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 70–1SUMMARY OF FEATURES OF THE HEAVY-CHAIN DISEASES |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 |
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
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 h) but may reach 20 g/24 h.
Patients commonly have moderate, normochromic, normocytic anemia.
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