What are the management options for myeloproliferative neoplasms (MPNs) presenting with a diffuse macular petechial rash with central necrosis?

Myeloproliferative Neoplasms Presenting with Diffuse Macular Petechial Rash with Central Necrosis

This clinical presentation is most consistent with essential thrombocythemia (ET) or polycythemia vera (PV) complicated by cutaneous vasculitic toxicity, which requires immediate discontinuation of hydroxyurea if the patient is receiving it, and initiation of alternative cytoreductive therapy with interferon-alpha. 1, 2

Recognition of Vasculitic Complications

Cutaneous vasculitic toxicities, including vasculitic ulcerations and gangrene, occur most frequently in MPN patients receiving hydroxyurea therapy, particularly those with a history of or currently receiving interferon. 2

• The diffuse macular petechial rash with central necrosis represents a vasculitic process that is a known complication of hydroxyurea treatment in myeloproliferative disorders 2
• This presentation is most commonly seen in ET and PV patients on cytoreductive therapy 1, 2
• The vasculitic lesions can progress to ulceration and gangrene if not promptly recognized and managed 2

Immediate Management Steps

If cutaneous vasculitic ulcers occur, institute treatment and discontinue hydroxyurea immediately. 2

Discontinuation of Offending Agent

• Stop hydroxyurea immediately upon recognition of vasculitic skin lesions 2
• Do not rechallenge with hydroxyurea once vasculitic toxicity has occurred 2

Alternative Cytoreductive Therapy

• For high-risk PV patients (age >60 years or prior thrombosis history), switch to interferon-alpha as cytoreductive therapy while maintaining phlebotomy to keep hematocrit <45% and aspirin 81-100 mg daily 1
• For high-risk ET patients, transition to interferon-alpha as the alternative cytoreductive agent 1
• Anagrelide may be considered as an alternative in ET patients, though it does not address the underlying vasculitic process 3

Supportive Care for Vasculitic Lesions

• Wound care for any ulcerations that develop 2
• Monitor for signs of infection in necrotic areas 2
• Consider dermatology consultation for severe or extensive cutaneous involvement 2

Risk Stratification Context

The presence of vasculitic complications does not change the underlying risk stratification but necessitates modification of the treatment approach. 1

• High-risk PV is defined as age >60 years or prior thrombosis history 1
• High-risk ET is defined by the same criteria 1
• These patients require cytoreductive therapy regardless of the vasculitic complication, but the agent must be changed 1

Ongoing Management After Resolution

For Polycythemia Vera

• Continue phlebotomy to maintain hematocrit <45% 1
• Maintain aspirin 81-100 mg daily for vascular symptoms 1
• Use interferon-alpha as the cytoreductive agent 1
• Manage cardiovascular risk factors 1
• Monitor for disease progression every 3-6 months 1

For Essential Thrombocythemia

• Continue cytoreduction with interferon-alpha or consider anagrelide 1, 3
• Maintain aspirin therapy unless contraindicated 1
• Monitor platelet counts and adjust therapy to maintain near-normal levels 1

Critical Pitfalls to Avoid

• Never continue hydroxyurea once vasculitic toxicity has been identified - this can lead to progression to gangrene and severe tissue loss 2
• Do not assume the rash is infectious or allergic without considering drug-induced vasculitis in MPN patients on hydroxyurea 2
• Avoid rechallenge with hydroxyurea even after lesions have healed 2
• Do not delay switching to alternative cytoreductive therapy, as high-risk patients require ongoing disease control to prevent thrombotic complications 1

Monitoring for Disease Progression

• Perform bone marrow aspirate and biopsy if there are signs of disease progression to myelofibrosis 1
• Watch for new thrombosis, disease-related major bleeding, progressive splenomegaly, progressive leukocytosis, or worsening constitutional symptoms 1
• Assess symptom burden regularly 1