Waldenström's macroglobulinemia history and symptoms
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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]; Grammar Reviewer: Natalie Harpenau, B.S.[4]
Overview
Many patients with Waldenstrom's macroglobulinemia are asymptomatic. The disease is subtle and symptoms are nonspecific and are caused by tumor infiltration, circulating monoclonal IgM, IgM deposition into tissues, amyloidogenic properties of IgM, and autoantibody activity of IgM. The most common symptoms of Waldenstrom's macroglobulinemia include weakness, anorexia, unexplained weight loss, fever, heavy sweating, blurry vision, peripheral neuropathy, and abdominal pain. Less common symptoms of the disease include enlarged lymph nodes, abdominal distension, headache, painless lumps, raynaud phenomenon, altered mental status, mucosal bleeding, vision problems, kidney issues, heart problems, infections, GIT problems, and other symptoms due to cryoglobulinemia, cold agglutinin disease, hyperviscosity syndrome, and bing-neel syndrome.
History and Symptoms
History
- The onset of Waldenstrom's 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 Waldenstrom's macroglobulinemia
Following is a list of WM manifestations with attributable causes:[3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24]
Common Symptoms
Common symptoms of Waldenstrom's macroglobulinemia include:[1][25]
- 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 Waldenstrom's macroglobulinemia include:[1][25]
- 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).
- Pain or a feeling of fullness below the ribs on the left side.
- Painless lumps in the neck, underarm, stomach, or groin.
- 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:
- 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:
- 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:
- Clinical manifestations of cryoglobulinemia include:
- Numbness and tingling in hands and feet
- Joint aches
- Small bruises
- Skin ulcers
- Purpura
- Digital ischemia
- Arthralgia
- Fever
- Raynaud phenomenon
- Clinical manifestations of Cold agglutinin disease include:
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, 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
- Dizziness
- Headache
- Loss of coordination
- Nystagmus
- Tinnitus
- 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.
- ↑ Kwaan HC, Bongu A (1999). "The hyperviscosity syndromes". Semin Thromb Hemost. 25 (2): 199–208. doi:10.1055/s-2007-994921. PMID 10357087.
- ↑ Farhangi M, Merlini G (1986). "The clinical implications of monoclonal immunoglobulins". Semin Oncol. 13 (3): 366–79. PMID 3094151.
- ↑ "Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 3-1990. A 66-year-old woman with Waldenström's macroglobulinemia, diarrhea, anemia, and persistent gastrointestinal bleeding". N Engl J Med. 322 (3): 183–92. 1990. doi:10.1056/NEJM199001183220308. PMID 2104668.
- ↑ Gertz, M A; Kyle, R A; Noel, P (1993). "Primary systemic amyloidosis: a rare complication of immunoglobulin M monoclonal gammopathies and Waldenström's macroglobulinemia". Journal of Clinical Oncology. 11 (5): 914–920. doi:10.1200/JCO.1993.11.5.914. ISSN 0732-183X.
- ↑ Gertz MA, Kyle RA (2003). "Amyloidosis with IgM monoclonal gammopathies". Semin Oncol. 30 (2): 325–8. doi:10.1053/sonc.2003.50060. PMID 12720162.
- ↑ Gardyn J, Schwartz A, Gal R, Lewinski U, Kristt D, Cohen AM (2001). "Waldenström's macroglobulinemia associated with AA amyloidosis". Int J Hematol. 74 (1): 76–8. PMID 11530809.
- ↑ Ropper AH, Gorson KC (1998). "Neuropathies associated with paraproteinemia". N Engl J Med. 338 (22): 1601–7. doi:10.1056/NEJM199805283382207. PMID 9603799.
- ↑ Vital A (2001). "Paraproteinemic neuropathies". Brain Pathol. 11 (4): 399–407. PMID 11556684.
- ↑ Crisp D, Pruzanski W (1982). "B-cell neoplasms with homogeneous cold-reacting antibodies (cold agglutinins)". Am J Med. 72 (6): 915–22. PMID 6807086.
- ↑ Lindström FD, Hed J, Eneström S (1980). "Renal pathology of Waldenström's macroglobulinaemia with monoclonal antiglomerular antibodies and nephrotic syndrome". Clin Exp Immunol. 41 (2): 196–204. PMC 1537007. PMID 6777101.
- ↑ Sen HN, Chan CC, Caruso RC, Fariss RN, Nussenblatt RB, Buggage RR (2004). "Waldenström's macroglobulinemia-associated retinopathy". Ophthalmology. 111 (3): 535–9. doi:10.1016/j.ophtha.2003.05.036. PMID 15019332.
- ↑ 25.0 25.1 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.