Lymph nodes, in conjunction with the spleen, tonsils, adenoids, and Peyer patches, are highly organized centers of immune cells that filter antigen from the extracellular fluid. Directly interior to the fibrous capsule is the subcapsular sinus. This allows lymph, an ultrafiltrate of blood, to traverse from the afferent lymph vessels, through the sinuses, and out the efferent vessels. The sinuses are studded with macrophages, which remove 99% of all delivered antigens.
Interior to the subcapsular sinus is the cortex, which contains primary follicles, secondary follicles, and the interfollicular zone. Follicles within the cortex are major sites of B-cell proliferation, whereas the interfollicular zone is the site of antigen-dependent T-cell differentiation and proliferation. The deepest structure within the lymph node is the medulla, consisting of cords of plasma cells and small B lymphocytes that facilitate immunoglobulin secretion into the exiting lymph.
The lymph node, with its high concentration of lymphocytes and antigen-presenting cells, is an ideal organ for receiving antigens that gain access through the skin or gastrointestinal tract. Nodes have considerable capacity for growth and change. Lymph node size depends on the person's age, the location of the lymph node in the body, and antecedent immunological events. In neonates, lymph nodes are barely perceptible, but a progressive increase in total lymph node mass is observed until later childhood. Lymph node atrophy begins during adolescence and continues through later life.
Lymphadenopathy reflects disease involving the reticuloendothelial system, secondary to an increase in normal lymphocytes and macrophages in response to an antigen. Most lymphadenopathy in children is due to benign self-limited disease such as viral infections. Other less common etiologies responsible for adenopathy include nodal accumulation of inflammatory cells in response to an infection in the node (lymphadenitis), neoplastic lymphocytes or macrophages (lymphoma), or metabolite-laden macrophages in storage diseases (Gaucher disease).
The precise incidence of lymphadenopathy is not known, but estimates of palpable adenopathy in childhood vary from 38-45%, and lymphadenopathy is one of the most common clinical problems encountered in pediatrics. Determining whether adenopathy is simply a normal response to frequent viral infections within an age group or if it is significant enough to consider more serious underlying disease is often difficult.
In the United States, common viral and bacterial infections are overwhelmingly the most common cause of adenopathy. Infectious mononucleosis and cytomegalovirus (CMV) are important etiologies, but adenopathy is usually caused by common viral upper respiratory tract infections. Localized lymphadenitis is most often caused by staphylococci and beta-hemolytic streptococci.
Other infections, such as human immunodeficiency virus (HIV), malignancies, and autoimmune diseases, are less common causes of adenopathy.
Infections that are rarely observed in the United States, such as tuberculosis, typhoid fever, leishmaniasis, trypanosomiasis, schistosomiasis, filariasis, and fungal infections, are common causes of lymphadenopathy in developing nations. HIV infections must be strongly considered in areas of high incidence.
In the United States, mortality and serious morbidity caused by adenopathy are unusual given the common infectious etiologies.
Malignancies, such as leukemia, lymphomas, and neuroblastoma, are the primary causes of mortality in the United States.
Significant morbidity and mortality are also associated with autoimmune disorders (eg, juvenile rheumatoid arthritis, systemic lupus erythematosus), histiocytoses, and storage diseases.
HIV is an uncommon cause of adenopathy in the United States, but its associated mortality requires consideration.
Race is not a factor in most lymphadenopathy. Rare causes may be associated with particular ethnic groups (eg, sarcoidosis in Africans, Kikuchi-Fujimori disease in Asians).
Sex does not influence childhood lymphadenopathy.
Adenopathy is most common in young children whose immune systems are responding to newly encountered infections. Adenopathy may be seen in one third of neonates and infants, usually in nodes that drain areas with mild skin irritation. Generalized adenopathy is rare in the neonate and suggests congenital infections, such as CMV. Adenopathy related to malignancy is rare at all ages. If diagnosed, it is often secondary to leukemia or neuroblastoma in younger children, and to Hodgkin lymphoma in adolescents.
The differential diagnosis of acute lymphadenopathy is broad. A patient's medical history and review of systems is important in narrowing this differential. Upon examination, recognizing the pattern of lymph drainage aids in seeking an infectious focus.
Although the underlying etiology is often self-limited infection, more serious underlying etiologies must be quickly recognized. Serious infections and malignancies are important considerations, as discussed in Outline - Etiologies of Lymphadenopathy.
In adolescents, screening for intravenous drug use and sexual activity is important.
Assess the size, location, and character of the adenopathy, along with any associated physical findings. Erythema, tenderness, warmth, and fluctuance suggests lymphadenitis, and nodes that are fixed (nonmoveable), matted together, firm, and nontender suggest malignancy, although this distinction is not invariable.
Recognize that most children have palpable lymph nodes in the anterior cervical, inguinal, and axillary regions that, if evaluated by adult standards, would qualify as lymphadenopathy. Lymphoid mass steadily increases after birth until age 8-12 years, and undergoes progressive atrophy during puberty.
In young children, anterior cervical lymph nodes as large as 2 cm, axillary nodes as large as 1 cm, and inguinal nodes as large as 1.5 cm in diameter are normal, and further evaluation is usually not indicated. In a series of 457 children, malignancy was usually associated with nodes larger than 3 cm in diameter. However, the presence of even shotty (< 0.5 cm) supraclavicular or epitrochlear adenopathy may be associated with malignancy and warrants further evaluation. Newborns usually have small adenopathy (< 0.5 cm), and larger nodes not associated with a focus of inflammation are an indication for further evaluation.
Seek a focus of infection or inflammation in the territory drained by the lymph nodes. For example, the classic manifestation of group A streptococcal pharyngitis is sore throat, fever, and anterior cervical lymphadenopathy (tonsillar node). When examining the oropharynx, pay special attention to the dentition. Similarly, impetigo of the buttock area is associated with inguinal adenopathy. Scalp lesions, such as seborrheic dermatitis ("cradle cap"), can cause newborn occipital adenopathy.
Consider the possibility that palpable "lymph nodes" may in fact be other masses; for example, branchial cysts and other benign tumors can mimic cervical adenopathy.
A careful history and physical examination, with a consideration of the factors listed above, help determine whether an enlarged lymph node merits further investigation.
Generalized lymphadenopathy is defined as enlargement of more than 2 noncontiguous lymph node groups. A thorough history and physical examination are critical in establishing a diagnosis. Causes of generalized lymphadenopathy include infections, autoimmune diseases, malignancies, histiocytoses, storage diseases, benign hyperplasia, and drug reactions.
Generalized lymphadenopathy is most often associated with systemic viral infections.
Infectious mononucleosis results in widespread adenopathy.
Roseola infantum (caused by human herpes virus 6), cytomegalovirus (CMV), varicella, and adenovirus all cause generalized lymphadenopathy.
Human immunodeficiency virus (HIV) is often associated with generalized adenopathy, which may be the presenting sign. Children with HIV are at increased risk for tuberculosis, as well.
Although usually associated with localized node enlargement, some bacterial infections present with generalized adenopathy. Examples include typhoid fever caused by Salmonella typhi, syphilis, plague, and tuberculosis. Less common bacteremias, including those caused by endocarditis, result in generalized lymphadenopathies.
Concern about malignant etiologies often drives further diagnostic testing in children with adenopathy. Malignancy is often associated with constitutional signs, such as fever, anorexia, nonspecific aches and pains, weight loss, and night sweats. The acute leukemias and lymphomas often present with these nonspecific findings.
Generalized lymphadenopathy is present at diagnosis in two thirds of children with acute lymphoblastic leukemia (ALL) and in one third of children with acute myeloblastic leukemia (AML). Abnormalities of peripheral blood counts usually lead to the correct diagnosis. The lymphomas more often present with regional lymphadenopathy, but generalized lymphadenopathy occurs.
Constitutional signs and symptoms observed in the leukemias are less reliable findings in the lymphomas. Only one third of children with Hodgkin disease and 10% with non-Hodgkin lymphoma display them. Malignancies usually present with nodes that tend to be firmer and less mobile or matted; however, this finding can be misleading. Benign reactive lymph nodes may be associated with fibrotic reactions that make them firm.
Storage diseases: Generalized lymphadenopathy is an important manifestation of the lipid storage diseases. In Niemann-Pick disease, sphingomyelin and other lipids accumulate in the spleen, liver, lymph nodes, and CNS. In Gaucher disease, the accumulation of the glucosylceramide leads to the engorgement of the spleen, lymph nodes, and the bone marrow. Although widespread lymphadenopathy is common, additional findings, such as hepatosplenomegaly and developmental delay in Niemann-Pick disease and blood dyscrasias in Gaucher disease, are usually present. These diagnoses are established by leukocyte assay.
Drug reactions: Adverse drug reactions can cause generalized lymphadenopathy. Within a couple of weeks of initiating phenytoin, some patients experience a syndrome of regional or generalized lymph node enlargement, followed by a severe maculopapular rash, fever, hepatosplenomegaly, jaundice, and anemia. These symptoms abate 2-3 months after discontinuation of the drug. Several other drugs are implicated in similar symptomatology, including mephenytoin, pyrimethamine, phenylbutazone, allopurinol, and isoniazid.
Other nonneoplastic etiologies: Rare nonneoplastic causes of generalized lymphadenopathy include Langerhans cell histiocytosis and Epstein-Barr virus (EBV)-associated lymphoproliferative disease. Autoimmune etiologies include juvenile rheumatoid arthritis, which often presents with adenopathy, especially during the acute phases of the disease. Sarcoidosis and graft versus host disease also merit consideration.
Regional lymphadenopathy involves enlargement of a single node or multiple contiguous nodal regions. Lymph nodes are clustered in groups throughout the body and are concentrated in the head and neck, axillae, mediastinum, abdomen, and along the vascular trunks of the extremities. Each group drains lymph from a particular region of the body. Knowledge of the pattern of lymph drainage aids in determining the etiology.
Cervical lymphadenopathy: Cervical lymphadenopathy is a common problem in children. Cervical nodes drain the tongue, external ear, parotid gland, and deeper structures of the neck, including the larynx, thyroid, and trachea. Inflammation or direct infection of these areas causes subsequent engorgement and hyperplasia of their respective node groups. Adenopathy is most common in cervical nodes in children and is usually related to infectious etiologies. Lymphadenopathy posterior to the sternocleidomastoid is typically a more ominous finding, with a higher risk of serious underlying disease.
Cervical adenopathy is a common feature of many viral infections. Infectious mononucleosis often manifests with posterior and anterior cervical adenopathy. Firm tender nodes that are not warm or erythematous characterize this lymph node enlargement. Other viral causes of cervical lymphadenopathy include adenovirus, herpesvirus, coxsackievirus, and CMV. In herpes gingivostomatitis, impressive submandibular and submental adenopathy reflects the amount of oral involvement.
Bacterial infections cause cervical adenopathy by causing the draining nodes to respond to local infection or by the infection localizing within the node itself as a lymphadenitis. Bacterial infection often results in enlarged lymph nodes that are warm, erythematous, and tender. Localized cervical lymphadenitis typically begins as enlarged, tender, and then fluctuant nodes. The appropriate management of a suppurative lymph node includes both antibiotics and incision and drainage. Antibiotic therapy should always include coverage for Staphylococcus aureus and Streptococcus pyogenes.
In patients with cervical adenopathy, determine whether the patient has had recent or ongoing sore throat or ear pain. Examine the oropharynx, paying special attention to the posterior pharynx and the dentition. The classic manifestation of group A streptococcal pharyngitis is sore throat, fever, and anterior cervical lymphadenopathy. Other streptococcal infections causing cervical adenopathy include otitis media, impetigo, and cellulitis.
Atypical mycobacteria cause subacute cervical lymphadenitis, with nodes that are large and indurated but not tender. The only definitive cure is removal of the infected node.
Mycobacterium tuberculosis may manifest with a suppurative lymph node identical to that of atypical mycobacterium. Intradermal skin testing may be equivocal. A biopsy may be necessary to establish the diagnosis.
Catscratch disease, caused by Bartonella henselae, presents with subacute lymphadenopathy often in the cervical region. The disease develops after the infected pet (usually a kitten) inoculates the host, usually through a scratch. Approximately 30 days later, fever, headache, and malaise develop, along with adenopathy that is often tender. Several lymph node chains may be involved. Suppurative adenopathy occurs in 10-35% of patients. Antibiotic therapy has not been shown to shorten the course.
Malignant childhood tumors develop in the head and neck region in one quarter of cases. In the first 6 years of life, neuroblastoma, leukemia, non-Hodgkin lymphoma, and rhabdomyosarcoma (in order of decreasing frequency) are most common in the head and neck region. In children older than 6 years, Hodgkin disease and non-Hodgkin lymphoma both predominate. Children with Hodgkin disease present with cervical adenopathy in 80-90% of cases as opposed to 40% of those with non-Hodgkin lymphoma.
Kawasaki disease is an important cause of cervical adenopathy. These children have fever for at least 5 days, and cervical lymphadenopathy is one of the 5 diagnostic criteria (of which 4 are necessary to establish the diagnosis).
Submaxillary and submental lymphadenopathy: These nodes drain the teeth, tongue, gums, and buccal mucosa. Their enlargement is usually the result of localized infection, such as pharyngitis, herpetic gingivostomatitis, and dental abscess.
Occipital lymphadenopathy: Occipital nodes drain the posterior scalp. These nodes are palpable in 5% of healthy children. Common etiologies of occipital lymphadenopathy include tinea capitis, seborrheic dermatitis, insect bites, orbital cellulitis, and pediculosis. Viral etiologies include rubella and roseola infantum. Rarely, occipital lymphadenopathy may be noted after enucleation of the eye for retinoblastoma.
Preauricular lymphadenopathy: Preauricular nodes drain the conjunctivae, skin of the cheek, eyelids, and temporal region of the scalp and rarely are palpable in healthy children. The oculoglandular syndrome consists of severe conjunctivitis, corneal ulceration, eyelid edema, and ipsilateral preauricular lymphadenopathy. Chlamydia trachomatis and adenovirus can cause this syndrome.
Mediastinal nodes drain the thoracic viscera, including the lungs, heart, thymus, and thoracic esophagus. Because these nodes are not directly demonstrable upon physical examination, their enlargement must be indirectly assessed. Supraclavicular adenopathy is often associated with mediastinal adenopathy. Mediastinal nodes may cause cough, wheezing, dysphagia, airway erosion with hemoptysis, atelectasis, and the obstruction of the great vessels, which constitutes superior vena cava syndrome. Airway compromise may be life threatening.
Mediastinal lymphadenopathy is usually a sign of serious underlying disease. More than 95% of mediastinal masses are caused by tumors or cysts. Lymphomas and acute lymphoblastic leukemia are the most common etiologies and usually involve the anterior mediastinum. These malignancies are associated with a high risk of superior vena cava syndrome and are associated with several potentially life-threatening complications, as follows:
The danger of sedation of patients, especially in the supine position for scans and procedures (The prone position actually may be safer.)
The risk during intubation of these patients, usually at the time of biopsy or placement of a central venous catheter
The risk of cardiovascular collapse during general anesthesia because of compression of venous return or because of previously undiagnosed pleural effusions
The risk of losing the ability to establish a pathologic diagnosis because of the use of steroids or radiation therapy
Unlike most other adenopathies, mediastinal lymphadenopathy is less frequently a result of infection. Infections frequently involve the hilar region and include histoplasmosis, coccidioidomycosis, and tuberculosis.
Nonlymphoid mediastinal tumors may be confused with adenopathy. These include neurogenic tumors (usually found in the posterior mediastinum), germ cell tumors, and teratomas.
Nonneoplastic conditions may also be confused with mediastinal adenopathy. These include the typically large thymus of a child, substernal thyroid glands, bronchogenic cysts, and abnormalities of the great vessels.
Supraclavicular nodes drain the head, neck, arms, superficial thorax, lungs, mediastinum, and abdomen. Left supraclavicular nodes also reflect intra-abdominal drainage and enlarge in response to malignancies in that region. This is particularly true when adenopathy in this region occurs in the absence of other cervical adenopathy.
Right supraclavicular nodes drain the lung and mediastinum and are typically enlarged with intrathoracic lesions.
Serious underlying disease is frequent in children with supraclavicular adenopathy and always merits further evaluation. The potential for malignancy necessitates peripheral blood counts, skin testing for tuberculosis, and chemical studies, including uric acid, lactate dehydrogenase, calcium (Ca), phosphorus (P), and renal and hepatic function studies. Chest radiography and possibly CT scanning are indicated.
Several important infections may occur with supraclavicular adenopathy, including tuberculosis, histoplasmosis, and coccidioidomycosis.
Early lymph node biopsy should be considered in children with supraclavicular adenopathy.
Axillary nodes drain the hand, arm, lateral chest, abdominal walls, and the lateral portion of the breast.
A common cause of axillary lymphadenopathy is catscratch disease. Local axillary skin infection and irritation commonly are associated with local adenopathy. Other etiologies include recent immunizations in the arm (particularly with bacille Calmette-Guerin vaccine), brucellosis, juvenile rheumatoid arthritis, and non-Hodgkin lymphoma.
Hidradenitis suppurativa is a condition of enlarged tender lymph nodes that typically affects children with obesity and is caused by recurrent abscesses of lymph nodes in the axillary chain. The etiology is unknown, and treatment may include antibiotics. Many patients require incision and drainage.
Abdominal nodes drain the lower extremities, pelvis, and abdominal organs. Although abdominal adenopathy is not usually demonstrable upon physical examination, abdominal pain, backache, increased urinary frequency, constipation, and intestinal obstruction secondary to intussusception are possible presentations.
Mesenteric adenitis is thought to be viral in etiology and is characterized by right lower quadrant abdominal pain caused by nodal enlargement near the ileocecal valve. Differentiating mesenteric adenitis from appendicitis may be difficult.
Mesenteric adenopathy may be caused by non-Hodgkin lymphoma or Hodgkin disease.
Typhoid fever and ulcerative colitis are other etiologies of mesenteric adenopathy.
Iliac and inguinal lymphadenopathy: The lower extremities, perineum, buttocks, genitalia, and lower abdominal wall drain to these nodes. They are typically palpable in healthy children, although they are usually no larger than 1-1.5 cm in diameter. Regional lymphadenopathy is typically caused by infection; however, insect bites and diaper dermatitis are also frequent. Nonlymphoid masses that may be confused with adenopathy include hernias, ectopic testes, and lipomas.
The laboratory evaluation of lymphadenopathy must be directed by the history and physical examination and is based on the size and other characteristics of the nodes and the overall clinical assessment of the patient. When a laboratory evaluation is indicated, it must be driven by the clinical evaluation.
The following studies should be considered for chronic lymphadenopathy (>3 wk):
CBC count, including a careful evaluation of the peripheral blood smear
Lactate dehydrogenase (LDH) and uric acid
B henselae (catscratch) serology if exposed to a cat
Tuberculosis skin test (TST) and interferon-gamma release assay (eg, Quantiferon Gold)
Evaluation of hepatic and renal function and a urine analysis are useful in identifying underlying systemic disorders that may be associated with lymphadenopathy. When evaluating specific regional adenopathy, lymph node aspirate for culture may be important if lymphadenitis is clinically suspected.
Titers for specific microorganisms may be indicated, particularly if generalized adenopathy is present. These may include Epstein-Barr virus, cytomegalovirus (CMV), Toxoplasma species, and human immunodeficiency virus (HIV).
Chest radiography may be helpful in elucidating mediastinal adenopathy and underlying diseases affecting the lungs, including tuberculosis, coccidioidomycosis, lymphomas, neuroblastoma, histiocytoses, and Gaucher disease.
Supraclavicular adenopathy, with its high associated rate of serious underlying disease, may be an indication for CT scan of the chest, abdomen, or both.
Positron-emission tomography (PET) scanning is not helpful as a screening tool as benign and malignant conditions may cause intense uptake. However, PET scanning is helpful in the staging of lymphomas once a diagnosis is made.
Ultrasonography may be helpful in documenting the extent of lymph node involvement and any changes in the lymph nodes. In children with inguinal adenopathy or abdominal complaints, ultrasonography of the abdomen, CT scan of the abdomen, or both may be indicated. Ultrasonography is rarely of diagnostic value for lymphadenopathy in childhood, even with advanced techniques.
The critical question is often whether or not to perform a lymph node biopsy; this requires an overall assessment of the history and physical examination as described above.
Images taken during and after a lymph node biopsy are shown below.
A lymph node biopsy is performed. Note that a marking pen has been used to outline the node before removal and that a silk suture has been used to pro....
A lymph node after removal by means of biopsy, which was performed completely under a local anesthetic technique.
A gross image of a node following excision. The cut surface of the node shows the typical fish-flesh appearance seen with lymphoma.
Treatment with antibiotics covering bacterial pathogens frequently implicated in lymphadenitis, followed by reevaluation in 2-4 weeks is reasonable, if clinical findings suggest lymphadenitis. Benign reactive adenopathy may be safely observed for months.
If the size, location, or character of the lymphadenopathy suggests malignancy, the need for laboratory studies and biopsy is more urgent. If laboratory testing is inconclusive, a lymph node biopsy is immediately indicated.
Fine needle aspiration and core needle biopsy yield small samples with limited ability to perform flow cytometry and chromosomal analysis; most pediatric hematologists and pathologists prefer excisional biopsy.
Excisional biopsy also has limitations and may yield a definitive diagnosis in only 40-60% of patients because of inadequate specimen size, improper handling, or node-sampling error (eg, Hodgkin lymphoma) may be associated with reactive changes in surrounding nodes; sampling more accessible nodes may miss the underlying malignancy.
The surgeon should therefore biopsy larger, firmer, and most recently enlarging nodes, even if it is technically difficult, with appropriate handling of the specimen. If an excisional biopsy does not reveal the diagnosis, a second biopsy may be indicated.
Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a widespread technique for tissue sampling from hilar and mediastinal lymph nodes; however, the predominant finding in routine care is a nondiagnostic cytology in more than 70% of patients.
Histiologic findings depend on the underlying etiology of the lymphadenopathy. Nonspecific changes consistent with reactive adenopathy are often the only findings. This is helpful in ruling out malignancy, histiocytoses, granulomatous disorders, and storage diseases. Specific infections can be diagnosed if tissues are appropriately stained.
When examining the tissue, histiologic findings are often inadequate. Flow cytometric and chromosomal analysis may provide critical information to permit a diagnosis to be established.
Treatment is determined by the specific underlying etiology of lymphadenopathy.
Most clinicians treat children with cervical lymphadenopathy conservatively. Antibiotics should be given only if a bacterial infection is suspected. This treatment is often given before biopsy or aspiration is performed. This practice may result in unnecessary prescription of antimicrobials. However, the risks of surgery often outweigh the potential benefits of a brief course of antibiotics. Most enlarged lymph nodes are caused by an infectious process. If aspects of the clinical picture suggest malignancy, such as persistent fevers or weight loss, biopsy should be pursued sooner.
Management of superior vena cava syndrome requires emergency care, including chemotherapy and possibly radiation therapy.
Consultation with a pediatric hematologist, pediatric oncologist, or both is often useful, especially if the adenopathy seems to be more than reactive. Often, the most important decision for these children is whether further evaluation is necessary at all; experience in evaluating these children is frequently very helpful. The ability to provide a careful assessment of the peripheral blood smear may be particularly important.
Surgical consultation is usually helpful for lymph node biopsy, needle aspiration for culture, and for incision and drainage of obviously infected fluctuant nodes.
Transfer of the patient usually depends on the specific diagnosis. Patients who develop superior vena cava syndrome with either respiratory symptoms or obstruction to blood flow require emergency medical care and may require transfer to a tertiary care center.
Complications are usually related to the specific underlying disorder causing the lymphadenopathy; however, the lymphadenopathy itself can cause potentially serious complications.
Mediastinal adenopathy can result in several potentially life-threatening complications. Recognition of these complications is important because mediastinal adenopathy cannot be directly assessed clinically and therefore may be easily missed.
Mediastinal adenopathy can cause superior vena cava syndrome with obstruction of blood flow; bronchial or tracheal obstruction with cough, wheezing, and ultimately respiratory tract obstruction (which can be life threatening); and dysphagia from esophageal compression. Occasionally, erosion of a node into a bronchus or trachea can result in hemoptysis.
When the diagnosis of an underlying malignancy is missed, serious metabolic complications can occur. These include uric acid nephropathy, hyperkalemia, hypercalcemia, hypocalcemia, hyperphosphatemia, and acid renal failure.
Abdominal adenopathy can cause abdominal or back pain, constipation, and urinary frequency. Intestinal obstruction caused by intussusception can be life threatening.
The prognosis of lymphadenopathy almost entirely depends on the underlying etiology. Patients with specific complications, such as superior vena cava syndrome, are at risk unless this specific complication is managed. Their prognosis is dependent on the management of the neoplastic process resulting in superior vena cava syndrome.
Vikramjit S Kanwar, MBBS, MBA, MRCP(UK), FAAP, Associate Professor and Division Chief of Pediatric Hematology and Oncology, Department of Pediatrics, Albany Medical Center
Disclosure: Jazz Pharmaceutical Honoraria Speaking and teaching
Richard H Sills, MD, Professor of Pediatrics, Upstate Medical University
Disclosure: Nothing to disclose.
Gary J Noel, MD, Professor, Department of Pediatrics, Weill Cornell Medical College; Attending Pediatrician, New York-Presbyterian Hospital
Disclosure: Nothing to disclose.
Mary L Windle, PharmD, Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Nothing to disclose.
Larry I Lutwick, MD, Professor of Medicine, State University of New York Downstate Medical School; Director, Infectious Diseases, Veterans Affairs New York Harbor Health Care System, Brooklyn Campus
Disclosure: Nothing to disclose.
Helen SI Chan, MBBS, FRCP(C), FAAP, Associate Senior Scientist, Research Institute; Professor, Division of Hematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto Faculty of Medicine, Canada
Disclosure: Nothing to disclose.
Russell W Steele, MD, Head, Division of Pediatric Infectious Diseases, Ochsner Children's Health Center; Clinical Professor, Department of Pediatrics, Tulane University School of Medicine
Disclosure: Nothing to disclose.
The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author Stephanie Jorgensen, MD, to the original writing and development of this article.