Basics
Description
- Term used to describe ≥1 enlarged lymph nodes >10 mm in diameter (for inguinal nodes, >15 mm; for epitrochlear nodes, >5 mm)
- Any palpable supraclavicular and popliteal lymph node is considered abnormal.
Epidemiology
Incidence
Depends on the underlying process that causes lymph node enlargement
Prevalence
Palpable nodes are present in 5 " 25% of newborns (cervical, axillary, inguinal) and in >50% of older children (all areas except epitrochlear, supraclavicular, and popliteal).
Pathophysiology
- Lymph nodes are often palpable in normal, healthy children.
- Normal lymph nodes: generally <10 mm
- They are present from birth, peak in size between 8 and 12 years of age, and then regress during adolescence.
- Lymph nodes drain contiguous areas.
- Cervical nodes drain head and neck area (up to 15% of biopsied nodes are malignant).
- Axillary nodes drain arm, thorax, and breast.
- Epitrochlear nodes drain forearm and hand.
- Inguinal nodes drain leg and groin.
- Supraclavicular nodes drain thorax and abdomen.
- Lymphatic flow from adjacent nodes or inoculation site brings microorganisms to lymph nodes.
- Lymph node enlargement may occur via any of the following mechanisms:
- Nodal cells may replicate in response to antigenic stimulation (e.g., Kawasaki disease) or malignant transformation (e.g., lymphoma).
- Lymphocyte proliferation due to immune defect (e.g. primary immunodeficiency disease [PIDD])
- Large number of reactive cells from outside node (e.g., neutrophils or metastatic cells) may enter node.
- Foreign material may be deposited into node by lipid-laden histiocytes (e.g., lipid storage diseases).
- Vascular engorgement and edema may occur secondary to local cytokine release.
- Suppuration secondary to tissue necrosis (e.g., Mycobacterium tuberculosis)
- Many systemic infections (e.g., HIV) cause hepatic or splenic enlargement in addition to generalized lymphadenopathy.
Etiology
Usually determined by performing a thorough history and physical exam
Commonly Associated Conditions
Many systemic infections, malignancy, and lymphoproliferative disorders cause hepatic or splenic enlargement in addition to generalized lymphadenopathy.
Diagnosis
History
- Preceding symptoms (e.g., URI symptoms preceding cervical lymphadenopathy)
- Localizing signs or symptoms (e.g., stomatitis may be associated with submandibular lymphadenopathy)
- Duration
- Acute (<3 weeks)
- Subacute (3 " 6 weeks)
- Chronic (>6 weeks)
- Constitutional or associated symptoms (e.g., fever, weight loss, or night sweats)
- Exposures
- Cat exposure (cat-scratch disease)
- Uncooked meat (Toxoplasmosis)
- Tick bite (Lyme disease)
- Medications (e.g., phenytoin or isoniazid) or prior treatments
- Travel to or residence in an endemic area should raise suspicion for tuberculosis and Lyme disease.
- History of recurrent, deep seated, or opportunistic infections, family history of PIDD
- Signs and symptoms
- Localized lymphadenopathy: involves enlarged nodes in any 1 region
- Generalized lymphadenopathy: involves ≥2 noncontiguous regions secondary to a systemic process, such as EBV infection
- Supraclavicular nodes seen with malignancy: Right-sided supraclavicular node is associated with mediastinal malignancy; left-sided node suggests abdominal malignancy.
Physical Exam
- Complete physical exam is imperative to look for signs of systemic disease such as skin, oropharyngeal, or ocular findings or hepatosplenomegaly.
- The child 's weight should also be checked to be sure there has been no weight loss.
- If localized lymphadenopathy is suspected, examine the area that the lymph node drains for pathology. For example, an arm papule may be associated with axillary lymphadenopathy in cat-scratch disease.
- Cervical, axillary, and inguinal nodes, as well as liver and spleen, must be palpated to help determine if signs of systemic disease or infection are present.
- Characterize nodes. Be sure to note the following:
- Location: Be as exact as possible (see above).
- Size: specify dimensions.
- Consistency: soft, firm, solid, cystic, fluctuant, rubbery. Firm, rubbery nodes may be associated with lymphomas, whereas soft nodes are generally palpated with reactive lymphadenopathy.
- Fixation: normally freely mobile; infection or malignancy may cause adherence to surrounding tissues or nodes.
- Tenderness: suggests inflammation
Diagnostic Tests & Interpretation
Lab
Consider the following tests if ≥1 node is persistently enlarged, has increased in size, has changed in consistency or mobility, or if systemic symptoms are present:
- CBC with differential: Consider with generalized lymphadenopathy, or if malignancy is in differential diagnosis.
- ESR or CRP: increased with infection or inflammation
- Lactate dehydrogenase (LDH), uric acid, and liver enzymes: Consider if history and physical exam raise concern for malignancy or hepatomegaly.
- Throat culture: if concern for group A ²-hemolytic streptococcal (GAS) pharyngitis
- EBV/cytomegalovirus (CMV) titers: Consider with persistent generalized adenopathy.
- Bartonella henselae titers: Consider with persistently enlarged unilateral node and/or history of cat exposure.
- Purified protein derivative (PPD) testing: Consider with persistently enlarged node (2 " 4 weeks) or travel to areas where tuberculosis is endemic.
- HIV testing: Consider with persistent generalized lymphadenopathy and failure to thrive.
- Antinuclear antibody (ANA): if other signs of systemic disease to rule out systemic lupus erythematosus (SLE)
- Consider STD testing in adolescents (e.g., RPR).
- Other infectious workup as dictated by history and physical findings (e.g., Lyme titers for bull 's eye rash)
Imaging
- Chest radiograph: helpful with supraclavicular nodes, systemic symptoms, or if positive PPD
- Ultrasound: may help differentiate cystic from solid masses
- CT: may help delineate anatomy or extent of the lesion, iliac lymphadenopathy is abnormal
Diagnostic Procedures/Other
- Biopsy should be considered if
- Nodes are persistently enlarged, especially if accompanied by signs of systemic disease such as hepatosplenomegaly, weight loss, and exanthema.
- Nodes are fixed to underlying skin.
- Ulcerations or skin changes are present.
- Not responsive to conventional therapy
- Node is supraclavicular, nontender, or increasing in size or firmness.
- Fine-needle aspiration: cost-effective but sometimes nondiagnostic (e.g., unable to assess architecture); may result in fistulous tract
- Open biopsy: often diagnostic but requires general anesthesia
Differential Diagnosis
Must be carefully differentiated from lymphadenitis, defined as lymph node enlargement with signs of inflammation (including erythema, tenderness, induration, warmth); often treated with antibiotics
- Localized lymphadenopathy
- Generally occurs as reactive adenopathy in response to local infection
- Differential diagnosis for localized adenopathy varies depending on affected site.
- Cervical adenopathy: includes cystic hygroma, branchial cleft cyst, and thyroglossal duct cyst
- Inguinal adenopathy: lower extremity infection (e.g., osteomyelitis) or perineal disease
- Generalized lymphadenopathy: may be seen in many systemic illnesses
- Viral infections: EBV, CMV, adenovirus, HSV, HIV, enterovirus, rubella, measles virus, varicella virus, viral hepatitides
- Bacterial infections: Staphylococcus aureus, B. henselae, GAS, Salmonella, Yersinia, brucellosis, tularemia, Mycobacterium tuberculosis, Mycoplasma pneumoniae, rickettsiae
- Primary immunodeficiency diseases: common variable immunodeficiency disease, X-linked lymphoproliferative syndrome, autoimmune lymphoproliferative syndrome, hyper-IgM syndrome
- Malignancy: lymphoma, neuroblastoma, leukemia
- Autoimmune disorders: SLE, juvenile rheumatoid arthritis
- Other infections: parasites (e.g., Chagas disease) or fungal infections
- Medications can cause drug-induced hypersensitivity syndromes (e.g., DRESS): aromatic anticonvulsants, sulfonamides, allopurinol
- Miscellaneous: Kawasaki disease, Castleman disease, Kikuchi-Fujimoto disease (histiocytic necrotizing lymphadenitis), Gianotti-Crosti syndrome (papular acrodermatitis), sarcoidosis, lipid storage diseases (Niemann-Pick, Gaucher, Wolman, Faber diseases)
Treatment
Medication
Acute lymphadenitis should be treated with antibiotics directed against Streptococcus and Staphylococcus.
First Line
- Dicloxacillin 50 " 100 mg/kg/24 h PO in 4 divided doses; max 4 g/24 h OR
- Amoxicillin-clavulanic acid 45 mg/kg/24 h PO in 2 divided doses, children >40 kg adult dosing
- Consider using clindamycin 30 mg/kg/24 h PO in 3 divided doses OR trimethoprim-sulfamethoxazole (TMP " SMX) 8 " 10 mg TMP/kg/24 h PO/IV in 2 divided doses in areas with a high prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in the community.
- Penicillin-allergic patients: clindamycin 30 mg/kg/24 h PO in 3 divided doses or: erythromycin 50 mg/kg/24 h PO in 4 divided doses
Second Line
Consider broader antibiotic coverage for B. henselae and atypical mycobacterium: oral: azithromycin 10 mg/kg dose on day 1, followed by 5 mg/kg divided once for 4 more days
Additional Treatment
General Measures
- Treat underlying disease.
- Close observation, unless history and physical suggest malignancy or lymphadenitis
Issues for Referral
Refer to surgery or otolaryngology if biopsy or excision required.
Surgery/Other Procedures
Excision for special, prolonged cases
Ongoing Care
Follow-up Recommendations
Patient Monitoring
- Localized lymphadenopathy: Observe for several weeks or treat with antibiotics if indicated.
- Serial observation if nodes are persistently enlarged
Prognosis
- Depends on underlying diagnosis
- Excellent for reactive lymphadenopathy
Complications
- Lymphadenitis
- Local infection (e.g., cellulitis)
- Lymph node abscess
- Sepsis via hematogenous spread of inadequately contained infection
- Fistula (e.g., with atypical mycobacteria)
- Fibrosis secondary to purulence or lymphadenitis
- Stridor secondary to enlarged cervical lymph nodes
- Wheezing secondary to enlarged parabronchial mediastinal lymph nodes
Additional Reading
- Albright JT, Pransky SM. Nontuberculous mycobacterial infections of the head and neck. Pediatr Clin North Am. 2003;50(2):503 " 514. [View Abstract]
- Bamji M, Stone RK, Kaul A, et al. Palpable lymph nodes in healthy newborns and infants. Pediatrics. 1986;78(4):573 " 575. [View Abstract]
- Brook I. Microbiology and antimicrobial management of head and neck infections in children. Adv Pediatr. 2008;55:305 " 325. [View Abstract]
- Friedmann AM. Evaluation and management of lymphadenopathy in children. Pediatr Rev. 2008;29(2):53 " 60. [View Abstract]
- Gosche JR, Vick L. Acute, subacute, and chronic cervical lymphadenitis in children. Semin Pediatr Sur. 2006;15(2):99 " 106. [View Abstract]
- Nield LS, Kamat D. Lymphadenopathy in children: when and how to evaluate. Clin Pediatr. 2004;43(1):25 " 33. [View Abstract]
- Rajasekaran K, Krakovitz P. Enlarged neck lymph nodes in children. Pediatr Clin North Am. 2013;60(4): 923 " 936. [View Abstract]
- Twist CJ, Link MP. Assessment of lymphadenopathy in children. Pediatr Clin North Am. 2002; 49(5):1009 " 1025. [View Abstract]
Codes
ICD09
- 785.6 Enlargement of lymph nodes
- 130.7 Toxoplasmosis of other specified sites
- 771.2 Other congenital infections specific to the perinatal period
- 289.3 Lymphadenitis, unspecified, except mesenteric
ICD10
- R59.1 Generalized enlarged lymph nodes
- R59.0 Localized enlarged lymph nodes
- P37.1 Congenital toxoplasmosis
- B58.89 Toxoplasmosis with other organ involvement
SNOMED
- 30746006 Lymphadenopathy (disorder)
- 274741002 Generalized enlarged lymph nodes
- 281898005 Lymphadenopathy due to congenital toxoplasmosis (disorder)
- 274744005 Localized enlarged lymph nodes (disorder)
FAQ
- Q: When should there be concern about malignancy in a child with lymphadenopathy?
- A: Malignancy should be considered in any child who has lymphadenopathy that does not improve in spite of antibiotic therapy, that has a location of concern (e.g., supraclavicular) or physical exam features of concern (hard, large size [>2 cm]) that persistently enlarges, or if the child shows signs of systemic disease.
- Q: When should a workup of a well child with localized lymphadenopathy be pursued?
- A: As long as the lymph nodes are soft, mobile, and nontender, the lymphadenopathy is likely to be self-limited. If the cause is unclear, then children should be observed for a couple of weeks. Further workup is needed if the nodes persist or enlarge, if the location is worrisome (e.g., supraclavicular), or if there are signs of systemic disease (e.g., hepatomegaly or weight loss).
- Q: When should a child with lymphadenopathy be referred to a specialist?
- A: Most cases of lymphadenopathy in children are self-limited and can be observed for a few weeks and/or treated with antibiotics, if appropriate. Referral to a surgeon should be considered in any child with persistently enlarged lymphadenopathy (>4 weeks) or immediately if there are signs of malignancy. If there is a history of recurrent or opportunistic infections, referral to an immunologist or infectious disease specialist is warranted.