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1724 Part XI: Malignant Lymphoid Diseases Chapter 106: Essential Monoclonal Gammopathy 1725

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TABLE 106–3. Disorders Reported in Coincidence with relationship in most patients. Gaucher disease type I has a high-
er-than-expected frequency of polyclonal (approximately 40 percent)
Monoclonal Gammopathy
and monoclonal (approximately 20 percent) gammopathy, and, prob-
Axial bone fracture 138,139 ably, of myeloma. 160–162 Elaboration of proinflammatory cytokines,
Connective tissue diseases and autoimmune diseases: Crohn growth factors, and chemokines, several involved in B-cell function, is
disease, cryoglobulinemia, Hashimoto thyroiditis, lupus eryth- disturbed in type I Gaucher disease. An increase of interleukin (IL)-
ematosus, myasthenia gravis, pernicious anemia, polymyalgia 10 and pulmonary and activation-regulated chemokine is notable. A
rheumatica, psoriatic arthritis, rheumatoid arthritis, scleroderma, high frequency of B-cell clonality and IgH gene rearrangements have
Sjögren disease 140–149 also been described. The administration of recombinant glucocer-
162
Corneal and other ocular diseases: pseudo–Kayser-Fleischer ebrosidase therapy may decrease the occurrence and progression of
ring, corneal gammopathy 102-106,244 gammopathies. 161
243
In inflammatory, autoimmune, and infectious diseases, the asso-
Cutaneous diseases: Schnitzler syndrome, urticaria, hyperkeratotic
spicules, pyoderma gangrenosum (neutrophilic dermatoses), pso- ciation is viewed as an unusual expansion of a restricted population of
riasis, scleromyxedema 150–156 B lymphocytes. Following marrow transplantation, the presence of oli-
goclonal blood B-lymphocyte populations often reflects the process of
Diffuse idiopathic skeletal hyperostosis 157
reconstitution of the B-cell population.
Endocrine diseases: hyperparathyroidism 158,159
Gaucher disease, type I 160–162 LABORATORY FEATURES
Hepatic disease: cirrhosis, hepatitis, 163,164
148
Hereditary spherocytosis 165 PLASMA AND URINARY MONOCLONAL
Infectious diseases: bacterial endocarditis, Corynebacterium IMMUNOGLOBULINS
species, cytomegalovirus, Epstein-Barr virus, human immu- The monoclonal protein usually is an IgG; however, IgM, IgA, IgD, and
nodeficiency virus, Mycobacterium tuberculosis, purpura IgE, urinary light chains, double gammopathy involving IgA and IgG or
fulminans 19,148,166–169,212,215 IgM and IgA, and triple gammopathy can occur. Rare cases may have
Metabolic disease: hyperlipidemia 170 the isotype IgD or IgE (see Table 106–1). 12,63–66,178,203 By definition, no
Neutropenia, chronic 85,86,171 findings other than a serum monoclonal Ig or monoclonal light chain
is present with no other features of a B-lymphocyte or plasma cell
Osteoporosis 172,174,175 malignancy.
Pituitary macroadenoma 173 In monoclonal gammopathy of the IgG type, the concentration
Pregnancy 174 of monoclonal Ig usually is less than 3 g/dL. In the IgA or IgM type,
the concentration usually is less than 2.5 g/dL. 10,12,203 However, dra-
Systemic capillary leak syndrome 177 matic exceptions to this rule exist. Occasional patients with essential
Carcinomas: colon, lung, prostate, other 3,5,6,178–181 monoclonal gammopathy have concentrations as high as 6 g/dL. Some
Myeloproliferative diseases: acute and chronic myelogenous patients have urinary monoclonal light chain excretion (Bence Jones
1,10
leukemia, 182–184 chronic neutrophilic leukemia, polycythemia proteinuria) as the sole manifestation of monoclonal gammopathy.
vera 185–189 The amount of urinary light chains excreted occasionally is so large
(>1.0 g/day) that renal dysfunction may develop. 93,96,97
T-cell lymphomas, Hodgkin lymphoma 190–193
Most patients with myeloma or macroglobulinemia have sig-
After chemotherapy, radiotherapy, or marrow, kidney, or liver nificantly depressed nonmonoclonal Ig levels. For example, patients
transplantation 194–198,213–215 with IgG myeloma usually have very low IgA and IgM concentrations
Miscellaneous diseases 200–202 and a reduced polyclonal IgG level. Patients with monoclonal gam-
mopathy usually have normal polyclonal Ig levels; and, if a decrease
Transient, monoclonal, or oligoclonal gammopathies 204–206
of their polyclonal Ig levels is present, it is usually not as severe as in
Factitious hyperferremia 207 myeloma. 10,12,203,210
Factitious increase in C-reactive protein 208 Depression of normal polyclonal immunoglobulin concentrations
is considered one of several factors that may portend the likelihood of
Vitamin B deficiency 140,209
12 progression to a B-cell malignancy.

OLIGOCLONAL IMMUNOGLOBULINS
by one group of scientists 183–184 but a large longitudinal study did not Oligoclonal or monoclonal serum Ig levels have been detected with
find this association. Some observers propose that in clonal myeloid high-resolution agarose gel electrophoresis in hospitalized patients with
12
diseases the monoclonal protein reflects B-cell lineage involvement. acute-phase reactions or polyclonal hyperglobulinemia. Oligoclonal
206
Chemotherapy, radiotherapy, organ or marrow transplanta- Ig bands are frequently seen in the cerebrospinal fluid and serum of
tion, 194–199 and other miscellaneous disorders 5,7,10,24–26,147,148,200–202 are asso- patients with a variety of neurologic conditions, especially multiple scle-
211
ciated with a transient or persistent monoclonal Ig (see Table 106–3). rosis, when the fluids are analyzed by isoelectric focusing. Patients
The high prevalence of monoclonal proteins and associated diseases, with AIDS have B-cell activation and aberrancies of B-cell regulation.
especially after age 50 years, indicates some of these associations are High-resolution electrophoresis indicates most AIDS patients with
coincidental. Thus, although surgical correction of hyperparathy- advanced disease have monoclonal or oligoclonal serum Ig bands.
roidism is associated with disappearance of the plasma monoclonal Persons with AIDS, lymphadenopathy syndrome, or antibody to the
protein, statistical studies of this disorder suggest a coincidental human immunodeficiency virus also have oligoclonal or monoclonal
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