Current pathophysiological classification of the main MGCS-related disorders: cytokine mediated or MGCS due to autoantibody activity, CAP activation, cytokine-mediated, or of unknown mechanism
. | Mechanism . | Main characteristics of monoclonal gammopathy . | Main organ(s) involved . | Reference . |
---|---|---|---|---|
Autoantibody activity | ||||
Type II mixed cryoglobulinemia* | Rheumatoid | IgM | Immune complex–mediated vasculitis; skin +++, kidney, peripheral nerve; may be systemic | 28,60 |
C1 inhibitor deficiency | C1 inhibitor | Angioedema | 25 | |
Von Willebrand disease | vW factor | Bleeding | 26 | |
Bullous skin diseases | Dermoepidermal junction (collagen VII) | Skin | 21 | |
Xanthomatosis | Various lipoproteins | Usually IgG | Cholesterol accumulation in macrophages; skin and tendons; other localizations (necrobiotic xanthogranumathosis) | 29,30 |
Cold agglutinin disease | Red blood cell (Ii) | IgM | Cold-induced skin manifestations + intravascular hemolysis | 27 |
IgM-associated peripheral neuropathy | MAG +++ | IgM | Peripheral nerve; ataxic polyneuropathy (anti-MAG) CANOMAD | 22,23 |
Gangliosides | ||||
CAP*activation | ||||
C3 glomerulonephritis Atypical hemolytic-uremic syndrome | Mechanism to be determined; autoantibody activity against CAP regulator protein (factor H) in some cases | IgG | Kidney only Systemic | 31,,-34 |
Cytokine mediated | ||||
POEMS syndrome | VEGF | λ LC (∼100%), | Peripheral nerve (100%) and various other manifestations | 35,36 |
IgA 50% | ||||
Vλ1 (#100%) | ||||
Osteosclerotic bone lesions | ||||
Unknown mechanism | ||||
Systemic capillary leak syndrome | IgG, IgA (rare) | Systemic | 45 | |
TEMPI syndrome | IgG | Systemic | 46,47 | |
Neutrophilic dermatosis† | IgA >80% (except Sweet syndrome) | Skin +++; different types and different associated manifestations | 39 | |
Acquired cutis laxa | Usually IgG; association with γ HCDD | Skin +++Other manifestations (lung, digestive tract) | 43 | |
Scleromyxedema | IgG with slow electrophoretic mobility | Skin +++; other localizations | 40,41,52 | |
Scleroedema | IgG | Skin only | 41 | |
Schnitzler syndrome | Acquired autoinflammatory syndrome by IL-1 deregulation? | IgM | Skin +++; systemic symptoms; osteosclerotic bone lesions | 44 |
Sporadic late-onset nemaline myopathy | Exclusively muscles (skeletal and possibly cardiac) | 48 |
. | Mechanism . | Main characteristics of monoclonal gammopathy . | Main organ(s) involved . | Reference . |
---|---|---|---|---|
Autoantibody activity | ||||
Type II mixed cryoglobulinemia* | Rheumatoid | IgM | Immune complex–mediated vasculitis; skin +++, kidney, peripheral nerve; may be systemic | 28,60 |
C1 inhibitor deficiency | C1 inhibitor | Angioedema | 25 | |
Von Willebrand disease | vW factor | Bleeding | 26 | |
Bullous skin diseases | Dermoepidermal junction (collagen VII) | Skin | 21 | |
Xanthomatosis | Various lipoproteins | Usually IgG | Cholesterol accumulation in macrophages; skin and tendons; other localizations (necrobiotic xanthogranumathosis) | 29,30 |
Cold agglutinin disease | Red blood cell (Ii) | IgM | Cold-induced skin manifestations + intravascular hemolysis | 27 |
IgM-associated peripheral neuropathy | MAG +++ | IgM | Peripheral nerve; ataxic polyneuropathy (anti-MAG) CANOMAD | 22,23 |
Gangliosides | ||||
CAP*activation | ||||
C3 glomerulonephritis Atypical hemolytic-uremic syndrome | Mechanism to be determined; autoantibody activity against CAP regulator protein (factor H) in some cases | IgG | Kidney only Systemic | 31,,-34 |
Cytokine mediated | ||||
POEMS syndrome | VEGF | λ LC (∼100%), | Peripheral nerve (100%) and various other manifestations | 35,36 |
IgA 50% | ||||
Vλ1 (#100%) | ||||
Osteosclerotic bone lesions | ||||
Unknown mechanism | ||||
Systemic capillary leak syndrome | IgG, IgA (rare) | Systemic | 45 | |
TEMPI syndrome | IgG | Systemic | 46,47 | |
Neutrophilic dermatosis† | IgA >80% (except Sweet syndrome) | Skin +++; different types and different associated manifestations | 39 | |
Acquired cutis laxa | Usually IgG; association with γ HCDD | Skin +++Other manifestations (lung, digestive tract) | 43 | |
Scleromyxedema | IgG with slow electrophoretic mobility | Skin +++; other localizations | 40,41,52 | |
Scleroedema | IgG | Skin only | 41 | |
Schnitzler syndrome | Acquired autoinflammatory syndrome by IL-1 deregulation? | IgM | Skin +++; systemic symptoms; osteosclerotic bone lesions | 44 |
Sporadic late-onset nemaline myopathy | Exclusively muscles (skeletal and possibly cardiac) | 48 |
CAP, complement alternative pathway; CANOMAD, chronic ataxic neuropathy, ophthalmoplegia, monoclonal IgM protein, cold agglutinins, anti-disialosyl antibodies; HCDD, heavy-chain deposition disease; IL-1, interleukin 1; POEMS, polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes; TEMPI, telangiectasias, erythrocytosis with elevated erythropoietin level, monoclonal gammopathy, perinephric fluid collection, and intrapulmonary shunting.
Type II mixed cryoglobulinemia was observed in ∼10% of patients with chronic virus C infection.
Including pyoderma gangrenosum, Sweet syndrome, subcorneal pustular dermatosis, and erythema elevatum diutinum.