Advertisement

Rheumaderm pp 221-225 | Cite as

Triggered Psoriasis

  • Ronni WolfEmail author
  • V. Ruocco
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 455)

Abstract

There are conflicting reports in the literature concerning the use of antimalarials in psoriatic patients with arthropathy or coexisting systemic lupus erythematosus. On the basis of a review of 18 publications in English, it was estimated that up to 18% of patients with psoriasis would develop an exacerbation of their disease following antimalarial therapy.

In contrast to lithium and α-blockers, antimalarials do not induce psoriasis de novo, but they only trigger already existing psoriasis, via a pharmacologic mechanism, probably due to an alteration of the activity of enzymes involved in the epidermal proliferation process. The chemical structure of the antimalarials is very similar to dansylputrescine, a potent transglutaminase (TGase) inhibitor. We suggested therefore that antimalarials trigger psoriasis through the modulation of the TGase activity.

To verify this hypothesis, we examined the effect of hydroxychoroquine sulphate (HCQS) on cultured human skin and on TGase activity in vitro.

Significant changes of epidermal morphology were seen in all explants cultured in the presence of HCQS. HCQS showed a concentration-dependent inhibition of TGase activity. We suggest that HCQS caused an initial break in the barrier function of the epidermis by inhibiting TGase activity; this was followed by a physiologic response of the epidermis aimed at barrier restoration. This rather non-specific stimulus to epidermal proliferation is probably sufficient to trigger psoriasis in predisposed individuals.

Drug eruption is an age-old but timeless and fascinating subject. Of particular interest are those drug eruptions that may mimic idiopathic skin diseases. Apart from their obvious practical importance they are also of theoretical interest, because they provide an opportunity to investigate possible pathogenic mechanisms of the mimicked disease.

In this paper, I would like to review briefly the characteristics of drug-induced psoriasis, and then propose a hypothesis concerning the pathogenesis of this phenomenon.

In all, we found 258 reported cases of drug-induced psoriasis [1]. The drugs mainly involved are the antimalarials, lithium, beta blockers, and a large group of miscellaneous drugs.

Three out of the four groups of drugs (lithium, beta blockers and miscellaneous drugs) can both induce or trigger psoriasis with almost equal frequency, namely they induce psoriasis de novo or they exacerbate an already existing psoriasis in 30-50% of the reported cases. Only one group of drugs, the antimalarials is an exception. In contrast to lithium and beta blockers, antimalarials do not induce psoriasis de novo, but only trigger already existing psoriasis. There are only three reported cases of psoriasis induced by antimalarials in patients who did not have the disease previously. Of these three patients, one had a seronegative arthritis and a family history of psoriasis, and, as stated by the author, there is evidence that the patient had pre-existing latent psoriasis. We believe that the other two cases may also have had latent psoriasis.

That antimalarial drugs only trigger latent psoriasis and do not induce psoriasis de novo can be suspected from the fact that psoriasis cleared up completely after withdrawal of the drug in only 30% of patients on antimalarials, as compared with more than 60% of those receiving lithium and nearly 50% of those receiving beta blockers.

This is probably also why the incubation period of the cases induced by antimalarial drugs is much shorter than that of lithium and beta blockers. Possibly, in triggered psoriasis (as in antimalarials) the drug only sets off with a chain of pathologic events previously programmed and ready t6 be set off, whereas in true drug-induced cases (as in some cases of lithium and betablockers) the drug is supposed to cause more profound changes and, therefore, more time is needed for these changes to occur.

Keywords

Stratum Corneum Beta Blocker Lamellar Body Psoriatic Patient Epidermal Hyperplasia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Wolf R, Lo Schiavo A. Is transglutaminase the mediator between antimalarial drugs and psoriasis? Int J Dermatol 36: 10–13 (1997).PubMedCrossRefGoogle Scholar
  2. 2.
    Gottlieb AB. Immunopathogenesis of psoriasis. The road from bench to bedside is a 2-way street. Arch Dermato l33: 781–782(1997).Google Scholar
  3. 3.
    Kadunce DP, Krueger GG. Pathogenesis of psoriasis. Dermatol Clin 13: 723–737 (1995).PubMedGoogle Scholar
  4. 4.
    Williams ML, Elias PM. From basket weave to barrier. Unifying concepts for the pathogenesis of the disorders of cornification. Arch Dermatol 129: 626–629 (1993).Google Scholar
  5. 5.
    Downing DT, Stewart ME, Wertz PW, Strauss JS. Lipids of the epidermis and the sebaceous glands. In Fitzpatrick TB, Eisen AZ, Wolff K, Freedberg IM, Austen KF. Dermatology in General Medicine. Mc Graw-Hill, Inc. New York, 4th Edition 210–221 (1993).Google Scholar
  6. 6.
    Hohl D. Cornified cell envelope. Deramtologica 180: 201–211 (1990).CrossRefGoogle Scholar
  7. 7.
    Proksch E, Feingold KR, Mao-Qiang M, Elias PM. Barrier function regulates epidermal DNA synthesis. J Clin Invest 87: 1668–1673 (1991).PubMedCrossRefGoogle Scholar
  8. 8.
    Grubauer G, Elias PM, Feingold KR. Transepidermal water loss: the signal for recovery of barrier structure and function. J Lipid Res 87: 588–591 (1989).Google Scholar
  9. 9.
    Proksch E, Holleran WM, Menon GK, Elias PM. Feingold KR. Barrier function regulates epidermal lipid and DNA synthesis. Br J Deramtol 128: 473–482 (1993).CrossRefGoogle Scholar
  10. 10.
    Nickoloff BJ, Naidu Y. Perturbation of epidermal barrier function correlates with initiation of cytokine cascade in human skin. J Am Acad Deramtol 30: 535–546 (1994).CrossRefGoogle Scholar
  11. 11.
    Wood LC, Elias PM, Sequeira-Martin SM, Grunfeld C, Feingold KR. Occlusion lowers cytokine mRNA levels in essential fatty acid-deficient and normal mouse epidermis, but not after acute barrier disruption. J Invest Dermatol 103: 834–838 (1994).PubMedCrossRefGoogle Scholar
  12. 12.
    David M, Lowe NJ. Psoriasis therapy: comparative studies with hydrocolloid dressing, plastic film occlusion, and triamcinolone acetonide cream. J Am Acad Dermatol 21: 511–514 (1989).PubMedCrossRefGoogle Scholar
  13. 13.
    Fisher DA, Elias PM, LeBoit P. Exacerbation of psoriasis by the hypolipidemic agent gemfibrozil. Arch Dermatol 124: 854–855 (1988).PubMedCrossRefGoogle Scholar
  14. 14.
    Williams ML, Feingold KR, Grubauer G. Ichthyosis induced by cholesterol-lowering drugs. Arch Deramtol 123: 1535a–1538a (1987).CrossRefGoogle Scholar
  15. 15.
    Feingold KR, Mao-Qiang M, Procksch E, Menon GK, Brown BE, Elias PM. The lovastatin-treated rodent: A new model of barrier disruption and epidermal hyperplasia. J Invest Dermatol 96: 201–209 (1991).PubMedCrossRefGoogle Scholar
  16. 16.
    Pharmacologic doses of lovastatin do not predictably affect the course of psoriasis. Arch Deramtol 128: 124 (Letter) (1992).Google Scholar
  17. 17.
    Gupta AK, Sibbald GR, Knowles SR, Lynde CW, Shear NH. Terbinafine therapy may be associated with the development of psoriasis de novo or its exacerbation: Four case reports and a review of drug-induced psoriasis. J Am Acad Dermatol 36: 858–862 (1997).PubMedCrossRefGoogle Scholar
  18. 18.
    Ryder NS. Terbinafme: mode of action and properties of the squalene epoxidase inhibition. Br J Dermatol 126 (Suppl. 39): 2–7 (1992).PubMedCrossRefGoogle Scholar
  19. 19.
    Wolf R, Lombardi ML, Esposito C, Ruocco V. The in vitro effect of hydroxychloroquine on skin morphology and transglutaminase. Int J Dermatol 36: 704–708 (1997).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1999

Authors and Affiliations

  1. 1.The Department of DermatologyTel-Aviv Sourasky Medical Center Ichilov HospitalIsrael
  2. 2.The Sackler Faculty of MedicineTel-Aviv UniversityTel-AvivIsrael
  3. 3.The Department of DermatologyUniversity of Naples II School of Medicine and SurgeryNaplesItaly

Personalised recommendations