Classification of diseases with increased immunoglobulins

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Chapter 29	SECTION 6 - Appendices
	Classification of diseases with increased immunoglobulins

Contents 1 29.1. Monoclonal gammopathies 2 29.2. Polyclonal gammopathies 3 References

29.1. Monoclonal gammopathies

In May 2003, The International MyelomaWorking Group published a review of the criteria for the diagnosis and classification of monoclonal gammopathies, MM and related disorders ^[1]. The aim was to standardise and simplify previous classification systems and provide easy definitions based on routinely available investigations. A uniform approach should facilitate comparisons of therapeutic trial data. The disease groups are as follows and their definitions are found in the respective chapters of this book.

1. MGUS. (Chapter 19)
2. Asymptomatic MM (smouldering MM or Durie and Salmon Stage I). (Chapter 14)
3. Symptomatic MM. (Chapters 8, 9, 10, 11, 12 and 13)
4. Nonsecretory MM. (Chapter 9)
5. Solitary plasmacytoma of bone. (Chapter 18.1)
6. Extramedullary plasmacytoma. (Chapter 18.2)
7. Multiple solitary plasmacytoma. (Chapter 18.3)
8. Plasma cell leukaemia. (Chapter 18.4)

This classification includes the diseases indicated above and other types of monoclonal gammopathies ^[2]. Percentages refer to the frequency of a disease in relation to the total number of monoclonal gammopathies detected, although some variation occurs between different series of patients. The co-occurrence of monoclonal immunoglobulins with non-malignant conditions is uncommon but a proportion of such patients will contain chance associations with MGUS.

a. Multiple myeloma (IgG, IgA, IgD, IgE, and FLC) 18%

1. Smouldering MM 4%

2. Plasma cell leukaemia

3. Nonsecretory MM 2%

4. Osteosclerotic MM (POEMS syndrome)

5. Plasmacytoma 3%

(a) Solitary plasmacytoma of bone

(b) Extramedullary (soft tissue) plasmacytoma

a. Gamma-HCD (γ-HCD)

b. Alpha-HCD (α-HCD)

c. Mu-HCD (µ-HCD)

a. Single clone (IgG, IgA, IgD, IgM, and free light chains)

b. Biclonal and triclonal gammopathies.

Lichen myxoedematosus (IgGl), scleroderma, pyoderma gangrenosum, necrobiotic xanthogranuloma, discoid lupus erythematosus, psoriasis, cutaneous lymphoma

AIDS and HIV infection, renal transplantation, bone marrow transplantation

Chronic hepatitis, cirrhosis, primary biliary cirrhosis

Rheumatoid arthritis, inflammatory seronegative polyarthritis, polymyositis (IgGκ), polymyalgia rheumatica, myasthenia gravis, angioneurotic oedema (C1 inactivator deficiency)

29.2. Polyclonal gammopathies

Chronic infections, autoimmune diseases and many tumours cause increases in polyclonal immunoglobulins and presumably polyclonal FLC concentrations (Chapter 21). Skin, pulmonary and gut diseases are more likely to cause increases in IgA concentrations while systemic infections will increase all immunoglobulins but particularly IgG. The percentages indicate the frequency of the various disorders from a study at The Mayo Clinic ^[3]. Clearly, results will vary in different parts of the world.

Sjögren's syndrome, Rheumatoid arthritis, Systemic lupus erythematosus, Mixed connective tissue disease, Overlap syndrome, Juvenile rheumatoid arthritis, Progressive systemic sclerosis, Ankylosing spondylitis, Fibrosing alveolitis, CREST syndrome, Temporal arteritis, Raynaud’s phenomenon, Cutaneous vasculitis, Familial Mediterranean fever, Eosinophilic fasciitis, Inclusion body myositis

Autoimmune hepatitis, Viral hepatitis, Primary biliary cirrhosis, Primary sclerosing cholangitis, Cryptogenic cirrhosis, Primary hemochromatosis, Ethanol-induced liver injury, α1-antitrypsin deficiency

Subacute bacterial endocarditis, Renal abscess, Cystic fibrosis, Whipple's disease,

Brucellosis, Lyme disease

Malaria, Worm infestations, Tropical splenomegaly syndrome

Mycobacterium Tuberculosis, Mycobacterium leprae, Leishmania organisms,

Trypanosoma cruzi, Toxocara canis

HIV-1, Varicella, Vaccinia

Pseudolymphoma, Kikuchi disease, Malignant lymphoma, Castleman disease

Angioimmunoblastic lymphadenopathy with dysproteinemia

Large granular lymphocytic leukemia, Chronic lymphocytic leukemia, Hairy cell leukemia, Plasma cell leukaemia

Histiocytosis X, Sinus histiocytosis with massive lymphadenopathy

Cutaneous eruptive histiocytoma

Intracranial plasma cell granulomata

Systemic cutaneous plasmacytosis

Proteinaceous lymphadenopathy with hypergammaglobulinemia

Chronic active EBV infection syndrome

Severe autoimmune lymphoproliferative syndrome

Myelodysplastic syndromes

Idiopathic neutropenia, Idiopathic thrombocytopenic purpura

Severe hemophilia A, Thalassemia major, Sickle cell anemia

Benign hypergammaglobulinemic purpura of Waldenström, Cryoglobulinemia

Fanconi anemia

Gastric carcinoma, Lung cancer, Hepatocellular carcinoma, Renal cell carcinoma, Ovarian cancer, Chondrosarcoma

Acquired chronic dysimmune demyelinating polyneuropathy

HTLV-1-associated myelopathy

Chronic progressive sensory ataxic neuropathy

Pure motor neuron disease and plasma cell dyscrasia

Microangiopathy of vasa nervorum in dysglobulinemic neuropathy

Graves’ disease, Chronic ulcerative colitis, Chronic autoimmune pancreatitis

Sarcoidosis

Syndrome of IgG2 subclass deficiency, Hyper IgE syndrome

Hyperimmunoglobulinemia D and Periodic fever syndrome

Aminophenazone, asparaginase, ethotoin, hydralazine hydrochloride, mephenytoin, methadone, oral contraceptives, phenylbutazone, phenytoin.

Gaucher’s disease, Meniére’s disease, Cardiac myxoma, Asbestos exposure

Cryptogenic organising pneumonitis, Lymphoid interstitial pneumonia

Distal renal tubular acidosis

Hyperimmunisation

Chapter 28

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Chapter 30

References