Sections View Full Chapter Figures Tables Videos Annotate 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 71–1 summarizes the clinical features of the three types of HCD. ++Table Graphic Jump LocationTABLE 71–1SUMMARY OF FEATURES OF THE HEAVY-CHAIN DISEASESView Table||Download (.pdf) TABLE 71–1 SUMMARY OF FEATURES OF THE HEAVY-CHAIN DISEASES Type of Heavy-Chain Disease Feature 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 ++ 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. The etiology of γ-HCD and μ-HCD is unknown. +++ CLINICAL AND LABORATORY FEATURES +++ α-HCD ++ This form of HCD is defined by the recognition of truncated monoclonal α chains without associated light chains. The characteristic sharp spike of monoclonal gammopathy is not found on serum protein electrophoresis. Identification of the α-HCD protein depends on immunoselection or immunofixation. Majority of cases have been reported in northern Africa, Israel, and surrounding Middle Eastern countries. At presentation, the patients commonly are in their teens or early twenties. Common clinical features on presentation include recurrent or chronic diarrhea, weight loss, fevers, and/or growth retardation. Digital clubbing is a frequent finding. Moderate hepatomegaly occurs in about 25% of patients. Mesenteric lymphadenopathy is common, sometimes presenting as an abdominal mass, whereas extra-abdominal lymphadenopathy is rare. In many cases, the abnormal heavy chain only can be found in the intestinal secretions. The jejunum is the usual ... Your Access profile is currently affiliated with '[InstitutionA]' and is in the process of switching affiliations to '[InstitutionB]'. Please click ‘Continue’ to continue the affiliation switch, otherwise click ‘Cancel’ to cancel signing in. Get Free Access Through Your Institution Learn how to see if your library subscribes to McGraw Hill Medical products. Subscribe: Institutional or Individual Sign In Username Error: Please enter User Name Password Error: Please enter Password Forgot Password? Forgot Username? Sign in via OpenAthens Sign in via Shibboleth You already have access! Please proceed to your institution's subscription. Create a free a profile for additional features.