POEMS syndrome differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Syed Hassan A. Kazmi BSc, MD [2]

Overview

The diagnosis of POEMS syndrome presents a diagnostic challenge for the physician. A thorough examination of organ systems should be attempted in order to reach a confirmed diagnosis. POEMS syndrome should be differentiated from other conditions presenting as a polyneuropathy (metabolic syndrome, vitamin B12 deficiency, Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy and multifocal motor polyneuropathy), organomegaly with lymphadenopathy (malaria, leshmaniasis or kala-azar, infective hepatitis, chronic myelogenous leukemia, lymphoma, primary amyloidosis, Gaucher's disease), endocrinopathy (hypogonadism, hypothyroidism, hypopituitarism), monoclonal plasma cell proliferation (multiple myeloma, monoclonal gammopathy of undetermined significance, plasmacytoma), mixed lytic/sclerotic bone lesions (osteomalacia, osteogenesis imperfecta) and skin changes.

Differentiating POEMS Syndrome From Other Diseases

The diagnosis of POEMS syndrome presents a diagnostic challenge for the physician. A thorough examination of organ systems should be attempted in order to reach a confirmed diagnosis. POEMS syndrome should be differentiated from other conditions presenting as a polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell proliferation, mixed lytic/sclerotic bone lesions and skin changes. The differentials include the following:

Organ System Involvement Differential Diagnosis Causes Clinical Features Laboratory Findings Gold Standard Test Therapy
P = Polyneuropathy POEMS syndrome (Demyelinating)[1]
Metabolic Syndrome (Axonal pathology)[8]
Vitamin Deficiencies (Axonal Pathology)[10]
Guillain-Barre Syndrome (Demyelinating)[16]
  • Clinical diagnostic criteria (progressive weakness of more than two limbs, areflexia, and progression for no more than four weeks)[21]
Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) (Mixed axonal and demyelinatiing)[24][25]
  • EFNS/PNS criteria[33]
  • Koski criteria[34]
Multifocal Motor Neuropathy[35]
  • Progressive, asymmetric, distal and upper limb predominant weakness
  • No significant sensory abnormalities
  • Areflexia
  • Clinical criteria (EFNS/PNS):[36]
    • Slowly progressive or step-wise progressive, focal, asymmetric limb weakness; i.e., motor involvement in the motor nerve distribution of at least two nerves for > 1 month.
    • No objective sensory abnormalities except for minor vibration sense abnormalities in the lower limbs
Organ System Involvement Differential Diagnosis Causes Features Laboratory Findings Gold Standard Test Therapy
O = Organomegaly (Hepatosplenomegaly and Lymphadenopathy) Malaria[37][38][39]
Kala-azar[40][41]
Infective Hepatitis[42][43]
Chronic Myelogenous Leukemia (CML)[44][45][46][47][48][49][50][51][52][51]
Lymphoma
Primary (AL) Amyloidosis[54][55]
  • Typical green birefringence under polarized light after Congo red staining (appears in red under normal light)
  • Congo red staining
  • Melphalan-prednisone/dexamethasone[58]
  • Dexamethasone plus Cyclophosphamide-thalidomide [59]
  • Stem cell transplantation[60]
Gaucher's Disease[61]
Organ System Involvement Differential Diagnosis Causes Features Laboratory Findings Gold Standard Test Therapy
E = Endocrinopathy (Hypogonadism, Hypothyroidism, Hypopituitarism) Hypogonadism[62][63] Primary Hypogonadism (Hypergonadotrophic)
Secondary Hypogonadism (Hypogonadotrophic)
Hypothyroidism[64][65] Primary Hypothyroidism
Secondary Hypothyroidism
Tertiary Hypothyroidism
Hypopituitarism[66][67] Congenital
  • Decreased FSH, LH
  • Decreased TSH
  • Decreased ACTH
  • Decreased GH
  • Decreased ADH
  • Decreased oxytocin
  • Serum hormone levels produced by pituitary
  • Hormone replacement therapy
Acquired
Organ System Involvement Differential Diagnosis Causes Features Laboratory Findings Gold Standard Test Therapy
M = M-protein ( Hematological Abnormality/Plasma Cell Dyscrasias) Multiple myeloma[68][69][70]
  • Anemia
  • Thrombocytopenia
  • Leukopenia
  • Decreased albumin (reversed albumin:globulin ratio)
  • Increased serum creatinine, urea
  • Hypercalcemia
  • Elevated ESR
  • Normal-low alkaline phosphatase
  • RBC rouleaux formation
  • Bence-Jones proteins in urine
  • Clonal plasma cells on bone marrow exam greater than equal to 10%

AND

  • Any one of the following:
    • Evidence of end-organ damage
    • Hypercalcemia (>11 mg/dl)
    • Renal insufficiency
    • Anemia (Hb < 10 mg/dl)
    • Bone lesions
    • Greater than 1 lesions on MRI
Monoclonal gammopathy of undetermined significance (MGUS)[71]
  • Serum M protein (IgG or IgA) <3g/dl

AND

  • Clonal bone marrow plasma cells < 10%

AND

  • No end-organ damage
  • Observation
Asymptomatic Plasma Cell Myeloma

(Smoldering and Indolent plasma cell myeloma)

  • Serum M protein (IgG or IgA greater than equal to 3 g/dl

OR

  • Urinary M protein greater than equal to 500 mg/24 h

AND/OR

  • Clonal bone marrow plasma cells 10-60%

AND

  • No end-organ damage
  • Observation
Plasmacytoma
  • On biopsy:
    • Solitary infiltrate of clonal plasma cells in bone (SBP) or soft tissue (EMP).
    • No evidence of infiltration by clonal plasma cells.
  • Negative skeletal survey plus MRI/CT spine and pelvis except for the solitary lesion.
  • Lack of hypercalcemia, renal insuffieciency, anemia, multiple bone lesions which would suggest MM
  • Diagnosis of exclusion
  • Radiotherapy
Bone Lesions Osteoporosis
  • Normal serum calcium, phosphate, alkaline phosphatase and parathyroid hormone levels
  • Decreased bone mass
  • T score less than -2.5 on DEXA scan
Osteomalacia[72]
  • Decreased serum calcium
  • Decreased serum phosphate
  • Increased serum alkaline phosphatase
  • Increased serum parathyroid hormone levels
  • Bone biopsy (increased osteoid and decreased calcification)
Osteogenesis imperfecta
  • Normal serum calcium
  • Normal serum phosphate
  • Increased serum alkaline phosphatase
  • DNA analysis
  • Collagen analysis
Skin Changes Scurvy

Other Differentials

POEMS syndrome must also be differentiated from other similar conditions which lead to multiple endocrine disorders such as autoimmune polyendocrine syndrome, Hirata syndrome, Kearns–Sayre syndrome and Wolfram syndromes.[73][74][75][76][77]

Disease Addison's disease Type 1 diabetes mellitus Hypothyroidism Other disorders present
POEMS syndrome + Less common Less common Hypoparathyroidism
Candidiasis
Hypogonadism
APS type 2 + + + Hypogonadism
Malabsorption
APS type 3 - + + Malabsorption
Thymoma + - + Myasthenia gravis
Cushing syndrome
Chromosomal abnormalities
(Turner syndrome,
Down's syndrome)
- + + Cardiac dysfunction
Kearns–Sayre syndrome - + - Myopathy
Hypoparathyroidism
Hypogonadism
Wolfram syndrome - + - Diabetes insipidus
Optic atrophy
Deafness
POEMS syndrome - + - Polyneuropathy
Hypogonadism
Plasma cell dyscrasias

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