Rare osteosclerotic form of plasmacytoma.
A paraneoplastic syndrome from an underlying plasmaproliferative disorder.
Rare paraneoplastic syndrome associated with a monoclonal plasma cell dyspraxia.
Criteria for diagnosis: major-polyneuropathy, monoclonal plasma proliferative disorder: minor-sclerotic bone lesions, Castleman’s disease, organomegaly, hepatomegaly, or lymphadenopathy, edema with pleural effusion or ascites, endocrinopathy involving possibly the adrenals, thyroid, pituitary, gonads, parathyroids or pancreas, skin changes include hyperpigmentation, hypertrichosis, plethora, hemangiomata and white nails, papilledema: associated factors include: clubbing, thrombocytosis, polycythemia, weight loss, hyperhidrosis, and possible associations: pulmonary hypertension, restrictive lung disease, thromboses, arthralgias, cardiomyopathy, fever, low vitamin B12 levels and diarrhea.
Peripheral neuropathy in the presence of the monoclonal protein are mandatory criteria for diagnosis and in patients with these findings a thorough investigation for POEMS syndrome should be undertaken.
Diagnosis requires the two major criteria and at least one minor criterion.
Prevalence reported to be 0.3 per 100 thousand in a Japanese study.
More than 95% of patients have bone marrow infiltration or monoclonal lambda plasmacytomas.
Characteristics include sclerotic bone lesions, Castleman’s disease, edema, ascites, pleural effusions, papilledema, clubbing, thrombocytosis, and polycythemia.
Sclerotic bone lesions are present in 95% of patients, but do not typically cause bone pain unless they have a lytic component.
Endocrinopathies occur in 84% of patients with hypogonadism as the most common problem.
Endocrineopathies manifest as low total testosterone levels, gynecomastia, and irregular menses.
Abnormal glucose metabolism and thyroid arrangements are common.
Multiple endocrinopathies are found in 54% of patients.
The major manifestation of the disease is usually progressive sensorimotor neuropathy.
Most patients do not have a measurable M protein.
Pathophysiology suggests a cytokine imbalance is present characterized by an excessive production of multiple pro-inflammatory and angiogenic cytokines – interleukin1 beta, interleukin 6, fibroblast growth factor, hepatocyte growth factor, and interleukin12, and suppression of anti-inflammatory cytokine transforming growth factor beta1, which is activated by a plasma cell clone.
Associated with serum or plasma level elevation of vascular endothelial growth (VEGF), sclerotic bone lesions, Castleman’s disease, skin changes of hyperpigmentation, hypertrichosis, plethora, cyanosis, hemangiomas, white nails, papilledema, and glomeruloid hemangiomas of the skin.
Dermatologic manifestations include hyperpigmentation and hemangiomas in almost half of the patients, followed by hypertrichosis, vascular skin changes and fingernail changes.
Over production of proinflammatory and proangiogenic cytokines.
Extravascular fluid volume overload occurs in at least 1/3 of patients and manifests peripherally or ascites or pleural effusions.
Papilledema is the most common ocular manifestation and is seen in at least 1/3 of patients.
Marked overproduction and secretion of VEGF by plasma cells.
VEGF induced neovascularization and microvascular permeability associated with clinical manifestations.
IL-12 overproduced.
Lymph node changes compatible with Castleman disease are reported up to 30% of patients.
Sclerotic bone lesions or Castleman’s disease present in nearly all cases.
A progressive and chronic disorder.
Median survival 13.8 years.
Skin manifestations correlate with serum vascular endothelial growth factor levels.
Skin lesions include hemangiomas (86%) hyperpigmentation (76%), skin thickening (57%), acrocyanosis (57%), hypertrichosis (52%), acquired facial lipoatrophy (52%), and white nails (38%) (Barete S).
Lambda light chain monoclonal protein is the M protein abnormality in almost all cases.
Typically the monoclonal proteins spike is small, with the median size of 1 g/dL.
Serum light chains are abnormal and at least 2/3 patients.
The plasma cell clone can be detected in only 2/3 of patients, and if present it is often less than 5%,.
Increased levels of VEGF and other cytokines are a common finding in plasma cells.
Associated with elevated VEGF levels and polycythemia.
Both serum and plasma VEGF levels may be helpful in supporting the diagnosis and monitoring patient’s responses to therapy, as levels are thought to reflect the activity of the disease.
POEMS is associated with a hypercoagulable syndrome, with the arterial and venous thrombosis reported up to 30% of patients, and is likely associated with increased levels of procoagulants such as fibrinogen, and thrombin antithrombin complexes.
Pulmonary hypertension occurs in about 1/4 of patients, the result of chronic vascular wall inflammation and stiffening.
Peripheral neuropathy is the dominant feature of the process and a frequent presenting symptom.
Long-standing neuropathy that progressively worsens is often present throughout the course of the disease.
long-standing neuropathy that progressively worsens is often present throughout the course of the disease.
The peripheral neuropathy is length dependent and demyelinating.
The neuropathy starts with sensory symptoms and over time produces motor symptoms with distal weakness in the hands and feet, muscle atrophy, areflexia, and gait dysfunction.
Frequently misdiagnosed as chronic inflammatory type demyelinating polyneuropathy.
Endocrinopathy include: diabetes, hypogonadism, hypothyroidism, hyperprolactinemia, adrenal insufficiency, gynecomastia in men, hyperestrogenemia and hypoparathyroidism.
Hypogonadism most common endocrinopathy in men.
All patients should have an endocrine evaluation with testosterone, prolactin, fasting glucose, cortisol , ACTH, thyrotropin, and calcium specimens.
Associated with pulmonary hypertension, restrictive lung disease, weight loss, clubbing, and hyperhidrosis.
TREATMENT:
Treatment depends on the eradication of the culprit plasma cell clone.
For localized disease radiation is the major treatment, while for widespread lesions chemotherapy is the treatment of choice.
In patients with one to three bone lesions and no clonal bone marrow plasma cell involvement, radiation is the preferred treatment with excellent clinical responses in long-term disease-free survival.
Patients who have more than three bone lesions or bone marrow involvement by clonal plasma cells should receive systemic therapy.
Systemic therapy involves all conventional agents and regimens for multiple myeloma.
Peripheral blood cell stem cell transplantation is an effective therapy.
Glucocorticoids and melphalan have symptomatic benefit, and other agents that are effective include thalidomide, lenalidomide, or bortezomib.