Lymphoma - Hodgkin's; Hodgkin's lymphoma; Hodgkins disease; HD
Hodgkin disease is a lymphoma, a cancer of the lymphatic system. Hodgkin disease and non-Hodgkin lymphoma are the two types of lymphomas. Hodgkin disease is distinguished by the presence of large abnormal cells, called Reed-Sternberg cells. The disease is less common than non-Hodgkin lymphoma.
Hodgkin disease is classified into two main types:
Hodgkin disease is considered one of the most curable forms of cancer, especially if it is diagnosed and treated early. Five-year survival rates for people diagnosed with stage I or stage II Hodgkin disease are 90 to 95%. Many people with late-stage Hodgkin disease also have good odds for survival.
Hodgkin disease occurs most often in people ages 15 to 40 (especially in their 20s), and in people over age 55. About 10 to 15% of Hodgkin disease cases are diagnosed in children and teenagers. It is slightly more common in males than in females.
Certain types of viral infections may increase the risk of Hodgkin disease. Infectious mononucleosis, which is caused by the Epstein-Barr virus, is associated with increased risk as is infection with the human immunodeficiency virus (HIV).
Chemotherapy and radiation are the main treatments for Hodgkin disease. People who have relapsed may be treated with autologous stem cell transplantation, a procedure which uses the person's own blood cells.
Preventing Infection after Cancer Treatment
Both chemotherapy and stem cell transplants increase the risk for serious infections. People who undergo these procedures must take precautions to avoid exposure to germs. Ways to prevent infection include:
Hodgkin disease is a type of lymphoma. Lymphomas are cancers of the lymphatic system. They are generally subdivided into two groups: Hodgkin disease (HD) and non-Hodgkin lymphoma (NHL). Hodgkin disease is also called Hodgkin lymphoma.
The lymphatic system filters fluid from around cells. It is an important part of the immune system. When people talk about swollen glands in the neck, they are usually referring to enlarged lymph nodes. Common areas where lymph nodes can be easily felt, especially if enlarged, are: the groin, armpits (axilla), above the clavicle (supraclavicular), in the neck (cervical), and the back of the head just above hairline (occipital).
Hodgkin disease is marked by the presence of abnormal large cells called Reed-Sternberg cells. Reed-Sternberg cells are derived from B cell lymphocytes (white blood cells). Reed-Sternberg cells are specific to Hodgkin disease. They are not found in non-Hodgkin lymphoma.
Hodgkin disease usually starts in B cell lymphocytes located in lymph nodes in the neck area, although any lymph node may be the site of initial disease.
There are two main types of Hodgkin disease:
Classical Hodgkin Lymphoma: Classical Hodgkin lymphoma accounts for about 95% of Hodgkin disease cases. It has four major subtypes:
Nodular Lymphocyte-Predominant Hodgkin Disease: Nodular lymphocyte-predominant Hodgkin disease occurs in about 5% of cases. It is distinct from classical Hodgkin lymphoma. The cells look like and are referred to as "popcorn" cells, which are variants of Reed-Sternberg cells. This type of HD typically affects younger people and usually originates in the neck lymph nodes. It is sometimes confused with non-Hodgkin lymphoma (NHL). In fact, there is a 3 to 5% risk that nodular lymphocyte-predominant Hodgkin disease can transform into diffuse large B-cell NHL.
Lymphomas are tumors of the lymphatic system. This system is a network of organs, ducts, and nodes. The lymphatic system transports a watery clear fluid called lymph throughout the body. The lymphatic system contains lymphocytes, which are important cells involved in defending the body against infections.
Lymphocytes: Lymphocytes are a type of white blood cell. They are an essential part of the immune system:
Lymphatic vessels: Lymphatic vessels begin as tiny tubes. These tubes collect and carry fluids that leak from body tissues, lymphocytes, proteins, and other substances collected from the body's tissues. The tubes lead to larger lymphatic ducts and branches, which drain into two ducts in the neck, where the fluid re-enters the bloodstream.
Lymph Nodes: Along the way, the fluid passes through lymph nodes, which are oval structures made up of lymph vessels, connective tissue, and white blood cells:
Other Structures in the Lymphatic System: The tonsils and adenoids are secondary lymphatic organs. They are composed of masses of lymph tissue that also play a role in the lymphatic system. The spleen is another important organ that processes lymphocytes from incoming blood.
Spread of Cancer: Tumor cells can enter the lymph fluid and travel to the lymph nodes. Hodgkin disease usually progresses in an orderly way from one lymph node region to the next. This process may be slow, particularly in younger people, or very rapid. The disease typically spreads downward from the initial site:
Hodgkin disease is less common than non-Hodgkin lymphoma. It accounts for about 10% of all lymphomas. According to the American Cancer Society, about 9,000 new cases of Hodgkin disease (HD) are diagnosed in the United States each year.
The exact causes of Hodgkin disease are unknown. Research indicates that the malignant process leading to Hodgkin disease may be triggered by a combination of environmental and genetic factors along with a susceptible immune system.
Hodgkin disease occurs most often in people ages 15 to 40 (especially in their 20s), and in people over age 55. About 10 to 15% of Hodgkin disease cases are diagnosed in children and teenagers.
Hodgkin disease is slightly more common among males than females. Women who get Hodgkin disease may have a slightly lower risk for relapse after treatment than men.
Infectious mononucleosis ("mono"), which is caused by the Epstein-Barr virus (EBV), is linked with increased risk for Hodgkin disease. However, only 1 in 1,000 people with mononucleosis develops Hodgkin disease. The Epstein-Barr virus is present in 90% of all people and, in the great majority of these cases, the virus causes a mild case of mononucleosis or no illness at all. Only a very small percentage of people who have had mononucleosis go on to develop HD. Other factors must be present to trigger the malignancy.
People infected with the human immunodeficiency virus (HIV), which weakens the immune system, are also at increased risk of developing Hodgkin disease.
Hodgkin disease runs in families in about 5% of cases. Siblings of people with Hodgkin disease have a 3 times higher risk than the general population.
Symptoms of Hodgkin disease may include:
The last three symptoms (weight loss, fever, and night sweats) are classified as "B symptoms." B symptoms are used in staging Hodgkin disease and can indicate that more aggressive treatment will be required.
Sometimes people with Hodgkin disease do not experience any symptoms, or symptoms may not appear until the cancer is very advanced. Enlarged lymph nodes can also be caused by many noncancerous conditions, such as infections.
The doctor will take a medical history and perform a physical examination. If these procedures indicate Hodgkin disease, a number of additional tests may be needed to either rule out other diseases or confirm HD and determine the extent of the cancer.
The doctor will examine not only the affected lymph nodes but also the surrounding tissues and other lymph node areas for signs of infection, skin injuries, or tumors. The consistency of the node is evaluated. For example, a stony, hard node is often a sign of cancer, usually one that has metastasized (spread to another part of the body). A firm, rubbery node may indicate lymphoma (including Hodgkin). Soft tender nodes suggest infection or inflammatory conditions.
Blood tests are performed to measure white and red blood cells, blood protein levels, the uric acid level, blood proteins, and the liver's function.
Chest X-Ray: A chest x-ray may show lymph nodes in the chest, where Hodgkin disease usually starts. It is a useful step for detecting enlarged lymph nodes.
Computed Tomography (CT): CT scans are much more accurate than x-rays. They can detect abnormalities in the chest and neck area, as well as revealing the extent of the cancer and whether it has spread. CT scans are used to evaluate symptoms and help diagnose lymphomas, help with staging of the disease, and monitor response to treatment. A CT scan is also often used to detect lymphomas in the abdominal and pelvic areas, the brain, and chest area.
Positron Emission Tomography (PET): PET scans combined with CT scans can help doctors clarify the location of the cancer. PET scans can also provide information on whether or not an enlarged lymph node is benign or cancerous and can be used for staging lymphomas. PET scans may also help determine treatment response, if any residual cancer exists, and if a person has achieved remission.
A biopsy of the suspicious lymph node is the definitive way to diagnose Hodgkin disease. The lymph node sample will be examined by a pathologist for the presence of Reed-Sternberg cells or other abnormal features.
The type of biopsy performed depends in part on the location and accessibility of the lymph node. The doctor may surgically remove the entire lymph node (excisional biopsy) or a small part of it (incisional biopsy). In some cases, fine needle aspiration is used to withdraw a small amount of tissue from the lymph node. Biopsies of bone marrow may also be performed in people with existing Hodgkin disease to see if the cancer has spread to the marrow.
Hodgkin disease is considered one of the most curable forms of cancer, especially if it is diagnosed and treated early. Unlike other cancers, Hodgkin disease is even potentially curable in late stages.
A 5-year survival rate is the percentage of people who live at least 5 years after their cancer is first diagnosed. Five-year survival rates for people diagnosed with stage I or stage II Hodgkin disease are about 90%. With advances in treatment, even most people diagnosed with advanced Hodgkin disease live longer than 5 years.
Outlook tends to be poorer for people who do not respond to first-line therapy or who relapse within a year of treatment. People who survive 15 years after treatment are more likely to later die from other causes than from Hodgkin disease.
Survival rates are a general term based on data collected from large numbers of people. A person's prognosis depends on factors specific to that individual. Factors that influence prognosis and survival include age, overall health, stage of cancer at time of diagnosis, symptoms associated with the cancer, and how well the cancer responds to treatment.The International Prognostic
Factors Project on Advanced Hodgkin Disease uses 7 factors to help determine which people with advanced Hodgkin disease have a more serious prognosis and could benefit from more aggressive chemotherapy. These factors are also used to predict success in people with relapsed or persistent HD who are undergoing stem cell transplantation.
The more of these factors that are present, the worse the outlook and the more likely the person needs to be treated aggressively:
The good news about Hodgkin disease is that treatment can cure the disease. The bad news is that survivors face a higher than average risk for long-term complications of these treatments, some very serious.
Many people experience chronic fatigue that can sometimes last for years. The most serious complications are secondary cancers and heart disease, which may develop over the 20 to 30 years following treatments.
Secondary cancers include non-Hodgkin lymphoma, leukemia, melanoma, stomach and lung cancers, and breast and uterine cancers. Heart disease complications include coronary artery disease, stroke, heart valve problems, and cardiomyopathy (weakening of the heart muscle). Thyroid and other endocrine disorders are also a potential complication. Combinations of radiation and chemotherapies pose the highest risk of these problems.
Studies of adult survivors of various childhood cancers have found that 30 years after treatment, people with cured Hodgkin disease are especially likely to have other serious health problems. Female survivors face a significantly greater risk than male survivors. In particular, women who received chest radiation are at very high risk for developing breast cancer.
People with Hodgkin disease should get a written record of the treatments they received as children, and the potential risks of these treatments. These records can help the doctors who later oversee their care monitor for potential health problems.
Survivors of Hodgkin disease should receive regular screening tests for cancer and heart disease. They may need to get these tests at a younger age than most people. In particular, people who were treated with chest radiation should consider getting blood tests every 5 years to measure their cholesterol levels. Women who received chest radiation should be sure to get regular mammograms and breast magnetic resonance imaging (MRI).
Treatment options for Hodgkin disease depend on:
Certain factors may determine whether more intensive treatment is required. For example, the presence of B symptoms and "bulky" (large mass) tumors usually indicates a more aggressive treatment approach.
Chemotherapy and radiation are the main treatments for Hodgkin disease. Stem cell transplantation or a biologic drug may be recommended for people whose cancer has recurred.
Hodgkin disease is staged (I through IV) depending on how far the cancer has spread. Staging is the primary method for determining both treatment options and prognosis.
Stage I: Disease is limited to a single node region or has involved one neighboring area or a single nearby organ.
Stage II: Disease is limited to two or more lymph nodes on the same side of (above or below) the diaphragm or extends locally from the lymph node into a nearby organ.
Stage III: Disease is in lymph nodes on both sides of the diaphragm or has spread to nearby organs, the spleen, or both.
Stage IV: Disease has become widespread involving organs outside the lymph system, such as liver, lung, or bone marrow.
Early Stages (I or II): Hodgkin disease in stages I or II is usually treated with chemotherapy alone, less commonly radiation alone, or some combination of chemotherapy and radiation.
Later Stages (III and IV): Hodgkin disease in stages III and IV is usually treated with chemotherapy alone. .
Refractory and Relapsed Hodgkin: Treatment is considered successful when the signs and symptoms of cancer disappear. This is referred to as remission. Cancer that does not respond to treatment is called refractory or resistant. Cancer that recurs after remission is called relapsed.
Treatments for refractory or relapsed Hodgkin include high dose chemotherapy with stem cell transplantation. People who are not good candidates for transplantation or who have not been helped by it may benefit from treatment with the biologic drug brentuximab (Adcetris).
Preventing Infection: Both the disease and some of the treatments suppress the immune system, increasing the risk for infections. Widespread, life-threatening infection is a particular danger if the spleen has been removed and both radiation and chemotherapy are administered. People with Hodgkin disease should be vaccinated against pneumococcus, meningococcus, and Haemophilus influenza bacteria before receiving treatment.
Preserving Fertility: If you may wish to have children in the future, you should ask your cancer team about fertility-preserving treatments. It is very important to have these discussions before cancer treatment starts. The American Society for Clinical Oncology (ASCO) has guidelines for the best fertility preservation methods for males and females with cancer. For men, ASCO recommends banking and freezing sperm (sperm cryopreservation) for later use in assisted reproductive therapies.
For women, egg (oocyte) cryopreservation is recommended. This procedure involves harvesting and freezing a woman's eggs (oocytes), and can be followed by in vitro fertilization and freezing of embryos for later use. It requires several weeks of pre-treatment with ovarian stimulation drugs, so timing is very important. For women who will receive radiation therapy to the pelvic region, a surgical procedure that moves the ovaries out of the path of radiation (ovarian transposition) can also help preserve fertility.
Relapse of Hodgkin disease is not uncommon, even after treatment for early stages. It can occur a decade or more after treatment. Relapse can occur in early-stage disease, probably because the limited radiation normally used in such cases does not destroy the disease outside of the area irradiated. People who had large tumors in the chest are also at higher risk for recurrence.
Periodic examinations and imaging tests are necessary for years after treatment, both to check for signs of relapse as well as to monitor the long-term effects of treatments.
Because Hodgkin disease often occurs in younger adults, treatment during pregnancy is of particular concern. Therapy must be effective enough to protect the mother without hurting the fetus. Chemotherapy is rarely used early in the term, because it poses a risk for birth defects.
Treatment choice must be individualized, taking into consideration the mother's wishes, the severity and pace of the disease, and the remaining length of the pregnancy. The treatment plan may need to be changed as the pregnancy progresses. If the disease develops in the second half of the pregnancy, it may be possible to postpone chemotherapy or radiation therapy until after an early induced delivery.
Chemotherapy is usually the first treatment for all stages of Hodgkin disease. Chemotherapy uses drugs to kill cancer cells. The drugs are called cytotoxic (toxic to cells) medications. Chemotherapy is considered a systemic, therapy because the drugs affect cells throughout the body.
Chemotherapy drugs may be taken by mouth as pills or given by injection or infusion. Treatment may be administered at a medical center, outpatient infusion center, medical office, or even at home. Some people receiving chemotherapy may need to remain in the hospital for several days so the effects of the drugs can be monitored.
People typically receive 2 to 6 cycles of chemotherapy, depending on the stage. A cycle is usually 28 days and consists of several doses of drug administration followed by a period of rest.
Several chemotherapy regimens are used for treating Hodgkin disease. Standard regimens include ABVD, Stanford V, and BEACOPP.
ABVD is used to treat adults and children in both early and late stages of Hodgkin disease. For early stages (I and II), people typically receive 2 cycles of the drugs, followed by radiation. In late stages (III and IV), people receive 6 to 8 cycles of chemotherapy. ABVD consists of a 4-drug combination:
Stanford V consists of a 7-drug combination often given with radiation:
BEACOPP is a chemotherapy regimen reserved for late-stage Hodgkin disease. It is effective but can increase risk for developing secondary cancers such as leukemia. People who are treated with BEACOPP should receive long-term follow-up care to monitor for side effects from this therapy. BEACOPP consists of 7 drugs:
Brentuximab (Adcetris) is a newer biologic drug that is used by itself. It is approved for people with Hodgkin disease who have either:
Brentuximab works by targeting CD-30, a protein found on Hodgkin cancer cells. The drug is given by intravenous infusion. The most common side effects are neutropenia, peripheral sensory neuropathy, fatigue, nausea, and anemia. A more serious but rare side effect is the brain disorder progressive multifocal leukoencephalopathy (PML).
Side effects and complications of any chemotherapeutic regimen are common, are more severe with higher doses, and increase over the course of treatment.
Common Side Effects of chemotherapy include:
Serious Side Effects: Serious side effects can also occur and may vary depending on the specific drugs used. They include:
Long-Term Complications: Some side effects of chemotherapy may linger after treatment or may develop long after the treatment has ended. Be sure to discuss with your doctor what tests you may need to monitor the long-term effects of chemotherapy treatment. Long-term complications of chemotherapy for Hodgkin disease may include:
Radiation therapy, which shrinks tumors, used to be the main treatment for Hodgkin disease. Today, radiation therapy is mainly used to treat early stage (I or II) Hodgkin disease and is usually given following chemotherapy.
Involved site radiation is the preferred method of radiation therapy for treating Hodgkin disease. It targets only the lymph node regions that are known to have cancer, not the adjacent, uninvolved lymph node regions. Involved-site radiation is usually given after several rounds of chemotherapy.
Involved site radiation is a type of external-beam radiation therapy. You lie on a table while a machine delivers high-energy x-rays to specific targets on your body.
Extended field radiation, an older approach that targeted both the diseased lymph nodes as well as surrounding healthy lymph nodes, is no longer used.
Doctors are working on refining radiation therapies for Hodgkin disease so that they more precisely target the affected lymph nodes and deliver the lowest possible effective dose of radiation. The aim is to destroy the cancerous cells while minimizing the damage to healthy cells and causing fewer side effects.
Newer radiation techniques for Hodgkin disease include involved node radiation therapy, involved site radiation therapy, intensity modulated radiation therapy, and proton therapy.
Fatigue, nausea, diarrhea, dry mouth, skin irritation, and increased risk for infections are common short-term side effects of radiation therapy. These side effects generally go away after treatment is completed.
Radiation therapy can cause more serious long-term complications, which is why researchers are working on techniques to reduce the radiation doses and increase the accuracy of the beams. These side effects generally depend on the radiation target site in the body. They include:
Relapsed or resistant Hodgkin disease is sometimes treated with high-dose chemotherapy followed by stem cell transplantation. This approach allows a person to receive higher doses of chemotherapy than could normally be used.
Transplantation involves removal and replacement of stem cells, which are produced in the bone marrow. Stem cells are the early forms for all blood cells in the body (including red, white, and immune cells). Intensive cancer treatments harm stem cells as well as cancer cells, and so the healthy stem cells must be replaced by transplanting them.
For Hodgkin disease, the most common type of transplant is an autologous procedure, using the person's own stem cells. An allogeneic transplant, using cells from a donor, is more risky for people with Hodgkin disease and is generally used only when an autologous transplant has failed. Allogeneic transplants are sometimes used as treatments for non-Hodgkin lymphoma. They have a greater risk than autologous transplants for complications such as graft-versus-host disease.
Stem cells must first be collected in one of the following ways:
Stem cells are collected several weeks before the procedure. They are frozen and stored while the person undergoes high-dose chemotherapy. Some people receive high-dose whole body radiation therapy along with chemotherapy.
After pre-transplant therapy is completed, the frozen cells are thawed and then infused into the person through a central line catheter implanted in the chest. The infusion process takes several hours. Within a few weeks, these cells start to generate new white blood cells and then new red blood cells.
The risk for infection is greatest during the first 6 weeks following the transplant. During this period, the person usually remains in isolation and receives antibiotics and intravenous nutrition. It takes 6 to 12 months post-transplant for a person's immune system to fully recover.
Many people develop severe herpes zoster virus infections (shingles) or have a recurrence of herpes simplex virus infections (cold sores and genital herpes). Pneumonia, cytomegalovirus, Aspergillus (a type of fungus), and Pneumocystis jiroveci (a fungus) are among the most serious life-threatening infections.
It is very important that people who have stem cell transplants take precautions to avoid infections. Guidelines for infection prevention include:
Early side effects of transplantation are similar to chemotherapy and include nausea, vomiting, fatigue, mouth sores, and loss of appetite. Bleeding because of reduced platelets is a high risk during the first 4 weeks and may require transfusions. Later side effects may include fertility problems (if the ovaries are affected), thyroid gland problems (which can affect metabolism), lung damage (which can cause breathing problems), other organ damage, and bone damage.
In younger people, there is a small long-term risk for leukemia after transplantation. Chemotherapy itself increases the risk of secondary cancers. Studies suggest that transplantation after chemotherapy does not add any additional risks.
Armitage JO. Early-stage Hodgkin's lymphoma. N Engl J Med. 2010;363(7):653-662.
Bartlett NL, Foyil KV. Hodgkin lymphoma. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE, eds. Abeloff's Clinical Oncology. 5th ed. Elsevier Saunders; 2013:2018-2032.e4.
Brenner H, Gondos A, Pulte D. Ongoing improvement in long-term survival of patients with Hodgkin disease at all ages and recent catch-up of older patients. Blood. 2008;111(6):2977-2983.
Castellino SM, Geiger AM, Mertens AC, et al. Morbidity and mortality in long-term survivors of Hodgkin lymphoma: a report from the Childhood Cancer Survivor Study. Blood. 2011;117(6):1806-1816.
de Fine Licht S, Winther JF, Gudmundsdottir T, Holmqvist AS, Bonnesen TG, Asdahl PH, et al. Hospital contacts for endocrine disorders in Adult Life after Childhood Cancer in Scandinavia (ALiCCS): a population-based cohort study. Lancet. 2014 Jun 7;383(9933):1981-9. Epub 2014 Feb 18. PMID: 24556022
Eichenauer DA, Engert A, Dreyling M; ESMO Guidelines Working Group. Hodgkin's lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2011;Suppl 6:vi55-vi58.
Engert A, Plütschow A, Eich HT, et al. Reduced treatment intensity in patients with early-stage Hodgkin's lymphoma. N Engl J Med. 2010;363(7):640-652.
Fermé C, Eghbali H, Meerwaldt JH, et al. Chemotherapy plus involved-field radiation in early-stage Hodgkin's disease. N Engl J Med. 2007;357(19):1916-1927.
Juweid ME, Stroobants S, Hoekstra OS, et al. Use of positron emission tomography for response assessment of lymphoma: consensus of the Imaging Subcommittee of International Harmonization Project in Lymphoma. J Clin Oncol. 2007;25(5):571-578.
Loren AW, Mangu PB, Beck LN, et al. Fertility preservation for patients with cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2013;31(19):2500-2510.
Meyer RM, Gospodarowicz MK, Connors JM, et al. ABVD alone versus radiation-based therapy in limited-stage Hodgkin's lymphoma. N Engl J Med. 2012;366(5):399-408.
Morris B, Partap S, Yeom K, et al. Cerebrovascular disease in childhood cancer survivors: A Children's Oncology Group Report. Neurology. 2009;73(22):1906-1913.
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Hodgkin Lymphoma. V.2.2014.
Oeffinger KC, Ford JS, Moskowitz CS, et al. Breast cancer surveillance practices among women previously treated with chest radiation for a childhood cancer. JAMA. 2009;301(4):404-414.
Rancea M, Monsef I, von Tresckow B, Engert A, Skoetz N. High-dose chemotherapy followed by autologous stem cell transplantation for patients with relapsed/refractory Hodgkin lymphoma. Cochrane Database Syst Rev. 2013;6:CD009411.
Specht L, Yahalom J, Illidge T, et al. Modern radiation therapy for Hodgkin lymphoma: field and dose guidelines from the International Lymphoma Radiation Oncology Group (ILROG). Int J Radiat Oncol Biol Phys. 2013 Jun 18. pii: S0360-3016(13)00534-8 [Epub ahead of print]
Townsend W, Linch D. Hodgkin's lymphoma in adults. Lancet. 2012;380(9844):836-847.
Viviani S, Zinzani PL, Rambaldi A, et al. ABVD versus BEACOPP for Hodgkin's lymphoma when high-dose salvage is planned. N Engl J Med. 2011;365(3):203-212.
Last reviewed on: 3/8/2015
Reviewed by: Todd Gersten, MD, Hematology/Oncology, Florida Cancer Specialists & Research Institute, Wellington, FL. Review provided by VeriMed Healthcare Network. Also reviewed by David Zieve, MD, MHA, Isla Ogilvie, PhD, and the A.D.A.M. Editorial team. Author: Julia Mongo, MS.