What is the cause of ulcers in a patient with essential thrombocytosis (ET) treated with hydroxyurea, who also received levofloxacin with a delta pairing protocol?

From the Guidelines

The cause of ulcers in an essential thrombocytosis patient taking hydroxyurea who was also prescribed levofloxacin is likely multifactorial, with hydroxyurea being a common culprit due to its known side effect of mucocutaneous ulcerations, as reported in approximately 10-15% of patients with myeloproliferative neoplasms 1. These ulcers typically develop after prolonged therapy and may be exacerbated by the underlying microvascular disturbances from essential thrombocytosis. Adding levofloxacin could worsen this condition through several mechanisms:

• fluoroquinolones can delay wound healing by inhibiting fibroblast function
• may cause photosensitivity reactions when combined with hydroxyurea
• both medications can potentially cause vasculitic reactions. Management should include:
• evaluating the necessity of continuing hydroxyurea (possibly reducing the dose or switching to an alternative like anagrelide or interferon)
• providing proper wound care
• considering topical treatments like nitroglycerine ointment for painful ulcers
• potentially discontinuing levofloxacin if clinically appropriate. The patient should also be advised to:
• avoid sun exposure
• use compression therapy if there's no arterial insufficiency
• receive regular monitoring of platelet counts to ensure adequate disease control while minimizing medication side effects, as recommended by recent guidelines 1. It is also important to consider the potential benefits of alternative treatments, such as ruxolitinib, which has been shown to improve symptoms and reduce spleen volume in patients with myeloproliferative neoplasms 1.

From the FDA Drug Label

1. 5 Vasculitic Toxicities Cutaneous vasculitic toxicities, including vasculitic ulcerations and gangrene, have occurred in patients with myeloproliferative disorders during therapy with hydroxyurea.

The cause of ulcers in a patient with essential thrombocytosis (ET) treated with hydroxyurea is likely due to vasculitic toxicities, a known adverse reaction of hydroxyurea, particularly in patients with myeloproliferative disorders. 2

From the Research

Cause of Ulcers in ET Patients Treated with Hydroxyurea

• The development of ulcers in patients with essential thrombocytosis (ET) treated with hydroxyurea is a known side effect, as reported in studies 3, 4.
• Hydroxyurea has been shown to cause leg ulcers in patients with ET, with some cases being refractory to treatment 3, 4.
• The exact mechanism of hydroxyurea-induced ulcers is not fully understood, but it is thought to be related to the drug's effect on the bone marrow and blood vessels 4.
• The use of levofloxacin with a delta pairing protocol is not directly related to the development of ulcers in ET patients treated with hydroxyurea, as there is no evidence to suggest a link between the two 3, 4, 5, 6, 7.
• Other factors, such as hypertension, diabetes, and arterial disease, may contribute to the development of ulcers in ET patients treated with hydroxyurea 4.

Management of Hydroxyurea-Induced Ulcers

• Treatment of hydroxyurea-induced ulcers typically involves reducing the dose of hydroxyurea or switching to an alternative therapy 4, 5.
• Wound care and dressings may also be used to promote healing and prevent further complications 4.
• In some cases, ulcers may persist or recur despite treatment, highlighting the need for close monitoring and individualized management plans 4.