Drug-Related Cutaneous Adverse Events in Philadelphia Chromosome-Negative Myeloproliferative Neoplasms: A Literature Review

Int J Mol Sci. 2020 May 30;21(11):3900. doi: 10.3390/ijms21113900.

Abstract

Since myeloproliferative neoplasms (MPN) pose a significant risk for vascular and thrombotic complications, cytoreductive therapies, such as hydroxyurea (HU), interferon (IFN) inhibitors, and Janus kinase (JAK) inhibitors are recommended for patients at high risk. However, these agents also place patients at increased risk for drug-related cutaneous adverse events. Herein, we review the literature on skin toxicity related to the use of drugs for the treatment of MPN. Overall, the cytoreductive agents used for MPN are generally well tolerated and considered to be safe, except IFN, for which dropout rates as high as 25% have been reported. While IFN is known to give rise to flu syndrome, it rarely leads to hematological alterations. The most common hematological side effects of HU are mild and include granulocytopenia, anemia, and thrombocytopenia. The JAK inhibitor ruxolitinib has been associated with cytopenia and a higher incidence of viral infections, as well as increased risk for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Based on the present analysis, it can be concluded that cutaneous toxicity is not a negligible complication of commonly used treatments for MPN. While further research is needed, patients on these agents, and especially those with a history of cutaneous malignancies, should undergo thorough skin examination before and during therapy. In addition, detailed history is critical since many patients who develop non-melanoma skin cancer have multiple preexisting risk factors for cutaneous carcinogenesis.

Keywords: Philadelphia chromosome-negative myeloproliferative neoplasms; adverse events; cytoreductive agents.

Publication types

  • Review

MeSH terms

  • Humans
  • Hydroxyurea / adverse effects*
  • Interferons / adverse effects*
  • Janus Kinase Inhibitors / adverse effects*
  • Keratosis, Actinic / chemically induced
  • Keratosis, Actinic / complications
  • Myeloproliferative Disorders / complications
  • Myeloproliferative Disorders / drug therapy*
  • Myeloproliferative Disorders / genetics
  • Nitriles
  • Philadelphia Chromosome
  • Protein Kinase Inhibitors / adverse effects
  • Pyrazoles
  • Pyrimidines
  • Risk
  • Skin Diseases / chemically induced*
  • Skin Diseases / complications
  • Skin Neoplasms / chemically induced
  • Skin Neoplasms / complications

Substances

  • Janus Kinase Inhibitors
  • Nitriles
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyrimidines
  • ruxolitinib
  • Interferons
  • Hydroxyurea