Polycythemia Vera Leg Ulcer: Multimodal Case & Protocol

Polycythemia Vera–Associated Leg Ulcer: How a Multimodal Plan (JAK Inhibition + Anti‑Biofilm Care) Unstalled Healing

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

Quick take

(Initial visit of 76 year old female with chronic non-healing ulcer to lower-left extremity)

A 76‑year‑old woman with polycythemia vera (PV) and a chronic lower‑extremity ulcer improved only after two pivotal changes: stopping long‑term hydroxyurea and starting ruxolitinib for systemic PV control, and adding cadexomer iodine to aggressively target suspected biofilm in the wound bed. Case reports of PV‑ and hydroxyurea‑associated leg ulcers responding to ruxolitinib and robust data on cadexomer iodine in chronic wounds support this combined systemic and local strategy.[1,2]

Across the course of care, noncontact low‑frequency ultrasound (LFU) appeared to reduce slough and bioburden but then plateaued; in contrast, sharp debridement and biopsy were followed by wound deterioration, likely reflecting fragile PV‑related microvasculature and impaired perfusion. Clinical and preclinical data show that LFU can meaningfully reduce chronic‑wound area and biofilm burden, but functions best as an adjunctive modality rather than a stand‑alone fix.[8,9]

From an initial wound size of 17 × 12.5 × 0.3 cm in 2018, the ulcer ultimately decreased to 7.6 × 4.6 × 0.1 cm by early 2025—an 83.5% area reduction—after hematologic optimization, de‑escalation of hydroxyurea, introduction of ruxolitinib, and sustained anti‑biofilm dressing use. Similar patterns of improvement have been reported when systemic PV control is combined with aggressive local management in PV‑ and hydroxyurea‑associated ulcers.[1,4]

Case at a glance

PV was diagnosed in 2014, and the leg ulcer began in March 2018 on the lower extremity, against a background of longstanding PV and cardiovascular risk factors. The patient also had prolonged exposure to World Trade Center (9/11) dust and toxins; World Trade Center–exposed responders have demonstrated increased rates of multiple myeloma and clonal hematopoiesis, supporting the idea that this complex exposure can contribute to myeloid and marrow neoplasms, even though a direct causal link to PV specifically has not been established.[12,13]

Before the turning point, multiple standard therapies were tried with only partial or transient benefit: hyperbaric oxygen therapy (HBOT) for ischemia, serial LFU sessions, collagenase and calcium alginate dressings, and a bilayered bioengineered skin substitute. Systematic reviews show that HBOT and LFU can enhance healing in selected chronic wounds, but effects are variable and both are viewed as adjunctive to meticulous standard wound care.[8,15]

Biopsies and sharp debridement, performed to rule out atypia and remove slough, provoked bleeding and subsequent wound worsening, underscoring how PV‑related vascular dysfunction and hydroxyurea‑related skin toxicity can translate into leg ulcers that are unusually fragile and slow to granulate.[4,5]

The major inflection points were discontinuation of hydroxyurea with initiation of ruxolitinib in 2019, followed by escalation of topical anti‑biofilm therapy with cadexomer iodine in 2023. Published experience in hydroxyurea‑associated PV leg ulcers echoes this pattern—ulcers often improve after hydroxyurea cessation, and dramatic healing has been documented after switching to ruxolitinib in refractory cases.[1,5]

Why PV ulcers stall (and what to fix first)

PV is characterized by erythrocytosis, leukocytosis, and thrombocytosis, leading to increased blood viscosity and a high burden of both macrovascular and microvascular events that can impair tissue perfusion and endothelial health. Randomized data from the CYTO‑PV trial show that keeping hematocrit below 45 % significantly reduces major cardiovascular and thrombotic events, and this target is now embedded in modern PV management strategies.[6,7]

Hydroxyurea (HU), a cornerstone cytoreductive agent in higher‑risk PV, is also linked to a distinctive pattern of painful ankle and lower‑leg ulcers that are often slow to heal; case series highlight that these ulcers typically develop after long‑term HU at higher daily doses and frequently resolve only after the drug is discontinued.[4,5]

For patients whose PV is controlled but who develop nonhealing leg ulcers while on HU—or whose ulcers clearly worsen on HU—case reports describe healing when HU is stopped and the patient is transitioned to ruxolitinib, a JAK1/2 inhibitor used as a second‑line option in HU‑intolerant or HU‑resistant PV.[1,7]

Baseline PV management remains foundational for any complex wound: phlebotomy to maintain hematocrit <45 %, low‑dose aspirin when not contraindicated, cardiovascular risk reduction, and appropriately selected cytoreductive therapy. International and NCCN‑aligned guidance emphasize that cytoreduction (with HU, interferon, or ruxolitinib) is indicated for high‑risk patients or those with symptomatic or progressive disease, and wound teams should partner early with hematology so the systemic plan supports local healing.[7,17]

Local wound strategy that worked here

Given the chronicity of the ulcer and its behavior on sharp debridement, the local plan prioritized biofilm control with low‑trauma methods. After an initial response to LFU plateaued, cadexomer iodine became the workhorse topical agent; randomized trials and a meta‑analysis show that cadexomer iodine can reduce slough and microbial burden, manage exudate, and accelerate healing compared with standard care alone in chronic pressure and venous ulcers.[2,3]

Because the ulcer bled readily and flared after biopsies and aggressive sharp debridement, subsequent debridement was restrained and individualized, using noncontact LFU, gentle curettage, and autolytic or enzymatic methods to avoid further injury. Wound bed preparation frameworks emphasize that debridement intensity should match vascular supply and tissue resilience, and that in fragile, poorly perfused wounds, conservative debridement is safer than repeated aggressive excision.[10,11]

LFU remained in the toolbox as an adjunct: pooled clinical data suggest that noncontact low‑frequency ultrasound can produce substantial reductions in chronic‑wound area over 6–12 weeks, and preclinical work demonstrates decreased Pseudomonas aeruginosa biofilm and inflammatory cytokines in treated wounds. Authors of these studies characterize LFU as a helpful adjunctive energy‑based therapy rather than a replacement for fundamentals like perfusion, infection control, and moisture balance.[8,9]

Clinician‑ready protocol: PV‑associated chronic leg ulcer

1) Stabilize the hematology first

Aim for hematocrit <45 % and ensure guideline‑concordant use of low‑dose aspirin and phlebotomy, because tighter hematocrit control reduces the risk of major thrombosis and likely improves downstream tissue perfusion for wound healing.[6,7]

If an ulcer emerges or stalls on hydroxyurea—especially in the characteristic malleolar distribution—discuss HU interruption or discontinuation and second‑line options such as ruxolitinib with hematology; HU‑induced ulcers often heal after the drug is stopped, and PV‑related ulcers have been reported to resolve after switching from HU to ruxolitinib.[1,5]

2) Map vascular status

Obtain ABI and/or toe pressures and assess for venous hypertension (edema, varicosities) and arterial disease (rest pain, diminished pulses); treat venous disease with appropriate compression if arterial inflow is adequate, and refer for revascularization when significant peripheral arterial disease is identified. Contemporary PAD guidelines for patients with foot ulcers stress formal vascular testing, correction of inflow problems, and tailored compression as prerequisites for wound healing.[10,14]

3) Control biofilm and moisture

For sloughy, exudative PV ulcers, cadexomer iodine is a practical first‑line topical because it combines sustained iodine release with an absorbent starch matrix, allowing simultaneous exudate management and reduction of surface bioburden; randomized and pooled data show improved wound‑area reduction and cleanliness versus standard dressings.[2,3]

Pair cadexomer iodine with moisture‑balancing secondary dressings such as alginates or hydrophibers to handle exudate without over‑drying the base, in keeping with wound bed preparation principles that emphasize “moist but not macerated” conditions.[10]

4) Debridement—go gently

In PV patients with friable microvasculature and HU‑related skin fragility, consider noncontact or low‑trauma debridement options (LFU, autolytic or enzymatic agents, careful mechanical cleansing) as first‑line, reserving sharp debridement for clearly nonviable tissue and performing it under close hemostatic control. Reviews of debridement techniques stress matching debridement choice to vascular status and bleeding risk, and note that energy‑based methods like ultrasound should be deployed judiciously until safety data are more robust.[9,11]

5) Reevaluate every 2–4 weeks

Track wound area, depth, pain, and granulation; if the ulcer is not trending toward smaller size and healthier tissue within 2–4 weeks, escalate both systemic and local care. Wound bed preparation paradigms recommend iterative reassessment and, once perfusion and bioburden are optimized, consideration of adjuncts such as negative pressure wound therapy or skin substitutes for appropriately selected wounds.[10,11]

Fast facts

PV target hematocrit for wound‑prone patients

Aim for <45 % hematocrit to reduce thrombotic risk and improve microvascular flow; this target is supported by randomized data and incorporated into modern PV management guidelines.[6,7]

When to rethink hydroxyurea

Consider HU as a contributor when a PV patient on long‑term HU develops new or worsening painful malleolar ulcers or when an existing ulcer stalls despite adequate local care; HU‑associated ulcers are well documented, and case reports show healing after HU withdrawal.[4,5]

Best first‑line topical for sloughy PV ulcers

Cadexomer iodine is a strong candidate when exudate and suspected biofilm are prominent, given its ability to absorb exudate, reduce microbial load, and accelerate healing in chronic wounds, especially when paired with an absorptive secondary dressing.[2,3]

Debridement caution

PV and HU exposure can coexist with venous or arterial disease, creating ulcers that bleed easily and worsen after aggressive sharp debridement; expert frameworks recommend tailoring debridement intensity to vascular status and tissue resilience and prioritizing conservative approaches in fragile wounds.[4,11]

Role of HBOT

HBOT may improve short‑term healing and reduce amputation risk in selected chronic wounds (particularly diabetic foot ulcers), but evidence for broad use is mixed, and therapy is limited by cost, access, and contraindications such as certain pulmonary and ear conditions.[15,16]

FAQs

Why do PV patients get stubborn leg ulcers?

PV‑driven hyperviscosity and microvascular dysfunction can compromise tissue perfusion, while long‑term HU exposure adds a risk of drug‑induced leg ulcers; these ulcers may be particularly slow to granulate and can worsen with trauma. Achieving evidence‑based hematocrit targets and reassessing the need for HU are critical early steps when confronted with a nonhealing PV ulcer.[4,6]

Does ruxolitinib really help leg ulcers?

Ruxolitinib is an established second‑line agent for HU‑intolerant or HU‑resistant PV, and case reports describe dramatic healing of chronic PV‑ and HU‑associated leg ulcers after switching from HU to ruxolitinib, likely through both improved disease control and removal of HU‑related skin toxicity.[1,5]

Why cadexomer iodine?

Cadexomer iodine delivers sustained iodine within an absorbent matrix that can sequester exudate, pus, and slough; randomized trials and meta‑analyses report superior reductions in wound area, bioburden, and pain compared with standard care in pressure and venous ulcers, making it attractive for heavily exudative, biofilm‑suspect leg ulcers.[2,3]

Should I sharply debride PV ulcers?

Maybe—but cautiously. In PV patients, especially those on HU or with significant vascular disease, sharp debridement can sometimes trigger bleeding and tissue breakdown; debridement reviews and wound bed preparation frameworks support using low‑trauma methods first and reserving sharp debridement for clearly nonviable tissue in a well‑perfused field.[10,11]

Bottom line

For PV‑associated leg ulcers, durable progress typically requires aligning systemic and local strategies: optimize hematocrit and antithrombotic therapy, reconsider HU when ulcers stall, and pair that with deliberate biofilm‑focused local care (for example, cadexomer iodine plus adjunctive LFU and cautious debridement). Existing PV and wound‑healing literature supports this dual focus and suggests that even long‑stalled, treatment‑refractory ulcers can re‑enter a healing trajectory when both drivers are addressed.[1,6]

References

1. Shanmugam VK, McNish S, Shara N, et al. Chronic leg ulceration associated with polycythemia vera responding to ruxolitinib (Jakafi). J Foot Ankle Surg. 2013;52(6):781–785. PMC

2. Paustian C, Bailey M, Brookshire R, et al. Efficacy of topical cadexomer iodine treatment in chronic wounds: systematic review and meta‑analysis of comparative clinical trials. Int Wound J. 2021;18(2):192–204. PubMed

3. Moberg S, Hoffman L, Grennert ML, Holst A. A randomized trial of cadexomer iodine in decubitus ulcers. J Am Geriatr Soc. 1983;31(8):462–465. PubMed

4. Bader U, Banyai M, Böni R, Burg G, Hafner J. Leg ulcers in patients with myeloproliferative disorders: disease‑ or treatment‑related? Dermatology. 2000;200(1):45–48. PubMed

5. Khaled A, El Guellali N, Aissaoui L, et al. Hydroxyurea induced‑leg ulcer in polycythemia vera. Tunis Med. 2011;89(3):292–294. PubMed

6. Marchioli R, Finazzi G, Specchia G, et al. Cardiovascular events and intensity of treatment in polycythemia vera. N Engl J Med. 2013;368(1):22–33. PubMed

7. Mesa RA. New Guidelines From the NCCN for Polycythemia Vera. J Natl Compr Canc Netw. 2017;15(10):1193–1197. PMC+1

8. Driver VR, Yao M, Miller CJ. Noncontact low‑frequency ultrasound therapy in the treatment of chronic wounds: a meta‑analysis. Wound Repair Regen. 2011;19(4):475–480. PubMed

9. Seth AK, Nguyen KT, Geringer MR, et al. Noncontact, low‑frequency ultrasound as an effective therapy against Pseudomonas aeruginosa–infected biofilm wounds. Wound Repair Regen. 2013;21(2):266–274. PubMed

10. Sibbald RG, Elliott JA, Persaud‑Jaimangal R, et al. Wound Bed Preparation 2021. Adv Skin Wound Care. 2021;34(4):183–195. PubMed

11. Thomas DC, Tsu CL, Nain RA, et al. The role of debridement in wound bed preparation in chronic wound: a narrative review. Ann Med Surg (Lond). 2021;71:102876. PubMed+1

12. Landgren O, Zeig‑Owens R, Giricz O, et al. Multiple myeloma and its precursor disease among firefighters exposed to the World Trade Center disaster. JAMA Oncol. 2018;4(6):821–827. JAMA Network

13. Bolton KL, Zeig‑Owens R, Gillis NK, et al. High burden of clonal hematopoiesis in first responders exposed to the World Trade Center disaster. Nat Med. 2022;28(7):1308–1313. PubMed

14. Fitridge R, Chuter V, Mills J, et al. The intersocietal IWGDF, ESVS, SVS guidelines on peripheral artery disease in people with diabetes mellitus and a foot ulcer. J Vasc Surg. 2023;78(5):1101–1131. Cambridge Media Journals

15. Kranke P, Bennett MH, Martyn‑St James M, Schnabel A, Debus SE, Weibel S. Hyperbaric oxygen therapy for chronic wounds. Cochrane Database Syst Rev. 2015;(6):CD004123. Cochrane

16. Hampson NB, Holm JR, Courtney‑Shapiro C, et al. Hyperbaric oxygen therapy: descriptive review of the technology and current application in chronic wounds. Int Wound J. 2020;17(3):631–642. PMC

17. Passamonti F. How I treat polycythemia vera. Blood. 2012;120(2):275–284. air.unimi.it+1