Lymph node enlargement is a common clinical finding with a wide range of underlying disease states, but can sometimes be the primary nuisance of a condition.
Technically, the term “lymphodomegaly” is the correct description for enlarged lymph nodes, but “lymphadenopathy” (pathology of the lymph nodes) is generally used synonymously.
Lymphadenopathy can involve peripheral (palpable) lymph nodes and / or internal visceral lymph nodes. Lymphadenopathy can be localized (solitary or regional) or generalized in distribution.
“Lymphadenopathy” could also encompass situations in which the lymph nodes are reduced in size. For example in senility, cachexia , primary immunodeficiency disease or with a viral infection or immunosuppression that depletes lymphoid tissue.
In addition, the lymph nodes can show a pathological change (for example, the presence of a metastatic tumor) without necessarily being enlarged.
Causes and symptoms of lymphonodomegaly
Generalized lymphadenopathy is defined as the enlargement of more than 2 groups of non-contiguous lymph nodes. A complete history and physical examination are critical to establishing a diagnosis.
The causes of generalized lymphadenopathy include infections, autoimmune diseases, malignant tumors, histiocytosis, storage diseases, benign hyperplasia , and drug reactions.
Generalized lymphadenopathy is most often associated with systemic viral infections.
Infant roseola (caused by human herpes virus 6), cytomegalovirus (CMV), chickenpox, and adenovirus cause generalized lymphadenopathy.
The human immunodeficiency virus (HIV) is often associated with generalized adenopathy, which may be the presenting sign. Children with HIV are also at increased risk for tuberculosis.
Although generally 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 bacteremia, including those caused by endocarditis , lead to generalized lymphadenopathy.
In an ultrasound study, they found that 46 of 102 pediatric patients (45%) with microbiologically confirmed pulmonary tuberculosis or had abdominal lymphadenopathy suggestive of abdominal tuberculosis.
This indicated that abdominal tuberculosis is a common complication of pulmonary tuberculosis in children.
Concern about malignant etiologies often prompts more 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.
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).
Peripheral blood count abnormalities usually lead to the correct diagnosis. Lymphomas most often present with regional lymphadenopathy, but generalized lymphadenopathy occurs.
The constitutional signs and symptoms seen in leukemias are less reliable findings in lymphomas. Only a third of children with Hodgkin’s disease and 10% with non-Hodgkin’s lymphoma show them.
Malignant tumors usually present with nodes that tend to be firmer and less mobile or tangled; however, this finding can be misleading.
Benign reactive lymph nodes may be associated with fibrotic reactions that make them firm.
Generalized lymphadenopathy is an important manifestation of 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 glucosylceramide leads to congestion of the spleen, lymph nodes, and bone marrow.
Although disseminated lymphadenopathy is common, additional findings, such as hepatosplenomegaly and delayed development of Niemann-Pick disease, are usually present.
These diagnoses are established by the leukocyte assay.
Adverse drug reactions can cause generalized lymphadenopathy.
Within a couple of weeks after starting phenytoin , some patients experience a regional lymph node enlargement syndrome, followed by a severe maculopapular rash, fever, hepatosplenomegaly, and anemia.
These symptoms disappear 2-3 months after stopping the drug.
Several other medications are implicated in similar symptoms, including mephenytoin, pyrimethamine, phenylbutazone, allopurinol, and isoniazid.
Other non-neoplastic etiologies
Rare non-neoplastic 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.
The sarcoidosis and graft versus host disease also deserve consideration.
Regional lymphadenopathy involves enlargement of a single node or multiple contiguous nodal regions.
Lymph nodes are grouped throughout the body and are concentrated in the head and neck, armpits, mediastinum, abdomen, and along the vascular trunks of the extremities.
Each group drains lymph from a particular region of the body. Knowledge of the lymphatic drainage pattern helps determine the etiology.
Cervical lymphadenopathy is a common problem in children. The cervical nodes drain the tongue, outer ear, parotid gland, and deeper structures in the neck, such as the larynx, thyroid, and trachea.
Direct inflammation or infection of these areas causes subsequent engorgement and hyperplasia of their respective node groups.
Denopathy is more common in the cervical nodes in children and is generally related to infectious etiologies.
Lymphadenopathy posterior to the sternocleidomastoid is usually a more ominous finding, with an increased risk of serious underlying disease.
Chronic adenopathy is a common feature of many viral infections. Infectious mononucleosis often presents with posterior and anterior cervical adenopathy.
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 herpetic gingivostomatitis, an impressive submandibular and submental adenopathy reflects the amount of oral involvement.
Bacterial infections cause cervical adenopathy by causing the draining nodes to respond to a local infection or by localizing the infection within the node as lymphadenitis.
Bacterial infection often results in enlarged lymph nodes that are warm, erythematous, and tender. Localized cervical lymphadenitis usually begins as enlarged, tender, and then fluctuating nodes.
Proper 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 if the patient has had a recent or ongoing sore throat or earache. Examine the oropharynx, paying particular attention to the posterior pharynx and dentition.
The classic manifestation of group A streptococcal pharyngitis is a sore throat, fever, and anterior cervical lymphadenopathy.
Other strep infections that cause cervical adenopathy include otitis media, impetigo, and cellulitis.
Atypical mycobacteria cause subacute cervical lymphadenitis, with large, indurated but not tender nodules. The only definitive cure is the removal of the infected node.
Mycobacterium tuberculosis can present with a suppurative lymph node identical to that of the atypical mycobacterium. Intradermal skin tests can be misleading.
A biopsy may be necessary to establish the diagnosis. Poultice 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.
About 30 days later, a fever, headache, and malaise develop, along with adenopathy that is often painful. Several chains of lymph nodes may be involved.
Suppurative adenopathy occurs in 10-35% of patients. Antibiotic treatment has not been shown to shorten the course.
In a quarter of cases, childhood malignant tumors develop in the head and neck region.
In the first 6 years of life, neuroblastoma, leukemia, non-Hodgkin’s lymphoma, and rhabdomyosarcoma (in order of decreasing frequency) are most common in the head and neck region.
In children older than 6 years, Hodgkin’s disease and non-Hodgkin’s lymphoma predominate.
Children with Hodgkin’s disease have cervical adenopathy in 80-90% of cases, compared with 40% of those with non-Hodgkin’s lymphoma.
Kawasaki disease is a major cause of cervical adenopathy.
These children have a 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 lymphonodomegaly
These nodules drain the teeth, tongue, gums, and oral mucosa. Its enlargement is usually the result of a localized infection, such as pharyngitis , herpetic gingivostomatitis, and dental abscess.
The occipital ganglia drain the posterior scalp. These nodules 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 seen after enucleation of the eye for retinoblastoma.
The preauricular nodes drain the conjunctiva, the skin of the cheek, the eyelids, and the temporal region of the scalp and are rarely palpable in healthy children.
Oculoglandular syndrome consists of severe conjunctivitis, corneal ulceration, eyelid edema, and ipsilateral preauricular lymphadenopathy. Chlamydia trachomatis and adenovirus can cause this syndrome.
The mediastinal nodes drain the thoracic viscera, including the lungs, heart, thymus, and thoracic esophagus.
Because these nodes are not directly demonstrable on physical examination, their enlargement must be assessed indirectly. Supraclavicular adenopathy is often associated with mediastinal adenopathy.
The mediastinal nodes can cause coughing, wheezing, dysphagia , erosion of the airways with hemoptysis, atelectasis, and obstruction of the great vessels, constituting superior vena cava syndrome.
Airway compromise can be life threatening. Mediastinal lymphadenopathy is usually a sign of a 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 generally involve the anterior mediastinum.
These malignant tumors are associated with a high risk of superior vena cava syndrome and are associated with several life-threatening complications, including the following:
- The danger of sedation of patients, especially in the supine position for examinations and procedures (the prone position may be safer.)
- Risk during intubation in these patients, usually at the time of biopsy or central venous catheter placement.
- The risk of cardiovascular collapse during general anesthesia due to compression of venous return or previously undiagnosed pleural effusions.
- The risk of losing the ability to make a pathological diagnosis due to the use of steroids or radiation therapy.
Unlike most other lymphadenopathies, mediastinal lymphadenopathy is less common as a result of infection.
Infections frequently involve the hilar region and include histoplasmosis, coccidioidomycosis, and tuberculosis. Non-lymphoid tumors of the mediastinum can be mistaken for adenopathy.
These include neurogenic tumors (usually found in the posterior mediastinum), germ cell tumors, and teratomas.
Non-neoplastic conditions can also be confused with mediastinal adenopathy.
These include a child’s typically large thymus, substernal thyroid glands, bronchogenic cysts, and abnormalities of the great vessels.
Supraclavicular nodules drain the head, neck, arms, superficial chest, lungs, mediastinum, and abdomen.
The left supraclavicular nodes also reflect intra-abdominal drainage and are enlarged in response to malignant tumors in this region.
This is particularly true when adenopathy in this region occurs in the absence of other cervical adenopathy.
The right supraclavicular nodes drain the lung and mediastinum and are usually enlarged with intrathoracic lesions.
Serious underlying disease is common in children with supraclavicular adenopathy and always warrants further evaluation.
The potential for malignancy requires peripheral blood counts, skin tests for tuberculosis, and chemical studies, including uric acid, lactate dehydrogenase, calcium (Ca), phosphorus (P), and studies of kidney and liver function.
Chest radiography and possibly computed tomography are indicated. Several major infections with supraclavicular adenopathy can occur, including tuberculosis, histoplasmosis, and coccidioidomycosis.
An early lymph node biopsy should be considered in children with supraclavicular adenopathy.
The axillary nodes drain the hand, arm, lateral thorax, abdominal walls, and the lateral portion of the breast. A common cause of axillary lymphadenopathy is cat disease .
Local infection of the axillary skin and irritation are commonly associated with local adenopathy.
Other etiologies include recent arm immunizations (particularly with Calmette-Guerin vaccine bacillus), brucellosis, juvenile rheumatoid arthritis, and non-Hodgkin lymphoma.
Hyporadenitis suppurativa is an enlarged lymph node condition that typically affects obese children and is caused by recurrent lymph node abscesses in the axillary chain.
The etiology is unknown, and treatment may include antibiotics. Many patients require incision and drainage.
Abdominal lymph node enlargement
The abdominal ganglia drain the lower extremities, pelvis, and abdominal organs.
Although abdominal adenopathy is not usually demonstrable on physical examination, abdominal pain, back pain, increased urinary frequency, and constipation are possible presentations.
Mesenteric adenitis is believed to be etiologic and characterized by right lower quadrant abdominal pain caused by lymph node dilation near the ileocecal valve.
Differentiating mesenteric adenitis from appendicitis can be difficult. Mesenteric adenopathy can be caused by non-Hodgkin’s lymphoma or Hodgkin’s disease.
Typhoid fever and ulcerative colitis are other etiologies of mesenteric adenopathy.
Lyme and inguinal lymph node enlargement
They are found in the lower extremities, perineum, buttocks, genitals, and drainage of the lower abdominal wall to these nodules. They are typically palpable in healthy children, although they are generally no more than 1-1.5 cm in diameter.
Regional lymphadenopathy is usually caused by an infection. However, insect bites and diaper rash are also common.
Non-lymphoid masses that can be mistaken for adenopathy include hernias, ectopic testes, and lipomas.
If a particular disorder is suspected, tests are done to check for that condition.
If the medical history and the patient’s findings after physical examination do not point to any particular cause, further tests are done based on which nodes are involved and what other findings are present.
Examples of tests that can be performed include the following:
A complete blood count to check the number of red blood cells, white blood cells, and blood clotting cells. Urine tests and other types of blood tests may also be done.
Pictures of the chest are taken to check for enlarged lymph nodes or other problems.
Most doctors think that if the adenopathy is localized and there are no other findings, then the patient can be safely watched for three to four weeks, unless there is a possibility of cancer.
If cancer is suspected, a lymph node tissue biopsy is taken and sent for microscopic analysis in a laboratory. A biopsy is also done if the adenopathy does not resolve after three to four weeks.
Initial treatment is directed at the cause of the adenopathy rather than the adenopathy itself.
Corticosteroids are not used to treat adenopathy without an identifiable cause, as these drugs can shrink enlarged lymph nodes caused by cancer and delay diagnosis.
Antibiotics are also not prescribed, unless the cause is thought to be a suppurating lymph node infection.
Complications are generally related to the specific underlying disorder causing the lymphadenopathy; however, lymphadenopathy itself can cause potentially serious complications.
Mediastinal adenopathy can lead to several life-threatening complications.
Recognition of these complications is important because mediastinal adenopathy cannot be directly assessed clinically and therefore can be easily missed.
Mediastinal adenopathy can cause superior vena cava syndrome with obstruction of blood flow; bronchial or tracheal obstruction with coughing and wheezing.
Ultimately, it causes obstruction of the respiratory tract (which can be life threatening); and esophageal compression dysphagia.
Occasionally, erosion of a nodule in a bronchus or trachea can lead to 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 acidic kidney failure .
Abdominal adenopathy can cause abdominal or back pain, constipation, and urinary frequency. Intestinal obstruction caused by intussusception can be life-threatening.