Cytotoxic/immunosuppressive drugs are regularly used to treat proliferative diseases of the skin and immunologically mediated inflammatory disorders.
Objective:
The rational use of cytotoxic/immunosuppressive drugs, which depends on the proper selection of both the patient and the drug, is discussed.
Conclusion:
Methotrexate, azathioprine, cyclophosphamide, chlorambucil, cyclosporine, and other related drugs have potential benefits in the treatment of severe recalcitrant cutaneous disease. Patients may survive otherwise fatal disorders, or may improve their life-style and become productive again. However, the beneficial effect of these agents is achieved when the blood level is at or near toxic level. Thus, the prescribing physician should have a familiarity with the potential toxicities and a knowledge of proper monitoring techniques.
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References
1.
JeffesEWBIIIWeinsteinGD. Methotrexate and other chemotherapeutic agents used to treat psoriasis. Dermatol Clin1995; 13:875–890.
2.
JeffesEWBMcCulloughJLPittelkowMR. Methotrexate therapy of psoriasis: Differential sensitivity of proliferating lymphoid and epithelial cells to the cytotoxic and growth-inhibitory effects of methotrexate. J Invest Dermatol1995; 104:183–188.
3.
GroenendalHRampenFHJ. Methotrexate and trimethroprim-sulfamethoxazole — a potentially hazardous combination. Clin Exp Dermatol1990; 15:358–360.
4.
RoenigkHHJrAuerbachRMaibachHIWeinsteinGD. Methotrexate guidelines — revised. J Am Acad Dermatol1982; 6:145–154.
5.
GilbertSCKlintmalmGMenterASilvermanA. Methotrexate-induced cirrhosis requiring liver transplantation in three patients. Arch Intern Med1990; 150:889–891.
6.
KaplanMM. Low incidence of hepatotoxicity associated with long-term, low-dose oral methotrexate in treatment of refractory psoriasis, psoriatic arthritis, and rheumatoid arthritis: An acceptable risk/benefit ratio. Dig Dis Sci1985; 30:104–109.
WantzinGLThomsenK. Methotrexate in lymphomatoid papulosis. Br J Dermatol1984; 111:93–95.
9.
PaulMAJorizzoJLFleischerABJrWhiteWL. Low-dose methotrexate therapy in elderly patients with bullous pemphigoid. J Am Acad Dermatol1994; 31:620–625.
10.
MetzgerALBohanAGoldbergLS. Polymyositis and dermatomyositis: Combined methotrexate and corticosteroid therapy. Ann Intern Med1974; 81:182–189.
11.
KasteierJSCallenJP. Low-dose methotrexate is an effective, corticosteroid sparing agent for the treatment of cutaneous manifestations of dermatomyositis. J Am Acad Dermatol (In press)
12.
JorizzoJLWhiteWLWiseCM. Low-dose, weekly methotrexate for unusual neutrophilic vascular reactions. Cutaneous polyarteritis and Behçet's disease. J Am Acad Dermatol1991; 24:973–978.
13.
LowerEEBaughmanRP. Prolonged use of methotrexate for sarcoidosis. Arch Intern Med1995; 155:846–851.
14.
DuhraP. Treatment of gastrointestinal symptoms associated with methotrexate therapy for psoriasis. J Am Acad Dermatol1993; 28:466–469.
15.
KamelOVan de RijnMWeissL. Reversible lymphomas associated with Epstein-Barr virus occurring during methotrexate therapy for rheumatoid arthritis and dermatomyositis. N Engl J Med1993; 328:1317–1321.
16.
BachmanTRSvawitzkeADPerkinsSL. Methotrexate-associated lymphoma in patients with rheumatoid arthritis. Arthritis Rheum1996; 39:325–329.
17.
SnowJLGibsonLE. A pharmacogenetic basis for the safe and effective use of azathioprine and other thiopurine drugs in dermatologic patients. J Am Acad Dermatol1995; 32:114–116.
18.
OstensenM. Treatment with immunosuppressive and disease modifying drugs during pregnancy and lactation. Am J Reprod Immunol1992; 28:148–152.
19.
ZimmermanSWEschJ. Skin lesions treated with azathioprine and prednisone: Comparison of nontransplant patients and renal transplant recipients. Arch Intern Med1978; 138:912–914.
20.
HickeyARMaguireLUrowitzMB. Monitoring cancer incidence in the rheumatoid arthritis azathioprine registry. Arthritis Rheum1992 Annu Meeting Suppl: Abstr.
21.
KnowlesSRGuptaAKShearNHSauderD. Azathioprine hypersensitivity-like reactions — a case report and a review of the literature. Br J Dermatol1995; 20:353–356.
22.
KawanishiHRudolphENBullFE. Azathioprine-induced acute pancreatitis. N Engl J Med1973; 289:357–358.
23.
JonesJJAshworthJ. Azathioprine-induced shock in dermatology patients. J Am Acad Dermatol1993; 29:795–796.
24.
BystrynJ-CSteinmanNM. The adjuvant therapy of pemphigus. Arch Dermatol1996; 132:203–212.
25.
CallenJPSpencerLVBurrussJBHoltmanJ. Azathioprine: An effective, corticosteroid-sparing therapy for recalcitrant cutaneous lupus erythematosus or with recalcitrant cutaneous leukocytoclastic vasculitis. Arch Dermatol1991; 127:515–522.
26.
CohenLMTyringSKRádyPCallenJP. Human papilloma virus type 11 in multiple squamous cell carcinomas in a patient with subacute cutaneous lupus erythematosus. J Am Acad Dermatol1992; 26:840–845.
27.
BunchTW. Long-term followup of azathioprine for polymyositis. Arthritis Rheum1980; 23:658–662.
PandyaAGSontheimerRD. Treatment of pemphigus vulgaris with pulse intravenous cyclophosphamide. Arch Dermatol1992; 28:1626–1630.
35.
Talar-WilliamsCHijaziYMWaltherMM. Cyclophosphamide-induced cystitis and bladder cancer in patients with Wegener granulomatosis. Ann Intern Med1996; 124:477–484.
36.
HashimotosTTakeguchiA. Treatment of Behçet's disease. Curr Opin Rheumatol1992; 4:31–34.
37.
BurrussJBFarmerERCallenJP. Chlorambucil is an effective, corticosteroid-sparing agent for recalcitrant pyoderma gangrenosum. J Am Acad Dermatol (In press)
38.
SinowayPACallenJP. Chlorambucil is an effective corticosteroid-sparing agent for dermatomyositis. Arthritis Rheum1993; 36:319–324.
39.
French Cooperative Group on Chronic Lymphocytic Leukemia.Effects of chlorambucil and therapeutic decision in initial forms of chronic lymphocytic leukemia (stage A): Results of a randomized clinical trial on 612 patients. Blood1990; 75:1414–1421.
40.
KeoghASprattPMcCoskerC. Ketoconazole to reduce the need for cyclosporine after cardiac transplantation. N Engl J Med1995; 333:628–633.
41.
YeeGCStanleyDLPessaLJ. Effect of grapefruit juice on blood cyclosporin concentration. Lancet1995; 345:955–956.
42.
EllisCNGorsulowskyDRHamiltonTA. Cyclosporine improves psoriasis in a double-blind study. JAMA1986; 256: 3110–3116.
43.
MrowietzUFärberLZepelinHH Henneicke-Von. Long-term maintenance therapy with cyclosporine and post-treatment survey in severe psoriasis. J Am Acad Dermatol1995; 33:470–475.
44.
MatisWLEllisCNGriffithsCEMLazarusGS. Treatment of pyoderma gangrenosum with cyclosporine. Arch Dermatol1992; 128:1060–1064.
45.
FunyJJAlessaniMAbu-ElmagundK. Adverse effects associated with the use of FK 506. Transplant Proc1991; 23:3105–3158.
