POEMS syndrome differential diagnosis

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

## Overview[edit | edit source]

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[edit | edit source]

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

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P = Polyneuropathy | POEMS syndrome (Demyelinating)[1] |

* Monoclonal plasma cell proliferation
* Cytokine storm (IL-1, IL-6, IL-12, TNF alpha, VEGF)

* Symmetrical, ascending chronic progressive polyneuropathy with both sensory (pin-prick and vibration) and motor disability (motor > sensory)
* Generalized/extermity pain
* Areflexia

* Increased number of thrombocytes[2][3][4]
* Increased number of erythrocytes[2][3][4]
* Elevated cerebrospinal fluid (CSF) protein content[3]
* Increased number of leukocytes[4]
* High levels of IgG lambda or IgA lambda M-protein in the serum[4]
* Increased number of plasma cells in the bone marrow[4]
* Increased serum VEGF level[5]
* Elevated levels of antitiroglobulin antibody and antithyroid peroxydase antibody[6]

* International Myeloma Working Group (IMWG) clinical and laboratory diagnostic criteria[7]

Metabolic Syndrome (Axonal pathology)[8] |

* Diabetes mellitus

* Symmetric sensorimotor distal polyneuropathy
* Asymmetric proximal neuropathy
* 3rd nerve palsy
* Carpel tunnel syndrome
* Autonomic neuropathy
* "Glove and stocking" type pain
* Muscle wasting
* Hammer toes
* Polyuria
* Polydipsia

* Uncontrolled hyperglycemia
* Slowed nerve conduction
* Small fiber dysfunction
* Monofilament testing

* Fasting blood sugar level greater than equal to 126 mg/dl on 2 separate occasions[9]

* Anti-diabetic therapy
* Gabapentin
* Carbamazepine
* Foot care

Vitamin Deficiencies (Axonal Pathology)[10] |

* Vitamin B12 deficiency (Decreased S-adenosyl methionine)[11]
* Vitamin B1 deficiency

* Primarily sensory deficits
* Vibration and proprioception affected
* Gait abnormalities
* Cognitive impairment
* Irritability
* Glossitis

* Anemia (megaloblastic in case of B12 deficiency)[12]
* Decreased serum Vitamin B12 levels (< 200 pg/ml)
* Elevated methylmalonic acid

* Serum Vitamin B12 levels[13]
* Methylmalonic acid levels
* Intrinsic factor antibodies[14]

* Vitamin B12 supplement (parenteral)[15]

Guillain-Barre Syndrome (Demyelinating)[16] |

* Anti-ganglioside and anti-myelin antibodies[17]
* Viral infections:[18]
* Epstein Barr virus
* HIV
* Cytomegalovirus
* Varicella Zoster virus
* Bacterial infections:[19]
* Campylobacter infection
* Mycoplasma pneumoniae

* Rapid onset and quick progression
* Progression stops after 2-3 weeks
* Bilateral ascending paraesthesias and paralysis (generalized)
* Weakness
* Ataxia
* Areflexia
* No fever
* 4 sub-types:
* Acute inflammatory demyelinating polyneuropathy
* Acute motor axonal neuropathy
* Acute motor and sensory axonal neuropathy
* Miller Fisher syndrome

* Delayed F waves[20]

* Clinical diagnostic criteria (progressive weakness of more than two limbs, areflexia, and progression for no more than four weeks)[21]

* Intravenous immunoglobulins[22]
* Plasma exchange[23]
* Respiratory support
* DVT/PE prevention

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) (Mixed axonal and demyelinatiing)[24][25] |

* Abnormal immune response (both IgG based humoral and T-Cell mediated) response to unknown antigen (possible culprits include myelin proteins P0, P2 and PMP22)[26][27][28]

* Slow onset and gradual progression
* Relapsing and remitting course
* Symmetrical proximal and distal motor and sensory weakness (legs>arms)
* Foot drop
* Numbness, tingling and pain
* Areflexia

* Elevated CSF protein (oligoclonal bands with normal WBCs)[29]
* Slowed motor nerve conduction velocities[30]
* Prolonged distal motor latencies (period between F wave and initial stimulation)
* Delayed F wave latencies (recorded from the feet, hence called "F" waves)[31]
* MRI contrast enhancement and enlargement of T2 spinal segments[32]

* EFNS/PNS criteria[33]
* Koski criteria[34]

* Corticosteroids
* Intravenous immunoglobulin (IVIG)
* Immunosupressants (Alemtuzemab Azathioprine Cyclophosphamide Cyclosporin Etanercept Interferon-alpha)

Multifocal Motor Neuropathy[35] |

* Abnormal immune response (Anti ganglioside GM-1 IgM antibodies)

* Progressive, asymmetric, distal and upper limb predominant weakness
* No significant sensory abnormalities
* Areflexia

* Elevated CSF protein

* 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

* Intravenous immunoglobulins
* Cyclophosphamide
* Rituximab

Organ System Involvement | Differential Diagnosis | Causes | Features | Laboratory Findings | Gold Standard Test | Therapy
O = Organomegaly (Hepatosplenomegaly and Lymphadenopathy) | Malaria[37][38][39] |

* Plasmodium falciparum
* P. ovale
* P. malariae
* P. knowlesi

* Tertian (vivax, ovale, falciparum), quartan (malariae), quotidian fever (knowlesi)
* Vector is female Anopheles mosquito
* Hepatosplenomegaly
* Lymphadenopathy
* Jaundice
* Icterus
* Tachycardia
* Tachypnea
* Productive cough
* Hematuria
* Altered mental status

* Microcytic anemia
* Thick and thin blood films (Giemsa staining)

* Rapid diagnostic test (antigen detection
* Polymerase chain reaction (PCR)
* Enzyme linked immunosorbent assay (ELISA)

* Thick and thin films

* Non-falciparum species:
* Chloroquine (in susceptible)
* Artemisinin plus mefloquin or lumefantrine (in chloroquine resistant)
* Falciparum species:
* Chloroquine (in susceptible)
* Artemether plus lumefantrine (in chloroquin resistant) OR
* Artesunate plus mefloquin OR
* Artesunate plus sulfadoxine-pyrimethamine
* Atovaquone plus proguanil

Kala-azar[40][41] |

* Leshmania donovani
* L. infantum
* L. chagasi

* Fever
* Vector is sandfly
* Hepatosplenomegaly
* Lymphadenopathy
* Hyperpigmentation

* Anemia
* Direct agglutination test (DAT)
* rk39 dipstick
* ELISA

* Splenic aspiration

* Liposomal amphotericin B
* Sodium stibogluconate
* Pentamidine

Infective Hepatitis[42][43] |

* Hepatitis A virus (HAV)
* HBV
* HCV
* HDV (co-infection with HBV)
* HEV

* Fever
* Transmitted via fecal-oral route (HAV, HBV, HDV, HEV), infected sera (HCV), sexual contact with infected individuals
* Hepatosplenomegaly (may become shrunken in cases of cirrhosis due to chronic infection)
* Lymphadenopathy
* Jaundice
* Palmar erythema
* Spider angiomata
* Gynecomastia
* Arthritis-dermatitis syndrome

* Antigen and antibody detection
* Total and direct bilirubin (increased)
* Severe disease is often associated with persistent bilirubin levels >340 mmol/L
* ALT and AST (increased)
* Alkaline phosphatase (normal or mildly elevated)
* Prothrombin time (prolonged from synthetic defect, caused by hepatocellular necrosis)
* Total protein (decreased)
* Globulin (mildly elevated)
* Initial lymphopenia and neutropenia, followed by relative lymphocytosis
* Low hemoglobin

* Antigen and antibody detection

* Interferon (IFN)

* Nucleoside analogs

* Nucleotide analogs

Chronic Myelogenous Leukemia (CML)[44][45][46][47][48][49][50][51][52][51] |

* BCR/ABL gene fusion product due to translocation mutation t(9;22)(q34;q11)[53]

* Fever
* Weight loss
* Hepatosplenomegaly
* Lymphadenopathy

* Bruises
* Petechiae
* Ulcers
* Vesicles
* Malaise
* Early satiety

* Anemia

* Leukocytosis (median of 100,000/µL) with a left shift
* Thrombocytosis
* Blasts usually <2%
* Absolute basophilia
* Absolute eosinophilia
* Monocytosis
* Thrombocytosis
* Thrombocytopenia suggests an alternative diagnosis or the presence of advanced stage
* Elevated uric acid
* Elevated histamine levels

* Fluoroscent insitu hybridization (FISH)

* Imatinib
* Dasatinib
* Nilotinib
* Bosutinib
* Ponatinib

* Cytarabine
* HDAC (high-dose cytarabine)
* Hydroxyurea
* Busulfan
* Busulfex
* Stem cell transplantation

Lymphoma |

* Various causes based on type:
* Hodgkin's
* Non-Hodgkin's

* Fever
* Weight loss
* Lymphadenopathy
* Hepatosplenomegaly
* Night sweats, constant fatigue
* Purplish scaly rash in cases of cutaneous lymphoma

* Elevated ESR
* Increased CRP
* Increased LDH
* Anemia of chronic disease

* Lymph node biopsy

Primary (AL) Amyloidosis[54][55] |

* Aggregation and deposition of immunoglobulin light chains that are usually produced by plasma cell clones[56][57]

* Nephrotic syndrome (peripheral edema)
* Restrictive cardiomyopathy (fatigue, dyspnea, syncope)
* Peripheral neuropathy (numbness, tingling)
* Hepatomegaly with elevated liver enzymes
* Macroglossia
* Purpura
* Bleeding diathesis

* 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] |

* GBA gene mutation
* Aberrant metabolism of glucocerebroside (lipid)

* Hydrops fetalis
* Dry, scaly skin (ichthyosis) or other skin abnormalities
* Hepatosplenomegaly
* Distinctive facial features
* Neurological problems
* Gall stones
* Growth retardation

* Hypocholesterolemia
* Splenic nodules
* Cytopenias (especially thrombocytopenia)
* Increased ferritin levels
* Increased tartarate resistant acid phosphatase (TRAP) levels

* Enzyme assay for glucocerebrosidase
* DNA analysis for GBA mutation

* Enzyme replacement
* Splenectomy
* Blood transfusion

Organ System Involvement | Differential Diagnosis | Causes | Features | Laboratory Findings | Gold Standard Test | Therapy
E = Endocrinopathy (Hypogonadism, Hypothyroidism, Hypopituitarism) | Hypogonadism[62][63] | Primary Hypogonadism (Hypergonadotrophic) |

* Klinefelter's syndrome
* Myotonic dystrophy
* Sertoli-cell tumor
* Enzymatic defects
* Viral orchitis (mumps)
* Cryptorchidism
* Polyglandular autoimmune syndrome
* Testicular trauma and tumors
* Polycystic ovarian syndrome

* Fatigue
* Decreased libido
* Delayed secondary sexual characteristics:
* Absent/scant pubic hair
* Impotence
* Erectile dysfunction
* Amenorrhea
* Delayed breast development
* Small testicular size
* Decreased muscle mass
* Osteoporosis
* Depression
* Infertility
* Irritability
* Mood swings
* Pot belly
* Weight gain

* Decreased sex hormone levels:
* Decreased testosterone
* Decreased dihydrotestosterone
* Decreased estrogen
* Increased gonadotropins:
* Increased LH
* Increased FSH

* Serum sex hormone levels

* Hormone replacement therapy

Secondary Hypogonadism (Hypogonadotrophic) |

* Panhypopituitarism
* Hyperprolactinemia
* Isolated gonadotropin deficiency
* Kallman's syndrome
* Congenital
* Prader-Willi syndrome
* Hemochromatosis
* Massive obesity
* Malnutrition

* Decreased sex hormone levels:
* Decreased testosterone
* Decreased dihydrotestosterone
* Decreased estrogen
* Decreased gonadotropins:
* Decreased LH
* Decreased FSH

Hypothyroidism[64][65] | Primary Hypothyroidism |

* Congenital hypothyroidism
* Autoimmune (Hashimoto's) thyroiditis
* Resistance to TSH

* Fatigue
* Cold intolerance
* Decreased sweating
* Hypothermia
* Coarse skin
* Weight gain

* Puffiness
* Hair loss
* Constipation
* Fever (thyroiditis)

* Hoarseness
* Goiter
* Fullness in the throat and neck

* Depression
* Emotional lability
* Attention deficit

* Macroglossia
* Obstructive sleep apnea
* Paresthesia
* Nerve entrapment syndromes (carpal tunnel syndrome)
* Blurred vision (central hypothyroidism)
* Ataxia
* Myxedema coma (with non-pitting edema)
* Cardiomegaly
* Pericardial effusion
* Ascites
* Hyperlipidemia
* Galactorrhea
* Infertility

* Decreased T3 and T4
* Increased TSH

* Serum T3, T4, TSH levels

* Hormone replacement therapy

Secondary Hypothyroidism |

* Pituitary mass lesions, especially pituitary adenomas
* Brain cysts and abscesses
* Meningiomas
* Dysgerminomas
* Metastatic tumors
* Craniopharyngiomas
* Pituitary apoplexy
* Sheehan syndrome (postpartum pituitary necrosis)
* Idiopathic isolated TSH deficiency
* Lymphocytic or granulomatous hypophysitis

* Decreased T3 and T4
* Decreased TSH

Tertiary Hypothyroidism |

* Hemochromatosis
* Histiocytosis
* Developmental abnormalities
* Internal carotid aneurysms
* Idiopathic isolated TRH deficiency

* Decreased T3 and T4
* Decreased TRH
* Decreased TSH

Hypopituitarism[66][67] | Congenital |

* Idiopathic
* Anatomic lesion in sella turcica (Rathke's cyst)
* CNS malformations:
* Septo-optic-dysplasia
* Kallmann syndrome
* Pituitary stalk interruption syndrome

* Headache
* Nausea and vomiting
* Visual impairment
* Fatigue
* Cold intolerance
* Hypotension
* Dizziness
* Weight loss

* Features of hormonal deficiencies

* Decreased FSH, LH
* Decreased TSH
* Decreased ACTH
* Decreased GH
* Decreased ADH
* Decreased oxytocin

* Serum hormone levels produced by pituitary

* Hormone replacement therapy

Acquired |

* Posterior pituitary tumor: astrocytoma, ganglioneuroma
* Metastatic: breast, lungs, colon, prostate
* Peripituitary lesions: Craniopharyngioma, meningioma, chordoma, optic nerve glioma
* Transsphenoidal or transcranial surgery
* Radiation
* Traumatic brain injury
* Sheehan's syndrome
* Pituitary apoplexy
* Meningitis
* Hypophysitis
* Lymphoma

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] |

* Chromosomal aberrations or other genetic insults
* Malignant transformation of plasma cells
* Clonal plasma cell proliferation

* Diffuse bone pain and tenderness with osteolytic lesions
* Renal failure
* Hypercalcemia
* Anemia

* 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

* Induction chemotherapy with bortezomib, lenalidomide, and dexamethasone
* Bisphosphonates
* RANK ligand inhibitors (denosumab)
* Autologous stem cell transplantation

Monoclonal gammopathy of undetermined significance (MGUS)[71] |

* Chromosomal aberrations or other genetic insults
* Clonal plasma cell proliferation

* Asymptomatic

* Serum M protein of <3 g/L
* Fewer than 10% plasma cells in the bone marrow
* No evidence of bone or organ damage

* 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)

* Chromosomal aberrations or other genetic insults
* Malignant transformation of plasma cells
* Clonal plasma cell proliferation

* Asymptomatic

* Serum M protein of greater than equal to 3 g/L
* Greater than 10% plasma cells in the bone marrow
* No evidence of bone or organ damage

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

* 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 |

* Chromosomal aberrations or other genetic insults
* Malignant transformation of plasma cells

* Solitary bone plasmacytoma (bone)
* Extramedullary plasmacytoma (soft tissues)
* Clinical manifestations related to tumor mass and compression symptoms

* 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 |

* Imbalance between bone resorption and bone formation
* Preceded by osteopenia
* Decreased bone mineral density

* Acute musculoskletal pain if fractures develop
* Severe decrease in BMD on dual-energy X-ray absorptiometry (DEXA) test
* T score less than -2.5 on DEXA scan

* Normal serum calcium, phosphate, alkaline phosphatase and parathyroid hormone levels
* Decreased bone mass

* T score less than -2.5 on DEXA scan

* Calcium and vitamin D supplementation
* Bisphosphonates
* Weight-bearing exercise
* Teriparatide
* RANK ligand inhibitors (denosumab)

Osteomalacia[72] |

* Inadequate mineralization of bone
* Deficiency of vitamin D calcium, or phosphorus
* Renal tubular acidosis
* Malabsorption

* Diffuse bone pain, fatigue, and fractures
* Low bone mineral density (BMD)
* Hypocalcemia

* Decreased serum calcium
* Decreased serum phosphate
* Increased serum alkaline phosphatase
* Increased serum parathyroid hormone levels

* Bone biopsy (increased osteoid and decreased calcification)

* Vitamin D3 supplementation

Osteogenesis imperfecta |

* Mutations in COL1A1 or COL1A2
* Impaired type I collagen synthesis

* Short stature, scoliosis, and propensity for fractures
* Blue discoloration of sclera

* Normal serum calcium
* Normal serum phosphate
* Increased serum alkaline phosphatase

* DNA analysis
* Collagen analysis

* Bisphosphonates
* Physical therapy
* Surgical fixation of brittle bones
* Genetic counseling for offspring

Skin Changes  | Scurvy |

* Vitamin C deficiency
* Malabsorption
* Hemodialysis

* Gum disease such as gum bleeding
* Loose teeth
* Easy bruising
* Impaired immune response
* Impaired wound healing

|  |  |

* Vitamin C supplementation
* Citrus fruits

## Other Differentials[edit | edit source]

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

## References[edit | edit source]

1. ↑ Gherardi RK, Bélec L, Soubrier M, Malapert D, Zuber M, Viard JP, Intrator L, Degos JD, Authier FJ (February 1996). "Overproduction of proinflammatory cytokines imbalanced by their antagonists in POEMS syndrome". Blood. 87 (4): 1458–65. PMID 8608236.
2. ↑ 2.0 2.1 Nozza A (2017). "POEMS SYNDROME: an Update". Mediterr J Hematol Infect Dis. 9 (1): e2017051. doi:10.4084/MJHID.2017.051. PMC 5584767. PMID 28894560.
3. ↑ 3.0 3.1 3.2 Bardwick PA, Zvaifler NJ, Gill GN, Newman D, Greenway GD, Resnick DL (July 1980). "Plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes: the POEMS syndrome. Report on two cases and a review of the literature". Medicine (Baltimore). 59 (4): 311–22. PMID 6248720.
4. ↑ 4.0 4.1 4.2 4.3 4.4 Takatsuki K, Sanada I (September 1983). "Plasma cell dyscrasia with polyneuropathy and endocrine disorder: clinical and laboratory features of 109 reported cases". Jpn. J. Clin. Oncol. 13 (3): 543–55. PMID 6315993.
5. ↑ Nobile-Orazio E, Terenghi F, Giannotta C, Gallia F, Nozza A (March 2009). "Serum VEGF levels in POEMS syndrome and in immune-mediated neuropathies". Neurology. 72 (11): 1024–6. doi:10.1212/01.wnl.0000344569.13496.ff. PMID 19289745.
6. ↑ Güneş HN, Bilecenoğlu NT, Şener U, Yoldaş TK (April 2015). "POEMS syndrome with peripheral and central nervous system demyelination: case report". Neurologist. 19 (4): 101–3. doi:10.1097/NRL.0000000000000017. PMID 25888197.
7. ↑ "IMWG | International Myeloma Working Group (IMWG) Criteria for the Diagnosis of Multiple Myeloma".
8. ↑ Schreiber AK, Nones CF, Reis RC, Chichorro JG, Cunha JM (April 2015). "Diabetic neuropathic pain: Physiopathology and treatment". World J Diabetes. 6 (3): 432–44. doi:10.4239/wjd.v6.i3.432. PMID 25897354.
9. ↑ "Diagnosis and classification of diabetes mellitus". Diabetes Care. 33 Suppl 1: S62–9. January 2010. doi:10.2337/dc10-S062. PMID 20042775.
10. ↑ Ekabe CJ, Kehbila J, Abanda MH, Kadia BM, Sama CB, Monekosso GL (January 2017). "Vitamin B12 deficiency neuropathy; a rare diagnosis in young adults: a case report". BMC Res Notes. 10 (1): 72. doi:10.1186/s13104-017-2393-3. PMID 28129784.
11. ↑ Doi T, Kawata T, Tadano N, Iijima T, Maekawa A (February 1989). "Effect of vitamin B12 deficiency on S-adenosylmethionine metabolism in rats". J. Nutr. Sci. Vitaminol. 35 (1): 1–9. PMID 2738712.
12. ↑ Berg RL, Shaw GR (February 2013). "Laboratory evaluation for vitamin B12 deficiency: the case for cascade testing". Clin Med Res. 11 (1): 7–15. doi:10.3121/cmr.2012.1112. PMID 23262189.
13. ↑ Lindenbaum J, Savage DG, Stabler SP, Allen RH (June 1990). "Diagnosis of cobalamin deficiency: II. Relative sensitivities of serum cobalamin, methylmalonic acid, and total homocysteine concentrations". Am. J. Hematol. 34 (2): 99–107. PMID 2339684.
14. ↑ Berg RL, Shaw GR (February 2013). "Laboratory evaluation for vitamin B12 deficiency: the case for cascade testing". Clin Med Res. 11 (1): 7–15. doi:10.3121/cmr.2012.1112. PMC 3573090. PMID 23262189.
15. ↑ Lane LA, Rojas-Fernandez C (2002). "Treatment of vitamin b(12)-deficiency anemia: oral versus parenteral therapy". Ann Pharmacother. 36 (7–8): 1268–72. doi:10.1345/aph.1A122. PMID 12086562.
16. ↑ Winer JB (December 2001). "Guillain Barré syndrome". MP, Mol. Pathol. 54 (6): 381–5. PMC 1187127. PMID 11724912.
17. ↑ Rees JH, Gregson NA, Hughes RA (November 1995). "Anti-ganglioside GM1 antibodies in Guillain-Barré syndrome and their relationship to Campylobacter jejuni infection". Ann. Neurol. 38 (5): 809–16. doi:10.1002/ana.410380516. PMID 7486873.
18. ↑ Winer JB, Hughes RA, Anderson MJ, Jones DM, Kangro H, Watkins RP (May 1988). "A prospective study of acute idiopathic neuropathy. II. Antecedent events". J. Neurol. Neurosurg. Psychiatry. 51 (5): 613–8. PMC 1033063. PMID 3404161.
19. ↑ Yuki N, Koga M (October 2006). "Bacterial infections in Guillain-Barré and Fisher syndromes". Curr. Opin. Neurol. 19 (5): 451–7. doi:10.1097/01.wco.0000245367.36576.e9. PMID 16969154.
20. ↑ Kimura J (April 1978). "Proximal versus distal slowing of motor nerve conduction velocity in the Guillain-Barré syndrome". Ann. Neurol. 3 (4): 344–50. doi:10.1002/ana.410030412. PMID 666277.
21. ↑ Winer JB (December 2001). "Guillain Barré syndrome". MP, Mol. Pathol. 54 (6): 381–5. PMC 1187127. PMID 11724912.
22. ↑ "Randomised trial of plasma exchange, intravenous immunoglobulin, and combined treatments in Guillain-Barré syndrome. Plasma Exchange/Sandoglobulin Guillain-Barré Syndrome Trial Group". Lancet. 349 (9047): 225–30. January 1997. PMID 9014908.
23. ↑ "Plasmapheresis and acute Guillain-Barré syndrome. The Guillain-Barré syndrome Study Group". Neurology. 35 (8): 1096–104. August 1985. PMID 4022342.
24. ↑ "Chronic Inflammatory Demyelinating Polyradiculoneuropathy: Clinical Characteristics, Course, and Recommendations for Diagnostic Criteria | JAMA Neurology | JAMA Network".
25. ↑ "onlinelibrary.wiley.com".
26. ↑ Milner P, Lovelidge CA, Taylor WA, Hughes RA (July 1987). "P0 myelin protein produces experimental allergic neuritis in Lewis rats". J. Neurol. Sci. 79 (3): 275–85. PMID 2440998.
27. ↑ Gabriel CM, Gregson NA, Hughes RA (May 2000). "Anti-PMP22 antibodies in patients with inflammatory neuropathy". J. Neuroimmunol. 104 (2): 139–46. PMID 10713353.
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