Severe combined immunodeficiency
|Also listed as: Combined immunodeficiency, SCID||Integrative Therapy Quick Links:|
- Antibody, antigen, autosomal recessive, B-cell lymphocytes, B-cells, bacterial infection, bone marrow, bone marrow transplant, combined immune deficiency, combined immunodeficiency, cytotoxic, cytotoxic T-cells, foreign antigen, fungal infection, genetic disease, genetic disorder, graft versus host disease, IgA, IgM, immune defense system, immune system, immunoglobulin, immunoglobulin A, immunoglobulin M, infections, lymphocyte dysfunction, lymphocytes, natural killer cells, neutropenia, NK-lymphocytes, phagocytes, primary immunodeficiency, T-cell lymphocytes, T-helper cells, thymus gland, viral infection, white blood cells, X-linked inheritance, X-linked SCID.
- Severe combined immunodeficiency (SCID) is a genetic disorder of the immune system that occurs when the T-lymphocyte system does not function properly. SCID is the most severe type of primary immune deficiency diseases. Primary immunodeficiencies are disorders that occur because part of the body's immune system does not function properly. Unlike secondary immunodeficiencies, which are caused by external factors like viruses or chemotherapy, primary immunodeficiencies are caused by problems that originate within the patient's own body. SCID is usually diagnosed during childhood. A milder form of T-lymphocyte dysfunction causes combined immunodeficiency, which is typically diagnosed in adults.
- The immune system protects the body from harmful antigens (foreign substances that enter the body) like bacteria, viruses, fungi, or parasites. A specialized tissue inside bones called marrow produces immune system cells, which are also called stem cells. These stem cells then develop into B-lymphocytes, T-lymphocytes and natural killer (NK)-lymphocytes and phagocytes. All of these cells produce proteins that help them detect antigens that enter the body. The cells and proteins are spread throughout the body to protect the body from diseases and infections.
- There are three types of T-lymphocytes:
T-helper cells, cytotoxic T-cells, and regulatory (T-reg or T-suppressor) T-cells. When an antigen enters the body, T-helper cells direct B-lymphocytes (B-cells) to make antibodies against it. These antibodies then bind to the foreign substance, which is called an antigen. This binding tells the T-cytotoxic cells to destroy the unwanted antigen. T-reg cells direct the resolution of the immune system response, which means they "turn off" the immune response.
- The defining characteristic of SCID is always a severe defect in T-cell production and function. Patients also have dysfunctional B-lymphocytes, which may or may not be caused by the dysfunctional T-cells. Some genetic types of SCID also cause a shortage of NK-cell production as well. Consequently, SCID patients produce little or no antibodies, and they are extremely vulnerable to developing opportunistic infections (infections that occur in individuals with weakened immune systems).
- Unless these problems in the immune system are corrected, the child will die from severe opportunistic infections by the age of one or two. Most patients are diagnosed when they are six and a half months old.
- There are several types of SCID, including autosomal recessive severe combined immunodeficiency, X-linked recessive severe combined immunodeficiency, adenosine deaminase deficiency (ADA), bare lymphocyte syndrome, severe combined immunodeficiency with leukopenia (reticular dysgenesis), and Swiss-type agammaglobulinemia.
- SCID is genetically inherited as either an X-linked (gene on the X chromosome) or autosomal recessive (two copies of a single mutated gene) trait. Each type is caused by a different genetic defect in the patient's DNA. However, the genetic defect has not been discovered for all forms of the disease. Since SCID patients have impaired immune systems, they are vulnerable to diseases and infections. Patients commonly suffer from pneumonia, meningitis, and/or blood system infections.
- Without a bone marrow transplant, a child with SCID is at risk of developing a severe or deadly infection. While waiting for a bone marrow transplant, patients are treated with intravenous immune globulin (IVIG), which helps the immune system fight off illness. Antibiotics, antifungals and antivirals are given to treat infections associated with SCID. Without treatment, most patients do not live beyond one year from birth.
- SCID is considered a rare disorder, but the exact incidence of SCID is unknown. Researchers estimate that about 1 out of 1,000,000 people have the disease. Overall, the male-to-female ratio is 3:1 because some forms of SCID are X-linked, while other forms of SCID are autosomal recessive.
- This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).
- National Jewish Medical and Research Center. .
- National Primary Immunodeficiency Resource Center. .
- National Organization for Rare Disorders. .
- Natural Standard: The Authority on Integrative Medicine. .
- SCID.net. Severe Combined Immunodeficiency. .
- General: Severe combined immunodeficiency (SCID) is genetically inherited as either an X-linked or autosomal recessive in trait. Each type is caused by a different genetic defect. However, the genetic defect has not been discovered for all forms of the disease.
- Autosomal recessive inheritance: Autosomal (chromosome that is not involved in sex determination) recessive forms of SCID occur when a child inherits two defective copies of the same autosomal gene. Each parent must carry at least one abnormal copy of the gene. If each parent has one defective and one normal gene, there is a 25% chance that each of their children will inherit the disease.
- One form of SCID is called adenosine deaminase (ADA) deficiency. This condition results from the lack of an enzyme that helps cells to get rid of toxic byproducts that are created from normal bodily processes like breathing and digestion. Without ADA, toxins accumulate in the body and kill the body's lymphocytes. ADA deficiency has an autosomal recessive inheritance pattern that affects males and females equally.
- X-linked inheritance or X-SCID: X-linked SCID accounts for about 45% of all cases of SCID. This form of the disease is inherited as an X-linked recessive trait. This means the gene that causes the disorder is located on the X chromosome. Women have two X chromosomes, while men have one X chromosome and one Y chromosome. Therefore, this form of the disease affects males almost exclusively. If a male inherits the mutated gene that causes the specific type of SCID, he will develop the disease because he has only one X chromosome.
- Females, on the other hand, have two X chromosomes. Even if a female inherits the mutated gene, chances are the other gene will be healthy because the disease is rare. The female would need to inherit two mutated X chromosomes in order to develop the disease. If the female inherits one mutated gene she is a carrier for the disease, and there is a 50% chance she will pass the gene to each of her children. Carriers do not express symptoms of the disease.
- General: Infants who have severe combined immunodeficiency (SCID) experience an unusual number of bacterial, viral, fungal, and/or protozoan infections that are much more serious and less responsive to medical treatment, such as antibiotics, than would normally be expected because they have weakened immune systems. Patients commonly suffer from pneumonia, meningitis, and/or infections of the blood. Skin problems, including chronic (ongoing) bacterial and fungal infections, may also occur.
- Symptoms suggestive of graft-versus-host disease (when the immune cells of a transplant from a donor attack the tissues of the transplant recipient) may appear in newborns up to six weeks old. These symptoms include dermatitis (skin rash), hepatitis (liver inflammation), difficulty breathing (due to stiffening of lungs), diarrhea (sometimes containing blood), jaundice (yellowing of the skin and eyes), and enteritis (inflammation of the intestine). This occurs because the maternal cells that circulate in the baby's blood until he/she reaches six months old cannot be destroyed by the neonate's immune system.
- Viral infections: Exposure to the chicken pox virus, either through a vaccination or in the environment, can be life threatening for SCID patients. Exposure may cause infection of the lungs and brain. The relatively common and harmless cytomegalovirus (a common type of herpes virus) found in the salivary glands of many people can cause fatal pneumonia in children with SCID. Pregnant women with cytomegalovirus can transmit the infection to their fetus. It can also be transmitted through bodily fluids, including breast milk, saliva, blood, urine, semen, and vaginal discharge. Even the herpes simplex virus (that causes the common cold sore) and the measles virus can pose serious health risks in SCID patients. In children without SCID, these diseases are not usually life threatening.
- Fungal infections: Fungal infections, including mouth thrush (Candida albicans) or yeast infections may be less resistant to treatment that would be effective for infants with healthy immune systems.
- Pulmonary infections: Common pulmonary (lung) infections that occur in SCID patients include staphylococci, pneumococcus or hemophilus, Pneumocystis jiroveci pneumonia (previously called Pneumocystis carinii pneumonia), cytomegalovirus (type of herpes virus), or the measles virus. Symptoms often include a cough without mucous and low levels of oxygen in the blood. These patients may also have chronic (ongoing) inflammation around the bronchial tubes, which are the airway passages that carry oxygen from the mouth to the lungs. There may be no symptoms of this bronchial inflammation, or there may be symptoms such as prominent bronchospasm (involuntary muscle contraction involving the bronchus ), which may cause difficulty breathing. Some patients may have interstitial (spaces within an organ or a tissue) or alveolar (within the air cells of the lungs) pneumonia on both sides. Other symptoms may include may include shortness of breath, cough, fever, chest discomfort, weight loss, chills, spitting up blood (rare), tachypnea (rapid breathing), tachycardia (fast heart rate), mild crackles (bubbling, or rattling sounds that occur when air moves through fluid-filled airways), cyanosis (bluish discoloration of the skin), nasal flaring, and intercostals retractions (visible use of muscles between the ribs that indicates labored breathing).
- Gastrointestinal: Persistent diarrhea is common among SCID patients, and it may be fatal in young children because it can lead to dehydration and prevent the absorption of important nutrients. Diarrhea may also cause severe weight loss. Chronic hepatitis (inflammation of the liver) caused by cytomegalovirus or other bacteria or viruses may also occur. If the liver is affected by this disorder, the bile ducts (small passage that carries bile, a digestive aid, from the liver into the stomach) are likely to be damaged.
- Blood abnormalities: SCID patients often experience abnormalities of the blood, including neutropenia (low levels of white blood cells called neutrophils), red cell aplasia (bone marrow does not produce enough red blood cells), or megaloblastic anemia (anemia with abnormally large red blood cells) that is resistant to the usual medical treatment of vitamin B12 or folic acid. Eosinophilia (high levels of a white blood cell called eosinophils) and monocytosis (high levels of white blood cells called monocytes) may signal an infection like Pneumocystis jiroveci pneumonia (previously called Pneumocystis carinii pneumonia or PCP).
- General: Severe combined immunodeficiency (SCID) is generally suspected in infants younger than one year old who suffer from frequent and/or serious infections (especially fungal infections that are resistant to treatment), persistent diarrhea, weight loss, and chronic (ongoing) skin infections. These patients may have an enlarged liver, spleen, and/or lymph nodes, which indicate that the body is fighting off an infection. A series of tests (listed below) are necessary to confirm a diagnosis.
- Complete blood count (CBC): A complete blood count (CBC) can be conducted to determine the number of lymphocytes in the blood. Lymphocytes are special cells in the bloodstream that support the immune system and keep a patient healthy. The blood count can also show if other immune cells in the blood are absent or out of balance. During the procedure, a small sample of blood is taken and analyzed under the microscope. Decreased levels of lymphocytes may indicate the presence of SCID.
- Blood smear: A blood smear is often used to measure the number of lymphocytes (a kind of white blood cell in the patient's blood). The white blood cells, which are part of the body's immune system, help fight against diseases and infections. Healthy patients typically have more than 1,500 lymphocytes per cubic millimeter of blood. Infants who have SCID usually have significantly decreased numbers of white blood cells.
- Mitogen stimulation assay: Lymphocyte function can be tested by its reaction to specific stimulation with plant extracts called mitogens. Mitogens are added to a sample of the patient's blood to stimulate mitosis (cell division) of lymphocytes. This allows the healthcare provider to observe the lymphocytes during mitosis. This test can detect abnormal or dysfunctional lymphocytes that cause SCID.
- Immunoglobulin test: An immunoglobulin test measures the levels of antibodies (glycoprotein that detects and binds to foreign substances that enter the body) in the blood. Patients who have SCID will have extremely low levels of immunoglobulin, especially two types called immunoglobulin A (IgA) and immunoglobulin (IgM). However, soon after birth, immunoglobulin G (IgG) levels may still be high because the newborn still has healthy maternal IgG that it received through the umbilical cord before birth.
- X-ray: An X-ray may detect an absent or abnormally small thymus gland, which is associated with SCID. Some T-cells are produced in the thymus gland. If the thymus gland is abnormally small, an insufficient amount of T-cells may be produced causing SCID. An X-ray may also detect inflammation of the lung caused by pulmonary infections like interstitial pneumonitis or pneumonia.
- Prenatal testing: Amniocentesis, chorionic villous sampling, or cord blood can be used to diagnose a fetus with SCID. These procedures are most often conducted in patients who have a family history of SCID. Amniocentesis is performed at about 15-18 weeks of gestation. During the procedure, a long, thin needle is inserted into the pregnant woman's abdominal wall to the uterus. A small amount of fluid is removed from the sac that surrounds the fetus. The fluid is then analyzed for genetic abnormalities. There is a risk of infection or injury to the fetus, and a chance of miscarriage.
- During chronionic villus sampling (CVS), a small piece of tissue (chorionic villi) is removed from the uterus during early pregnancy to screen the fetus for genetic defects. Depending on where the placenta is located, CVS can be performed through the cervix (transcervical) or through the abdomen (transabdominal). The risks of infections or fetal damage are slightly higher than the risks of amniocentesis. Fetal loss occurs about two percent of the time.
- During a cord blood test, a sample of blood is taken from the umbilical cord at the time of birth. The sample is then analyzed in a laboratory to determine whether the newborn has genetic abnormalities that indicate SCID.
- General: The only cure for severe combined immunodeficiency (SCID) is a bone marrow transplant. Antibiotics, antifungals, and antivirals are used to treat infections that are commonly associated with SCID. Intravenous immune globulin (IVIG) can help prevent infections. Gene therapy (inserting new, healthy genes into a cell) may be a possible treatment option in the future. However, further research is necessary before it is a standard treatment option for SCID patients.
- Antibiotics: Antibiotics, such as erythromycin (ERYC®), azithromycin (Zithromax®), and clarithromycin (Biaxin® Filmtab, Biaxin® Granules, Biaxin® XL Filmtab, or Biaxin® XL Pac), are used to treat bacterial infections that are often associated with SCID.
- Antifungals: Antifungals, such as trimethoprim and sulfamethoxazole (Bactrim® or Septra®), pentamidine (NebuPent®, Pentam®, Pentacarinat®), amphotericin B (Abelcet®), fluconazole (Diflucan®), ketoconazole (Nizoral®), nystatin (Mycostatin®), and atovaquone (Mepron®), are used to treat fungal infections that are commonly associated with SCID.
- Antivirals: Antivirals, such asganciclovir (Cytovene®), foscarnet (Foscavir®) and acyclovir (Zovirax®), are used to treat viral infections that are often associated with SCID.
- Bone marrow transplant: A bone marrow transplant can cure SCID if the patient is diagnosed within the first three months of life. HLA-identical donor bone marrow transplantation is optimal, followed by HLA-mismatched unrelated donor transplantation.
- However, not everyone is a candidate for a bone marrow transplant. The transplant must come from a donor whose body tissues are a close biological match to the recipient. Serious health risks are also associated with the procedure, as with any major surgery. Individuals who have weakened immune systems are at risk of developing graft-versus-host disease after surgery. This condition occurs when the transplanted bone marrow attacks the recipient's weakened immune system. Other recipients may experience transplant rejection, which occurs when the body's immune system attacks the donated organ.
- In addition, patients who undergo organ transplants must take immunosuppressive medications for the rest of their lives in order to prevent their bodies from attacking the transplanted organs. The most common oral immunosuppressants prescribed in the United States include tacrolimus (Prograf®), mycophenolate mofetil (CellCept®), sirolimus (Rapamune®), prednisone (Prednisone Intensol®), cyclosoporine (Neoral®, Sandimmune®, or Gengraf®), and azathioprine (Imuran®).
- HLA-mismatched related donor transplantation is an alternative treatment that is often successful if an HLA-matched donor cannot be identified.
- Intravenous immune globulin therapy (IVIG): Intravenous immune globulin (IVIG) consists of the antibodies extracted from pooled blood donations from 3,000-10,000 of healthy donors. In some instances, blood from as many as 100,000 donors is used. The beneficial effects of IVIG for the preventative treatment of patients with primary immunodeficiency syndromes are well established. IVIG has been shown to prevent severe lower respiratory tract infections, but not upper respiratory tract and non-respiratory infections in patients with common variable immune deficiency (CVID).
- Immune globulin products contain sterile, purified immunoglobulin G (IgG). The products typically contain more than 95% unmodified IgG. The IgG antibodies are the smallest but most abundant antibodies in the body, making up 75-80% of all the antibodies in the body. Most IVIG preparations contain trace amounts of IgA, which can sensitize an IgA-deficient person during long-term treatment. Patients who suffer from severe recurrent viral or bacterial respiratory tract infections or have isolated IgA deficiency (and additional IgG2 and IgG4 deficiency) may develop a severe allergic reaction called anaphylaxis after an IVIG infusion. These patients should receive the first infusion in the hospital under medical supervision.
- The immune globulin is typically administered intravenously for about two to four hours a day for two to seven days. The patient usually receives another single dose every 10-21 days, or every three to four weeks depending on the condition. Patients typically start responding to treatment after eight days.
- IVIG is available in different concentrations (strengths). The U.S. Food and Drug Administration (FDA) has approved Gammagard S/D®, Gammar-P IV®, Gamimune-N®, Iveegam®, Polygam® S/D, Sandoglobulin® Venoglobulin-I®, Venoglobulin-S®, Carimune/Panglobulin®, Gamunex®, and Baxter AG®.
- Gene therapy: Gene therapy involves inserting genes into an individual's cells and tissues to treat a hereditary (passed down from parents to children) disease. Several gene therapy clinical trials based on gene transfer to hematopoietic cells (blood-forming cells in the bone marrow) have been performed. However, further research is necessary before gene therapy can be recommended. Recently, two fetuses were successfully treated with gene therapy in utero with an injection of haploidentical CD34+ cells for a type of SCID called gamma chain deficiency.
- Blessed thistle: Laboratory studies report that the herb blessed thistle and chemicals in blessed thistle, such as cnicin and polyacetylene, have activity against several types of bacteria and no effects on other 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 in patients with a history of bleeding diseases or gastroesophageal reflux disease (GERD), or if taking drugs for blood disorders, stroke, stomach diseases, or to control stomach acid. Avoid if pregnant or breastfeeding. Stop use two weeks before surgery/dental/diagnostic procedures with bleeding risk and do not use immediately after these procedures.
- Bladderwrack: Laboratory study suggests antifungal and antibacterial activity of bladderwrack. However, there are no reliable human studies to support its use as an antibacterial or antifungal agent.
- Avoid if allergic or hypersensitive to Fucus vesiculosus and iodine. Avoid with a history of thyroid disease, bleeding, acne, kidney disease, blood clots, nerve disorders, high blood pressure, stroke, or diabetes. Avoid if pregnant or breastfeeding.
- Cranberry: Study results of cranberry as an antibacterial in other conditions show conflicting results. Further research is needed before a conclusion can be drawn.
- Avoid if allergic to cranberries, blueberries or other plants of the Vaccinium genus. Sweetened cranberry juice can affect blood sugar levels. Use cautiously with a history of kidney stones. Avoid more than the amount usually found in foods if pregnant or breastfeeding.
- Iodine: Iodine is commonly applied to the skin's surface to clean wounds, sterilize the skin before surgical/invasive procedures, or sterilize the place for catheters before they are put in to collect urine. Betadine solution (topical disinfectant), for example, contains povidone-iodine. Other topical disinfectants include alcohol and antibiotics; iodine is sometimes used in combination with these. Commercially prepared iodine products are recommended in order to assure appropriate concentrations (strengths).
- Reactions can be severe and deaths have occurred with exposure to iodine. Avoid iodine-based products if allergic or hypersensitive to iodine. Do no use for more than 14 days. Avoid Lugol solution and saturated solution of potassium iodide (SSKI, PIMA) with medical conditions including hyperkalemia (high amounts of potassium in the blood), pulmonary edema (fluid in the lungs), bronchitis, or tuberculosis. Use cautiously when applying to the skin because it may irritate/burn tissues. Use sodium iodide cautiously with kidney failure. Avoid sodium iodide with blockage of the stomach or large intestine.
- Probiotics: An increasing number of studies support the use of probiotics as a supplement to antibiotic therapy. Probiotic supplementation during a treatment of antibiotics may reduce the side effects of antibiotics in the digestive tract. This includes reducing growth of Clostridium difficile bacteria, which can lead to colitis, a common complication of antibiotics, especially in the elderly. Some probiotics may also help prevent the development of antibiotic resistance. In acutely ill children, synbiotics (nutritional supplements containing probiotics and prebiotics) have been linked to greater weight gain and fewer bacterial illnesses after antibiotics are ended. The evidence consistently supports supplementation of antibiotics.
- Limited evidence with day care children suggests that supplementation with a type of good bacteria, Lactobacillus GG, may reduce number of sick days, frequency of respiratory tract infections, and frequency of related antibiotic treatments.
- Fermented milk (with yogurt cultures and a type of probiotics called L. casei DN-114001) may reduce the duration of winter infections (digestive and respiratory), as well as average body temperature, in elderly people.
- There are many different types of potentially disease-causing bacteria in the nose. 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.
- 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 patients who get an infection after elective abdominal surgery and critical care patients.
- Probiotics are generally considered safe and well tolerated. Avoid if allergic or hypersensitive to probiotics. Lactose-sensitive people may develop abdominal discomfort from dairy products containing probiotics.
- Propolis: Animal and laboratory studies suggest that propolis may be able to treat various types of infections. Initial human research reports possible benefits against oral/dental bacteria, genital herpes, urine bacteria, intestinal giardia infections (infection that causes diarrhea), or Helicobacter pylori (bacteria that causes a digestive disease). Additional research is needed before a firm conclusion 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. There has been one report of kidney failure with the ingestion of propolis that improved upon discontinuing therapy and deteriorated with re-exposure. Avoid if pregnant or breastfeeding because of the high alcohol content in some products.
- Selenium: Preliminary research reports that selenium may be beneficial in the prevention of several types of infection, including recurrence of erysipelas (bacterial skin infection associated with lymphedema that causes swelling in the arms and legs) 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. Selenium is generally regarded as safe for pregnant or breastfeeding women. However, animal research reports that large doses of selenium may lead to birth defects.
- 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 (test tube) study, sorrel did not demonstrate activity against herpes simplex virus-1, herpes simplex virus-2, HIV, B. subtilis, E. coli, Proteus morganii, Pseudomonas aeruginosa, P. vulgaris, Serratia marcescens,or Staphylococcus aureus.
- Avoid if allergic or hypersensitive 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 when driving or operating heavy machinery. These sorrel formulations may cause nausea or vomiting when taken with the prescription drugs metronidazole (Flagyl®) or disulfiram (Antabuse®). Avoid if pregnant or breastfeeding.
- Because severe combined immunodeficiency (SCID) is a genetic disorder, there is currently no known method of prevention. However, individuals can be tested to determine whether they are carriers of the disease.
- Preventative treatment against Pneumocystis jiroveci pneumonia (previously called Pneumocystis carinii pneumonia) is recommended for patients who are older than two months, until their T-cell function returns to normal after a bone marrow transplant. Trimethoprim-Sulfamethoxazole (Bactrim®, Bactrim® DS, Septra®, Septra® DS) is the standard drug of choice. Patients receive intravenous (IV) injections into their bloodstream three times a week.
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.