The thiopurine drugs azathioprine and 6-thioguanine have been shown to induce significant clinical improvement in patients with moderate to severe psoriasis and/or psoriatic arthritis.
Objective
The aim of this paper is to present a comprehensive review of the available literature concerning the off-label role of thiopurine drugs in the treatment of psoriasis and psoriatic arthritis.
Methods
Studies published with English abstracts between 1960 and 2008 identified in MEDLINE and PubMed with the keywords purine synthesis inhibitors, thiopurine, 6-thioguanine, azathioprine, psoriasis and psoriatic arthritis were reviewed.
Results
Although 6-thioguanine and azathioprine have shown significant efficacy, their side effect profiles have discouraged their use for moderate to severe psoriasis.
Conclusion
For treatment of psoriasis and psoriatic arthritis, purine synthesis inhibitors should not be forgotten. They represent an entirely different option and provide an alternative therapy, especially for difficult cases.
Get full access to this article
View all access options for this article.
References
1.
GelfandJ.M., GladmanD.D., MeaseP.J., SmithN., MargolisD.J., NijstenT.Epidemiology of psoriatic arthritis in the population of the United States. J Am Acad Dermatol.2005; 53: 573.
2.
ZachariaeH.Prevalence of joint disease in patients with psoriasis: implications for therapy. Am J Clin Dermatol.2003; 4: 441–7.
3.
DubertretL., MrowietzU., RankiA., van de KerkhofP.C., ChimentiS., LottiT.European patient perspectives on the impact of psoriasis: the EUROPSO patient membership survey. Br J Dermatol.2006; 155: 729–36.
WuY., MillsD., BalaM.Psoriasis: cardiovascular risk factors and other disease comorbidities. J Drugs Dermatol.2008; 7: 373–7.
6.
ChristophersE.Comorbidities in psoriasis. Clin Dermatol.2007; 25: 529–34.
7.
GladmanD.D., FarewellV.T., WongK., HustedJ.Mortality studies in psoriatic arthritis: results from a single outpatient center. II. Prognostic indicators for death. Arthritis Rheum.1998; 41: 1103–10.
8.
WongK., GladmanD.D., HustedJ., LongJ.A., FarewellV.T.Mortality studies in psoriatic arthritis: results from a single outpatient clinic. I. Causes and risk of death. Arthritis Rheum.1997; 40: 1868–72.
9.
WolvertonS.E.Comprehensive Dermatologic Drug Therapy.2007. p. P. 167–8.
10.
Tabloid [Prescribing Information].Greenville, NC.
11.
LennardL.Assay of 6-thioinosinic acid and 6-thioguanine nucleotides, active metabolites of 6-mercaptopurine, in human red blood cells. J Chromatogr.1987; 423: 169–78.
SwannP.F., WatersT.R., MoultonD.C., XuY.Z., ZhengQ., EdwardsM.Role of postreplicative DNA mismatch repair in the cytotoxic action of thioguanine. Science.1996; 273: 1109–11.
14.
KarranP., AttardN.Thiopurines in current medical practice: molecular mechanisms and contributions to therapy-related cancer. Nat Rev Cancer.2008; 8: 24–36.
15.
GisbertJ.P., NinoP., RodrigoL., CaraC., GuijarroL.G.Thiopurine methyltransferase (TPMT) activity and adverse effects of azathioprine in inflammatory bowel disease: long-term follow-up study of 394 patients. Am J Gastroenterol.2006; 101: 2769–76.
16.
LennardL., LilleymanJ.S., Van LoonJ., WeinshilboumR.M.Genetic variation in response to 6-mercaptopurine for childhood acute lymphoblastic leukaemia. Lancet.1990; 336: 225–9.
17.
LennardL., WelchJ.C., LilleymanJ.S.Thiopurine drugs in the treatment of childhood leukaemia: the influence of inherited thiopurine methyltransferase activity on drug metabolism and cytotoxicity. Br J Clin Pharmacol.1997; 44: 455–61.
18.
WeinshilboumR.M., SladekS.L.Mercaptopurine pharmacogenetics: monogenic inheritance of erythrocyte thiopurine methyltransferase activity. Am J Hum Genet1980; 32: 651–62.
19.
SebbagL., BoucherP., DaveluP., BoissonnatP., ChampsaurG., NinetJ.Thiopurine S-methyltransferase gene polymorphism is predictive of azathioprine-induced myelosuppression in heart transplant recipients. Transplantation.2000; 69: 1524–7.
20.
EvansW.E., HornerM., ChuY.Q., KalwinskyD., RobertsW.M.Altered mercaptopurine metabolism, toxic effects, and dosage requirement in a thiopurine methyltransferase-deficient child with acute lymphocytic leukemia. J Pediatr.1991; 119: 985–9.
21.
MurphyF.P., CovenT.R., BurackL.H., GilleaudeauP., CardinaleI., AuerbachR.Clinical clearing of psoriasis by 6-thioguanine correlates with cutaneous T-cell depletion via apoptosis: evidence for selective effects on activated T lymphocytes. Arch Dermatol.1999; 135: 1495–502.
22.
WiseM., CallenJ.P.Azathioprine: a guide for the management of dermatology patients. Dermatol Ther.2007; 20: 206–15.
23.
PatelA.A., SwerlickR.A., McCallC.O.Azathioprine in dermatology: the past, the present, and the future. J Am Acad Dermatol.2006; 55: 369–89.
24.
YoungerI.R., HarrisD.W., ColverG.B.Azathioprine in dermatology. J Am Acad Dermatol.1991; 25: 281–6.
25.
ZackheimH.S., GlogauR.G., FisherD.A., MaibachH.I.6-Thioguanine treatment of psoriasis: experience in 81 patients. J Am Acad Dermatol.1994; 30: 452–8.
26.
ZackheimH.S., MaibachH.I.Treatment of psoriasis with 6-thioguanine. Australas J Dermatol.1988; 29: 163–7.
27.
SilvisN.G., LevineN.Pulse dosing of thioguanine in recalcitrant psoriasis. Arch Dermatol.1999; 135: 433–7.
28.
CorleyC.C.Jr., LessnerH.E., LarsenW.E.Azathioprine therapy of “autoimmune” diseases. Am J Med.1966; 41: 404–12.
29.
ScerriL.Azathioprine in dermatological practice. An overview with special emphasis on its use in non-bullous inflammatory dermatoses. Adv Exp Med Biol.1999; 455: 343–8.
30.
GreavesM.W., DawberR.Azathioprine in psoriasis. Br Med J.1970; 2: 237–8.
31.
Du VivierA., MunroD.D., VerbovJ.Treatment of psoriasis with azathioprine. Br Med J.1974; 1: 49–51.
32.
MunroD.D.Azathioprine in psoriasis. Proc R Soc Med.1973; 66: 747–8.
33.
HackerS.M., Ramos-CaroF.A., FordM.J., FlowersF.P.Azathioprine: a forgotten alternative for treatment of severe psoriasis. Int J Dermatol.1992; 31: 873–4.
34.
LeeJ.C., GladmanD.D., SchentagC.T., CookR.J.The long-term use of azathioprine in patients with psoriatic arthritis. J Clin Rheumatol.2001; 7: 160–5.
35.
DemisD.J., BrownC.S., CrosbyW.H.Thioguanine in the Treatment of Certain Autoimmune, Immunologic and Related Diseases. Am J Med.1964; 37: 195–205.
36.
MolinL., ThomsenK.Thioguanine treatment in psoriasis. Acta Derm Venereol.1987; 67: 85–8.
37.
ShererD.W., LebwohlM.G.6-thioguanine in the treatment of psoriasis: a case report and literature review. J Cutan Med Surg.2002; 6(6): 546–50.
38.
MasonC., KruegerG.G.Thioguanine for refractory psoriasis: a 4-year experience. J Am Acad Dermatol.2001; 44: 67–72.
39.
LebwohlM., Berth-JonesJ., CoulsonI., editors. Treatment of skin disease.Philadelphia: Mosby; 2002.
40.
SilvisN.G.Antimetabolites and cytotoxic drugs. Dermatol Clin.2001; 19: 105–18, viii–ix.
41.
SahasranamanS., HowardD., RoyS.Clinical pharmacology and pharmacogenetics of thiopurines. Eur J Clin Pharmacol.2008; 64: 753–67.
42.
ColonnaT., KorelitzBlThe role of leukopenia in the 6-mercaptopurine-induced remission of refractory Crohn's disease. Am J Gastroenterol.1994; 89: 362–6.
43.
GellerS.A., DubinskyM.C., PoordadF.F., VasiliauskasE.A., CohenA.H., AbreuM.T.Early hepatic nodular hyperplasia and submicroscopic fibrosis associated with 6-thioguanine therapy in inflammatory bowel disease. Am J Surg Pathol.2004; 28: 1204–11.
44.
KrivoyN., RazR., CarterA., AlroyG.Reversible hepatic veno-occlusive disease and 6-thioguanine. Ann Intern Med.1982; 96: 788.
45.
KaoN.L., RosenblateH.J.6-Thioguanine therapy for psoriasis causing toxic hepatic venoocclusive disease. J Am Acad Dermatol.1993; 28: 1017–8.
46.
SilmanA.J., PetrieJ., HazlemanB., EvansS.J.Lymphoproliferative cancer and other malignancy in patients with rheumatoid arthritis treated with azathioprine: a 20 year follow up study. Ann Rheum Dis.1988; 47: 988–92.
47.
TanB.B., LearJ.T., GawkrodgerD.J., EnglishJ.S.Azathioprine in dermatology: a survey of current practice in the U.K. Br J Dermatol.1997; 136: 351–5.
48.
LennardL., Van LoonJ.A., WeinshilboumR.M.Pharmacogenetics of acute azathioprine toxicity: relationship to thiopurine methyltransferase genetic polymorphism. Clin Pharmacol Ther.1989; 46: 149–54.
49.
SnowJ.L., GibsonL.E.A pharmacogenetic basis for the safe and effective use of azathioprine and other thiopurine drugs in dermatologic patients. J Am Acad Dermatol.1995; 32: 114–6.
