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

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.

Diverse landscape of dermatologic toxicities from small‐molecule inhibitor cancer therapy

“…203 Among these reactions, which have been reported in 7% to 89% of patients, the most common is a maculopapular rash ($67%) ranging from mild to severe erythroderma/exfoliative dermatitis. [204][205][206] Imatinib was the culprit in nearly 10% of lichenoid adverse reactions of the skin and oral mucosa, described as similar to lichen planus on histopathologic analysis (Figure 2), but may also exhibit eosinophils in the cellular infiltrate, focal parakeratosis, and deep perivascular inflammation. [207][208][209][210][211] One patient had a pruritic eruption with large, hyperchromatic, epidermotropic lymphocytes along with superficial and mid-perivascular inflammation, raising the possibility of mycosis fungoides.…”

Second Cancer Onset in Myeloproliferative Neoplasms: What, When, Why?

“…Undoubtedly, one of the most evident links between MPNs and SC is the cytotoxic effect of treatment [ 4 , 5 , 13 ]. In 2019, an international nested case–control study (involving 30 centers) was conducted, aiming to evaluate the risk of SC after exposure to cytoreductive drugs, in a cohort of 1881 Philadelphia-negative MPNs [ 4 ].…”

Non-melanoma Skin Cancers in Patients on Hydroxyurea for Philadelphia Chromosome-Negative Myeloproliferative Neoplasms: A Systematic Review

“…Eight out of 10 studies reported an association between HU and NMSC [ 7 , 11 , 15 - 18 , 20 , 22 ]. Two studies found no statistical significance between HU and the development of secondary solid cancers (including cutaneous malignancies) [ 19 , 21 ].…”

“…Antonioli et al described worsening of lesions and progression to SCC on continuing the HU treatment in three patients [ 15 ]. These cancers are predominantly seen on the scalp, ears, neck, hands, and feet [ 15 - 18 , 22 ]. This shows that excessive exposure to sunlight may play a contributory role in carcinogenesis.…”

“…All review articles implied a definite association between NMSC and HU treatment after an in-depth critical evaluation of every reported case [ 7 , 16 , 18 , 20 ]. A total of 140 cases reported from all the reviews were included in our study.…”