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Case Report

A Possible Case of Statin-Induced Ichthyosis in an Elderly Woman

Korean Journal of Family Medicine 2018;39(1):51-53.
Published online: January 23, 2018

1Department of Family Medicine, Gachon University Gil Medical Center, Incheon, Korea.

2Department of Dermatology, Gachon University Gil Medical Center, Incheon, Korea.

Corresponding Author: Kyoung Kon Kim. Tel: +82-32-460-3354, Fax: +82-32-460-3354, zaduplum@gilhospital.com
• Received: July 7, 2016   • Revised: August 23, 2016   • Accepted: August 24, 2016

Copyright © 2018 The Korean Academy of Family Medicine

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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  • Ichthyosis is a heterogeneous group of hereditary or acquired skin disorders, characterized by increased stratum corneum production. Several systemic diseases and many drugs can occasionally cause acquired ichthyosis. We report a case of statin-induced ichthyosis in which the causality between statin and ichthyosis was found possible by using the Naranjo scale. A 79-year-old woman presented with pruritic skin lesions on both legs that appeared erythematous, scaly, and cracked. A clinical diagnosis of acquired ichthyosis was made and the statin was suspected as the cause. The skin lesions improved after 6 weeks of dose reduction of the statin.
Ichthyosis is a heterogeneous group of hereditary or acquired scaly skin disorders, characterized by increased stratum corneum production. Acquired ichthyosis is rare and usually occurs in the elderly in association with several systemic diseases (e.g., solid or blood cancers, infectious diseases, endocrinopathies, autoimmune diseases, nutritional deficiency).1) Many drugs may also cause this skin disease and these drugs include allopurinol, cimetidine, and some types of antipsychotics and lipid-lowering drugs.1) Hydroxymethylglutaryl-CoA reductase inhibitors, namely statins, are the most widely used class of lipid-lowering drugs. Here, we report a rare possible case of statin-induced ichthyosis.
A 79-year-old woman presented with a 2-week history of pruritic skin lesions on both legs. The lesions appeared erythematous, scaly, and cracked and were more prominent on the extensor surfaces of her legs (Figure 1A). According to her medical history, she had hypertension and was taking medications (perindopril 4 mg and torasemide 2.5 mg) without changing the prescription for 5 years. Moreover, she started taking pitavastatin 2 mg once daily for dyslipidemia 3 months ago. She had no personal or family history of ichthyosis. She denied smoking or drinking. Her vital signs were within normal ranges. On physical examination, there were no bilateral lung crackles, hepatomegaly, splenomegaly, or lymphadenopathy. Total cholesterol and triglyceride were 115 mg/dL and 125 mg/dL, respectively, which were relatively low lipid levels. Other hematological and biochemical blood tests were in normal ranges. A chest X-ray showed no active lung lesion.
A clinical diagnosis of acquired ichthyosis was made by a dermatologist. The statin was suspected as the cause. However, she did not want to stop the drug. As an alternative, the dose was reduced by half (pitavastatin 1 mg). Moreover, the dermatologist started topical treatment with urea cream and tretinoin cream. No skin biopsy was performed, because of her reluctance and significant improvement in the skin lesions after 6 weeks of statin dose reduction (Figure 1B). Over a period of a few months, she had a complete remission of the skin lesions.
We assessed the causality between statin and ichthyosis by using the Naranjo adverse drug reaction probability scale.2) Taking all relevant data into account, a possible relationship was found with a score of 3 (with the answers for this case underlined in Table 1).
To the best of our knowledge, this is the first report of statin-induced ichthyosis in Asia. A few case reports have described acquired ichthyoses related to lipid-lowering drugs.3)4) Sparsa et al.3) reported a 52-year-old woman with localized acquired ichthyosis on her arms after treatment for 2 months with pravastatin. Lacour et al.4) also reported a case of acquired ichthyosis during fenofibrate treatment. Authors of these case reports proposed that prolonged lipid-lowering therapy could lower skin cholesterol concentrations, worsen the barrier and desquamation functions in the epidermis, and thus cause acquired ichthyosis.
In contrast, a previous randomized trial found that an effect of statins on epidermal cholesterol concentrations was unlikely.5) A recent systematic review also demonstrated that skin cholesterol and serum cholesterol concentrations were not correlated.6) Therefore, an asyet-unidentified disruption of lipid composition, not the diminution of cholesterol levels in the epidermis, could be responsible for the loss of epidermal functions and acquired ichthyosis. In conclusion, pathophysiological mechanisms explaining statin-induced ichthyosis are far from clear and it is uncertain whether ichthyosis is a class effect of statins or is specific to individual statins. Further research is needed.
Common side effects of statins are dyspepsia, muscle or joint pain, elevation of liver transaminase, and a slightly increased risk of diabetes.7) Statin-induced skin manifestations are infrequent but include ichthyosis, cheilitis, autoimmune reactions, drug reaction with eosinophilia and systemic symptoms, acute generalized pustulosis, phototoxicity, alopecia, and contact dermatitis.8) Recently, it has been reported that statins may increase the likelihood of developing zoster.9) Concerns about adverse reactions may be appropriate in Asians who have higher plasma levels at the same doses and heightened responses to the same plasma levels of statins compared with Caucasians.10)

CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported.

  • 1. DiGiovanna JJ, Robinson-Bostom L. Ichthyosis: etiology, diagnosis, and management. Am J Clin Dermatol 2003;4:81-95. PMID: 12553849.
  • 2. Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981;30:239-245. PMID: 7249508.
  • 3. Sparsa A, Boulinguez S, Le Brun V, Roux C, Bonnetblanc JM, Bedane C. Acquired ichthyosis with pravastatin. J Eur Acad Dermatol Venereol 2007;21:549-550. PMID: 17373993.
  • 4. Lacour JP, Adrien A, Ortonne JP. Acquired ichthyosis during lipid-normalizing treatment. Presse Med 1986;15:668.
  • 5. Reiter M, Wirth S, Pourazim A, Baghestanian M, Minar E, Bucek RA. Statin therapy has no significant effect on skin tissue cholesterol: results from a prospective randomized trial. Clin Chem 2005;51:252-254. PMID: 15613725.
  • 6. Tashakkor AY, Mancini GB. The relationship between skin cholesterol testing and parameters of cardiovascular risk: a systematic review. Can J Cardiol 2013;29:1477-1487. PMID: 23850138.
  • 7. Macedo AF, Taylor FC, Casas JP, Adler A, Prieto-Merino D, Ebrahim S. Unintended effects of statins from observational studies in the general population: systematic review and meta-analysis. BMC Med 2014;12:51. PMID: 24655568.
  • 8. Jowkar F, Namazi MR. Statins in dermatology. Int J Dermatol 2010;49:1235-1243. PMID: 20964647.
  • 9. Antoniou T, Zheng H, Singh S, Juurlink DN, Mamdani MM, Gomes T. Statins and the risk of herpes zoster: a population-based cohort study. Clin Infect Dis 2014;58:350-356. PMID: 24235264.
  • 10. Cho YG, Song HJ, Park BJ. NECA-9 Lipid Lowering Agents Research Group. The comparison of guidelines for management of dyslipidemia and the appropriateness of them in Korea. Korean J Fam Med 2010;31:171-181.
Figure 1

(A) After 3 months of treatment with pitavastatin, she presented with localized acquired ichthyosis on both legs that appeared erythematous, scaly, and cracked. (B) The skin lesions improved after 6 weeks of dose reduction of pitavastatin.

kjfm-39-51-g001.jpg
Table 1

Naranjo ADR probability scale: items and score

Answers for this case are underlined. Scoring for Naranjo algorithm: ≥9, definite ADR; 5–8, probable ADR; 1–4, possible ADR; 0, doubtful ADR.

ADR, adverse drug reaction.

kjfm-39-51-i001.jpg

Figure & Data

References

    Citations

    Citations to this article as recorded by  
    • Safety and efficacy of topical simvastatin plus cholesterol cream versus topical simvastatin cream alone for porokeratosis ptychotropica: A randomized, single-blind, split-body, placebo-controlled, investigator-initiated trial
      Zhiming Chen, Yihe Liu, Hui Yu, Jing Li, Xin Huang, Ruiyu Xiang, Ran Mo, Hao Chen, Yong Yang
      Journal of the American Academy of Dermatology.2025;[Epub]     CrossRef
    • Acquired ichthyosis, asteatotic dermatitis or xerosis? An update on pathoetiology and drug‐induced associations
      Jason S. Park, Amir H. Saeidian, Leila Youssefian, Sylvia Hsu, Hassan Vahidnezhad, Jouni Uitto
      Journal of the European Academy of Dermatology and Venereology.2023; 37(1): 47.     CrossRef
    • Acquired ichthyosis: a clinical review
      Roger Haber, Joelle Feghali, Umer Nadir, Michael D. Yi, Brian A. Cahn
      Archives of Dermatological Research.2023; 315(9): 2529.     CrossRef
    • Ichthyosis (concept, pathohistology, clinical picture, treatment)
      Tatyana Gennadyevna Takhtarova, Zarema Rimovna Khismatullina, Lyudmila Dmitrievna Panova, Anastasia Nikolaevna Panova
      Vestnik dermatologii i venerologii.2021; 97(3): 6.     CrossRef

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    A Possible Case of Statin-Induced Ichthyosis in an Elderly Woman
    Image
    Figure 1 (A) After 3 months of treatment with pitavastatin, she presented with localized acquired ichthyosis on both legs that appeared erythematous, scaly, and cracked. (B) The skin lesions improved after 6 weeks of dose reduction of pitavastatin.
    A Possible Case of Statin-Induced Ichthyosis in an Elderly Woman

    Naranjo ADR probability scale: items and score

    Answers for this case are underlined. Scoring for Naranjo algorithm: ≥9, definite ADR; 5–8, probable ADR; 1–4, possible ADR; 0, doubtful ADR.

    ADR, adverse drug reaction.

    Table 1 Naranjo ADR probability scale: items and score

    Answers for this case are underlined. Scoring for Naranjo algorithm: ≥9, definite ADR; 5–8, probable ADR; 1–4, possible ADR; 0, doubtful ADR.

    ADR, adverse drug reaction.

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