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paraproteinemia (monoclonal gammopathy)

Etiology: 1) plasma cell disorder a) benign monoclonal gammopathy (MGUS) b) biclonal gammopathy of undetermined significance c) idiopathic Bence Jones proteinuria d) POEMS syndrome e) Castleman's disease f) AL amyloidosis, light chain amyloidosis g) solitary plasmacytoma h) multiple myeloma i) monoclonal immunoglobulin deposition disease j) proximal tubulopathy (MGUS, multiple myeloma) 2) B-cell proliferative disorder a) non-Hodgkin's lymphoma, marginal cell lymphoma b) chronic lymphocytic leukemia, small lymphocytic lymphoma c) lymphoblastic lymphoma, Waldenstrom's macroglobulinemia d) heavy chain disease [4] e) post-transplantation 3) connective tissue disease a) systemic lupus erythematosus b) rheumatoid arthritis c) Sjogren syndrome d) scleroderma e) psoriatic arthritis f) polymyalgia rheumatica ? 4) infection a) hepatitis C b) HIV1 5) skin disorders a) scleredema, lichen myxoedematosus b) diffuse plane xanthomatosis c) Schnitzler's syndrome d) subcorneal pustular dermatosis e) necrobiotic xanthogranuloma f) pyoderma gangrenosum 6) other a) acquired von Willebrand disease b) acquired C1 esterase deficiency c) eosinophilic fasciitis d) cryoglobulinemia e) myelodysplastic syndrome f) chronic myelocytic leukemia g) capillary leak syndrome h) T-cell leukemia, large granular lymphocytic Pathology: - organized glomerular immune deposition - AL amyloid - immunotactoid glomerulonephritis - fibrillary glomerulonephritis - cyoglobulinemia - disorganized glomerular immune deposition (no beta-pleated sheets) - monoclonal immunoglobulin deposition disease [4] Laboratory: 1) complete blood count (CBC) 2) urinalysis with 24 hour urine protein 3) complete metabolic panel for Ca+2, phosphorous 4) immunoglobulin light chains.free in serum* - most sensitive test for free light chain paraproteinemia [4] 5) serum protein electrophoresis* - serum immunofixation electrophoresis [4] 6) urine protein electrophoresis - urine immunofixation electrophoresis [4] 7) beta-2 microglobulin in serum * combination has sensitivity of ~100% diagnosing multiple myeloma requiring therapy Special laboratory: - bone marrow biopsy not necessary if monoclonal IgG < 1.5 g/dL & no end organ damage (renal function normal), i.e. MGUS Radiology: - whole body MRI for evaluation of smoldering multiple myeloma - bone scan not recommended [4] - multiple myeloma lesions are often purely lytic - a bone scan detects osteoblastic lesions

Specific

benign monoclonal gammopathy; monoclonal gammopathy of undetermined significance (MGUS) cryoglobulinemia (cryoglobulinemic vasculitis) heavy chain disease; Franklin disease monoclonal gammopathy of renal significance monoclonal gammopathy/neuropathy syndrome monoclonal immunoglobulin deposition disease (MIDD) multiple myeloma; plasmacytoma/plasma cell myeloma POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, & Skin changes); Crow-Fukase syndrome Waldenstrom's macroglobulinemia

General

blood protein disorder immunoproliferative disorder

References

  1. Bataille R, Harousseau JL. Multiple myeloma. N Engl J Med. 1997 Jun 5;336(23):1657-64. Review. PMID: 9171069
  2. Veterans Administration, Mather CA
  3. UpToDate 14.1 (2007) http://www.utdol.com
  4. Medical Knowledge Self Assessment Program (MKSAP) 17, 18, 19. American College of Physicians, Philadelphia 2015, 2018, 2022
  5. Katzmann JA, Kyle RA, Benson J et al Screening panels for detection of monoclonal gammopathies. Clin Chem. 2009 Aug;55(8):1517-22 PMID: 19520758
  6. Zivkovic SA, Lacomis D, Lentzsch S. Paraproteinemic neuropathy. Leuk Lymphoma. 2009 Sep;50(9):1422-33 PMID: 19637090
  7. Rison RA, Beydoun SR. Paraproteinemic neuropathy: a practical review. BMC Neurol. 2016 Jan 28;16:13. Review. PMID: 26821540 Free PMC Article
  8. Rosner MH, Edeani A, Yanagita M et al Paraprotein-Related Kidney Disease: Diagnosing and Treating Monoclonal Gammopathy of Renal Significance. Clin J Am Soc Nephrol. 2016 Dec 7;11(12):2280-2287. PMID: 27526705 Free PMC Article