Nonmalignant diseases associated with monoclonal gammopathy of undetermined significance and may respond to lymphoplasmacytic cell-directed therapy
Primary organ involved . | Clinical presentation . | Role of monoclonal protein/pathophysiology . | Reference . |
---|---|---|---|
Dermatologic | |||
Acquired C1 inhibitor deficiency | Recurrent angioedema without urticaria or pruritus | Antibody to C1 esterase inhibitor | 69 |
Cryoglobulinemia | Acrocyanosis, purpura, cutaneous ulcer, peripheral neuropathy, arthralgia, glomerulonephritis | Immunoglobulin precipitation or antibody binding to antigens causing hyperviscosity or vasculitis | 70 |
Necrobiotic xanthogranuloma | Yellow-orange papules/plaques with frequent ulcerations; may have proptosis and cardiopulmonary involvement | Unclear | 71 |
Schnitzler syndrome | Chronic urticaria, fever, bone pain, IgM-MGUS | Unclear | 72 |
Endocrinologic | |||
Insulin autoimmune syndrome | Episodic confusion, diaphoresis, dizziness, lethargy, palpitation, seizure | Antibody to insulin causing its inactivation | 73 |
Hematologic | |||
Acquired von Willebrand syndrome | Easy bruising, mucosal bleeding; may have soft tissue bleeding due to decreased factor 8 level | Antibody to von Willebrand factor causing its clearance or interference with platelet or collagen binding | 74 |
Cold agglutinin disease | Acrocyanosis, C3+ autoimmune hemolytic anemia, red cell agglutination, mostly IgMκ-MGUS | Antibody to red cell I antigen-causing agglutination and hemolysis | 75 |
TEMPI | Telangiectasias, erythrocytosis, elevated erythropoietin level, MGUS, perinephric fluid collections, and intrapulmonary shunting | Unclear | 76 |
Rheumatologic | |||
Scleromyxedema | Waxy papules or plaques, arthralgia, restrictive lung disease, seizure | Unclear | 77 |
Nephrologic | |||
Antiglomerular basement membrane disease | Hematuria, proteinuria | Antibody to glomerular basement membrane | 78 |
C3 glomerulonephritis | Hematuria, proteinuria | Antibody to C3 convertase or complement factors B, H, or I causing C3 deposition in glomeruli | 79 |
Dense deposit disease | Hematuria, proteinuria | Antibody to C3 convertase or complement factors B, H, or I causing C3 deposition in glomeruli | 80 |
Fibrillary glomerulonephritis | Hematuria, proteinuria, renal impairment, mostly IgG-MGUS | Fibrillary deposition of immunoglobulin in glomeruli | 81 |
Immunotactoid glomerulonephritis | Hematuria, hypertension, proteinuria, renal impairment, IgG-MGUS | Microtubular deposition of immunoglobulin in glomeruli | 82 |
Light-chain proximal tubulopathy | Aminoaciduria, hyperphosphaturia, normoglycemic glycosuria, proximal renal tubular acidosis, uricosuria, mostly κ-MGUS | Direct light-chain toxicity to proximal renal tubules | 83 |
Membranous nephropathy | IgG3κ-MGUS | Antibody to phospholipase A2 receptor | 84 |
Monoclonal immunoglobulin deposition disease | Hematuria, hypertension, proteinuria, renal impairment, mostly κ-MGUS | Granular deposition of immunoglobulin in glomeruli | 85 |
Progressive glomerulonephritis with monoclonal immunoglobulin deposits | Hematuria, hypertension, proteinuria, renal impairment, mostly IgG3κ-MGUS | Granular deposition of immunoglobulin in glomeruli | 86 |
Neurologic | |||
CANOMAD | Chronic ataxic neuropathy, ophthalmoplegia, IgM-MGUS, cold agglutinin, and disialosyl antibodies | Antibody to disialosyl ganglioside | 87 |
POEMS | Polyneuropathy, organomegaly, endocrinopathy, mostly λ-MGUS, skin changes | Unclear | 88 |
Sensorimotor neuropathy | Distal, acquired, demyelinating, symmetric neuropathy (sensory ataxia, motor involvement typically mild), IgM-MGUS | Antibody to myelin-associated glycoprotein, ganglioside, or asialo-GM1 | 25 |
Sporadic late-onset nemaline myopathy | Muscular weakness and atrophy frequently resulting in “head drop,” respiratory insufficiency, congestive heart failure | Unclear | 89 |
Ophthalmologic | |||
Corneal copper deposition | Decreased visual acuity, diffuse brownish discoloration of cornea, hypercupremia, IgG-MGUS | Corneal deposition of antibody with strong affinity to copper | 90 |
Crystalline keratopathy | Decreased visual acuity, corneal opacity, IgGκ-MGUS | Corneal deposition of antibody forming a crystalline structure | 91 |
Other | |||
Capillary leak syndrome | Recurrent hypovolemic shock with generalized edema | Unclear | 92 |
Crystal-storing histiocytosis | Mass or tissue infiltration, which may involve the bone marrow, breast, gastrointestinal tract, kidneys, lymph node, skin, or spleen | Accumulation of light-chain crystals in histiocytes | 93 |
Primary organ involved . | Clinical presentation . | Role of monoclonal protein/pathophysiology . | Reference . |
---|---|---|---|
Dermatologic | |||
Acquired C1 inhibitor deficiency | Recurrent angioedema without urticaria or pruritus | Antibody to C1 esterase inhibitor | 69 |
Cryoglobulinemia | Acrocyanosis, purpura, cutaneous ulcer, peripheral neuropathy, arthralgia, glomerulonephritis | Immunoglobulin precipitation or antibody binding to antigens causing hyperviscosity or vasculitis | 70 |
Necrobiotic xanthogranuloma | Yellow-orange papules/plaques with frequent ulcerations; may have proptosis and cardiopulmonary involvement | Unclear | 71 |
Schnitzler syndrome | Chronic urticaria, fever, bone pain, IgM-MGUS | Unclear | 72 |
Endocrinologic | |||
Insulin autoimmune syndrome | Episodic confusion, diaphoresis, dizziness, lethargy, palpitation, seizure | Antibody to insulin causing its inactivation | 73 |
Hematologic | |||
Acquired von Willebrand syndrome | Easy bruising, mucosal bleeding; may have soft tissue bleeding due to decreased factor 8 level | Antibody to von Willebrand factor causing its clearance or interference with platelet or collagen binding | 74 |
Cold agglutinin disease | Acrocyanosis, C3+ autoimmune hemolytic anemia, red cell agglutination, mostly IgMκ-MGUS | Antibody to red cell I antigen-causing agglutination and hemolysis | 75 |
TEMPI | Telangiectasias, erythrocytosis, elevated erythropoietin level, MGUS, perinephric fluid collections, and intrapulmonary shunting | Unclear | 76 |
Rheumatologic | |||
Scleromyxedema | Waxy papules or plaques, arthralgia, restrictive lung disease, seizure | Unclear | 77 |
Nephrologic | |||
Antiglomerular basement membrane disease | Hematuria, proteinuria | Antibody to glomerular basement membrane | 78 |
C3 glomerulonephritis | Hematuria, proteinuria | Antibody to C3 convertase or complement factors B, H, or I causing C3 deposition in glomeruli | 79 |
Dense deposit disease | Hematuria, proteinuria | Antibody to C3 convertase or complement factors B, H, or I causing C3 deposition in glomeruli | 80 |
Fibrillary glomerulonephritis | Hematuria, proteinuria, renal impairment, mostly IgG-MGUS | Fibrillary deposition of immunoglobulin in glomeruli | 81 |
Immunotactoid glomerulonephritis | Hematuria, hypertension, proteinuria, renal impairment, IgG-MGUS | Microtubular deposition of immunoglobulin in glomeruli | 82 |
Light-chain proximal tubulopathy | Aminoaciduria, hyperphosphaturia, normoglycemic glycosuria, proximal renal tubular acidosis, uricosuria, mostly κ-MGUS | Direct light-chain toxicity to proximal renal tubules | 83 |
Membranous nephropathy | IgG3κ-MGUS | Antibody to phospholipase A2 receptor | 84 |
Monoclonal immunoglobulin deposition disease | Hematuria, hypertension, proteinuria, renal impairment, mostly κ-MGUS | Granular deposition of immunoglobulin in glomeruli | 85 |
Progressive glomerulonephritis with monoclonal immunoglobulin deposits | Hematuria, hypertension, proteinuria, renal impairment, mostly IgG3κ-MGUS | Granular deposition of immunoglobulin in glomeruli | 86 |
Neurologic | |||
CANOMAD | Chronic ataxic neuropathy, ophthalmoplegia, IgM-MGUS, cold agglutinin, and disialosyl antibodies | Antibody to disialosyl ganglioside | 87 |
POEMS | Polyneuropathy, organomegaly, endocrinopathy, mostly λ-MGUS, skin changes | Unclear | 88 |
Sensorimotor neuropathy | Distal, acquired, demyelinating, symmetric neuropathy (sensory ataxia, motor involvement typically mild), IgM-MGUS | Antibody to myelin-associated glycoprotein, ganglioside, or asialo-GM1 | 25 |
Sporadic late-onset nemaline myopathy | Muscular weakness and atrophy frequently resulting in “head drop,” respiratory insufficiency, congestive heart failure | Unclear | 89 |
Ophthalmologic | |||
Corneal copper deposition | Decreased visual acuity, diffuse brownish discoloration of cornea, hypercupremia, IgG-MGUS | Corneal deposition of antibody with strong affinity to copper | 90 |
Crystalline keratopathy | Decreased visual acuity, corneal opacity, IgGκ-MGUS | Corneal deposition of antibody forming a crystalline structure | 91 |
Other | |||
Capillary leak syndrome | Recurrent hypovolemic shock with generalized edema | Unclear | 92 |
Crystal-storing histiocytosis | Mass or tissue infiltration, which may involve the bone marrow, breast, gastrointestinal tract, kidneys, lymph node, skin, or spleen | Accumulation of light-chain crystals in histiocytes | 93 |