Immunosuppressive therapy complications

Antibodies have and likely will find additional use in transplantation-related medicine. In general, cell-mediated immunological mechanisms are responsible for mediating rejection of transplanted organs. In many instances, transplant patients must be maintained on immunosuppressive drugs (e.g. some steroids and, often, the fungal metabolite cyclosporine). However, complications may arise if a rejection episode is encountered that proves unresponsive to standard immunosuppressive therapy. Orthoclone OKT-3 was the first monoclonal antibody-based product to find application in this regard. 

Nonspecific immunosuppressive therapy in an adult patient is usually through cyclosporin (35), started intravenously at the time of transplantation, and given orally once feeding is tolerated. Typically, methylprednisone is started also at the time of transplantation, then reduced to a maintenance dose. Azathioprine (31) may also be used in conjunction with the prednisone to achieve adequate immunosuppression. Whereas the objective of immunosuppression is to protect the transplant, general or excessive immunosuppression may lead to undesirable complications, eg, opportunistic infections and potential malignancies. These adverse effects could be avoided if selective immunosuppression could be achieved. Suspected rejection episodes are treated with intravenous corticosteroids. Steroid-resistant rejection may be treated with monoclonal antibodies (78,79) such as Muromonab-CD3, specific for the T3-receptor on human T-cells. Alternatively, antithymocyte globulin (ATG) may be used against both B- and T-cells. 

While the incidence of lymphoproliferative disorders was not higher n the SIMULECT treated patients than in placebo-treated patients, patients on immunosuppressive therapies are at increased risk for developing these complications and should be monitored accordingly... 

Intermediate uveitis may not warrant any therapeutic intervention in mild cases where the visual acuity is 20/40 or better. However, medical therapy is required for most patients. Macular edema is a frequent complication and requires prompt management to prevent permanent vision loss. In general, topical steroids are minimally effective in intermediate uveitis, except in those patients who are aphakic. Periocular and systemic steroids are substantially more efficacious. Periocular steroid injections are preferable in unilateral presentations and in children, whereas oral or other systemic routes are required for bilateral cases. For steroid-resistant intermediate uveitis, immunosuppressive therapy or surgery (cryotherapy and vitrectomy) may be necessary. Complications associated with intermediate uveitis include persistent CME,... 

In 1991 auxiliary partial orthotopic liver transplantation (APOLT) was successfully carried out for the first time in acute liver failure, with the subsequent possibility of dispensing with the transplant after regeneration of the patient s own liver. (112) The corresponding part of a donor liver is transplanted orthotopically as left lateral segments II and HI into the acutely diseased liver. The requisite partial resection of the liver is considered difficult. (121) A European multicentre study (12 centres) achieved equally good results in 30 patients compared to orthotopic liver transplantation with the removal of the native liver (M.-P. Chenard-Neu et al., 1996). APOLT is intended as a temporary measure in acute liver failure with the aim of discontinuing immunosuppressive therapy after the patient s own liver has regenerated. So far, results imply that more complications are experienced in APOLT than in OLT. 

Malignant tumors have been documented with increasing frequency over the last 35 years as a long-term complication of cytostatic and immunosuppressant therapy. 

Compared to the pre-1970 vaccination era, many more hospitalized patients are immunosuppressed, due to congenital or acquired illness, such as HIV infection, organ or bone marrow transplants, cancer, cancer therapy, eczema or other dermatological conditions, steroid or other immunosuppressive therapy, and autoimmune disease. Hospital administrators have been concerned that vaccinating large numbers of their staff might put these patients at risk of exposure and complications from the vaccinia virus. 

Treatment of acute CVHD is often unsuccessful and the resulting complications can be fatal. Patients undergoing allogeneic HSCT are given prophylactic immunosuppressive therapy which inhibits T-cell activation and/or proliferation. The most commonly used CVHD prophylaxis regimens are cyclosporine or tacrolimus and methotrexate. 

REFRACTORY CELIAC DISEASE Recently, immunohistochemistry has been shown to have utility in the evaluation of patients with refractory celiac disease. These patients continue to suffer from symptoms despite adherence to a gluten-free diet and are more likely to develop further complications such as ulcerative jejunoileitis and enteropathy-associated T-cell lymphoma. The group of patients with refractory sprue and loss of CDS expression in more than 50% of the CD3-positive intraepithelial lymphocytes are more likely to develop enteropathy-associated T-cell lymphoma. These patients with an abnormal T-cell phenotype are more likely to receive more aggressive immunosuppressive therapy. 

Hematologic Paroxysmal nocturnal hemoglobinuria occurred after alemtuzumab immunosuppressive therapy for myelodys-plastic syndrome and was complicated by recurrent life-threatening thrombosis... 

Cheng KL, Brody J, Warshall CE, Sloand EM, Allen SL. Paroxysmal nocturnal hemoglobinuria following alemtuzumab immunosuppressive therapy for myelodys-plastic syndrome and complicated by recurrent life-threatening thrombosis despite anticoagulation successful intervention with eculizumab and fondaparinux. Leuk Res 2010 34 e85-7. 

Infection risk Fatal Pneumocystis jirovecii pneumonia complicated immunosuppressive therapy in two patients with steroid-refractory ulcerative colitis taking steroids and tacrolimus [146" ]. Despite immediate therapy with high-dose co-trimoxazole and broad-spectrum antibiotics, both patients died with progressive respiratory failure. 

The principal cause of graft loss after the first year is chronic allograft nephropathy (CAN), followed by patient death, late acute rejections, nephropathy recurrence and polyomavirus infection (Hariharan 2001). However, prolongation of graft survival also means extended exposure of the patient to side-effects associated with immunosuppressive therapies, mainly infections and cancers, and other late-onset cardiovascular, bone and/or metabolic complications. The first year after transplantation is special, as it is characterized by the highest rates of acute rejection and opportunistic infections, such as cytomegalovirus. In this review, we successively address the presurgical evaluation of the patient, the operation itself and its possible complications, then the early (first year) and late (after the first year) medical complications. 

Among kidney transplant recipients, the 5%-10% who experienced immunological complications (acute then chronic graft rejection) and, as a consequence, were exposed to intense immunosuppressive therapy during the first year become more susceptible to developing opportunistic infections (Pneumocystis proved, Listeria monocytogenes, Nocardia asteroides. Cryptococcus neoformans or Aspergillus). Tberefore, it is extremely important to take preventive measures, i.e., vaccinations and prophylaxis. 

The most commonly used dose for fludarabine is 20 mg/m2 intravenously daily for 5 consecutive days, whereas chlorambucil can be taken daily as an oral tablet with the dose ranging from 4 to 10 mg/day.21 Fludarabine is associated with more toxicities than chlorambucil, including myelosuppression and prolonged immunosuppression.19 Resulting infectious complications may occur during the periods of prolonged immunosuppression. The ease of administration and limited side effects make chlorambucil a practical option for symptomatic elderly patients who require palliative therapy... 

Immunosuppression During therapy, do not use live virus vaccines (eg, smallpox). Do not immunize patients who are receiving corticosteroids, especially high doses, because of possible hazards of neurological complications and a lack of antibody response. This does not apply to patients receiving corticosteroids as replacement therapy. 

E) Eosinophilia this rare complication of ibuprofen therapy is exacerbated by the immunosuppression frequently seen in alcoholics... 

Nephrotic patients (especially children) are prone to bacterial infections. Before antibiotics and corticosteroids were introduced into the therapy, pneumonia, peritonitis, and sepsis (usually caused by pneumococci) were the most frequent cause of death of nephrotic children with minimal change disease. Infections are more frequent in nephrotic children and after the age of 20 their prevalence markedly decreases because the majority of adults have antibodies against the capsular antigens of pneumococci. Infections remain an important complication of nephrotic syndrome in developing countries. In developed countries, nephrotic patients treated by immunosuppressive agents may frequently suffer from viral infections (mainly herpesvirus infections, e.g., cytomegalovirus and Epstein-Barr virus infections). 

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