Hypogammaglobulinemia is an immune disorder characterized by a reduction in all types of gamma globulins, including antibodies that help fight infection. It may be congenital (present at birth), related to medication; it may be due to a kidney or gastrointestinal condition, cancer or severe burns.
How common is hypogammaglobulinemia cancer?
Hypogammaglobulinemia Cancer. Hypogammaglobulinemia is a disorder in which the body makes low amounts of infection-fighting antibodies (also known as gamma globulins). This leaves the person susceptible to infections. About 5% to 10% of thymoma patients develop hypogammaglobulinemia. About 10% of patients with hypogammaglobulinemia have a thymoma.
What is secondary hypogammaglobulinemia?
Secondary Hypogammaglobulinemia. Primary hypogammaglobulinemia is brought about by a disorder that indirectly hinders the manufacture or action of the antibodies. This can be a very excruciating condition because it can lead to the depletion of all amounts of the remaining antibodies.
What is Hypogammaglobulinemia (CVID)?
Hypogammaglobulinemia Symptoms, Cancer, Prognosis, Life expectancy. CVID is caused by a lack of B-lymphocytes, which results in low levels of immunoglobins (or antibodies), hence the effect on the immune system’s functionality.
What are the infectious complications of hypogammaglobulinemia?
Despite the hypogammaglobulinemia, most patients do not experience infectious complications prior to treatment with chemotherapy. Those who do, suffer recurrent sinopulmonary infections caused by bacteria that ravage patients with primary humoral immunodeficiency syndromes.
Is Hypergammaglobulinemia a cancer?
Hypergammaglobulinemia is an uncommon condition that is usually the result of an infection, autoimmune disorder, or malignancy such as multiple myeloma. It's characterized by elevated levels of immunoglobulins in your blood.
Is hypogammaglobulinemia serious?
Background: Most patients with primary antibody deficiency (PAD) suffer from less well-described and understood forms of hypogammaglobulinemia (unclassified primary antibody deficiency, unPAD).
What type of disorder is hypogammaglobulinemia?
Hypogammaglobulinemia is a disorder caused by low serum immunoglobulin or antibody levels. Immunoglobulins are the main components of the humoral immune response and able to recognize antigens to trigger a biological response and eradicate the infectious source.
What is the cause of hypogammaglobulinemia?
The most common cause is common variable immunodeficiency (CVID). Causes of secondary hypogammaglobulinemia include gastrointestinal losses (e.g., malabsorption/protein-losing enteropathy), nephrotic syndrome, hematologic malignancy, and medication (e.g., immunosuppressives, such as corticosteroids and chemotherapy).
What is the prognosis for hypogammaglobulinemia?
Without enough antibodies, you're more likely to get infections. People with hypogammaglobulinemia can more easily catch pneumonia, meningitis, and other infections that a healthy immune system would normally protect against. These infections can damage organs and lead to potentially serious complications.
Is hypogammaglobulinemia an auto immune disease?
Many autoimmune diseases have been described in the course of hypogammaglobulinemia, such as cytopenias, inflammatory bowel disease, seronegative arthritis, Sjögren's syndrome, uveitis, vasculitis, and vitiligo (22,23).
What medications can cause hypogammaglobulinemia?
Hypogammaglobulinemia may result from other anticonvulsants and anti-inflammatory medications, including valproic acid, phenytoin, gold, sulfasalazine, chloroquine, penicillamine, fenclofenac, hydantoin, zonisamide, lamotrigine, and cyclosporine A (1, 4, 5, 9).
Can hypogammaglobulinemia be reversed?
CONCLUSIONS: Hypogammaglobulinemia in some CVID patients may be reversible and measurements of IgA and IgM during therapy may detect this rare outcome.
Can you grow out of hypogammaglobulinemia?
Most children born with transient hypogammaglobulinemia of infancy will grow out of it between the ages of 2 and 5. Other types of hypogammaglobulinemia are lifelong conditions. The risk of infection can be reduced by different treatments, depending on the type and cause of hypogammaglobulinemia.
Does hypogammaglobulinemia cause neuropathy?
Hypogammaglobulinemia has rarely been linked with neuropathy. We report a case of a young female who presented with foot drop due to sciatic neuropathy in the context of hypogammaglobulinemia and had significant clinical improvement after intravenous immunoglobulin (IVIG) treatment.
What kind of doctor treats IgG deficiency?
You'll likely start by seeing your family doctor or primary doctor. You might then be referred to a doctor who specializes in disorders of the immune system (immunologist).
Does low IgG cause fatigue?
Individuals with immunoglobulin G deficiency (IgGsd) often complain of fatigue.
Can hypogammaglobulinemia be reversed?
CONCLUSIONS: Hypogammaglobulinemia in some CVID patients may be reversible and measurements of IgA and IgM during therapy may detect this rare outcome.
What is the life expectancy of someone with CVID?
The life expectancy of CVID patients has considerably improved over the past 30 years [5, 63], from initially 12 years to currently over 50 years [3]. Reduced survival was significantly associated with age at diagnosis, lower baseline IgG, higher IgM and fewer peripheral B cells.
Does hypogammaglobulinemia cause neuropathy?
Hypogammaglobulinemia has rarely been linked with neuropathy. We report a case of a young female who presented with foot drop due to sciatic neuropathy in the context of hypogammaglobulinemia and had significant clinical improvement after intravenous immunoglobulin (IVIG) treatment.
What medications can cause hypogammaglobulinemia?
Hypogammaglobulinemia may result from other anticonvulsants and anti-inflammatory medications, including valproic acid, phenytoin, gold, sulfasalazine, chloroquine, penicillamine, fenclofenac, hydantoin, zonisamide, lamotrigine, and cyclosporine A (1, 4, 5, 9).
What is the debilitating effect of hypogammaglobulinemia?
Hypogammaglobulinemia, also known as Common Variable Immunodeficiency (CVID), is a disorder that falls into the category of the primary immunodeficiency diseases, meaning its main debilitating effect on the body is a weakening of the immune system that makes the individual susceptible to higher rates of infection and illness, among other symptoms.
How to diagnose hypogammaglobulinemia?
Diagnosis of hypogammaglobulinemia starts with a physical test and evaluation of the patient’s family medical history. Normally, the physical assessment is standard for individuals having agammaglobulinemia.
What tests are performed to diagnose hypogammaglobulinemia?
Some of the tests that are carried out during the assessment of agammaglobulinemia are serum IgM test, serum IgA test, and serum IgG test and serum immunoelectrophoresis.
What is the medical term for elevated gamma globulin?
Hypogammaglobulinemia is a medical condition with elevated levels of gamma globulin. It is a type of immunoproliferative disorder. Hypogammaglobulinemia is an immune disorder characterized by a reduction in all types of gamma globulins, including antibodies that help fight infection.
How does prognosis affect IVIG?
Prognosis has improved significantly since the introduction of IVIG therapy to routine practice. The prognosis largely depends on whether there is severe autoimmune disease; whether there are recurrent infections that cause structural lung damage; and the development of a malignancy (cancer). Other major factors that influence prognosis include the extent of end-organ damage and how successfully infections can be prevented.
Can a negative family history exclude X-linked agammaglobulinemia?
A positive family history may suggest the diagnosis and guide testing, but a negative family history does not exclude X-linked agammaglobulinemia (Bruton agammaglobulinemia; XLA), as new mutations may constitute more than half of the cases in some series. Duloxetine, Sertraline and Paroxetine can be used as medications.
Can you use Duloxetine for hypogammaglobulinemia?
Duloxetine, Sertraline and Paroxetine can be used as medications. Before the start of hypogammaglobulinemia treatment, the health care provider should consider the dangers and advantages of administering any medications that can reduce the level of antibodies in the patient’s bloodstream.
What is hypogammaglobulinemia?
The presenting feature of hypogammaglobulinemia is usually a clinical history of recurrent, chronic, or atypical infections. These infections include but are not limited to: bronchitis, ear infections, meningitis, pneumonia, sinus infections, and skin infections.
How long does it take for a baby to show symptoms of hypogammaglobulinemia?
Babies with transient hypogammaglobulinemia (THI) usually become symptomatic 6 to 12 months after birth, with the symptoms usually consisting of frequent ear, sinus, and lung infections. Other symptoms include respiratory tract infections, food allergies, eczema, urinary tract infections, and intestinal infections.
What is the name of the condition where the immune system is not producing enough gamma globulins?
Hypogammaglobulinemia. Hypogammaglobulinemia is a problem with the immune system in which not enough gamma globulins are produced in the blood (thus hypo- + gamma + globulin + -emia ). This results in a lower antibody count, which impairs the immune system, increasing risk of infection. Hypogammaglobulinemia may result from a variety ...
Can hypogammaglobulinemia cause diarrhea?
Such infections can potentially damage organs, leading to severe complications. Other symptoms of hypogammaglobulinemia include chronic diarrhea and complications from receiving live vaccines. Certain symptoms of chronic damage may be related to recurrent infection.
Is hypogammaglobulinemia a synonym for agammaglobulinemia?
Etymology. "Hypogammaglobulinemia" is largely synonymous with "agammaglobulinemia". When the latter term is used (as in " X-linked agammaglobulinemia ") it implies that gamma globulins are not merely reduced, but completely absent.
Does hypogammaglobulinemia reduce morbidity?
Early detection and treatment of hypogammaglobulinemia is known to reduce rates of morbidity and the chance of long-term pulmonary complications. Evidence shows that there is an association between achieving higher IgG levels and reduced infection frequency.
What is the mean age of hypogammaglobulinemia?
9,10,13,36,56 The mean age of hypo- or dysgammaglobulinemia onset is 9 years. 56 Although the complications of hypogammaglobulinemia can be life threatening, patients with this manifestation generally have a better prognosis with one report suggesting a 13% mortality for patients with hypo- or dysgammaglobulinemia, with deaths in this group potentially related to HLH, infection, vasculitis and hemorrhage.9 Based on its clinical similarity to common variable immunodeficiency (CVID), which is also associated with humoral immune defects and/or lymphoma, XLP1 patients may be misdiagnosed as having CVID. 57–60
What percentage of CLL patients have hypogammaglobulinemia?
Hypogammaglobulinemia is present in up to 85% of CLL patients and, like impaired cell-mediated immunity, is seen in patients with early and small-volume disease.21 Most patients have depressed serum levels of IgG, IgM, and IgA.
How long do infants have low IgG levels?
However, in transient hypogammaglobulinemia of infancy, patients have low levels of Igs that extend beyond 6 months of age.
Is hypogammaglobulinemia congenital?
Hypogammaglobulinemia may be congenital or acquired. Among the acquired causes are multiple myeloma and primary amyloidosis. Panhypogammaglobulinemia can occur in approximately 10% of cases of multiple myeloma. Most of these patients have a Bence–Jones protein in the urine but lack intact immunoglobulins in the serum [30,31]. Bence–Jones proteins are monoclonal-free κ or λ light chains in the urine. Panhypogammaglobulinemia can also be seen in 20% of cases of primary amyloidosis. It is important to recommend urine immunofixation studies when panhypogammaglobulinemia is present in serum protein electrophoresis.
Can hypogammaglobulinemia be mistaken for CVID?
Hypogamma globulinemia may also be part of more complex immunodeficiencies and should not be mistaken for CVID. The age of the patient first needs to be considered as transient hypogammaglobulinemia of infancy presents in children, usually under the age of 3 years.
Is hypogammaglobulinemia a primary or secondary form?
Primary and secondary forms are distinguished. Among the primary forms of hypogammaglobulinemia, common variable immunodeficiency (CVID, see below) comprises many of these patients, but several monogenic disorders may present with hypogammaglobulinemia without fulfilling the criteria for CVID.
Is there a treatment for a low IgA?
There is no treatment for IgA deficiency other than prevention and aggressive treatment of the bacterial infections. Bruton’s agammaglobulinemia, or X-linked agammaglobulinemia (XLA) is a disorder characterized by very low or no Igs of all isotypes.
What is hypogammaglobulinemia?
Hypogammaglobulinemia is a disorder caused by low serum immunoglobulin or antibody levels. Immunoglobulins are the main components of the humoral immune response and able to recognize antigens to trigger a biological response and eradicate the infectious source. Hypogammaglobulinemia is the most common primary immunodeficiency and encompasses a majority of immune-compromised patients. In order to avoid the high morbidity and mortality associated with this condition, it must be promptly diagnosed and treated. The evaluation consists of lab tests, clinical findings, vaccination response, and genetic testing. Treatment is IVIG transfusions, antibiotics, and glucocorticoids. This activity highlights the role of the practitioner or interprofessional team to appropriately assess, evaluate, manage, and treat patients with this condition.
What causes elevated IgM levels?
It is a rare primary immunodeficiency disorder characterized by normal to elevated IgM levels with decreased levels of IgG, IgA, and IgE immunoglobulins caused by mutations in genes on the X-chromosome and autosomal chromosomes which are responsible for the B-cell class switch from IgM to other classes of antibodies. [18][19] On the X chromosome, the CD40 ligand (hyper-IgM syndrome type 1 [HIGM1]) and NEMO (nuclear factor κB essential modulator, XHM-ED) genes play an active role. Autosomal chromosomal involvement is seen with 3 genes including the activation-induced cytidine deaminase (AID) gene (hyper-IgM type 2 [HIGM2]) on chromosome 12, the uracil DNA glycosylase gene (UNG, hyper-IgM type 5 [HIGM5]) on chromosome 12, and the CD40 gene (hyper-IgM type 3 [HIGM3]) on chromosome 20. [14]
What is the IgM isotype?
Reduced IgA and IgM isotypes are also commonly seen with low IgG levels. IgM is the main immunoglobulin which is abundant during the primary immune response but is contained in the intravascular compartment. IgG is the most numerous in both vascular and extravascular compartments and interacts with different Fc fragments on immune cells to activate the complement pathway. Measurement of IgG is key in diagnosing Hypogammaglobulinemia.
Why is igg level normal in children?
It is characterized by hypogammaglobulinemia with adequate antibody response. It is observed during the first three to six months of life secondary to prolongation of the physiologic nadir of immunoglobulin levels. Ig levels normalize by three years of age in most children (age range 2-6 years).[15] The cause is unknown but some theories have been proposed including failure of T-cells to stimulate the synthesis of B -cells and antibodies, IgG production suppression by maternal IgG, low levels of critical cytokines, and familial genetic variations. [16]
Is agammaglobulinemia a genetic disease?
This leads to a lack of plasma cells with low levels of Ig and therefor no humoral response. [7][8] Inheritance of primary agammaglobulinemia is X-linked, with most mutations being familial with few autosomal recessive forms. [9]
Is hypogammaglobulinemia a secondary or primary cause?
Hypogammaglobulinemia can be of primary or secondary origin. Primary immunodeficiencies result from genetic disorders and/or chromosomal anomalies during the development of the immune system. Secondary causes are usually induced by an external or acquired factor such as a corticosteroid or immunosuppressant drug, nutritional disorders, infections, chemotherapy, malignancy, nephrotic syndrome, other metabolic diseases, and hazardous environmental conditions.[5] It is important that physicians distinguish between primary and secondary causes of hypogammaglobulinemia to provide appropriate treatment. [6]
What is the diagnosis of hypogammaglobulinemia?
Hypogammaglobulinemia diagnosis. Diagnosis of hypogammaglobulinemia starts with a physical test and evaluation of the patient’s family medical history. Normally, the physical assessment is standard for individuals having agammaglobulinemia. Examination is an important aspect of the diagnosis of hypogammaglobulinemia.
How to treat hypogammaglobulinemia?
Hypogammaglobulinemia is often controlled through the use of IVIG (Intravenous Gamma globulin). This should be administered after 21 or 28 days subcutaneously or intravenously.
What is secondary control of hypogammaglobulinemia?
Important information. Hypogammaglobulinemia is a medical complication brought about by a deficiency of B-cells (B-lymphocytes) in addition to a resultant decrease in the amount of antibodies (immunoglobulin) in the body system. These antibodies play a twofold part in the body’s immune system by allowing ...
What should be considered before starting hypogammaglobulinemia treatment?
Before the start of hypogammaglobulinemia treatment, the health care provider should consider the dangers and advantages of administering any medications that can reduce the level of antibodies in the patient’s bloodstream.
What are the congenital complications of B cells?
The most frequently experienced congenital complications of the B-cells are Hypogammaglobulinemia, (also referred to as Common Variable Immunodeficiency or common variable hypogammaglobulinemia) Agammaglobulinemia (X- linked), IgA Deficiency and Transient Hypogammaglobulinemia of infancy.
Is hypogammaglobulinemia a pitiable disease?
Results are pitiable in case hypogammaglobulinemia is not discovered and treated, especially in cases of a bronchiectasis or a severe destruction of the lungs. Sadly, the diagnosis ends up being overly late, thereby increasing the risks for a number of pulmonary infections and this attributes to reduced life expectancy of hypogammaglobulinemia.
Does hypogammaglobulinemia reduce morbidity?
However, early diagnosis and treatment for hypogammaglobulinemia may not help to minimize the rates of morbidity as well as the risks for lasting pulmonary infections. Proof indicates that there is a relationship between large amounts of IgG and decreased frequency of infections.
What is secondary hypogammaglobulinemia?
Secondary hypogammaglobulinemia is a common development in patients treated with immunomodulatory agents for autoimmune, connective tissue, and malignant diseases. It has been observed in the medical management of patients undergoing hematopoietic stem cell and solid organ transplantation.
What are the risk factors for rituximab-induced hypogammaglobulinemia?
It summarizes risk factors for rituximab-induced hypogammaglobulinemia, such as preexisting low immunoglobulin G levels, CD19 levels, host factors, and additive effect of all immunomodulatory drugs used. The evaluation and management of secondary hypogammaglobulinemia are discussed.
Overview
Hypogammaglobulinemia is a problem with the immune system in which not enough gamma globulins are produced in the blood (thus hypo- + gamma + globulin + -emia). This results in a lower antibody count, which impairs the immune system, increasing risk of infection. Hypogammaglobulinemia may result from a variety of primary genetic immune system defects, such as common variable immunodeficiency, or it may be caused by secondary effects such as …
Symptoms and signs
The presenting feature of hypogammaglobulinemia is usually a clinical history of recurrent, chronic, or atypical infections. These infections include but are not limited to: bronchitis, ear infections, meningitis, pneumonia, sinus infections, and skin infections. Such infections can potentially damage organs, leading to severe complications. Other symptoms of hypogammaglobulinemia include chronic diarrhea and complications from receiving live vaccine…
Causes
Hypogammaglobulinemia can be caused by either a primary or secondary immunodeficiency. Primary immunodeficiencies are caused by a mutation or series of mutations to the genome. For example, a study from 2012 found that a compound heterozygous deleterious mutation in the CD21 gene is associated with hypogammaglobulinemia. Genetic analysis revealed the patient was heterozygous for CD21, with the paternally inherited allele (also shared with one sister) having a …
Screening
Screening of immunoglobulin levels in relatives of CVID and IgA patients finds a familial inheritance rate of 10% to 20%. In cases where a carrier of such a mutation would like to have children, preimplantation genetic diagnosis (PGD) has been offered. PGD is defined as the testing of pre-implantation stage embryos or oocytes for genetic defects. It requires in vitro fertilization, embryo biopsy, and either fluorescent in situ hybridization or polymerase chain reaction on a sing…
Treatment
Protocols for different forms of primary immunodeficiency vary significantly. The aim of treatments implemented by specialist centers is usually to reduce the risk of complications. One method of treatment is by parenteral administration of gamma globulins, either monthly intravenously, subcutaneously, or more recently, by weekly self-administered hypodermoclysis. In either case, mild allergic reactions are common, and are usually manageable with oral diphenhyd…
Prognosis
Early detection and treatment of hypogammaglobulinemia is known to reduce rates of morbidity and the chance of long-term pulmonary complications. Evidence shows that there is an association between achieving higher IgG levels and reduced infection frequency. If hypogammaglobulinemia remains undetected and untreated, outcomes are generally poor, especially if chronic lung damage or bronchiectasis has occurred. Unfortunately, the diagnosis o…
Research
In 2015, a journal article by McDermott et al. reported on a case in which chromothripsis, normally a catastrophic event in which chromosomes undergo massive deletion and rearrangement within a single stem cell's DNA, cured a patient with WHIM syndrome, a primary immunodeficiency disease. WHIM is autosomal dominant and is caused by a gain-of-function mutation of the chemokine receptor CXCR4. The mutation in CXCR4 increases signaling because it disrupts ne…
Terminology
"Hypogammaglobulinemia" is largely synonymous with "agammaglobulinemia". When the latter term is used (as in "X-linked agammaglobulinemia") it implies that gamma globulins are not merely reduced, but completely absent. Modern assays have allowed most agammaglobulinemias to be more precisely defined as hypogammaglobulinemias, but the distinction is not usually clinically relevant.