Systemic immunosuppressive therapy

Secondary immunodeficiencies (9) are much more common than primary ones and frequently occur as a result of immaturity of the immune system in premature infants, immunosuppressive therapy, or surgery and trauma. Illnesses, particularly when prolonged and serious, have been associated with secondary immunodeficiencies, some of which may be reversible. Acquked immune deficiency syndrome (AIDS) (10—12) may be considered a secondary immunodeficiency disease caused by the human immunodeficiency vimses HIV-1 or HIV-2. Hitherto unknown, the disease began to spread in the United States during the latter part of the 1970s. The agent responsible for this infection has been isolated and identified as a retrovims. 

Varizella zoster vitus (VZV) is a highly contagious herpesvirus causing chickenpox upon primary infection. After recovery, the vims stays dormant in nerve roots. Weakening of the immune system, e.g. in people over the age of 60 or under immunosuppressive therapy, can lead to reactivation of VZV. This recurrence causes shingles (herpes zoster), a painful rash that develops in a well-defined band corresponding to the area enervated by the affected nerve cells. 

There is clear evidence linking defects of the immune system to the development of NMSC. For example, it is observed that patients receiving chronic immunosuppressant therapy for organ transplantation have a 50% risk of developing SCC within 20 years of transplantation, and 30% of these cancers are highly aggressive.21 Additionally, patients with human immunodeficiency virus (HIV) infection are predisposed to melanoma.18 Data also support the idea that UV radiation... 

Progressive multifocal leukoencephalopathy (PML) is historically a rare demyelinating disease that is usually associated with disorders of the reticuloendothelial system, neoplasias and immunosuppressive therapy [1, 2]. However, it has become more important in clinical medicine because it is frequently seen as an opportunistic secondary infection in immunocompromised persons with AIDS. PML is characterized by focal lesions that are noninflammatory and caused by infection of oligodendrocytes with the JC papovavirus. 

Only physicians experienced in the management of systemic immunosuppressive therapy for the indicated disease should prescribe cyclosporine. Patients receiving the drug should be managed in facilities equipped and staffed with adequate laboratory and supportive medical resources. The physician responsible for maintenance therapy should have complete information requisite for the follow-up of the patient. 

Echinacea (Echinacea purpurea) Uses immune system stimulant prevention/Rx of colds, flu as supportive th apy for colds chronic infxns of the resp tract lower urinary tract Action Stimulates phagocytosis cytokine production T resp cellular activity topically exerts anesthetic, antimicrobial, anti-inflammatory effects Efficacy Not established may X severity duration of URI Available forms Caps w/ powdered herb equivalent to 300-500 mg, PO, tid pressed juice 6-9 mL, PO, once/d tine 2-4 mL, PO, tid (1 5 dilution) tea 2 tsp (4 g) of powdered herb in 1 cup of boiling water Noles/SE Fever, taste p -version, urticaria, angioedema Contra w/ autoimmune Dz, collagen Dz, progressive systemic Dz (TB, MS, collagen-vascular disorders), HIV, leukemia, may interfere w/ immunosuppressive therapy Interactions t Risk of disulfiram-like reaction W/ disulfiram, metronidazole T risk of exacerbation of HIV or AIDS W/ chinacea amprenavir, other protease inhibitors X effects OF azathioprine, basiliximab, corticosteroids, cyclosporine, daclizumab, econazole vag cream, muromonab-CD3, mycophenolate, prednisone, tacrolimus EMS Possible immunosuppression... 

The islet cells transplanted into humans are obtained from pancreatic tissue of deceased human donors (Figure 8.9). Implantation of these cells in recipients displaying a competent immune system would, at best, be of transient therapeutic benefit. The ensuing immune response would quickly destroy the foreign cells. Studies conducted thus far in humans have utilized diabetic patients who have received kidney transplants, as these are already subject to immunosuppressive therapy. However, a major stumbling block to the widespread adoption of this therapeutic approach is, predictably, the requirement to induce concurrent immune suppression. 

The principal advantage of MMF over alternative systemic immunosuppressive agents (e.g., methotrexate, cyclosporine) is its relative lack of hepatotoxicity and nephrotoxicity. Adverse effects produced by MMF most commonly include nausea, abdominal cramps, diarrhea, and possibly an increased incidence of viral and bacterial infections. Whether MMF may be associated with an increased long-term risk of lymphoma or other malignancies is controversial however, any such risk is likely to be lower in patients treated for skin disease with MMF monotherapy than in transplant patients treated with combination immunosuppressive therapy. 

The effectiveness of immunosuppressive drugs in autoimmune disorders varies widely. Nonetheless, with immunosuppressive therapy, remissions can be obtained in many instances of autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura, type 1 diabetes, Hashimoto s thyroiditis, and temporal arteritis. Improvement is also often seen in patients with systemic lupus erythematosus, acute glomerulonephritis, acquired factor VIII inhibitors (antibodies), rheumatoid arthritis, inflammatory myopathy, scleroderma, and certain other autoimmune states. 

Systemic immunosuppressive therapies in the treatment of restenosis sirolimus and sirolimus analogs in experimental and clinical data... 

A number of animal data supported the use of systemic immunosuppressive therapies in reducing smooth muscle cell growth, the mediator of neointimal proliferation (26,37,38). Preclinical studies have demonstrated a significant reduction of neointimal proliferation after balloon injury in the porcine or rabbits model of restenosis, with the systemic use of rapamycin (26). 

Some phenylalanine-derived monocyclic azetidin-2-ones, for example, 564, have been reported as modest inhibitors of human cytomegalovirus (HCMV) serine protease <2004BML2253>. HCMV is a ubiquitous member of the herpes virus family. Severe manisfestations of HCMV can be seen in individuals with a weakened immune system due to late-stage cancer and AIDS, or by immunosuppressive therapy following organ transplantation. 

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,... 

Topical uses. Neomycin and framycetin, whilst too toxic for systemic use, are effective for topical treatment of infections of the conjunctiva or external ear. They are sometimes used in antimicrobial combinations selectively to decontaminate the bowel of patients who are to receive intense immunosuppressive therapy. Tobramycin is given by inhalation for therapy of infective exacerbations of cystic fibrosis. 

Two pregnancies (with normal outcomes) have been described in renal transplant patients using an lUCD. It seems that an intact immune system is needed for effective contraception by lUCD, and that immunosuppressive therapy can render an lUCD ineffective. Immunosuppressed patients should be advised to use another means of contraception (37). 

If no functional impairment is present, patients with fimited disease are not treated with systemic therapy. A variety of topical preparations may be used in patients with skin-only disease, snch as clo-betasol, tacrolimus, and pimecrofimus. Many patients with extensive chronic GVHD, if left untreated, will die of infections or become disabled. The long-term survival rate is worse in certain snbgronps of patients, such as patients with extensive skin involvement, thrombocytopenia, progressive onset of chronic GVHD, and those who fail to respond to immunosuppressive therapy. 

---