Sections View Full Chapter Figures Tables Videos Full Chapter Figures Tables Videos Supplementary Content +++ DEFINITION ++ The heavy-chain diseases (HCDs) are neoplastic disorders of B cells that produce monoclonal immunoglobulins (Ig) consisting of truncated heavy chains without attached light chains. In decreasing order of incidence, HCD involves synthesis of defective α, γ, or μ heavy chains. The diagnosis is established from immunofixation of serum, urine, or secretory fluids in the case of α-HCD or from immunohistologic analysis of the proliferating lymphoplasmacytic cells in nonsecretory disease. There is a high frequency of autoimmune disorders preceding or concurrent with the diagnosis of HCD, particularly γ-HCD. Table 70–1 summarizes the clinical features of the three types of HCD. ++Table Graphic Jump LocationTABLE 70–1SUMMARY OF FEATURES OF THE HEAVY-CHAIN DISEASESView Table|Favorite Table|Download (.pdf) TABLE 70–1 SUMMARY OF FEATURES OF THE HEAVY-CHAIN DISEASES Feature Type of Heavy-Chain Disease α γ μ Year described 1968 1964 1969 Incidence Rare Very rare Very rare Age at diagnosis Young adult (< 30 years) Older adult (60–70 years) Older adult (50–60 years) Demographics Mediterranean region Worldwide Worldwide Structurally abnormal monoclonal protein IgA IgG IgM MGUS phase No Rarely Rarely Urine monoclonal light chain No No Yes Urine abnormal heavy chain Small amounts Often present Infrequent Sites involved Small intestine, mesenteric lymph nodes Lymph nodes, marrow, spleen Lymph nodes, marrow, liver, spleen Pathology Extranodal marginal zone lymphoma (MALT or IPSID) Lymphoplasmacytoid lymphoma Small lymphocytic lymphoma, CLL Associated diseases Infection, malabsorption Autoimmune diseases None Therapy Antibiotics, chemotherapy Chemotherapy Chemotherapy CLL, chronic lymphocytic leukemia; Ig, immunoglobulin; IPSID, immunoproliferative small intestinal disease; MALT, mucosa-associated lymphoid tissue; MGUS, monoclonal gammopathy of undetermined significance. Adapted with permission from Witzig TE, Wahner-Roedler DL: Heavy chain disease, Curr Treat Options Oncol 2002 Jun;3(3):247–254. +++ ETIOLOGY AND PATHOGENESIS ++ The etiology of γ-HCD and μ-HCD is unknown. In α-HCD, the lymphoplasmacytic infiltration of the intestinal mucosa is thought to be a response of the alimentary tract immune system to protracted luminal antigenic stimulation. A causal relationship between infection and pathogenesis is supported by a response to antibiotics in some cases. +++ CLINICAL AND LABORATORY FEATURES +++ γ-HCD ++ Median age at presentation is in the late sixties. Clinical features are different than those of myeloma because renal disease and osteolytic lesions rarely occur. This form of HCD has various clinical and pathologic features that can be divided into three broad categories: — Disseminated lymphoproliferative disease: approximately 60% of patients — Localized proliferative disease: approximately 25% of patients — No apparent proliferative disease: approximately 15% of patients Most γ-HCD proteins are dimers of truncated heavy chains without associated light chains. The serum protein electrophoretic pattern is extremely variable, but a monoclonal peak is detected in over two-thirds of patients. The median value of the monoclonal spike at diagnosis in one study of 19 patients was 1.6 g/dL. The amount of HCD protein in the urine usually is small (< 1 g/24 ... GET ACCESS TO THIS RESOURCE Sign In Username Error: Please enter User Name Password Error: Please enter Password Forgot Username? Forgot Password? Sign in via OpenAthens Sign in via Shibboleth Get Free Access Through Your Institution Contact your institution's library to ask if they subscribe to McGraw-Hill Medical Products. Access My Subscription