Please refer to 'Immunoglobulins - high' and 'Immnuoglobulins - low' modules for individual immunoglobulin subclasses. Common causes of hypergammaglobulinaemia:
Osteomyelitis, SBE, TB- all immunoglobulins
SLE, RhA, Sjogren’s syndrome - all immunoglobulins;
elevated IgG1 in Sjogren's;
Sarcoidosis (predominantly IgG and IgA)
Primary Biliary Cirrhosis (IgM, may be very high with small monoclonal bands on polyclonal background])
Alcohol (IgA, polyclonal, 'beta-gamma bridging' on electrophoresis)
Fatty liver, autoimmune hepatitis (IgA)
IgE raised (also eosinophilia)
HIV - all Igs raised (IgG very high but polyclonal)
Hypogammaglobulinemia refers to the laboratory finding of low immunoglobulins (usually IgG). This is insufficient alone as a diagnosis, and needs to have any underlying causes identified, and any infectious/autoimmune complications reviewed. It may be primary or secondary. Please refer to 'Immunoglobulins - low' section for detailed differential diagnoses.
This module mainly applies to patients who are not known to immunology services, and advises on an initial work-up and management before involvement of immunologists.
Factors to be considered in the evaluation of Hypogammaglobulinemia include
Sites of infection:
Approach to a hospitalised patient with Immunodeficiency
Many patients with immunodeficiency need multiple hospital admissions for recurrent infections in their lifetime. They may also need admissions for non-infection related complications.
It is necessary to keep them in a side room away from other patients as they are very vulnerable to infectious agents transferred from other hospitalised patients. They may also have drug-resistant or opportunistic infections which may require isolation.
FBC, Renal function, Liver function, CRP
Please contact primary Immunology Team for further advice and monitoring.
Human Immunoglobulins are manufactured from large pools of plasma donors. The plasma is obtained from selected donors who are screened for HIV, HBV and HCV.
The indications for Immunoglobulin treatment are classified as Red (automatic approval), Blue (good evidence and needs panel approval) and Black (little or no evidence to be discussed).
Red indications: Primary immunodeficiencies, Thymoma with immunodeficiencies, HSCT (haemopoietic stem cell transplant) in primary immunodeficiencies, specific antibody deficiency, ITP (immune thrombocytopenic purpura), Haemolytic disease of newborn, Guillain-Barre syndrome, acute demyelinating polyneuropathy, Kawasaki disease, Toxic Epidermal Necrolysis.
Blue indications: Secondary immunodeficiencies, acquired red call aplasia, autoimmune haemolytic anaemia, haemophagocytosis syndrome, inflammatory myopathies etc.
Immunoglobulins can be administered intravenously (preferred in acute settings and for administering large doses) and subcutaneously (as weekly doses for home therapy in patients needing long term treatment).
These are more common in IV administration and when large doses are used.
Patients can have infusion reactions including shivering, myalgias, headache, rash, itching, chest tightness, wheezing and rarely anaphylactic reactions. These can be minimised by premedicating with antihistamine, paracetamol and Hydrocortisone as well as using slow rates to infuse. Patients need to be monitored continuously. Infusion is to be stopped immediately if any signs of adverse reactions are noted and administered anti histamine and Hydrocortisone.
There can also be acute renal injury at high doses.
It is preferable to avoid immunoglobulin infusions during acute episodes of infections as patients can develop adverse immunological reactions.