Hydroxyurea‑Associated Heel Ulcer in Polycythemia Vera + Diabetes: Rapid Healing After ON101 (Case Report & Clinical Takeaways)

Medical education note: This article is for clinicians and is not a substitute for patient‑specific medical advice.

Why this case matters (1‑minute summary)

A 67‑year‑old man with polycythemia vera (PV) on long‑term hydroxyurea and well‑controlled type 2 diabetes developed a chronic left‑heel ulcer that persisted 9 months and failed 5 months of growth‑factor gel + petroleum dressings. Vascular workup was normal (ABI 1.10; angiography no significant stenosis), and neurological exam was unremarkable. The team started ON101 topical cream once daily with dry gauze. Rapid epithelialization appeared by day 10, and near‑complete closure occurred by ~day 14—using less than one tube and without adverse events; closure was sustained on follow‑up. [4, 5]

Clinical signal: In PV patients who must remain on hydroxyurea, a topical that supports epithelial regeneration may avert prolonged nonhealing and the difficult trade‑off of stopping disease‑modifying therapy. [1, 2]

The backstory: PV, hydroxyurea, and ulcers

Hydroxyurea is a mainstay in PV, yet chronic lower‑extremity ulcers are a recognized—but uncommon—complication that can become refractory to standard dressings and topical growth factors. Coexisting diabetes brings additional microvascular/metabolic barriers, compounding the problem. In such overlap cases, clinicians often face a dilemma: discontinue hydroxyurea (and risk hematologic instability) or search for a topical that can restart epithelialization without systemic side effects. This case highlights ON101 cream as a potential topical adjunct in that exact scenario. [1, 2]

Case snapshot (for your notes)

Patient
67‑year‑old male; PV on long‑term hydroxyurea; 9‑year history of type 2 diabetes with fasting glucose 5–7 mmol/L (≈90–126 mg/dL).

Ulcer
Shallow heel ulcer, 9 months duration; no improvement after 5 months of growth‑factor gel + petroleum‑based dressings.

Workup
ABI 1.10; lower‑extremity angiography negative for arterial stenosis; neurologic exam unremarkable.

Intervention
ON101 applied daily; covered with dry gauze.

(ON101 being applied to patient)

Outcome
Rapid epithelialization by day 10; near‑complete closure by ~day 14, with <1 tube used; no adverse events; sustained closure on follow‑up.

(Rapid epithelialization of left-heel ulcer on day 10)

Practical lessons for wound clinics

1) Confirm (and document) that the basics are optimized

• Perfusion: Normal ABI/angiography here ruled out ischemia as the rate‑limiter. If vascular disease is present, address first. [7, 8]

• Infection control, cleanse, and cover: Continue evidence‑based cleansing (gentle irrigation with clean water or saline) and moisture‑balanced coverage while introducing any new topical. [10, 11]

• Systemic factors: Glycemic control in this patient was reasonable; optimize HbA1c and nutrition in parallel.

2) Think “drug‑related ulcer” in PV on hydroxyurea

Hydroxyurea‑associated ulcers are widely described and can be stubborn; they often push teams toward discontinuation. The Discussion in this case emphasizes that a safe, effective topical that triggers epithelial regeneration may avoid systemic changes and support closure—even in complex comorbidity stacks. [1, 2]

3) Consider ON101 as an adjunct when standard topicals stall

What stood out here was speed (epithelialization by day 10; near‑closure by ~day 14) and tolerability (no reported adverse events), despite prior failure with growth‑factor therapy. While one case cannot define standard of care, it suggests a trial of ON101 may be reasonable once ischemia is excluded and infection is controlled. [4, 5]

Suggested clinic protocol (adapt this to your formulary)

Patient selection: PV on hydroxyurea ± diabetes; chronic ulcer >8–12 weeks; perfusion adequate (e.g., ABI ≥0.9 and/or definitive imaging), no progressive infection, and prior basic care optimized.
Topical course: ON101 once daily to wound surface, cover with dry gauze. Continue offloading (especially for heel/plantar sites) and standard peri‑wound protection.
Monitoring: Photograph at baseline and every 3–4 days; track surface area and epithelial migration.
Escalation: If no response by 2–3 weeks, reassess for occult infection, pressure/offloading gaps, or systemic barriers; consider alternative advanced modalities or hematology consultation regarding hydroxyurea.
Safety: Stop if local hypersensitivity occurs; document adverse events. [4, 7]

(For cleansing/dressing checklists you can share with patients, see our evidence‑based guides to wound cleaning and dressings.)

Counseling points for patients (plain‑language)

• “Your blood condition (PV) and its medicine (hydroxyurea) can make skin wounds slow to heal. We’ll use a topical cream daily and protective dressings to help new skin grow.”

• “Keep pressure off the heel, watch for spreading redness, heat, swelling, fever, or foul drainage—call us if these show up.”

Limitations to keep in mind

This is a single case with strong visual and timeline documentation but no control arm; we can’t generalize efficacy, dose‑response, or recurrence risk to broader PV or diabetic populations. The report underscores the need for larger clinical studies of ON101 in non‑DFU etiologies and in drug‑associated ulcers. [3]

Frequently asked questions (clinician‑focused)

Is hydroxyurea discontinuation required to heal these ulcers?
Not always feasible in PV. The Discussion notes that ulcers often drive discontinuation, but this case healed without reporting systemic therapy changes, pointing to ON101 as a topical alternative worth evaluating case‑by‑case. [9]

What else should I rule out before trying ON101?
Arterial insufficiency (ABI/angiography), neuropathic pressure points/offloading deficits, and active infection; optimize glucose and local hygiene.

How fast should I expect a response?
Here, epithelialization by day 10 and near‑closure by ~day 14—unusually rapid after months of stalled healing. Individual results will vary. [4, 5]

Any safety concerns reported?
No adverse events were reported in this case; monitor as usual for local reactions.

Bottom line for clinicians

When a hydroxyurea‑associated leg ulcer stalls despite good fundamentals—and ischemia and infection are off the table—a time‑limited trial of ON101 may be a pragmatic, low‑risk adjunct. In this PV + diabetes case, that approach was followed by visible epithelial advance within 10 days and near‑complete closure in ~2 weeks, with sustained healing on follow‑up. Document, monitor closely, and keep the conversation open with hematology about systemic therapy if progress plateaus.

References

[1] Dissemond J, et al. Hydroxyurea-induced ulcers on the leg. Dtsch Arztebl Int. 2009. https://pmc.ncbi.nlm.nih.gov/articles/PMC2683228/

[2] Sirieix ME, et al. Leg Ulcers and Hydroxyurea: Forty-one Cases. Arch Dermatol. 1999. https://jamanetwork.com/journals/jamadermatology/fullarticle/477918

[3] Shanmugam VK, et al. Chronic Leg Ulceration Associated with Polycythemia Vera (case). Int J Angiol. 2013. https://pmc.ncbi.nlm.nih.gov/articles/PMC3925681/

[4] Huang YY, et al. Effect of a Novel Macrophage‑Regulating Drug (ON101) on Wound Healing in DFUs—Phase 3 RCT. JAMA Netw Open. 2021. https://pmc.ncbi.nlm.nih.gov/articles/PMC8417758/

[5] Chang SC, et al. Effects of ON101 for Hard‑to‑Heal Diabetic Foot Ulcers: Post hoc analysis. 2024. https://pubmed.ncbi.nlm.nih.gov/38780901/

[6] ClinicalTrials.gov NCT01898923 – Evaluate the Efficacy and Safety of ON101 Cream for DFU. https://clinicaltrials.gov/study/NCT01898923

[7] Aboyans V, et al. Measurement and Interpretation of the Ankle‑Brachial Index. Circulation. 2012. https://www.ahajournals.org/doi/10.1161/cir.0b013e318276fbcb

[8] McClary KN, et al. Ankle Brachial Index. StatPearls. 2023. https://www.ncbi.nlm.nih.gov/books/NBK544226/

[9] McMullin MF, et al. BSH Guideline: Diagnosis and management of polycythaemia vera. Br J Haematol. 2019. https://pubmed.ncbi.nlm.nih.gov/30478826/

[10] Holman M, et al. Using tap water vs normal saline for wound cleansing: systematic review. J Wound Care. 2023. https://pubmed.ncbi.nlm.nih.gov/37572340/

[11] Fernandez R, et al. Cochrane Review: Water vs other solutions for wound cleansing. 2022. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD003861.pub4/full