of the skin and cervix. Prednisone has important adverse effects, including hypertension, diabetes mellitus, osteoporosis, impaired healing, mental depression, psychoses, and increased risk for infection. In addition to these adverse effects, prednisone therapy may cause adrenal gland suppression. An increased incidence of certain cancers is seen in immunosuppressed patients.

17 Cancers commonly seen in the general population (carcinomas of lung, breast, prostate, and colon) show no change inoccurrence in immunosuppressed patients. However, two types of cancer found commonly in the general population are found with increased frequency in immunosuppressed patients: squamous cell carcinoma of the skin and in situ carcinoma of the uterine cervix. Cancers that are uncommon in the general population but that occur with increased frequency in immunosuppressed patients are lymphoma, lip carcinoma, Kaposi s sarcoma, carcinoma of the kidney, and carcinoma of the vulva and perineum. Cancer is a complication of intense immunosuppression and is not related to the use of any particular agent. However, certain agents (Cyclosporine and monoclonal antibodies(lymphomas)) may play a more direct role.

18 GVHD is an important and often lethal complication of allogeneic bone marrow transplantation. Acute GVHD occurs within the first 2 months after transplantation and is characterized by skin, liver, and gastrointestinal tract involvement. Chronic GVHD occurs later and is characterized by skin changes similar to scleroderma, sicca syndrome, malabsorption, and features of autoimmunity.

19 Pretransplant Medical Considerations: A number of significant medical problems must be considered during the dental treatment of patients who are being prepared for transplantation. First, the patient will have significant end-organ disease from the organ system, which is necessitating the transplant. Secondly, a thorough dental evaluation will be necessary and required for diagnosis and treatment of any existing dental disease, particularly any infection or oral condition that could result in an infection or in the need for oral surgery during the immediate posttransplant phase, when the patient will be immunocompromised and highly susceptible to infection.

20 Obviously, a consultation with the transplant surgeon and/or team will be important for precise determination of the patient s physical status and details of the procedure, as well as the likelihood of posttransplant complications such as infection. Further, it is best to avoid the need for any dental treatment for about 6 months post transplant because of the many potential complications aside from infection, such as fatigue, medication interactions, and adverse effects, as well as inadvertent saliva aspiration leading to aspiration pneumonia. The patient who is a candidate for a bone marrow transplant is generally very ill and prone to infection, bleeding, and delayed healing because of thrombocytopenia and leukopenia.

21 Posttransplant Medical Considerations:: Medical considerations of importance to the dentist in management of the transplanted patient fall into three stages: 1. Immediate posttransplant period 2. Stable transplant period 3. Chronic rejection period During the immediate posttransplant period, which is generally the first 3 months after transplantation, the patient is started on immunosuppressive therapy to prevent cytotoxic T cells from destroying the graft. This is the time that the patient is at greatest risk for technical complications, acute rejection, and infection.

22 The dentist must consult with the patient s physician to confirm the patient s status and the level and severity of immunosuppression, and to determine whether the patient has progressed beyond this critical stage. Medical complications are relatively common during the immediate posttransplant period. The patient may have acute respiratory distress syndrome; viral, bacterial, and fungal infections of varying types and severity; bleeding problems; hypertension; acute renal and or hepatic failure; acute pancreatitis; and other problems. For these reasons, during the first 3 months after organ transplantation, the patient should undergo only emergency dental treatment, and elective procedures should be postponed. Even emergency dental treatment must be provided in close association with the patient s physician(s). Antibiotic prophylaxis may be used during this time because of immunosuppression and the increased risk for infection.

23 The next stage is the period when the graft is stable and functional. In most cases, this occurs approximately 3 months post transplantation. The patient has undergone graft healing and the new organ should be functioning nearly normally. In most cases, coagulation factors, susceptibility to bleeding, and blood chemistry profiles will have returned to normal limits. The patient will continue to be susceptible to infection, but now, the major concern is overimmunosuppression, which increases the risk for infection, and underimmunosuppression, which increases the risk for acute rejection. Adverse effects of immunosuppressive agents may present significant medical problems during any of the stages after transplantation.

24 These adverse effects may increase the risk for infection; excessive bleeding; bone fracture; circulatory collapse after significant emotional, physical, or surgical stress; hypertension; diabetes mellitus; and anemia. Posttransplant patients are also particularly susceptible to fungal infection, especially with Candida albicans. Special organ complications observed in heart and bone marrow transplant recipients must be considered during the stable graft period. Symptomatic coronary artery disease develops in many heart transplantation patients. The transplanted heart has no nerve supply; thus, pain is not associated with angina or infarction.

25 BMT patients may develop GVHD after undergoing transplantation. Acute GVHD occurs during the immediate posttransplant period, whereas the chronic form of the disease may appear during the stable period. The patient is particularly susceptible to communitybased infection, such as influenza and pneumonia, so precautions such as vaccination should be taken to prevent those from occurring. The chronic rejection period begins with signs and symptoms usually associated with organ failure, along with histologic findings on biopsy indicating chronic rejection of the graft. This reaction is not reversible and will lead to retransplantation or death in heart and liver recipients. Kidney patients will require dialysis or retransplantation. Pancreas patients will require insulin or retransplantation.

26 Pretransplant Patients: Whenever possible, patients found to have active dental disease should receive indicated dental care before the transplant operation. Patients with advanced periodontal disease may best be advised to have their teeth extracted and dentures constructed. The same consideration would be involved for patients who have extensive caries and have demonstrated little interest in improving, or ability to improve, their level of oral hygiene or to modify their diet. Patients who have a very good level of dental health should be encouraged to keep their teeth, but they must be advised of the risks and problems involved if significant dental disease were to develop after transplantation.

27 The need for effective preventive dental procedures and more frequent recall visits to the dentist after transplantation must be pointed out to the patient. Before transplantation, all nonrestorable teeth and teeth with advanced periodontal disease should be extracted in those patients who decide to retain their dentition. Nonvital teeth should be endodontically treated or extracted, and all active carious lesions should be restored. Preventive dentistry techniques, including toothbrushing and flossing, diet modification, antiseptic mouth rinses such as chlorhexidine and the use of topical fluorides, should be initiated, reviewed, and implemented.

28 Dental Management of the Patient Being Prepared for Transplantation: Consultation with physician(s) KEY POINTS: Complete dental evaluation 1. Poor dental status consider extractions and dentures 2. Good dental status maintain dentition 3. Other decide on individual patient basis Patients maintaining their dentition 1. Extract all nonrestorable teeth 2. Extract all teeth with advanced periodontal disease 3. Perform endodontic treatment or extraction of nonvital teeth

29 4. Adjust dentures (if needed) 5. Provide dental prophylaxis 6. Perform elective dental treatment as time and necessity permit 7. Initiate an active, effective oral hygiene program a. Toothbrushing, flossing b. Diet modification, if indicated c. Topical fluorides d. Plaque control, calculus removal e. Chlorhexidine or Listerine mouthwash (daily)

30 Patients receiving dental treatment, including dental prophylaxis: 1. Medical consultation a. Degree of organ failure b. Current status of patient c. Need for antibiotic prophylaxis (white blood cell [WBC] count depressed) d. Need to modify drug selection or dosage (kidney or liver failure) e. Need to take special precautions to avoid excessive bleeding f. Other special management procedures that may be required 2. Laboratory tests (surgical procedures planned) a. Access to current international normalized ratio (INR; PT), activated partial thromboplastin time (aptt), BT, platelet count b. Access to WBC count and differential

31 Posttransplant Patients Immediate Posttransplant Period: During this phase, when operative complications and acute rejection of the graft are the major medical concerns, no routine dentistry is indicated. Only emergency dental care should be provided, after medical consultation, and it should be as noninvasive as possible. Stable Posttransplant Period. Once the graft has healed and the acute rejection reaction has been controlled, the patient is considered to be in the stable phase. Risk of infection : Many posttransplantation infections may occur (HBV, HCV, HIV, CMV, HSV, bacterial and fungal).

32 Patients in excellent to good dental health whose grafts are stable and who are not undergoing extensive dental procedures do not require prophylaxis. In contrast, patients who need an increased dosage of immunosuppressants and those with active dental infection (chronic periodontitis) may best be managed with antibiotic prophylaxis for invasive dental procedures. The basic prophylactic regimen consists of amoxicillin 2 g 1 hour before the dental procedure plus metronidazole 500 mg 1 hour before the dental procedure. In patients who are allergic to amoxicillin, vancomycin or imipenem 1 g infused slowly over 1 hour should be given before the dental procedure isperformed. Clindamycin may be toxic to the liver and kidneys and therefore should not be used in most posttransplant patients. In patients who cannot take a drug by the oral route, intravenous ampicillin 1 g should be given with metronidazole 500 mg 1 hour before the dental procedure is performed.

33 When acute infection does occur, it often is more advanced and severe than that found in other patients. Viral infection: Posttransplant patients may be especially susceptible to viral infection, including herpes simple virus (HSV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), hepatitis B and hepatitis C viruses (HBV, HCV), and human immunodeficiency virus (HIV). The most common infection in these patients is CMV. Patients who receive a transplant because of chronic complications of hepatitis may still be infected with HBV or HCV. In addition, during transplant surgery, additional blood is used, thereby increasing the risk of infection with HBV or HCV. Excessively immunosuppressed patients may become infected with HSV, CMV, EBV, or other microorganisms that could be transmitted to dental staff or other patients. Patients also are at increased risk for infection transmitted to them in the dental operatory.

34 Excessive bleeding: Liver transplantation patients may be taking anticoagulants to prevent recurrence of hepatic vein thrombosis. Heart transplantation patients may be taking anticoagulants to prevent thrombosis of the coronary vessels. Transplantation patients who are taking anticoagulants may need to have the dosage reduced by their physician before any dental surgical procedures are performed. If the level of anticoagulation (international normalized ration [INR]) is greater than 3.5, the patient s physician may have to reduce the dosage of medication. At least 3 to 4 days is required for the effect of the reduced dosage to lower the INR. When the patient s INR has been appropriately reduced, surgery can be performed. If the INR is greater than 3.5 the surgery may have to be delayed. After surgery has been performed, the dentist must be prepared to deal with excessive bleeding, if it should occur, with the use of splints, thrombin, antifibrinolytic agents, and so forth.

35 Liver, kidney, and bone marrow transplantation patients who are not taking anticoagulants still could be potential bleeders if rejection of the graft or GVHD and significant organ dysfunction occur. Therefore, before any dental surgical procedure is undertaken, the patient s physician should be consulted about the patient s current status. If necessary, selected screening tests (e.g., activated partial thromboplastin time [aptt], INR, PT, bleeding time) should be ordered. Adverse reactions to stress: Transplantation patients who are receiving steroids may not be able to adjust to the stress of various dental surgical procedures because of adrenal suppression and may require additional steroids before and after these surgical procedures to protect against an acute adrenal crisis.

36 Patients who are taking a very large daily dose of prednisone usually do not require supplementation. Also, many routine dental procedures, such as examinations, orthodontics, prophylaxis, simple restorations, and even minor oral surgery, may not require supplementation. Signs and symptoms of acute adrenal insufficiency include hypotension, weakness, nausea, vomiting, headache, and, frequently, fever. Immediate treatment of this complication is required and consists of 100 mg of hydrocortisone, given intravenously or intramuscularly, and emergency transportation to a medical facility. Hypertension: An important adverse effect of cyclosporine is renal damage and associated hypertension. Prednisone also can cause hypertension.

37 During each visit to the dentist, the patient s blood pressure should be measured, and, if it becomes elevated to above the patient s baseline level, the patient s physician should be consulted immediately. Chronic Rejection Period: The third posttransplant period begins when significant signs and symptoms of chronic rejection of the graft or GVHD are noted. In general, only emergency or immediate dental needs should be treated during this period. Oral Complications and Manifestations: Oral complications reported in patients with organ transplants usually are caused by the following: Rejection Overimmunosuppression Adverse effects of immunosuppressive agents GVHD (after bone marrow transplantation)

38 Oral findings associated with graft rejection are the same as those found in patients with organ failure before transplantation. Oral findings that may indicate overimmunosuppression include mucositis, herpes simplex infection, herpes zoster, CMV, candidiasis, large and slow-to-heal aphthous ulcers and other ulcerations, unusual alveolar bone loss, and, on occasion, lymphoma, Kaposi s sarcoma, squamous cell carcinoma of the lip, and hairy leukoplakia. In addition, the potential exists for progressive gingival and periodontal disease. Oral complications associated with adverse effects of the immunosuppressive agents include infection, bleeding, poor healing, and tumor formation.

39 Azathioprine may cause bone marrow suppression, and, when this occurs, patients may develop oral ulceration, petechiae and bleeding. ATG and ALG may cause bone marrow suppression, thus increasing the risk for bleeding and infection. Cyclosporine may cause poor healing, increase the risk for infection, and produce gingival hyperplasia. The increased incidence of lymphoma in transplant patients is related to immunosuppression in general but also is related to the adverse effects of cyclosporine and antilymphocyte monoclonal antibodies.

40 Burket Oral Health Considerations: Signs of oral infection may be muted due to a decreased inflammatory response, or, occasionally, the signs of infection may be exaggerated. Bacterial infections, including dentoalveolar abscesses, may not manifest in traditional patterns. therefore, treatment of bacterial infections requires prompt antibiotic therapy. Culture and sensitivity should be considered in severe infections or in those not responding quickly to empiric antibiotic therapy. dental caries, a bacterial infection, has been associated with many end-stage diseases. Caries in the posttransplantation period has been reported.

41 periodontal health in this patient population is often compromised. medications and their side effects have been related to periodontal disorders, particularly gingival overgrowth. Csa-associated gingival overgrowth may be exaggerated by the coadministration of nifedipine, a calcium channel blocker often used to treat hypertension in this patient population. nifedipine is often the drug of choice because it will not alter plasma levels of Csa, as do some other antihypertensive medications. Biopsy should be performed on gingival overgrowth as case reports of malignant tumors have been associated with some of these growths. impeccable oral hygiene has been noted to be helpful in preventing gingival overgrowth. partial reversal of Csa-induced overgrowth has been reported upon discontinuation of the medication. however, treatment of severe gingival overgrowth usually requires gingivectomy.

42 viral infections are a common problem in immunosuppressed patients. HSV is the most common viral pathogen cultured from oral infections. recurrent herpes simplex infections can be both of the labial and intraoral varieties. recurrent intraoral herpes may be chronic and difficult to diagnose based solely on clinical appearance. varicella-zoster virus and EBV, as well as other viruses, have also been implicated in oral disease. oral hairy leukoplakia (OHL) related to EBV has been seen in transplant recipients not infected with human immunodeficiency viruses. Treatment of viral infections involves the appropriate antiviral agent. occasionally, HSV mutants not responsive to acyclovir require treatment with foscarnet.

43 patients who are immunosuppressed are more susceptible to fungal infections. these infections vary from those of candidal species, including pseudomembranous candidiasis, to deep fungal infections, including aspergillosis, cryptococcosis, mucormycosis, and blastomycosis. Candidiasis can present as the classic pseudomembranous form, or it can be atrophic or even hyperplastic. hyperplastic candidiasis is not removed by scraping the lesion and often requires biopsy for definitive diagnosis. occasionally, candidiasis is not responsive to the typical azole-type antifungal agents, and may require treatment with amphotericin B.

44 deep fungal infections involving the upper respiratory tract/sinuses may manifest as necrotic plaques in the palatal areas of recipients of HTC. these fungal infections are very difficult to treat and often require intravenous antifungal agents, such as amphotericin B. The transplant recipient is at a higher risk of developing lymphoma and other cancers, such as Kaposi s sarcoma and squamous cell carcinoma of the skin. lymphoma and Kaposi s sarcoma can be present in the mouth, whereas epithelial malignancy often involves the lips.

45 GVHD isa unique complication of HCT. in the oral cavity, this process clinically resembles lichenoid inflammation/lichen planus. oral GVHD appears as an area of wispy hyperkeratosis on an erythematous base invarious areas of the oral mucosa. in more severe GVHD, the lesions can appear significantly eroded and may be associated with chronic mucosal ulceration. GVHD not only affects the mouth but also the entire gastrointestinal system, as well as the skin and the liver. Chronic GVHD may be considered somewhat beneficial if it functions as a graft-versus-leukemia reaction, an immunologic process to kill persistent leukemic cells. A novel approach for treating oral GVHD involves the use of topical aza.

46 In addition to GVHD, a patient who has had an allogeneic HCT may also experience a nongingival soft tissue growth, presumably related to the use of Csa. these lesions can be seen in the buccal mucosa, alveolar mucosa, and elsewhere. Oral mucositis (OM) is a common complaint of patients who have had chemotherapy. OM is a significant and doselimiting complication of high-dose chemotherapy. Mucositis after HCT is usually related to the preconditioning regimen, and it is difficult to distinguish from an oral infection. Often mucositis is treated with palliative agents; a mixture of an anesthetic, an antihistamine, and a coating agent iscommonly used. Salivary gland dysfunction is also quite common in patients after HCT. this may be acutely related to the chemotherapeutic regimens used to rid the bone marrow of leukemic cells.

47 Patients who have chronic GVHD also have diminution of salivary flow, presumably from a lymphocytic infiltrate of salivary tissue. Developmental tooth defects such as altered root formation and dentofacial alterations must also be considered as they have been reported in children who have undergone HCT.

48 Pretransplantation Considerations: Patients with end-stage liver disease may have difficulties with excessive bleeding due to coagulopathy. these patients may have difficulty metabolizing medications. patients awaiting a kidney transplant have end-stage renal disease and are usually receiving hemodialysis. these patients may be fluid overloaded and have hypertension; therefore, monitoring of the patient s blood pressure is usually prudent. when determining the blood pressure, the cuff must not be placed on the arm used for dialysis access. occasionally, electrolyte balance may be altered. variation of drug metabolism and excretion must also be considered in this population as changing of the dose of various medication.

49 Drug avoidance or dose change in liver failure: Acetaminophen, clindamycin, codeine, diazepam, ketoconazole, metronidazole, minocycline, naproxen, salicylates, tetracycline. Drug avoidance or dose change in kidney failure: Acyclovir, amoxicillin, co-amoxiclave, codeine, diazepam, metronidazole, naproxen, penicillin, salicylates, tetracycline. Patients awaiting a heart transplant are usually poor candidates for outpatient dental treatment. the majority of these patients have severe CAD or congestive heart failure. Both conditions can easily progress to life-threatening complications during invasive dental treatment.

50 Patients awaiting lung transplants are also critically ill. most are on oxygen therapy and have difficulty breathing. dental treatment should preclude the use of combustible sources near the patient if he or she is using oxygen therapy. inhaled anesthetics are contraindicated in these patients. narcotic medications that cause respiratory depression are also contraindicated. patients awaiting pancreatic transplants have significant problems in glucose management; therefore, considerations of serum glucose levels prior to initiating treatment must be made. these patients may be poor wound healers and may have brittle insulin-dependent diabetes ; that is, these patients may experience sharp alterations in blood glucose levels and be prone to both ketoacidosis and insulin shock. pancreatic dysfunction may be accompanied by hepatic failure. hence, coagulation complications and medication/ local anesthetic metabolism must be considered when performing dental procedures in these individuals.

51 HTC candidates are frequently also significantly ill. most have been through induction and have endured consolidation chemotherapy to treat a hematologic malignancy. many of these patients are pancytopenic and are prone to infections and bleeding. they are therefore considered poor candidates for routine outpatient dental treatment. other patients may have had a significant remission of their disease with normalizing blood counts, allowing emergency dental treatment prior to the HTC. Elective dental treatment in patients with end-stage disease should be postponed as the patient will be more medically stable after the transplantation. however, whenever possible, it is important for the dentist to eliminate dental infections prior to the transplantation.

52 Dental treatment planning must therefore take into account the patient s laboratory evaluation, including such parameters as blood cell and platelet counts, serum chemistry to determine the degree of organ dysfunction, and coagulation studies. Antibiotic prophylaxis prior to the dental treatment is often warranted in patients awaiting HCT or heart or kidney transplants. patients awaiting HCT or liver transplants may need platelets, coagulation factors, or other supportive products prior to dental treatment. post-transplantation Considerations: due to increased levels of immunosuppression used to foil rejection during immediate phase, the dentist should not perform elective dental treatment, and emergency treatment should be provided only after consultation with the transplantation physician.

53 In general, there are no absolute contraindications to any type of dental procedure in patients after a successful HCT without medical or oral complications. Corticosteroid supplementation may also be required due to adrenal suppression associated with higher dose chronic corticosteroid use. this supplementation may help avoid cardiovascular collapse during stressful procedures, and it is recommended when the stress of the procedure or the patient s perception of the stress (pain) of the procedure is increased. other considerations for the dental provider during the stable posttransplantation period involve medication interactions as several antirejection immunosuppressive medications have interactions with medications that a dentist may prescribe.

54 For example, patients who are taking Csa as one of their antirejection medications may require the use of clindamycin instead of erythromycin. Csa levels are affected by anti-inflammatory drugs such as diclofenac, sulindac, and naproxen; antifungal medications such as itraconazole, fluconazole, and ketoconazole; and antibiotics such as clarithromycin and erythromycin.

55 Oral mucositis/candidiasis in bone marrow transplantation

56 Gingival overgrowth in a kidney transplant recipient taking cyclosporine and nifedipine who also had poor oral hygiene.

57 Recurrent intraoral herpes in a cardiac transplant recipient.

58 Chronic herpes simplex in a chronically immunosuppressed transplant recipient.

59 Recurrent herpes labialis

60 Recurrent herpes labialis in an immunocompromised patint

61 Pseudomembranous candidiasis

62 Hyperplastic candidiasis in a kidney transplant recipient. This infection did not respond to fluconazole.

63 Deep fungal aspergillosis in a patient who underwent hematopoietic cell transplantation

64 Atrophic candidiasis.

65 Mucositis shortly after induction chemotherapy for acute myelogenous leukemia.

66 Graft-versus-host disease in a patient who had undergone hematopoietic cell transplantation. Note the clinical resemblance to Erosive lichen planus.

67 Nongingival soft tissue growth.

68 Salivary hypofunction

69 Dental root alteration as a result of childhood treatment for lymphoma