Waldenström's macroglobulinemia history and symptoms: Difference between revisions
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=== Manifestations of WM === | === Manifestations of WM === | ||
Following is a list of WM manifestations with attributable causes:<ref name="pmid15735132">{{cite journal| author=Dimopoulos MA, Kyle RA, Anagnostopoulos A, Treon SP| title=Diagnosis and management of Waldenstrom's macroglobulinemia. | journal=J Clin Oncol | year= 2005 | volume= 23 | issue= 7 | pages= 1564-77 | pmid=15735132 | doi=10.1200/JCO.2005.03.144 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15735132 }} </ref><ref name="DimopoulosPanayiotidis2000">{{cite journal|last1=Dimopoulos|first1=Meletios A.|last2=Panayiotidis|first2=Panayiotis|last3=Moulopoulos|first3=Lia A.|last4=Sfikakis|first4=Petros|last5=Dalakas|first5=Marinos|title=Waldenström’s Macroglobulinemia: Clinical Features, Complications, and Management|journal=Journal of Clinical Oncology|volume=18|issue=1|year=2000|pages=214–214|issn=0732-183X|doi=10.1200/JCO.2000.18.1.214}}</ref><ref name="pmid3110508">{{cite journal| author=Kyle RA, Garton JP| title=The spectrum of IgM monoclonal gammopathy in 430 cases. | journal=Mayo Clin Proc | year= 1987 | volume= 62 | issue= 8 | pages= 719-31 | pmid=3110508 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3110508 }} </ref><ref name="pmid12883242">{{cite journal| author=Lin P, Bueso-Ramos C, Wilson CS, Mansoor A, Medeiros LJ| title=Waldenstrom macroglobulinemia involving extramedullary sites: morphologic and immunophenotypic findings in 44 patients. | journal=Am J Surg Pathol | year= 2003 | volume= 27 | issue= 8 | pages= 1104-13 | pmid=12883242 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12883242 }} </ref><ref name="pmid8123836">{{cite journal| author=Dimopoulos MA, Alexanian R| title=Waldenstrom's macroglobulinemia. | journal=Blood | year= 1994 | volume= 83 | issue= 6 | pages= 1452-9 | pmid=8123836 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8123836 }} </ref><ref name="pmid6767276">{{cite journal| author=Fudenberg HH, Virella G| title=Multiple myeloma and Waldenström macroglobulinemia: unusual presentations. | journal=Semin Hematol | year= 1980 | volume= 17 | issue= 1 | pages= 63-79 | pmid=6767276 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6767276 }} </ref><ref name="pmid9671845">{{cite journal| author=Fadil A, Taylor DE| title=The lung and Waldenström's macroglobulinemia. | journal=South Med J | year= 1998 | volume= 91 | issue= 7 | pages= 681-5 | pmid=9671845 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9671845 }} </ref><ref name="pmid9198063">{{cite journal| author=Veltman GA, van Veen S, Kluin-Nelemans JC, Bruijn JA, van Es LA| title=Renal disease in Waldenström's macroglobulinaemia. | journal=Nephrol Dial Transplant | year= 1997 | volume= 12 | issue= 6 | pages= 1256-9 | pmid=9198063 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9198063 }} </ref><ref name="pmid10188670">{{cite journal| author=Daoud MS, Lust JA, Kyle RA, Pittelkow MR| title=Monoclonal gammopathies and associated skin disorders. | journal=J Am Acad Dermatol | year= 1999 | volume= 40 | issue= 4 | pages= 507-35; quiz 536-8 | pmid=10188670 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10188670 }} </ref><ref name="pmid6801795">{{cite journal| author=Orellana J, Friedman AH| title=Ocular manifestations of multiple myeloma, Waldenström's macroglobulinemia and benign monoclonal gammopathy. | journal=Surv Ophthalmol | year= 1981 | volume= 26 | issue= 3 | pages= 157-69 | pmid=6801795 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6801795 }} </ref><ref name="pmid9686227">{{cite journal| author=Civit T, Coulbois S, Baylac F, Taillandier L, Auque J| title=[Waldenström's macroglobulinemia and cerebral lymphoplasmocytic proliferation: Bing and Neel syndrome. Apropos of a new case]. | journal=Neurochirurgie | year= 1997 | volume= 43 | issue= 4 | pages= 245-9 | pmid=9686227 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9686227 }} </ref> | |||
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|+ '''Manifestations of WM''' | |+ '''Manifestations of WM''' | ||
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| style="background:#DCDCDC;" align="center" + |Autoantibody activity of IgM | | style="background:#DCDCDC;" align="center" + |Autoantibody activity of IgM | ||
| style="background:#F5F5F5;" align="center" + |Distal, symmetric, chronic demyelinating peripheral neuropathy, Type | | style="background:#F5F5F5;" align="center" + |Distal, symmetric, chronic demyelinating peripheral neuropathy, Type 2 cryoglobulinemia characterized by vasculitis affecting small vessels of skin, kidneys, liver, and peripheral nerves, Extravascular chronic hemolytic anemia called cold agglutinin disease exacerbated by cold exposure, glomerulonephritis, paraneoplastic pemphigus, and retinitis. | ||
|} | |} | ||
==== Common Symptoms ==== | ==== Common Symptoms ==== | ||
Revision as of 18:06, 7 February 2019
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Sara Mohsin, M.D.[2] Roukoz A. Karam, M.D.[3]
Overview
Many patients with Waldenström macroglobulinemia are asymptomatic. The disease is subtle and symptoms are nonspecific, but the most common symptoms of Waldenström macroglobulinemia include weakness, anorexia, blurry vision, peripheral neuropathy, and weight loss. Less common symptoms of the disease include bleeding and Raynaud phenomenon.
History and Symptoms
History
- The onset of Waldenström macroglobulinemia is insidious and non-specific.
- Approximately 25% of patients with WM are asymptomatic upon presentation; their diagnosis is often made incidentally from routine blood tests done for some other reason. WM found this way is sometimes called asymptomatic or Smoldering WM (SWM).[1]
- Symptoms develop depending on the tissues involved in the malignant cell infiltration or IgM deposition.[2]
Manifestations of WM
Following is a list of WM manifestations with attributable causes:[3][4][5][6][7][8][9][10][11][12][13]
| Cause | Manifestations |
|---|---|
| Tumor infiltration | Cytopenia, fever, night sweats, weight loss, lymphadenopathy, hepatomegaly, spleenomegaly, pulmonary infiltrates, nodules or masses, pleural effusion, abdominal pain, swelling and blood in stools secondary to stomach and bowel infiltration, renal and perirenal masses, maculopapular lesions, plaques or nodules secondary to dermis infiltration, lesions involving retro-orbital lymphoid tissue and lacrimal glands, infiltration of the conjunctiva and malignant vitreitis, Bing-Neel syndrome consists of confusion, memory loss, disorientation, motor dysfunction, and eventually coma. |
| Circulating monoclonal IgM | Hyperviscosity syndrome, Type 1 Cryoglobulinemia (consists of Raynaud's phenomenon, skin ulcers & necrosis and cold urticaria), frequent bruising, prolonged bleeding and clotting times. |
| IgM deposition into tissues | Sub-endothelial deposits in glomerular loops leading to non-selective proteinuria, dehydration, and uremia, Firm, flesh-colored skin papules and nodules have been reported and are called macroglobulinemia cutis, Diarrhea, malabsorption, or gastrointestinal bleeding. |
| Amyloidogenic properties of IgM | Organs more commonly affected by amyloidosis were the heart (44%), the peripheral nerves (38%), the kidneys (32%), the soft tissues (18%), the liver (14%), and lungs (10%), nephrotic syndrome and gastrointestinal involvement. |
| Autoantibody activity of IgM | Distal, symmetric, chronic demyelinating peripheral neuropathy, Type 2 cryoglobulinemia characterized by vasculitis affecting small vessels of skin, kidneys, liver, and peripheral nerves, Extravascular chronic hemolytic anemia called cold agglutinin disease exacerbated by cold exposure, glomerulonephritis, paraneoplastic pemphigus, and retinitis. |
Common Symptoms
Common symptoms of Waldenström macroglobulinemia include:[1][14]
- Constitutional B symptoms as seen in other types of NHL:
- Weakness (due to normocytic anemia associated with IgM binding to RBCs).
- Anorexia.
- Unexplained weight loss.
- Unexplained fever.
- Heavy sweating, especially at night causing drenching of one's cloths and bedsheet.
- Severe/extensive skin itchiness.
- Fatigue.
- Sensorimotor peripheral neuropathy (mostly associated with numbness and tingling, i.e. painful pins and needle sensation, of the fingers or toes).
- Blurry vision or blind spots.
- Abdominal pain.
Less Common Symptoms
Less common symptoms of Waldenström macroglobulinemia include:[1][14]
- Enlarged lymph nodes (appearing as 1-2 inches sized lumps under the skin in neck, groin or the armpits).
- Swollen belly/abdomen (due to hepatosplenomegaly).
- Headache.
- Raised pink/flesh-colored lesions on skin.
- Altered mental status due to decreased blood flow and infiltration of CNS leading to:
- Bing-Neel syndrome which includes:
- Confusion.
- Dizziness.
- Memory loss.
- Motor disorders.
- Bing-Neel syndrome which includes:
- Symptoms resembling stroke like slurred speech or weakness on one side of body (such patients are advised to consult from their doctor right away).
- Abnormal mucous membrane bleeding (epistaxis, bleeding gums).
- Vision problems (blurred vision, double vision or blind spots).
- Kidney problems (leading to weakness, trouble breathing and fluid buildup in body tissues associated with accumulation of excess salt, fluid and waste products in blood secondary to amyloidosis).
- Heart problems (Secondary to amyloidosis, build up of M protein in heart affects its pumping ability, and also the heart has to work harder to pump the thick blood ultimately leading to CHF with following symptoms).
- Palpitations.
- Feeling of tiredness and weakness.
- Cough.
- Shortness of breath.
- Rapid weight gain.
- Swelling of feet and legs.
- Infections (high levels of abnormal antibody in WM slows down the production of normal antibodies).
- Digestive problems due to deposition of IgM protein in the lamina propria of the intestinal wall include:
- Diarrhea.
- Poor absorption of vitamins.
- GIT bleeding/steatorrhea (blood in stools/dark stools).
- Sensitivity to cold (Raynaud's phenomenon due to cryoglobulinemia in 5% WM patients), which is associated with reduced blood flow leading to pain, itching, bluish discoloration or sores in following body parts:
- Tip of nose.
- Ears.
- Fingers.
- Toes.
- Cryoglobulinemia also leads to:
- Numbness and tingling in hands and feet.
- Joint aches.
- Small bruises.
- Skin ulcers.
Symptoms Secondary to Hyperviscosity Syndrome
The lymphoma cells make varying amounts of a monoclonal protein called immunoglobulin M (IgM, or macroglobulin). Higher amounts of this protein than normal in blood tends to make it thick leading to hyperviscosity syndrome which occurs in approximately 15-20% patients of WM. When blood becomes thick, it is harder for blood to flow through small blood vessels, and when this occurs, the condition is termed as Waldenstrom macroglobulinemia. This excess amount of IgM antibodies can be ultimately associated with circulatory problems leading to less blood flow to the brain, the eyes or other organs.Clinical manifestations of hyperviscosity syndrome occur only if serum viscosity is >4 centipoises and include:[1]
- Symptoms resembling those of stroke.
- Retinal hemorrhage with blurring of vision/loss of vision.
- Vertigo.
- Dizziness.
- Headache.
- Loss of coordination.
- Nystagmus.
- Tinnitus.
- Ataxia.
- Bleeding.
- Shortness of breath.
- Numbness and tingling of the fingers or toes (called peripheral neuropathy).
- Muscle weakness.
- Confusion.
- Not all people with WM develop hyperviscosity, cryoglobulins, or amyloidosis.
References
- ↑ 1.0 1.1 1.2 1.3 García-Sanz R, Montoto S, Torrequebrada A, de Coca AG, Petit J, Sureda A; et al. (2001). "Waldenström macroglobulinaemia: presenting features and outcome in a series with 217 cases". Br J Haematol. 115 (3): 575–82. PMID 11736938.
- ↑ Dimopoulos MA, Panayiotidis P, Moulopoulos LA, Sfikakis P, Dalakas M (2000). "Waldenström's macroglobulinemia: clinical features, complications, and management". J Clin Oncol. 18 (1): 214–26. doi:10.1200/JCO.2000.18.1.214. PMID 10623712.
- ↑ Dimopoulos MA, Kyle RA, Anagnostopoulos A, Treon SP (2005). "Diagnosis and management of Waldenstrom's macroglobulinemia". J Clin Oncol. 23 (7): 1564–77. doi:10.1200/JCO.2005.03.144. PMID 15735132.
- ↑ Dimopoulos, Meletios A.; Panayiotidis, Panayiotis; Moulopoulos, Lia A.; Sfikakis, Petros; Dalakas, Marinos (2000). "Waldenström's Macroglobulinemia: Clinical Features, Complications, and Management". Journal of Clinical Oncology. 18 (1): 214–214. doi:10.1200/JCO.2000.18.1.214. ISSN 0732-183X.
- ↑ Kyle RA, Garton JP (1987). "The spectrum of IgM monoclonal gammopathy in 430 cases". Mayo Clin Proc. 62 (8): 719–31. PMID 3110508.
- ↑ Lin P, Bueso-Ramos C, Wilson CS, Mansoor A, Medeiros LJ (2003). "Waldenstrom macroglobulinemia involving extramedullary sites: morphologic and immunophenotypic findings in 44 patients". Am J Surg Pathol. 27 (8): 1104–13. PMID 12883242.
- ↑ Dimopoulos MA, Alexanian R (1994). "Waldenstrom's macroglobulinemia". Blood. 83 (6): 1452–9. PMID 8123836.
- ↑ Fudenberg HH, Virella G (1980). "Multiple myeloma and Waldenström macroglobulinemia: unusual presentations". Semin Hematol. 17 (1): 63–79. PMID 6767276.
- ↑ Fadil A, Taylor DE (1998). "The lung and Waldenström's macroglobulinemia". South Med J. 91 (7): 681–5. PMID 9671845.
- ↑ Veltman GA, van Veen S, Kluin-Nelemans JC, Bruijn JA, van Es LA (1997). "Renal disease in Waldenström's macroglobulinaemia". Nephrol Dial Transplant. 12 (6): 1256–9. PMID 9198063.
- ↑ Daoud MS, Lust JA, Kyle RA, Pittelkow MR (1999). "Monoclonal gammopathies and associated skin disorders". J Am Acad Dermatol. 40 (4): 507–35, quiz 536-8. PMID 10188670.
- ↑ Orellana J, Friedman AH (1981). "Ocular manifestations of multiple myeloma, Waldenström's macroglobulinemia and benign monoclonal gammopathy". Surv Ophthalmol. 26 (3): 157–69. PMID 6801795.
- ↑ Civit T, Coulbois S, Baylac F, Taillandier L, Auque J (1997). "[Waldenström's macroglobulinemia and cerebral lymphoplasmocytic proliferation: Bing and Neel syndrome. Apropos of a new case]". Neurochirurgie. 43 (4): 245–9. PMID 9686227.
- ↑ 14.0 14.1 Merlini G, Baldini L, Broglia C, Comelli M, Goldaniga M, Palladini G; et al. (2003). "Prognostic factors in symptomatic Waldenstrom's macroglobulinemia". Semin Oncol. 30 (2): 211–5. doi:10.1053/sonc.2003.50064. PMID 12720138.