Table of contents :
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isotype | IgG | IgM | IgG |
temperature | 37°C | 4°C | 4°C and 37°C |
complement fixation | variable | yes | yes |
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autoimmune | a-methyl-DOPA![]() ![]() ![]() |
standard therapeutic dose for 3-6 months | gradual onset of hemolysis, progressive if drug is not discontinued | IgG |
high-affinity hapten | penicillins![]() ![]() ![]() |
high dosage for days of weeks | subacute extravascular hemolysis for 7-10 days, progressive if drug is not discontinued | IgG |
low-affinity hapten | quinidine![]() |
standard or low dose for days | rapid onset, sometimes hyperacute with extravascular hemolysis | IgG or IgM |
nonimmunological proein adsorption | cephalotin![]() |
high dosage for days or weeks | clinically not releant | IgG |
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heparin (new or remote [> 100 days] exposure) | high | patients undergoing orthopedic surgery | 14 | 3-5 | at baseline and at least every other day from days 4 to 14 of heparin therapy or until heparin discontinued |
intermediate | adults undergoing cardiac surgery. Children undergoing cardiac surgery | 25-50 | 1-2 | ||
intermediate | general medical patients, patients with neurological conditions, patients undergoing percutaneous coronary intervention for acute coronary syndrome, patients undergoing acute hemodialysis | 8-20 | 0.8-3.0 | ||
low to rare | general pediatric patients, pregnant women, patients undergoing chronnic hemodialysis | 0-2.3 | 0-0.1 | not essential | |
LMWH | intermediate | medical patients patients with neurologic conditions patients undergoing surgical or orthopedic procedures |
2-8 | 0-0.9 | at baseline and every 2 to 4 days after days 4 through 14 of LMWH therapy or until therapy discontinued |
rare | pregnant women general pediatric population |
unknown | 0-0.1 | routine monitoring not recommended | |
heparin or LMWH (exposure within 100 days) | unknown | all clinical populations | unknown | unknown | at baseline, within 24 hr, and every other days from days 4 through 14 until heparin is discontinued |
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prednisone![]() |
1.0 mg/kg PO qd | 1–4 weeks | hypokalemia, gastric upset, sodium and fluid
retention, hyperglycemia, hypertension, myopathy, osteoporosis, infection risk, psychosis |
colchicine | 0.6 mg PO tid | 4–8 weeks | diarrhea (may limit therapy), nausea, vomiting |
dapsone![]() |
75–100 mg PO qd | 4–8 weeks | hemolysis, agranulocytosis, aplastic anemia,
exfoliative dermatitis, toxic hepatitis, choleostatic jaundice, peripheral neuropathy. |
danazol![]() |
200 mg PO qid | 3–6 months | weight gain, fluid retention, seborrhea,
hirsutism, vocal changes, amenorrhea, acne, headache, liver toxicity |
rituximab![]() |
375 mg/m2 IV q week x 4 | 3–4 weeks | infusional symptoms: (fever, chills, headache,
broncho- spasm), severe B cell reduction and potential for infection |
cyclophosphamide![]() |
150 mg PO qd | 6–8 weeks | cytopenias, hemorrhagic cystitis, GI symptoms,
sterility, secondary malignancies (lymphoproliferative disorders or acute leukemia have occurred in patients with other disorders receiving these drugs) |
azathioprine![]() |
150 mg PO qd | 2–10 months | cytopenias, GI symptoms, secondary malignancies (lymphoproliferative disorders or acute leukemia have occurred in patients with other disorders receiving these drugs) |
cyclosporine
A![]() |
1.25–2.5 mg/kg PO bid | variable | renal insufficiency, hepatotoxicity, hypertension, tremor, hirsutism, gum hyperplasia, hypomagnesemia, secondary malignancies |
mycophenolate
mofetil![]() |
0.5–1.0 g BID PO | 3–4 weeks | diarrhea, leukopenia, headache, secondary malignancies (lymphoproliferative disorders or acute leukemia have occurred in patients with other disorders receiving these drugs) |
high-dose cyclophosphamide ![]() |
1.0–1.5 g/M2 IV q 4 weeks | 1–4 weeks | cytopenias, hemorrhagic cystitis, GI symptoms,
alopecia, sterility, myocardiopathy, secondary malignancies (acute leukemia or myelodysplasia have resulted from therapy with alkylating agents) |
combination chemotherapy |
several combinations have been usedref | 1–4 weeks | cytopenias, hemorrhagic cystitis, alopecia,
dermatitis, anaphylaxis, GI symptoms, sterility, myocardiopathy, mucositis, secondary malignancies (acute leukemia or myelodysplasia have resulted from therapy with alkylating agents) |
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normal plasma alone | 32 | 32 | 36 | 40 | |
normal plasma + | factor VIII-deficient plasma | 37 | 37 | 41 | 45 |
weak inhibitor (1 BU) | 37 | 38 | 45 | 53 | |
moderate inhibitor (5 BU) | 43 | 47 | 55 | 64 | |
strong inhibitor (20 BU) | 54 | 61 | 77 | 92 |
At a minimum, a patient should have the following: the peripheral neuropathy; osteosclerotic myeloma (i.e., a clonal plasma cell dyscrasia and at least one sclerotic bone lesion) or Castleman disease; and at least one of the other featuresref. Though the majority of patients have osteosclerotic myeloma, these same patients usually have only 5% bone marrow plasma cells or less, and rarely have hypercalcemia or renal insufficiency. These characteristics and the superior median survival differentiate POEMS syndrome from multiple myeloma. The plasma cells are virtually always l restricted. Though the pathophysiologic mechanism is not well understood, there is a correlation between treating the underlying plasmaproliferative disorder (clone) and clinical improvement. Radiation therapy produces substantial improvement of the neuropathy in more than half of the patients who have a single lesion or multiple lesions in a limited area. If there are widespread lesions, conventional chemotherapy or high-dose chemotherapy and peripheral blood support may be helpful. Criteria for the diagnosis of POEMS syndromeref :
Mayo seriesref | French seriesref | Japanese seriesref | |
% n=99 | % n=25 | % n=102 | |
peripheral neuropathy | 100 | 100 | 100 |
organomegaly | 46 | NS | NS |
hepatomegaly | 25 | 68 | 78 |
splenomegaly | 22 | 52 | 35 |
lymphadenopathy | 26 | 52 | 61 |
endocrinopathy | 71 (includes gonadal and adrenal abnormalities) | NS | NS |
diabetes mellitus | 3 | 36 | 25 |
hypothyroidism | 17 | 36 | |
monoclonal plasma cell dyscrasia | 100 | 100 | 75 |
skin changes | 68 | NS | NS |
hyperpigmentation | 46 | 48 | 93 |
acrocyanosis and plethora | 19 | NS | NS |
hemangioma/telangectasia | 9 | 32 | NS |
hypertrichosis | 26 | 24 | 74 |
thickening | 5 | 28 | 61 |
sclerotic bone lesions (of patients with bone lesions) | 97 | 68 | 54 |
osteosclerotic only | 47 | 41 | 56 |
mixed sclerotic and lytic | 51 | 59 | 31 |
lytic only | 2 | 0 | 13 |
> 1 lesion | 54 | 59 | 45 |
papilledema | 29 | 40 | 55 |
extravascular volume overload | 39 | NS | NS |
peripheral edema | 29 | 80 | 89 |
ascites | 15 | 32 | 52 |
pleural effusion | 9 | 24 | 35 |
Castleman disease | 11 | 24 | 19 |
other features | |||
thrombocytosis | 54 | 88 | NS |
polycythemia | 18 | 12 | 19 |
clubbing![]() |
5 | 32 | 49 |
Comment: the percentage for all series uses the total number of patients in the series as the denominator |
characteristic | MGUS | POEMS | multiple myeloma | AL amyloidosis | cryoglobulinemia |
peripheral neuropathy | ~5% | 100% | 1–8% | 15%–20% | ~25% |
sensory versus motor predominance | sensory, ataxia (IgM) sensorimotor | predominantly motor | sensory | sensory sensorimotor | predominantly sensory |
organomegaly | – | ++ | + | ++ | ++ |
skin involvement | – | ++ | + | + | +++ |
other symptoms | asymptomatic | edema, fatigue, endocrine abnormalities | bone pain, fatigue, infections | fatigue, edema, cardiomyopathy, nephrosis | purpura, arthralgia, hepatitis, nephritis |
monoclonal heavy chain | IgM >IgG >IgA | IgG > IgA >IgM | IgG > IgA | IgG > IgA > IgM | IgM >> IgG > IgA |
monoclonal light chain | k 75% of cases | l > 95% of cases | k 75% of cases | l 75% of cases | k 75% of cases |
serum M-spike, gm/dL | < 3 | usually < 2 | usually > 3 | usually < 2 | usually < 2 |
BM plasma cells, % | < 10 | usually < 5 | > 10 | usually < 10 | usually < 5 |
skeletal lesions | – | +++ (sclerotic, mixed sclerotic & lytic) | +++ (lytic, osteoporotic, or fracture) | – | – |
thrombocytosis | – | ++ | - | + to ++ | + |
anemia | - | + | ++ | + | ++ |
Reprinted with permission from Dispenzieri A. Suarez GA. Kyle RA. POEMS syndrome (osteosclerotic myeloma) In: Dyck PJ. Thomas PK, eds. Peripheral Neuropathy 4th edition. Philadelphia: Elsevier Saunders; 2005:2453–2469 |