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Transient hypogammaglobulinemia of infancy

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Related Terms
  • Allergic, allergy, antibodies, antibody, antibody levels, antigen, B-cells, bacterial infection, ear infection, hypogammaglobulinemia, IgA, IgG, IgM, immune disorder, immune system, immunodeficiency, immunoglobulin, immunoglobulin A, immunoglobulin G, immunoglobulin M, infection, intravenous immunoglobulin therapy, IVIG, otitis media, plasma cells, protein, recurrent infections, retrospective diagnosis, SCID, severe combined immunodeficiency, sinusitis, transient, transient hypogammaglobulinemia, vaccine, vaccination.

Background
  • An antibody (immunoglobulin) is an immune system protein that helps fight against infection and disease. The term "hypogammaglobulinemia" refers specifically to a low level of IgG, which is the most common antibody in the bloodstream. Additional types of antibodies, including immunoglobulin A (IgA) also may be low in children with transient hypogammaglobulinemia of infancy (THI).
  • In healthy babies, antibody levels in the blood reach a natural low point when they are between three and four months of age. This happens because babies are no longer receiving the antibody known as immunoglobulin G (IgG) from their mother, and they are unable to produce their own yet. Once healthy babies reach six months of age, their antibodies are produced at a normal rate.
  • In children who have THI, the levels of IgG and IgA levels remain low after six months of age because not enough immunoglobulin is produced. Babies who are born prematurely are at an even greater risk of developing THI because they had less time to build up antibody supplies before birth. There appears to be no correlation between breastfeeding and THI.
  • Many children who have THI require frequent treatments for infections because they have insufficient antibodies to fight off harmful microbes. However, some children may experience no symptoms.
  • The disorder is temporary. It usually resolves between the ages of two and four years old. In rare cases, the disorder can persist until the children reaches six year old.
  • Researchers estimate that THI affects about 1 out of 10,000 children. However, this number may be higher because some children experience few or no symptoms, and they might not be diagnosed.
  • The prognosis is good for children who have THI. Children with THI have normal life expectancies and are able to live healthy lives. Serious complications from infections are uncommon. The condition resolves on its own, with most children reaching normal antibody levels by two to four years of age, and the rest reaching normal levels by age six. Even if the antibody levels are low in patients who are older than three years of age, there appears to be a decrease in the number of infections.

Author information
  • This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography
  1. Madisons Foundation. .
  2. Natural Standard: The Authority on Integrative Medicine. . Copyright © 2008.
  3. Sorensen RU, Leiva LE, Giangrosso PA, et al. Response to a heptavalent conjugate Streptococcus pneumoniae vaccine in children with recurrent infections who are unresponsive to the polysaccharide vaccine. Pediatr Infect Dis J 1998 Aug; 17(8): 685-91.
  4. Walker AM, Kemp AS, Hill DJ, et al. Features of transient hypogammaglobulinaemia in infants screened for immunological abnormalities. Arch Dis Child 1994 Mar; 70(3): 183-6.

Causes
  • Pregnant mothers pass antibodies (immunoglobulins) from their bloodstream, through the placenta and to the fetus. Immediately after birth, the newborn has high levels of the mother's antibodies. However, during the next couple of months, the infant's antibodies steadily decrease. When healthy babies are about two to three months old, the immune system will start producing its own antibodies. During this time, when babies are about three to four months of age, they will experience the body's natural low point of antibodies in the bloodstream. This is because the maternal antibodies have decreased, and young children, who are producing antibodies for the first time, produce the antibodies at a much slower rate than adults. Once healthy babies reach six months of age, their antibodies are produced at a normal rate.
  • Children who have THI continue to have low antibody levels after six months of age because the immune system is slow to produce sufficient levels of new antibodies. This is because the B-cells, which are responsible for antibody production, do not develop properly.
  • Healthy B-cells will mature into plasma cells and then produce antibodies against specific microbes. Individuals who have THI have normal B-cells numbers, but the B-cells do not mature appropriately into plasma cells. Therefore, the antibodies are not produced.
  • The reason for B-cell developmental abnormalities is unknown. There may be a hereditary component to THI, which causes problems with the conversion of B-cells to plasma cells. Some children with THI have family members who suffered from the same condition. However, many children have no family history of THI or other immune disorders.

Symptoms
  • Symptoms of THI vary. Some children may experience few or no symptoms while others may experience recurrent infections. In general, children who have THI suffer from milder infections that are caused by more typical bacteria and viruses than children with more severe immune deficiencies.
  • Common symptoms of THI include, recurrent ear infections or non-infectious inflammation of the middle ear, recurrent bronchitis, frequent sinusitis (infection or inflammation of the sinuses), bacterial infection (like pneumonia) and infections of the skin or meningitis (infection of the membranes that cover the spinal cord and brain).

Diagnosis
  • General: THI is usually suspected if a child experiences recurrent infections past the age of six months. A blood test can indicate low levels of antibodies in the bloodstream. However, this is a nonspecific diagnostic test because many other immune disorders cause low levels of antibodies. A definitive diagnosis can only be made once the condition has resolved on its own.
  • Blood test: A blood test can measure the amount of antibodies present in the blood. If the antibody levels are less than what is considered normal for children of the same age, the child may have THI. However, low levels of antibodies are nonspecific because it can be the result of any other immunodeficiency disorder.
  • The blood sample can also be analyzed for antibodies that were produced in response to a vaccination. In general, most children with THI respond normally to vaccines (which is why they may have milder infections than children who have other immune disorders).
  • Retrospective diagnosis: A definitive diagnosis of THI is a retrospective diagnosis that can only be made after the child's antibody levels have increased to normal. Therefore, patients' antibody levels should be evaluated regularly to detect any change.

Treatment
  • General: THI will resolve on its own, without treatment. However, THI patients are at an increased risk of developing infection and may require antibiotics. Intravenous antibody therapy is controversial, but may be beneficial in some patients. A qualified healthcare provider should closely monitor the patient's antibody levels several times a year to check for improvement, and to ensure that a more serious immunodeficiency disorder is not present.
  • Antibiotics: Most children require antibiotics to treat bacterial infections associated with THI. For instance, Amoxacillin (like Amoxil®, Amoxil® Pediatric Drops or Trimox® Pediatric Drops) have been used to treat bacterial infections like pneumonia, bronchitis, gonorrhea, otitis media (middle ear infections), as well as nose, throat, urinary tract and skin infections. Another commonly prescribed antibiotic is cefuroxime (Ceftin® or Zinacef®). Cefuroxime is used to treat certain infections caused by bacteria, such as bronchitis, gonorrhea, Lyme disease, as well as infections of the ears, throat, sinuses urinary tract, and skin.
  • Intravenous immunoglobulin therapy: There is still debate over whether intravenous immunoglobulin therapy (IVIG) therapy is helpful for THI patients. Intravenous immunoglobulin solutions like Gamimune®, Gammagard®, Sandoglobulin® and Gammar-P® have been used. However, IVIG may delay the child's normal antibody formation. There is also the risk of allergic reaction to the therapy. Therefore, IVIG may be more beneficial in patients with severe infections who are not responding to antibiotics. Patients should consult their qualified healthcare providers to evaluate the risks and benefits of the treatment (pharmacoeconomics).
  • Immunizations: Children with THI are given routine immunizations. In general, most children with THI respond normally to vaccines (which is why they may have milder infections than children who have other immune disorders).
  • A conjugated heptavalent pneumococcal vaccine is recommended for routine immunization in children who are two months old. It is unclear whether this immunization can significantly reduce the incidence of otitis media (middle ear infection) in THI patients. The conjugated heptavalent pneumococcal vaccine prevents about 85% of the serotype responsible for invasive pneumococcal infection in children.

Integrative therapies
  • Strong scientific evidence:
  • Probiotics: An increasing number of studies support the use of probiotics as a supplement to antibiotic therapy. Probiotic supplementation during a course of antibiotics may reduce the adverse effects of antibiotics in the intestinal environment. This includes reducing growth of Clostridium difficile bacteria, which can lead to colitis (inflamed colon) - a common complication of antibiotics. Some probiotics may also help prevent the development of antibiotic resistance. In acutely ill children, synbiotics have been linked to greater weight gain and fewer bacterial illnesses after antibiotics are ended. The evidence consistently supports supplementation of antibiotics.
  • Probiotics are generally considered safe and well-tolerated. Avoid if allergic or hypersensitive to probiotics. Use cautiously if lactose intolerant.
  • Good scientific evidence:
  • Probiotics: Limited evidence with day care children suggests supplementation with Lactobacillus GG may reduce number of sick days, frequency of respiratory tract infections and frequency of related antibiotic treatments.
  • As a bacterial reservoir, the nose may harbor many varieties of potentially disease-causing bacteria. There is limited evidence that probiotic supplementation may reduce the presence of harmful bacteria in the upper respiratory tract. More studies are needed to establish this relationship and its implications for health.
  • Unclear or conflicting scientific evidence:
  • Blessed thistle: Laboratory studies report that blessed thistle (and chemicals in blessed thistle such as cnicin and polyacetylene) has activity against several types of bacteria and no effects on some types. Reliable human study is lacking. Further evidence is necessary in this area before a firm conclusion can be drawn.
  • Avoid if allergic to blessed thistle, mugwort, bitter weed, blanket flower, chrysanthemum, coltsfoot, daisy, dandelion, dwarf sunflower, goldenrod, marigold, prairie sage, ragweed, echinacea or any plants of the Asteraceae or Compositae families. Avoid if history of bleeding diseases or gastroesophageal reflux disease (GERD), or if taking drugs for blood thinning, stroke, stomach diseases or to control stomach acid. Stop use two weeks before surgery/dental/diagnostic procedures with bleeding risk, and do not use immediately after these procedures.
  • Cranberry: Study results of cranberry as an antibacterial in other conditions show conflicting results. Further study is needed before a conclusion can be drawn.
  • Avoid if allergic to cranberries, blueberries or other plants of the Vaccinium species. Sweetened cranberry juice can affect blood sugar levels. Use cautiously with history of kidney stones because it is unclear whether cranberry juice increases or decreases the risk of developing kidney stones.
  • Hydrotherapy: There is preliminary evidence that some hydrotherapy techniques may reduce bacteria on the surface of the skin. It is not known if there are benefits (or potentially harmful effects) of reducing skin bacteria. There may be benefits in people with skin wounds or ulcers who are at risk of infection. There is no evidence that infection of the skin itself (cellulitis) is improved.
  • Avoid sudden or prolonged exposure to extreme temperatures in baths, wraps, saunas or other forms of hydrotherapy. Avoid with implanted medical devices like pacemakers, defibrillators or hepatic (liver) infusion pumps. Vigorous use of water jets should be avoided with fractures, known blood clots, bleeding disorders, severe osteoporosis, open wounds or during pregnancy. Use cautiously with Raynaud's disease (a condition that affects blood flow to the extremities), chilblains (inflammation, itching and swelling due to frostbite), acrocyanosis (bluish discoloration of the extremities in response to cold temperatures), erythrocyanosis (reddish discoloration and swelling of the limbs in response to cold) and impaired temperature sensitivity, such as neuropathy. Hydrotherapy should not delay the time to diagnosis. Hydrotherapy should not be used in place of treatment with more proven techniques or therapies, and should not be used as the sole approach to illnesses. Patients with known illnesses should consult their physicians before starting hydrotherapy.
  • Lavender: Early laboratory studies suggest that lavender oils may have antibiotic activity. However, this has not been well tested in animal or human studies.
  • Avoid if allergic or hypersensitive to lavender. Avoid with history of seizures, bleeding disorders or anemia (low levels of iron).
  • Probiotics: Results are mixed regarding the ability of probiotics to reduce infective complications of medical treatment. Reduced incidence of infection has been seen in patients treated for brain injury, abdominal surgery and liver transplantation. Other studies have shown no such reduction in elective abdominal surgery and critical care patients.
  • Propolis: Animal and laboratory studies suggest activity of propolis in the treatment of various types of infections. Initial human research reports possible benefits against oral/dental bacteria, genital herpes, urine bacteria, intestinal giardia infections, or H. pylori. Additional research is needed before a recommendation can be made.
  • Avoid if allergic or hypersensitive to propolis, black poplar (Populas nigra), poplar bud, bee stings, bee products, honey and Balsam of Peru. Severe allergic reactions have been reported. Some products may contain alcohol, and therefore, should be avoided in children. There has been one report of kidney failure with the ingestion of propolis that improved upon discontinuing therapy, and deteriorated with re-exposure.
  • Seaweed, kelp, bladderwrack: Laboratory study suggests antifungal and antibacterial activity of bladderwrack. However, there are no reliable human studies to support use as an antibacterial or antifungal agent.
  • Avoid if allergic or hypersensitive to Fucus vesiculosus and iodine. Avoid with history of thyroid disease, bleeding, kidney disease, blood clots, nerve disorders or diabetes.
  • Selenium: Preliminary research reports that selenium can be beneficial in the prevention of several types of infections, including recurrence of erysipelas (bacterial skin infection associated with lymphedema) or Mycoplasma pneumonia. Further research is needed to confirm these results.
  • Avoid if allergic or sensitive to products containing selenium. Avoid with history of nonmelanoma skin cancer.
  • Sorrel: There are no well-conducted published studies that demonstrate sorrel to possess activity against viruses or bacteria that are important human pathogens. In an in vitro study, sorrel did not demonstrate activity against herpes simplex virus-1, herpes simplex virus-2, HIV, as well as B. subtilis, E. coli, Proteus morganii, Pseudomonas aeruginosa, P. vulgaris, Serratia marcescens,or Staphylococcus aureus, which are common pathogens of bacterial infections. Further research is needed before a firm conclusion can be drawn.
  • Avoid sorrel if allergic to sorrel or any member of the Rumex acetosa or Polygonaceae plant families. Avoid large doses of sorrel because there have been reports of toxicity and death, possibly caused by oxalate found in sorrel. Fatal oxalic acid poisoning has been reported from sorrel soup. Be aware that many tinctures contain high levels of alcohol and should be avoided in children. These sorrel formulations may cause nausea or vomiting when taken with the prescription drug metronidazole (Flagyl®).
  • Fair negative scientific evidence:
  • Probiotics: Bacterial translocation (passage of bacteria from the gut to other areas of the body where they can cause disease) is of special concern in surgery. Limited evidence suggests that supplementation with probiotics may not reduce this problem.

Prevention
  • Currently, there is no known method of prevention for THI.

Copyright © 2011 Natural Standard (www.naturalstandard.com)


The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.

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