Immunosuppression opportunistic infections,

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. A athioprine (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 compHcations, 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-ceUs. Alternatively, antithymocyte globulin (ATG) may be used against both B- and T-ceUs. 

The improved short-term outcomes gained from induction therapy come with a degree of risk. By using these highly immunosuppressive agents, particularly the antilymphocyte antibodies (ALAs), muronomab-CD3 (OKT-3), and the antithymocyte antibodies, the body loses much of its innate ability to mount a cell-mediated immune response, which increases the risk of opportunistic infections and cancer.7,10... 

Depending on the severity of immunosuppression (the CD4+ T lymphocyte count), patients may present with the following opportunistic infections (grouped by CD4+ count) ... 

Alemtuzumab is the antibody to the CD52 receptor present on B and T lymphocytes. The pharmacokinetics of alemtuzumab demonstrate a terminal half-life of 7 days. Alemtuzumab has shown clinical activity in the treatment of chronic lymphocytic leukemia. Severe and prolonged (6 months) immunosuppression may result, which necessitates prophylaxis with cotrimox-azole and antivirals to prevent opportunistic infections. 

After the graft is infused, monitor CBC with differential at least daily to evaluate engraftment. Allogeneic HCT patients experience an initial period of pancytopenia followed by a more prolonged period of immunosuppression, which substantially increases the risk of bacterial, fungal, viral, and other opportunistic infections. 

The therapeutic goal in autoimmune diseases such as RA is to control disease, to establish remission, and eventually to cure. In theory, this goal can be achieved using either Ag-specific approaches, for example, elimination of self-reactive T cells (assuming that a finite number of key Ags can be identified as the target of the autoimmune process in RA), or the non-Ag-specific approaches, for example, blockade of cytokines as in the case of TNF-a neutralization. Currently, only the latter types of approaches have yielded clinical benefit, and it is in this category that approaches to block chemokines or receptors may be included. Despite their appeal in terms of effectiveness, non-Ag-specific approaches carry a higher risk of immunosuppression and opportunistic infections (48). 

Acquired Immunodeficiency Syndrome (AIDS) A clinical syndrome due to infection with the RNA human immunodeficiency (retro)virus (HIV) which produces severe immunosuppression (depletion of natural killer T cells), thereby exposing the individual to a variety of opportunistic infections and cancers. 

Considerable data is available suggesting thatmild-to-moderate immunosuppression can lead to an increase in infectious disease. The types of infections that occur tend to result from either common pathogens (e.g., causing upper respiratory tract infections) or latent viruses (e.g., herpes cold sores), rather than opportunistic organisms such as Pnuemocyctis carinii. These are usually not life-threatening, except in certain susceptible populations, such as the elderly. Opportunistic infections, in contrast, are more prevalent in individuals where severe forms of immunosuppression are present, such as primary immunodeficiency diseases or HIV/AIDS. 

Immunosuppression in general is associated with two other unwanted effects. Firstly, there is not only an increased risk of bacterial, viral and fungal infections but also various opportunistic infections occur. The second draw back is the risk for secondary tumors, especially lymphomas. 

Warnings Should be administered in facilities equipped and staffed with adequate laboratory and supportive medical resources Administration of proteins may cause possible anaphylactoid reactions (none reported) Immunosuppressive therapies increase risk for lymphoproliferative disorders and opportunistic infections (incidence in basiliximab-treated patients is similar to placebo)... 

AZATHIOPRINE LEFLUNOMIDE T risk of serious infections (sepsis) and of opportunistic infections (Pneumocystis jiroveci pneumonia, tuberculosis, aspergillosis) Additive immunosuppression Monitor platelets, white bloods cell, haemoglobin and haematocrit at baseline and regularly - weekly, during concomitant therapy. With evidence of bone marrow suppression, discontinue leflunomide and administer colestyramine or charcoal to T elimination of leflunomide - For signs and symptoms of immunosuppression, see Qinical Features of Some Adverse Drug Interactions, Immunosuppression and blood dyscrasias... 

Isolated reports of Candida esophagitis or Pneumocystis proved Pneumocystis carinii) infections in immunocompetent patients and the possible decrease in CD4-I- T cells with or without opportunistic infections in several HIV-infected patients (SED-13,1097) (379) suggest that unexpected immunosuppressive effects of interferon alfa can occur. An autoimmune destruction of CD4 cells in patients with a particular HLA haplotype has been proposed as a possible mechanism (380). One patient also had an acute and fatal acute precipitation of infection with Entamoeba histolytica (SEDA-22, 403). However, the available evidence is still very limited and no firm conclusion can be drawn on a possible association between interferon alfa treatment and a fall in CD4 cell count or an immunosuppressive effect. 

Methotrexate-related immunosuppression can be expected to increase the likelihood of infections. The infection rate reported in patients taking low-dose methotrexate has varied from one study to another. In a literature review focusing on patients with rheumatoid arthritis taking methotrexate, the mean infection rate was 1.8% in retrospective studies, 4.6% in open studies, and 11.6% in double-blind studies (97). Infections usually occurred within 1.5 years of starting treatment and mostly comprised common respiratory or cutaneous bacterial infections, Herpes zoster, and, more rarely, opportunistic infections. In one comparative study, the overall risk of infections was considered to be low and similar in patients taking methotrexate and azathioprine (97), but others have found a higher prevalence of infections and an increase in antibiotic use in patients with rheumatoid arthritis taking methotrexate as compared to other DMARDs, except cyclophosphamide (98,99). 

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