A Case of Acute Vaso-Occlusive Retiform Purpura Secondary to Essential Thrombocythemia

Introduction. A 57-year-old woman with a past medical history of essential thrombocytosis, chronic obstructive pulmonary disease, hypertension, and treated chronic hepatitis C presented to the emergency department with several discrete areas of purplish discoloration on her right palm, fingertips, and bilateral feet.

History. The patient was diagnosed with essential thrombocythemia (ET) during a previous hospitalization 1 year prior, after thrombocytosis was identified on laboratory findings and a bone marrow biopsy revealed megakaryocytic hyperplasia. Her condition was controlled with oral chemotherapy (500 mg of hydroxyurea twice daily), but she had discontinued the use of her medication for the past 2 months because of social circumstances and the inability to attend her follow-up appointments.

The lesions she now presented with were painful and first appeared 3 weeks prior to her consultation, starting initially at the palmar base of the 5th digit and eventually progressing to involve all the digits (Figure 1) and the bilateral feet (Figure 2). While the pain had been present for approximately 1 month, it acutely worsened 24 hours prior to her admission. The pain was throbbing in nature and was aggravated by any palpation or pressure. She also reported 2 months of headache, blurry vision, shortness of breath, and chest pain.

Figure 1. Distal branching, central non-blanching purpura of the right hand without necrosis or ulcerations involving the 1st, 2nd, 3rd, and 5th digits.

Figure 2. Distal branching, central non-blanching purpura of the bilateral feet.

Diagnostic testing. Notable laboratory findings included white blood cell count 7.3 k/µL, hemoglobin 13.1 g/dl, and platelets 1,273K mcL. No blasts were present on blood smear and the liver function tests and alkaline phosphatase were within normal limits. Erythrocyte sedimentation rate, C-reactive protein, and complement levels were all within normal limits and antinuclear antibody was negative. Right hand plain film and computed tomography (CT) angiogram with contrast of the right upper extremity showed no acute abnormalities. Prior to dermatology specialist consultation, inflammatory vasculitis remained on the differential diagnosis. The rheumatology specialists ordered serum protein electrophoresis, rheumatoid factor, cryoglobulin, and antineutrophil cytoplasmic antibody tests as well as blood cultures, which were all negative.

Differential diagnoses. Retiform purpura presents a diagnostically challenging finding for which the differential diagnosis is broad. Retiform purpura may be precipitated by numerous conditions, including small and medium vessel vasculitides and microvascular occlusion from a thrombotic, infectious, or embolic cause.¹

For this patient, the primary considerations were ET given her known history of the condition, polyarteritis nodosa, Henoch-Schönlein purpura, cryoglobulinemia, meningococcemia, and calciphylaxis. These common causes of retiform purpura are differentiated by diagnostic laboratory testing, which were all negative in this patient and ruled out these conditions.

Although it is uncommon, retiform purpura can be a dermatologic manifestation of ET, and myeloproliferative neoplasms should be considered in the differential diagnosis, and correlated with additional presenting symptoms when purpura is identified on physical examination.^2,3 Early detection and awareness of dermatologic signs and symptoms can aid in diagnosis, as close to a quarter of patients with ET will present with skin findings.⁴

Treatment. She was initially restarted on her home regimen of 500 mg of hydroxyurea twice daily for her significant thrombocytosis but given her presentation with purpura and the concern for microvascular ischemia, her hydroxyurea was increased to 1500 mg after 2 days of restarting her medication. Contemporaneously she was started on 81 mg of aspirin once daily for anti-thrombotic therapy. Rheumatology consultants indicated a low index of suspicion clinically for vasculitis. Subsequently, dermatology specialists were consulted, and a diagnosis of acute vaso-oclusive retiform purpura secondary to megakaryocytic hyperplasia was rendered. In addition to continuing her medical treatments and ensuring adequate pain control, dermatology specialists recommended she be taken for plateletpheresis to rapidly reduce her thrombocythemia. After a single session, her platelet count decreased from 1,172K to 465K, and the patient had a significant reduction in pain and purpura.

Outcome and follow-up. Her purpura showed improvements following the treatment, and she also noted reduced severity of her symptoms and pain. She did not require further intravenous pain control and wanted to be able to attend an important family event, so she was discharged on her original home dose of hydroxyurea and scheduled for outpatient follow-up with oncology specialists. To date, she has had resolution of her symptoms and is doing well.

Discussion. Myeloproliferative neoplasms are a group of diseases precipitated by mutations in hematopoietic stem cells, leading to the overproduction of cells.⁵ ET, one such type of myeloproliferative neoplasm, is marked by thrombocytosis and megakaryocytic hyperplasia.⁶ ET can present with symptoms ranging from headache and dizziness, to easy bruising, transient ischemic attack, and venous thrombosis.⁷  ET may also be associated with several skin findings, including erythromelalgia, hematomas, ecchymoses, petechiae, and purpura.⁴ However, true retiform purpura, with arborizing purplish brown patches on the skin caused by the extravasation of red blood cells into the tissue from compromised endothelial cell integrity, is a less common manifestation of ET.^2,3

Pathologic purpura (non-senile purpura) may present a diagnostic challenge to the non-dermatologist. Two broad categories of meaningful distinction include palpable purpura (small papular areas of purpura) and retiform purpura (flat, arborizing/branching patterns of purpura).  The former is due to type III hypersensitivity reactions, as is the etiology in classic palpable purpura from antigen-antibody immune complex deposition on endothelial cell walls in small-vessel vasculitides, usually secondary to a drug-eruption, infection, autoimmune disorder, or malignancy.⁸ The latter is a finding seen in vascular occlusive disorders, such as calciphylaxis, angioinvasive infections, post-catheterization embolization, antiphospholipid antibody syndrome, and other hypercoagulable states.¹ Interestingly, cryoglobulinemia with its varying types (types I and II) may present in either fashion.⁹ While a thrombotic cause for the patient’s retiform purpura was more evident given her known history of ET and lack of medication compliance, the simultaneous development of a vasculitis or cryoglobulinemia superimposed on her myeloproliferative disorder could not be ruled out without further investigation.

For patients with ET, the recommended treatment is hydroxyurea with low-dose aspirin.¹⁰ Hydroxyurea is effective in preventing thrombosis in patients with ET, but the long-term benefits of using low-dose aspirin for antithrombotic therapy are inconclusive.^11,12 However, given the patient’s vaso-oclusive presentation, oncology and dermatology specialists agreed with the use of aspirin to prevent acute thrombosis. In the setting of significant thrombocytosis, as seen in this case, plateletpheresis may also be an effective acute therapy for rapidly reducing platelet levels, particularly in patients with platelet counts greater than 800K.^10,13 In this case, the implementation of plateletpheresis was effective in greatly diminishing the risk of acute ischemia and led to the expedited resolution of the patient’s symptoms.

Conclusion. Purpura presents a diagnostic challenge, for which the differential diagnosis is broad. The presence of retiform purpura should alert the clinician to etiologies that lead to vascular occlusion, including pro-thrombotic myeloproliferative neoplasms. A broad laboratory work-up is indicated, including consideration of testing for small and medium sized vessel vasculitides, and imaging for sources of thromboses, such as echocardiography and CT angiography, may also be warranted. For ET, hydroxyurea remains an effective treatment for preventing thrombosis, and low-dose aspirin may also be introduced for antithrombotic therapy. Plateletpheresis may be an especially important intervention in those with impending necrosis of tissue structures related to vaso-occlusion.

AFFILIATIONS
¹Department of Internal Medicine, College of Medicine, University of Arizona, Phoenix, AZ
²US Dermatology Partners, Phoenix, AZ

CITATION
Shah M, Nguyen G, Ackerman L. A case of acute vaso-occlusive retiform pupura secondary to essential thrombocythemia. Consultant. 2023;63(9):e3. doi:10.25270/con.2023.08.000004.

Received August 21, 2022. Accepted January 25, 2023. Published online August 9, 2023.

DISCLOSURES
The authors report no relevant financial relationships.

ACKNOWLEDGEMENTS
None.

CORRESPONDENCE
Milaan Shah, MD, Banner University Medical center, 1111 East McDowell Road, Pheonix, AZ 85006 (milaan8697@gmail.com)