Immunosuppression skin disorders

UV-B has various direct adverse effects on human health (skin cancer, immunosuppression, eye disorders), terrestrial plants and aquatic organisms [DNA alterations, photosynthesis inhibition, reduced growth, photoresponsiveness suppression (see Chapter 116)]. Moreover, due to the differences in UV-B sensitivity and adaptation among the various species, shifts in species composition may occur as a consequence of increased UV-B radiation, thus leading indirectly to alterations in ecosystems. ... 

This form of myositis stands apart from the classical PM/DM syndromes on account of its distinctive clinical and histopathological features. There is no clear difference in incidence between males and females and the disorder is typically one of middle or old age. In the majority of cases, progression is slow and skin involvement is not seen, so that the main question of differential diagnosis is its distinction from chronic PM. Unlike classic PM, weakness involves distal muscles as frequently as proximal muscles. CK levels are usually only moderately raised. A common finding which leads to the correct diagnosis of this condition is its nonresponsiveness to steroid treatment or other forms of immunosuppression. 

Prevention Minimize immunosuppressant doses avoid sun exposure (sunblock, hats, clothing) routine self-exams (skin, lymph nodes) yearly gynecologic/prostate exams AZA particularly associated with skin cancers CSA/TAC may be associated with lymphoproliferative disorders (lymphomas)... 

Cyclosporine demonstrates immunosuppressive activity by inhibiting the first phase of T-cell activation. It also inhibits release of inflammatory mediators from mast cells, basophils, and polymorphonuclear cells. It is used in the treatment of both cutaneous and arthritis manifestations of severe psoriasis. The usual dose is between 2.5 and 5 mg/kg/day given in two divided doses. Adverse effects include nephrotoxicity, hypertension, hypomagnesemia, hyperkalemia, alterations in liver function tests, elevations of serum lipids, GI intolerance, paresthesias, hypertrichosis, and gingival hyperplasia. Cumulative treatment for more than 2 years may increase the risk of malignancy, including skin cancers and lymphoproliferative disorders. 

Cytotoxic and immunosuppressive drugs, which inhibit the synthesis or action of crucial cellular macromolecules, such as nucleic acids, are used in three broad categories of skin disease hyperproUferative disorders, such as psoriasis immunological disorders, such as autoimmune bullous diseases and skin neoplasms. The pharmacology of these drugs is discussed in Chapter 57. 

Drying lotions should not be used on skin lesions because they may increase scarring. In the child or adult for whom the skin lesions itch or are irritating, an oral antihistamine may help to prevent scratching, which can lead to secondary infection and thereby scarring. Recommended agents include oral chlorpheniramine or diphenhydramine.The use of cimetidine is controversial as an H2 blocker, oral cimetidine has an immunosuppressive action. The effects are not always consistent, however, and use of cimetidine is risky in autoimmune disorders and organ transplant patients. 

Azathioprine, a prodrug converted to 6-mercaptopurine, is widely used as a post-transplant immunosuppressant and in various autoimmune or chronic inflammatory disorders, such as rheumatoid arthritis, dermatomyositis, systemic lupus eiythematosus, skin diseases, and inflammatory bowel diseases. 

Although tumor induction has mostly been documented in patients treated for cancer, long-term cyclophosphamide treatment for non-neoplastic conditions can also increase the incidence of certain neoplasms. Whether this oncogenic effect is a consequence of drug-induced chromosomal aberrations rather than immunosuppression is unclear. An increased incidence of bladder cancers, skin cancers, and myeloproliferative disorders was found in a 20-year follow-up study of 119 patients with rheumatoid arthritis, and a high dose of cyclophosphamide (mean total dose of 80 g) was the main susceptibihty factor (47). 

In 1990, etretinate (Tigason) was replaced by acitretin (Neo-Tigason), an aromatic retinoid, a carboxylic acid metabolite of etretinate (15). It is effective in pustular psoriasis and psoriatic palmoplantar keratoderma and in combination with PUVA or topical therapy (calci-potriol or glucocorticoids) in the treatment of other forms of psoriasis. It has also been used to treat disorders of keratinization (ichthyosis, palmoplantar keratoderma, Darier s disease) and severe cutaneous forms of lichen planus. It prevents new skin carcinomas in patients with xeroderma pigmentosum and those who are immunosuppressed. The main advantage of acitretin is its short half-life of 50 hours, compared with over 80 days for etretinate (16). 

Skin Eczema-like eruptions In a prospective cohort study in 92 patients treated with infliximab for a variety of disorders, with the exception of cutaneous psoriasis, 15 developed eczema [121 ]. In univariate analyses, a personal history of atopic symptoms was the only predictive factor (OR = 3.6) sex, age, principal diagnosis, dose and duration of infliximab, and concomitant use of other immunosuppressant had no effect. 

---