Immunoglobulin M deficiency
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
Synonyms and keywords:
Overview
Historical Perspective
[Disease name] was first discovered by [name of scientist], a [nationality + occupation], in [year]/during/following [event].
The association between [important risk factor/cause] and [disease name] was made in/during [year/event].
In [year], [scientist] was the first to discover the association between [risk factor] and the development of [disease name].
In [year], [gene] mutations were first implicated in the pathogenesis of [disease name].
There have been several outbreaks of [disease name], including -----.
In [year], [diagnostic test/therapy] was developed by [scientist] to treat/diagnose [disease name].
Classification
There is no established system for the classification of IgM deficiency.
- However, it may present as 2 types:
- Primary IgM deficiency- There ocuurs just IgM deficiency and no other associated condition.
- Secondary IgM- Alongwith IgM deficiency there occurs autoimmune disorders or some neoplasms.
Pathophysiology
- IgM is the first antibody that is present on the surface of B lymphocytes.
- It is the primary antibody against A and B antigens on red blood cells.
- Other immunoglublins such as IgG, IgA and IgE are produced after alteration in the structure of IgM heavy chains on the B lymphocytes.
- IgM is present in the circulation as a pentamer structure. and is the largest antibody in human circulatory system.
- Demonstrating IgM antibodies in a patient's serum indicates recent infection, or in a neonate's serum indicates intrauterine infection (e.g. congenital rubella).
- IgM activates the classic pathway of complement system.
- In IgM deficiency there occurs deficiency of IgM but normal levels of IgG and IgA.
- The level of IgM in serum is less than 40mg/dl (normal value 45-150mg/dl).
- The defeciency in IgM could be due to:
- B cell defect- inability of B cell differentiation into IgM secreting cells.
- T cell defect- decreased helper T cell activity for IgM.
- Genetics- chromosome 22q11.2 deletion syndrome.
- This results in decreased sysnthesis of IgM in the body.
- It can be primary or secondary.
- The primary IgM deficiency presents with chronic infections while secondary presents with associated autoimmune conditions or neoplasms.
- Due to absence of IgM infections like otitis media, chronic sinusitis, bronchitis, bronchiectasis, pneumonia, urinary tract infections, cellulitis, meningitis, sepsis, etc. are very common.
- Most common infections are staphylococcus aures, streptoccus pneumonia and haemophilus influenza.
- IgM deficiency increases the risk of acquiring autoimmune and some malignant conditions.
- Autoimmune glomerulonephritis
- Autoimmune hemolytic anemia
- Autoimmune thrombocytopenia
- Celiac disease
- Crohns disease
- Hashimotto thyroiditis
- Myathenia gravis
- Rheumatoid arthritis
- Sarcoma
- Lymphoma
- Plasmacytoma
Causes
The exact cause of IgM deficiency is not known.
- Primary IgM deficiency ouccrs in children and is congenital.
- Secondary igM deficiency occurs in adullts and is associated with autoimmune disorders and neoplasms.
- There is no identified cause but risk factors which are:
- Autoimmune glomerulonephritis
- Autoimmune hemolytic anemia
- Autoimmune thrombocytopenia
- Celiac disease
- Crohns disease
- Hashimotto thyroiditis
- Myathenia gravis
- Rheumatoid arthritis
- Systemic lupus erythematosus
- Sarcoma
- Lymphoma
- Plasmacytoma
Differentiating ((Page name)) from Other Diseases
- IgM deficiency can be differentiated from other diseases of the same kind by measuring the value of other immunoglobulins.
- In Igm deficiency only IgM levels are defiicent while the rest are within normal limits.
| Disease | IgM levels | IgG levels | IgA levels | IgE levels | B cell defect | T cell defect |
|---|---|---|---|---|---|---|
| IgM deficiency | ↓ | - | - | - | - | - |
| IgA deficiency | - | - | ↓ | - | - | - |
| IgG deficiency | - | ↓ | - | - | - | - |
| IgE deficiency | - | - | - | ↓ | - | - |
| Hypoproteinemia/Proteinuria | ↓ | ↓ | ↓ | ↓ | - | - |
| Comined Immunodeficiency | ↓ | ↓ | ↓ | ↓ | + | + |
| X linked agammaglobulinemia | ↓ | ↓ | ↓ | ↓ | + | - |
| Hyperimmunoglobulin M syndrome | ↑ | ↓ | ↓ | ↓ | + | - |
| Common variable immunodeficiency | ↓ | ↓ | ↓ | ↓ | + | - |
| Wiskott-Aldrich syndrome | ↓ | ↓ | ↑ | ↑ | - | + |
Epidemiology and Demographics
The incidence/prevalence of [disease name] is approximately [number range] per 100,000 individuals worldwide.
OR
In [year], the incidence/prevalence of [disease name] was estimated to be [number range] cases per 100,000 individuals worldwide.
OR
In [year], the incidence of [disease name] is approximately [number range] per 100,000 individuals with a case-fatality rate of [number range]%.
Patients of all age groups may develop [disease name].
OR
The incidence of [disease name] increases with age; the median age at diagnosis is [#] years.
OR
[Disease name] commonly affects individuals younger than/older than [number of years] years of age.
OR
[Chronic disease name] is usually first diagnosed among [age group].
OR
[Acute disease name] commonly affects [age group].
There is no racial predilection to [disease name].
OR
[Disease name] usually affects individuals of the [race 1] race. [Race 2] individuals are less likely to develop [disease name].
[Disease name] affects men and women equally.
OR
[Gender 1] are more commonly affected by [disease name] than [gender 2]. The [gender 1] to [gender 2] ratio is approximately [number > 1] to 1.
The majority of [disease name] cases are reported in [geographical region].
OR
[Disease name] is a common/rare disease that tends to affect [patient population 1] and [patient population 2].
Risk Factors
There are no established risk factors for [disease name].
OR
The most potent risk factor in the development of [disease name] is [risk factor 1]. Other risk factors include [risk factor 2], [risk factor 3], and [risk factor 4].
OR
Common risk factors in the development of [disease name] include [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].
OR
Common risk factors in the development of [disease name] may be occupational, environmental, genetic, and viral.
Screening
There is insufficient evidence to recommend routine screening for [disease/malignancy].
OR
According to the [guideline name], screening for [disease name] is not recommended.
OR
According to the [guideline name], screening for [disease name] by [test 1] is recommended every [duration] among patients with [condition 1], [condition 2], and [condition 3].
Natural History, Complications, and Prognosis
- The patient may be asysmptomatic or present with signs of chronic infections.
- Children born with IgM deficiency as in primary IgM deficiency present with chronic infections such as:
- Otitis media
- Chronic sinusitis
- Bronchitis
- Bronchiectasis
- Pneumonia
- Urinary tract infections
- Abscesses
- Meningitis
- Gastroenteritis
- Adlults with IgM deficiency as in secondary IgM deficiency also present with chronic and multiple infections.
- With time, autoimmune and neoplastic diseases may also occur such as:
- Autoimmune glomerulonephritis
- Autoimmune hemolytic anemia
- Autoimmune thrombocytopenia
- Celiac disease
- Crohns disease
- Hashimotto thyroiditis
- Myathenia gravis
- Rheumatoid arthritis
- Systemic lupus erythematosus
- Sarcoma
- Lymphoma
- Plasmacytoma
- The prgnosis is good in primary IgM deficiency if diagnosed early as IgM supplements can be given.
- In secondary IgM, autoiimune and neoplastic complications occur and prognosis is poor.
Diagnosis
Diagnostic Study of Choice
The diagnosis of IgM deficiency is made by measuring serum IgM levels.
- Serum IgM levels of >40mg/dl is diagnostic of igM deficiency
- Serum sample is taken and then anti immunoglobulins are added.
- The amount of IgM produced is then measured.
- Other tests include
- CBC
- Serum IgG, IgA, IgE and IgD levels
- Complement profile
- Serum and urine electrophoresis
- Serum ANA levels
History and Symptoms
- The majority of patients with IgM deficiency are asymptomatic.
- They may present with history of :
- Chronic infections
- Weight loss
- Chronic lung disease
- Chronic diarrhea
- Arthralgias
- Abscesses
- Allergic disorders
- Liver disease
Symptoms
- The patients may be asymptomatic.
- Symptoms of IgMdeficiency may include the symptoms of recurrent sinopulmonary infections include otitis media, rhinosinusitis, and pneumonia andmore serious infections that can occur include osteomyelitis, meningitis, septicemia, diarrhea, and various skin infections:
Physical Examination
- Physical examination of patients with longstanding IgM deficiency may present with
- :Fever
- Low body mass index
- Swelling and tenderness over maxilla and frontal sinuses.
- Perforated tympanic membrane or scarring over tympanic membrane.
- Chronic nasal discharge.
- Chronic cough, Crepitations, clubbing and wheezing.
- Abdominal dystension, tenderness
- Abscesses
- Ulcers.
Laboratory Findings
- Decreasedlevels of IgM(>40mg/dl) is considered diagnostic for IgM deficiency.
- Levels of other immunoglobulins(IgA, IgG, IgE and IgD)are within normal range.
- TLC may be raised.
Electrocardiogram
There are no ECG findings associated with IgM defiicency.
X-ray
There are no specific findings for IgM deficiency on x ray but signs of lung disease may be present.
- Increased bronchovascular markings in bronchitis.
- lung hyperinflation with flattened hemidiaphragms in emphysema.
- Consolidation in pneumonia.
- Tram track opacities in bronchiectasis.
Echocardiography or Ultrasound
There are no echocardiography/ultrasound findings associated with IgM deficiency
CT scan
- There are no CT scan findings associated with IgM deficiency.
- Changes of chronic lung disease, if present will be visible on CT and can help differentiate the cause and extent of the disease.
- Chronic sinusitis- mucosal thickening, complete opacification, bone remodeling and thickening due to osteitis, and polyposis.
MRI
There are no MRI findings associated with IgM deficiency.
However, signs of chronic lung disease or chronic sinsuitis may be present.
Other Imaging Findings
There are no other imaging findings associated with IgM deficiency.
Other Diagnostic Studies
There are no other diagnostic studies associated with IgM deficiency.
Treatment
Medical Therapy
- Asymptomatic individuals do not require any treatment.
- IVIG can be used in some patients but not effective in all the patients in a dose range of 400 to 600 mg/kg infused every three to four weeks intravenously or subcutaneosly.
- Conjugated pneumococcal vaccine, conjugated haemophillus influenza B and conjugated meningococcal vaccine administered to prevent infections.
- Prohphylactic antibiotics can be used for recurrent sinopulmonary infections:
- Amoxicillin
- Cefuroxime
- Trimethoprim/sulphamethoxazole
- Clarithromycin/eryhtromycin.
- Treatment of the infections with the appropriate antibiotics.
- Treatment of atopic diseases such as allergic rhinits with antihistamines can help in reducing sinopulmonary infections.
Surgery
Surgical intervention is not recommended for the management of IgM deficiency.
Primary Prevention
There are no established measures for the primary prevention of IgM deficiency.
Secondary Prevention
- Secondary prevention includes prevention of infections by:
- Avoidance- reduce exposure to others with potentially contagious illnesses, proper hand washing and immunization of family members and close contacts.
- Vaccination with conjugate vaccines -conjugated pneumococcal vaccine, conjugated haemophillus influenza B and conjugated meningococcal vaccine administered to prevent infections.
- Use of prophylactic broad spectrum antibiotics.