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Gamma Heavy Chain Disease Clinical Presentation

  • Author: Guy B Faguet, MD; Chief Editor: Emmanuel C Besa, MD  more...
 
Updated: May 19, 2014
 

History

See Physical Examination.

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Causes

The causes of or risk factors for γ-HCD are unknown.

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Physical Examination

It has been suggested that approximately 25% of patients with γ-heavy chain disease (HCD) present with localized disease, whereas two thirds exhibit disseminated disease, including medullary and extramedullary involvement, with the remainder showing gammopathy only.[7] Patients with disseminated γ-HCD present with a lymphomalike illness that includes lymphadenopathy, splenomegaly, and hepatomegaly, and often involves progressive weakness, fatigue, and intermittent fevers. Hepatosplenomegaly is present in 60% of patients.

Lymphadenopathy is present at the onset in approximately two thirds of patients with disseminated disease. It commonly involves cervical, axillary, thoracic, and abdominal nodes. It also involves the Waldeyer ring and mesenteric lymph nodes, often leading to an edematous tongue and soft palate. Lymphadenopathy becomes more pronounced as the disease progresses. Other features may include parotid gland tenderness, soreness of the tongue, autoimmune hemolytic anemia, and purpura. Skeletal involvement and hypercalcemia are rare but renal, adrenal, and CNS lymphoid infiltration have been reported postmortem.

The course of γ-HCD varies from an asymptomatic presence of a nonprogressive monoclonal heavy chain in serum or urine that occasionally disappears, to a rapidly progressive illness. A small percentage of γ-HCD exhibits a phase of monoclonal gammopathy of undetermined significance (MGUS). Most patients with progressive disease eventually succumb to bacterial infections. A series of 23 patients reported a median survival of 7.4 years.[2]

Symptoms of γ-HCD are variable but include the following:

  • Fevers are frequently recurrent and resemble that of lymphoproliferative disorders.
  • Malaise may be secondary to the disease state itself or to anemia. Mild anemia is universal in patients with disseminated γ-HCD.
  • Dysphagia is usually caused by edema of the soft palate, secondary to progressive lymphadenopathy of the Waldeyer ring. This edema may also lead to tongue soreness.
  • Recurrent upper respiratory tract infections develop because of impaired humoral and cellular immunity, although other factors also can contribute, including lymphoid hyperplasia of the oropharynx that can reduce clearance of airway pathogens.
  • Abdominal pain can be present and is caused by splenomegaly (see the image below), hepatomegaly, and/or abdominal lymphadenopathy.
    The margins of this massive spleen were palpated e The margins of this massive spleen were palpated easily preoperatively. Medially, the 3.18-kg (7-lb) spleen crosses the midline. Inferiorly, it extends into the pelvis.
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Contributor Information and Disclosures
Author

Guy B Faguet, MD Retired Professor, Department of Medicine, Section of Hematology and Oncology, Georgia Regents University

Guy B Faguet, MD is a member of the following medical societies: American Association of Immunologists, American Society of Hematology, International Society of Hematology, New York Academy of Sciences, Southern Medical Association, Southern Society for Clinical Investigation, American Federation for Clinical Research, Southeastern Cancer Research Association, Polycythemia Vera Study Group

Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Acknowledgements

Wendy Brick, MD Consulting Staff, Department of Internal Medicine, Division of Hematology and Oncology, Mecklenburg Medical Group

Wendy Brick, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Medical Association, and American Society of Hematology

Disclosure: Nothing to disclose.

Russell Burgess, MD (Retired) Chief, Division of Hematology/Oncology, Eastern Carolina Internal Medicine, PA

Russell Burgess, MD is a member of the following medical societies: American College of Physicians and American Medical Assocation

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

References
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  2. Wahner-Roedler DL, Witzig TE, Loehrer LL, Kyle RA. Gamma-heavy chain disease: review of 23 cases. Medicine (Baltimore). 2003 Jul. 82(4):236-50. [Medline].

  3. Husby G, Blichfeldt P, Brinch L, et al. Chronic arthritis and gamma heavy chain disease: coincidence or pathogenic link?. Scand J Rheumatol. 1998. 27(4):257-64. [Medline].

  4. Husby G. Is there a pathogenic link between gamma heavy chain disease and chronic arthritis?. Curr Opin Rheumatol. 2000 Jan. 12(1):65-70. [Medline].

  5. Faguet GB, Barton BP, Smith LL, Garver FA. Gamma heavy chain disease: clinical aspects and characterization of a deleted, noncovalently linked gamma1 heavy chain dimer (BAZ). Blood. 1977 Apr. 49(4):495-505. [Medline].

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  8. Nasr SH, Valeri AM, Cornell LD, Fidler ME, Sethi S, D'Agati VD, et al. Renal Monoclonal Immunoglobulin Deposition Disease: A Report of 64 Patients from a Single Institution. Clin J Am Soc Nephrol. 2011 Dec 8. [Medline].

  9. Tissot JD, Tridon A, Ruivard M, et al. Electrophoretic analyses in a case of monoclonal gamma chain disease. Electrophoresis. 1998 Jul. 19(10):1771-3. [Medline].

  10. Csako G. Immunodeletrophoresis: A method with many facets. Biji T, Kurien R, Schofield H. Protein Electrophoresis and Protocols, Methods in Molecular Biology. Springer Sciences-Business Media, LLC; 2012. 869:

  11. Gale DS, Versey JM, Hobbs JR. Rocket immunoselection for detection of heavy-chain diseases. Clin Chem. 1974 Oct. 20(10):1292-4. [Medline].

  12. Takano H, Nagata K, Mikoshiba M, Nakane M, Kato A, Hamaguchi H. Combination of rituximab and chemotherapy showing anti-tumor effect in gamma heavy chain disease expressing CD20. Am J Hematol. 2008 Dec. 83(12):938-9. [Medline].

  13. Inoue D, Matsushita A, Kiuchi M, et al. Successful treatment of ?-heavy-chain disease with rituximab and fludarabine. Acta Haematol. 2012. 128(3):139-43. [Medline].

  14. Agrawal S, Abboudi Z, Matutes E, Catovsky D. First report of fludarabine in gamma-heavy chain disease. Br J Haematol. 1994 Nov. 88(3):653-5. [Medline].

  15. Yeh CH, Tseng R, Albitar M. Plasma-based detection of clonality in lymphoid malignancies. Eur J Haematol. 2009 Jun. 82(6):450-3. [Medline].

  16. Zhang Y, Chen L, Xu W, et al. [Immunoglobulin variable heavy chain region genetic constitution and mutation status in Chinese patients with chronic lymphocytic leukemia] [Chinese]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2009 Apr. 26(2):196-9. [Medline].

 
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The margins of this massive spleen were palpated easily preoperatively. Medially, the 3.18-kg (7-lb) spleen crosses the midline. Inferiorly, it extends into the pelvis.
Lateral radiograph of the skull. This image demonstrates numerous lytic lesions, which are typical for the appearance of widespread myeloma.
Bone marrow biopsy specimen.
Bone marrow biopsy specimen in fixative solution.
Bone marrow aspiration and biopsy slides before staining.
Histology of eosinophilic granuloma.
Radiograph of the right femur. This image demonstrates the typical appearance of a single myeloma lesion as a well-circumscribed lucency in the intertrochanteric region. Smaller lesions are seen at the greater trochanter.
 
 
 
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