Steroids and Immunosuppressant Agents

Due to the lack of consistently effective treatment for primary focal segmental glomerular sclerosis, angiotensinconverting enzyme inhibitors or angiotensin receptor blockers are commonly used for patients with mild disease to control symptoms. Steroids and immunosuppressive agents are used only for patients with severe disease. 

Animal models of transplantation in the 1950 s and 1960 s used steroids empirically in combination with azathioprine. Steroids subsequently became a part of the immunosuppressive regimens used in the first human transplants and continue to be used in immunosuppressive protocols today. The efficacy of steroids is irrefutable based on the decades of clinical experience. Systematic studies comparing steroid-free immunosuppressive agent combinations with conventional therapy are difficult to perform due to the hundreds of potential combinations that now exist. However, recent studies of steroid-free immunosuppressive agent combinations with newer, more specific immunosuppressants suggests that steroids may in the future have less of a role in maintenance immunosuppression." " ... 

Immunosuppressive agents such as azathioprine and mercaptopurine (a metabohte of azathioprine) are sometimes used for the treatment of IBD. These agents are generally reserved for cases that are refractory to steroids and may be associated with serious adverse effects such as lymphomas, pancreatitis, or nephrotoxicity. Cyclosporine has been of short-term benefit in acute, severe ulcerative colitis when used in a continuous infusion. 

The immunosuppressive agents (azathioprine and mercaptopurine) are generally limited to use in patients not achieving adequate response to standard medical therapy, or to reduce steroid doses when toxic doses are required. The usual dose of azathioprine is 2 to 3 mg/kg/day and 1 to 1.5 mg/kg/day for mercaptopurine. Up to 3 to 4 months may be required to observe a response. Starting doses are typically 50 mg/day and increased at 2-week intervals while monitoring complete blood count with differential. 

Glucocorticoids have become important agents for use in the treatment of many inflammatory, immunologic, hematologic, and other disorders. This has stimulated the development of many synthetic steroids with anti-inflammatory and immunosuppressive activity. 

Initially, the immunosuppressive agents, such as cyclophosphamide (32), azathioprine, and methotrexate, were developed to inhibit malignant cell proliferation. The immunosuppressant activity was discovered later and these agents were then applied to treat autoimmune diseases, where patients did not respond to high doses of steroids (51). The potential side effects associated with these agents have encouraged the search for unique immunosuppressants having more acceptable safety and efficacy profiles (62). Future approaches need to incorporate early treatment with immunotherapy... 

The initial organ transplantation was performed in 1933 when a kidney was transplanted from a cadaver. Total lymphoid irradiation was used for the immune suppression but the tissue was rejected and the patient eventually died. This was followed by the use of corticosteroids as immunosuppressive agents, but unfortunately steroids by themselves also did not produce positive results. In the early 1960s, cytotoxic agents were introduced for immune suppression these were followed by the use of a combination of cytotoxic agents and corticosteroids until the mid-1980s when cyclosporine was discovered by Borel. 

Originally developed for chemotherapy, azathioprine is used today mainly as an immunosuppressive agent and rarely as an antineoplastic drug. It was introduced as an immunosuppressive agent by a British pioneer of tissue transplantation, Roy Caine. Azathioprine was used to prevent rejection after tissue transplantation as a replacement for 6-mercaptopurine because it was less toxic. In addition to tissue transplantation, it is also used for rheumatoid arthritis and Crohn s disease. Azathioprine is a prodrug which in the body is converted to its active metabolites 6-mercaptopurine and 6-thioinosinic acid. Until the discovery of cyclosporine, azathioprine in combination with steroids was the standard treatment to prevent rejection after tissue transplantation. 

All marine organisms have been proved to be a veritable cornucopia of unusual steroid metabolites, but some believe that marine sponges may provide the most diverse and biogenetically unprecedented array of unconventional steroids in the entire animal kingdom. These steroids are potent inhibitors of histamine release, are anti-inflammatory agents, immunosuppressants, antineoplastic agents, and antiviral agents. However, their full therapeutic potential remains to be delineated. 

Immediate withdrawal of suspected causative agents appears to improve outcome and survival in SJS. The condition is treated similarly to OCR Although still controversial, the use of systemic steroids and, in some instances of severe disease, immunosuppressive agents has been successful. Tetracycline and fluoroquinolone antibiotics may be used to combat any secondary infections of the bullous regions of the epidermis. Fluid and electrolyte levels must be monitored to assess potential dehydration secondary to the skin lesions, and intravenous fluids should be administered as necessary. 

Therapy for SEE is both complex and, in many instances, disappointing for both patient and practitioner. Management of the systemic signs and symptoms may not improve the ocular manifestations of the disease. The most common therapy for the arthritic and cardiac complications is NSAID use. Hydroxychloroquine and chloroquine are particularly effective in treating the discoid rash associated with the disease. In some cases oral steroids are used either alone or in combination with other immunosuppressive agents. Methotrexate can effectively reduce the need for systemic steroids in the treatment of mild to moderate SEE. Cyclophosphamide and... 

In recent years, because of overzealous use of antibacteml antibiotics, the use of immunosuppressive agents, cytulo.i ins, irradiation, and. steroids, a new category of syslemi. mycoses has become prominent. These are the opportumsti fungal infections. There has been a precipitous rise in Ui incidence of these disea.ses. The patient, as a result of dm ... 

Patients should receive treatment for secondary infections. Unless clearly indicated, clinicians should avoid using intravenous lines, catheters and other invasive techniques that increase the risk of hemorrhage. VHP patients require attention to pulmonary toilet, specifically the usual measures necessary to avoid superinfection, and the provision of supplementary oxygen. Clinicians should avoid using steroids and other immunosuppressive agents, which have no empiric benefit, except for treatment of Hantavirus Pulmonary Syndrome (HPS) (48). 

Corticosteroids and adrenocorticotropic hormone have been widely used for the treatment of ulcerative cohtis and Crohn s disease, given parenterally, orally, or rectally. Corticosteroids are believed to modulate the immune system and inhibit production of cytokines and mediators. It is not clear whether the most important steroid effects are systemic or local (mucosal). Budesonide is a corticosteroid that is administered orally in a controlled-release formulation. The drug undergoes extensive first-pass metabolism, so systemic exposure is thought to be minimized. Immunosuppressive agents such as azathioprine, mercaptopurine (a metabolite of azathioprine), methotrexate, or cyclosporine are sometimes used for the treatment of IBD. ... 

The relatively favorable prognosis of patients who are not nephrotic does not support the use of steroids or other immunosuppressive agents. However, close follow-up and good blood pressure control with ACEIs are necessary to minimize disease... 

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