A Novel Presentation of POEMS Syndrome (2024)

POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) is a paraneoplastic syndrome caused by plasma cell dyscrasias. We report hypertensive emergency and acral matlike telangiectasias as novel manifestations of POEMS syndrome (POEMS). Also, to our knowledge, this is the first reported case of calciphylaxis and POEMS occurring in the absence of sclerotic bone lesions or a peripheral monoclonal gammopathy, highlighting the diagnostic challenges posed by this disease.

A woman in her 30s with a 2-year history of distal polyneuropathy and matlike telangiectasias presented with a hypertensive emergency and peak blood pressure of 247/154 mm Hg. Workup revealed a serous pericardial effusion, hepatosplenomegaly, ascites, shotty lymphadenopathy, and diffuse subcutaneous edema; the remainder of her workup findings were negative, including those for rheumatoid factor, antineutrophil cytoplasmic antibodies, antinuclear antibodies, extractable nuclear antigen antibodies panel, serum and urine protein electrophoresis with immunofixation, and brain magnetic resonance imaging. After blood pressure was brought under control, prednisone treatment was empirically initiated, and the ascites improved.

Over the next 4 months, the patient developed hemangiomas, amenorrhea, refractory ascites, hepatosplenomegaly, weight loss, and fatigue. On readmission, she was found to have hypothyroidism, diabetes mellitus, hypogonadism, and papilledema. Significant laboratory findings included thrombocytosis (platelet level peaking at 2045 × 10⁹/dL) and transient renal insufficiency (creatinine level peaking at 3.04 mg/dL, then quickly decreasing). (To convert creatinine to micromoles per liter, multiply by 88.4.) Parathyroid hormone level was within normal limits, and the level of calcium phosphate product was 43.12 mg/dL (normal, <55.00 mg/dL). Light chain concentrations, both λ and κ, were elevated at 35 mg/dL (normal, 0.57-2.63 mg/dL) and 4.2 mg/dL (normal, 0.33-1.94 mg/dL), respectively, and the κ/λ ratio was low, at 0.12 (normal ratio, 0.26-1.65). The finding of a blood test for human herpesvirus 8 (HHV-8) was negative. Results of bone scans and skeletal surveys were unremarkable.

A dermatology consult was requested to evaluate painful abdominal purpura of 2 weeks’ duration. The patient was cachectic with bulging flanks and lower extremity edema; tender purpuric retiform plaques and eschars were present on the abdomen (Figure 1), and telangiectatic patches were noted on the dorsal surfaces of the feet (Figure 2A). Scattered on her lips, trunk, and extremities were numerous hemangiomas. A biopsy specimen from the abdomen demonstrated subcutaneous intravascular calcification, consistent with calciphylaxis.

Bone-marrow biopsy revealed atypical megakaryocyte hyperplasia, and flow cytometry revealed a small, monoclonal, λ-restricted plasma cell population, which, together with her symptoms, physical examination findings, and laboratory results, were consistent with POEMS. The patient’s level of vascular endothelial growth factor (VEGF) was unremarkable, but she was taking prednisone. Weekly infusions with cyclophosphamide and dexamethasone were started, followed by marked general improvement and resolution of her telangiectasias (Figure 2B). Reducing treatment to every 3 weeks resulted in worsening ascites and calciphylaxis and plasma VEGF levels increasing to 1499 pg/mL (normal, 0-115 pg/mL). Resuming weekly infusions and adding bortezomib to her treatment regimen resulted in substantial improvement.

POEMS has diverse cutaneous manifestations, including hyperpigmentation, sclerodermoid changes, acrocyanosis, acquired facial lipoatrophy, hemangiomas, hypertrichosis, Terry’s nails, and clubbing.¹ While telangiectasias have been reported in POEMS, they are not well characterized. The acral matlike telangiectasias in this patient were striking, similar to those in systemic sclerosis. Calciphylaxis in POEMS has been reported, but in all 5 cases, it occurred concomitantly with a monoclonal gammopathy or sclerotic bone lesions.^2-4 In cases of POEMS associated with diffuse bone-marrow infiltration, radiologic findings may be absent, and the monoclonal population small, with no detectable M-protein. Diagnosis requires either a bone-marrow biopsy with flow cytometry or recognition of atypical megakaryocyte hyperplasia and plasma cell rimming around lymphoid aggregates.⁵ To our knowledge, our patient’s presentation with hypertensive emergency has not been reported in POEMS and may be connected to the proliferative effects of VEGF on the glomerular endothelium. POEMS can be associated with multicentric Castleman disease; in this setting the result of HHV-8 testing is usually positive.⁶

POEMS may be treated with alkylating agents, corticosteroids, immunomodulatory agents, and autologous stem cell transplantation. The proteasome inhibitor bortezomib has shown significant promise through NF-κB inhibition in plasma cells and possible direct effects on endothelial cells via inhibition of VEGF and angiogenesis.⁷

Corresponding Author: Meg R. Gerstenblith, MD, Department of Dermatology, University Hospitals Case Medical Center, Case Western Reserve University School of Medicine, 11100 Euclid Ave, Lakeside Third Floor, Cleveland, OH 44106 (meg.gerstenblith@uhhospitals.org).

Published Online: April 9, 2014. doi:10.1001/jamadermatol.2013.7256.

Conflict of Interest Disclosures: Dr Honda has consulted for Genmab. No other disclosures are reported.

Funding/Support: Dr Gerstenblith received grants from The Char and Chuck Fowler Family Foundation, the Dermatology Foundation Career Development Award, and the National Rosacea Society.

Role of the Sponsor: The granting institutions had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Previous Presentation: This case was presented as a poster at the American Society of Dermatopathology meeting; October 13, 2012; Chicago, Illinois.