Lymphadenitis is the inflammation or enlargement of a lymph node. Lymph nodes are small, ovoid nodules normally ranging in size from a few millimeters to 2 cm. They are distributed in clusters along the course of lymphatic vessels located throughout the body. The primary function of lymph nodes is to filter out microorganisms and abnormal cells that have collected in lymph fluid.[1]
Lymph node enlargement is a common feature in a variety of diseases and may serve as a focal point for subsequent clinical investigation of diseases of the reticuloendothelial system or regional infection. The majority of cases represent a benign response to localized or systemic infection. Most children with lymphadenitis exhibit small, palpable cervical, axillary, and inguinal lymph nodes. Less common is enlargement of the suboccipital or postauricular nodes. Palpable supraclavicular, epitrochlear, and popliteal lymph nodes are uncommon, as are enlarged mediastinal and abdominal nodes.
Lymphadenitis may affect a single node or a group of nodes (regional adenopathy) and may be unilateral or bilateral. The onset and course of lymphadenitis may be acute, subacute, or chronic.
Increased lymph node size may be caused by the following:
Multiplication of cells within the node, including lymphocytes, plasma cells, monocytes, or histiocytes
Infiltration of cells from outside the node, such as malignant cells or neutrophils
Draining of an infection (eg, abscess) into local lymph nodes
Patients with a clinical history of any of the following may be at risk for developing lymphadenitis:
Symptoms of an upper respiratory tract infection, sore throat, earache, coryza, conjunctivitis, or impetigo
Fever, irritability, or anorexia
Contact with animals, especially kittens or livestock
Recent dental care or poor dental health
Recent use of hydantoin and/or mesantoin
Enlarged lymph nodes can be asymptomatic, or they can cause local pain and tenderness. Overlying skin may be unaffected or erythematous.
Cervical lymphadenitis can lead to neck stiffness and torticollis.
Preauricular adenopathy is associated with several forms of conjunctivitis, including unilocular granulomatous conjunctivitis (catscratch disease, chlamydial conjunctivitis, listeriosis, tularemia, or tuberculosis), pharyngeal conjunctival fever (adenovirus type 3 infection) and keratoconjunctivitis (adenovirus type 8 infection).
Retropharyngeal node inflammation can cause dysphagia or dyspnea.
Mediastinal lymphadenitis may cause cough, dyspnea, stridor, dysphagia, pleural effusion, or venous congestion.
Intra-abdominal (mesenteric and retroperitoneal) adenopathy can manifest as abdominal pain.
Iliac lymph node involvement may cause abdominal pain and limping.
Aspects of the physical examination are as follows:
Location - Depends on underlying etiology (see Causes section below)
Number - Single, local groupings (regional), or generalized (ie, multiple regions)
Size/shape - Normal lymph nodes range in size from a few millimeters to 2 cm in diameter; enlarged nodes are greater than 2-3 cm with regular/irregular shapes
Consistency - Soft, firm, rubbery, hard, fluctuant, warm
Tenderness - Suggestive of an infectious process but does not rule out malignant causes
Physical examination findings suggestive of malignancy are as follows:
Firm
Hard
Fixed
Nontender
Physical examination findings suggestive of infection are as follows:
Soft
Fluctuant
Tender
Overlying erythema or streaking
Infectious agents/causes and lymphadenitis characteristics are as follows[2] :
Bartonella henselae (catscratch disease) – Single-node involvement determined by scratch site; discrete, mobile, nontender
Coccidioides immitis (coccidioidomycosis) – Mediastinal
Cytomegalovirus – Generalized
Dental caries/abscess – Submaxillary
Epstein-Barr virus (mononucleosis) - Anterior cervical, mediastinal, bilateral; discrete, firm, nontender
Francisella tularensis (tularemia) - Cervical, mediastinal, or generalized; tender
Histoplasma capsulatum (histoplasmosis) – Mediastinal
Atypical Mycobacterium - Cervical, submandibular, submental (usually unilateral); most commonly in immunocompetent children aged 1-5 years[3, 14]
Mycobacterium tuberculosis - Mediastinal, mesenteric, anterior cervical, localized disease (discrete, firm, mobile, tender); generalized hematogenous spread (soft, fluctuant, matted, and adhere to overlying, erythematous skin)
Parvovirus - Posterior auricular, posterior cervical, occipital
Rubella - Posterior auricular, posterior cervical, occipital
Salmonella – Generalized
Seborrheic dermatitis, scalp infections - Occipital, postauricular
Staphylococcus aureus adenitis - Cervical, submandibular; unilateral, firm, tender
Group A streptococcal (GAS) pharyngitis - Submandibular and anterior cervical; unilateral, firm, tender
Toxoplasma gondii - Generalized, often nontender
Viral pharyngitis - Bilateral postcervical; firm, tender
Yersinia enterocolitica - Cervical or abdominal
Yersinia pestis (plague) - Axillary, inguinal, femoral, cervical; extremely tender with overlying erythema
Immunologic or connective tissue disorders causing lymphadenitis are as follows:
Juvenile rheumatoid arthritis
Graft versus host disease
Primary diseases of lymphoid or reticuloendothelial tissue causing lymphadenitis are as follows:
Acute lymphoblastic leukemia
Lymphosarcoma
Reticulum cell sarcoma
Non-Hodgkin lymphoma
Malignant histocytosis or histocytic lymphoma
Nonendemic Burkitt tumor
Nasopharyngeal rhabdomyosarcoma
Neuroblastoma
Thyroid carcinoma, chronic lymphocytic thyroiditis
Histiocytosis X
Kikuchi disease
Benign sinus histiocytosis
Angioimmunoblastic or immunoblastic lymphadenopathy
Chronic pseudolymphomatous lymphadenopathy (chronic benign lymphadenopathy)
Immunodeficiency syndromes and phagocytic dysfunction causing lymphadenitis are as follows:
Chronic granulomatous disease of childhood
Acquired immunodeficiency syndrome
Hyperimmunoglobulin E (Job) syndrome
Metabolic and storage diseases causing lymphadenitis are as follows:
Gaucher disease
Niemann-Pick disease
Cystinosis
Hematopoietic diseases causing lymphadenitis are as follows:
Sickle cell anemia
Thalassemia
Congenital hemolytic anemia
Autoimmune hemolytic anemia
Miscellaneous disorders causing lymphadenitis are as follows:
Kawasaki disease
PFAPA (periodic fever, aphthous stomatitis, pharyngitis, and adenitis) syndrome
Sarcoidosis
Castleman disease (also known as benign giant lymph node hyperplasia)
Medications causing lymphadenitis are as follows:
Mesantoin – most commonly causes cervical lymphadenitis
Hydantoin - Generalized lymphadenopathy
Regional lymphadenitis
In a patient with regional lymphadenitis, knowledge of lymphatic drainage patterns and pathologic processes most likely to affect these areas can facilitate diagnostic investigation.[4]
Cervical lymph nodes
Cervical lymph nodes receive lymphatic drainage from the head, neck, and oropharyngeal cavities.
Infections associated with cervical lymph nodes are as follows[5] :
Skin and soft tissue infections of the face
Dental abscesses
Otitis externa
Bacterial pharyngitis
Cytomegalovirus
Adenovirus infection
Rubella
Toxoplasmosis
Malignancies associated with cervical lymph nodes are as follows:
Hodgkin lymphoma
Non-Hodgkin lymphomas
Squamous cell carcinomas of nasopharyngeal or laryngeal structures
Axillary lymph nodes
Axillary lymph nodes receive lymphatic drainage from upper extremities and breasts.
Infections associated with axillary lymph nodes are as follows:
B henselae infection (catscratch disease)
Sporotrichosis
Tularemia
Staphylococcal or streptococcal skin infections
Malignancies associated with axillary lymph nodes are as follows:
Lymphoma
Melanoma
Carcinoma of the breast
Epitrochlear lymph nodes
Epitrochlear lymph nodes receive lymphatic drainage from the hands.
Infections associated with epitrochlear lymph nodes are as follows:
Skin and soft tissue infections from local trauma
Malignancies associated with epitrochlear lymph nodes are as follows:
Lymphoma
Supraclavicular lymph nodes
Supraclavicular lymph nodes receive lymphatic drainage from the chest and mediastinum.
Infections associated with supraclavicular lymph nodes are as follows:
Intrathoracic mycobacterial, fungal infections (not bacterial pneumonias or bronchial infections)
Malignancies associated with supraclavicular lymph nodes are as follows (Note: supraclavicular lymphadenitis is an ominous sign of malignancy):
Intrathoracic and intra-abdominal malignancies (Note: left-sided supraclavicular sentinel node or the Virchow node is highly suggestive of an occult abdominal neoplasm.)
Breast cancer
Other diseases associated with supraclavicular lymph nodes are as follows:
Inguinal lymph nodes
Inguinal lymph nodes receive lymphatic drainage from the lower extremities and skin of the lower abdomen, genitals, and perineum.[6]
Infections associated with inguinal lymph nodes are as follows:
Cellulitis of the lower extremities
Venereal infections - Syphilis, chancroid, herpes simplex virus infection, lymphogranuloma venereum
Malignancies associated with inguinal lymph nodes are as follows:
Lymphomas
Metastatic melanomas from lower extremity primary site
Squamous cell carcinomas from genital primary site
Note: lymphatic drainage from internal pelvic organs and testes drain via iliac nodes into the para-aortic chain. Therefore, deep pelvic infections or malignancies do not present as inguinal lymphadenitis.
Hilar or mediastinal lymph nodes
Hilar or mediastinal lymph nodes receive lymph drainage from local structures and are usually found on radiologic examination.
Infections associated with hilar or mediastinal lymph nodes are as follows:
Tuberculosis
Fungal infections
Malignancies associated with hilar or mediastinal lymph nodes are as follows:
Bronchogenic carcinoma
Lymphoma
Hodgkin lymphoma
Other diseases associated with hilar or mediastinal lymph nodes are as follows:
Intra-abdominal or retroperitoneal lymph nodes
Intra-abdominal or retroperitoneal lymph nodes receive lymph drainage from local structures, these are typically detected by finding a palpable mass on physical examination or by obstructive/pressure effects on surrounding structures.
Infections associated with intra-abdominal or retroperitoneal lymph nodes are as follows:
Tuberculosis[7]
Y enterocolitica infection
Deep abscess
Malignancies associated with intra-abdominal or retroperitoneal lymph nodes are as follows:
Hodgkin lymphoma (pelvic and retroperitoneal nodes)
Non-Hodgkin lymphoma (mesenteric nodes)
Generalized lymphadenitis
In a patient with generalized lymphadenitis, the differential includes systemic conditions.
Associated medication toxicities are as follows:
Hydralazine
Allopurinol
Associated infections are as follows:
Epstein-Barr virus infection
Cytomegalovirus infection
Toxoplasmosis
HIV disease
Tuberculosis (advanced)
Histoplasmosis
Coccidioidomycosis
Brucellosis
Bacterial endocarditis
Hepatitis
Syphilis (secondary)
Associated immunologic diseases are as follows:
Sarcoidosis
Rheumatoid arthritis
Lupus
Associated malignancies are as follows:
Acute lymphoblastic leukemia
Chronic lymphocytic leukemia
Lymphomas
Angiofollicular lymph node hyperplasia (Castleman disease)
Brucellosis
Tularemia
Yersinia Enterocolitica Infection
Laboratory studies are as follows[8] :
Gram stain of aspirated tissue - To evaluate bacterial etiologies
Culture of aspirated tissue or biopsy specimen - To determine the causative organism and its sensitivity to antibiotics
Monospot or Epstein-Barr virus (EBV) serologies - To confirm the diagnosis of infectious mononucleosis
Bhenselae serologies - To confirm the diagnosis of catscratch disease (if exposed to cats)
Skin testing or purified protein derivative (PPD) - To confirm the diagnosis of tuberculous lymphadenopathy; alternative is interferon-gamma release assays (IGRA)[15]
CBC count - Elevated WBC count may indicate an infectious etiology
Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) - Elevated ESR and CRP are nonspecific indicators of inflammation
Liver function tests - May indicate hepatic or systemic involvement; elevated transaminase levels can be seen in infectious mononucleosis
Ultrasonography may be useful for verifying lymph node involvement and taking accurate measurements of enlarged nodes. A study by Wang et al indicated that endobronchial ultrasonography can aid in differentiating between nonmalignant intrathoracic lymphadenopathies, including tuberculosis, sarcoidosis, and reactive lymphadenitis. The investigators found that the presence of reactive lymphadenitis is predicted by the existence of central hilar structure and a lack of clustered formation, as well as by vascular pattern (hilar perfusion or avascularity). Best diagnostic accuracies of 77.1%, 89.2%, and 87.1% were found for tuberculous nodes, sarcoid nodes, and reactive lymphadenitis, respectively.[9]
Chest radiography may be helpful in determining pulmonary involvement or spread of lymphadenopathy to the chest.
Lymph node biopsy (see the image below), either partial or excisional, should be considered in cases in which lymphadenitis is not obviously related to an infectious cause, lymph nodes have remained enlarged for a prolonged period (4-6 wk), lymph nodes are in a supraclavicular location, lymph nodes have firm/rubbery consistency, ulceration is present, the patient has not responded to antibiotic therapy, or the patient has systemic symptoms (eg, fever, weight loss).
Fine-needle aspiration (FNA) is a technique used to obtain specimens for diagnostic testing. If malignancy is suspected, partial or excisional biopsy is preferred over FNA as FNA sampling may be inadequate for diagnosis.
Incision and drainage is the treatment for lymphadenitis with abscess formation. For NonTuberculosis Mycobacteria (NTM) lymphadenitis complete surgical excision is curative.
For the diganosis of isolated mediastinal lymphadenitis due to Tuberculosis Mycobacteria (TB), EndoBronchial UltraSound (EBUS) transbronchial needle aspiration has been reported to be a safe and well tolerated procedure.[10]
In patients with lymphadenitis, treatment depends on the causative agent and may include expectant management, antimicrobial therapy, excision or chemotherapy and radiation (for malignancy).[11]
Expectant management is used when lymph nodes are smaller than 3 cm, without overlying erythema, not exquisitely tender, and present for 2 weeks or less.
A study by Haimi-Cohen et al indicated that an observation-only management strategy can be effective in cases of craniofacial nontuberculous mycobacterial lymphadenitis. The study, of 21 children with the condition, found that 18 patients demonstrated scar formation (26 scars total) at median 6.8-year follow-up, with 21 scars being 3 cm long or less, 20 having normal vascularity, 18 having normal pigmentation, and 21 having a normal to mildly uneven surface. Ninety-four percent of patients’ parents were content overall with the observation-only approach as a management alternative.[12]
Antimicrobial therapy is used when nodes are greater than 2-3 cm, are unilateral, have overlying erythema, and are tender. Antibiotics should target common infectious causes of lymphadenopathy, including S aureus and GAS. Owing to the increasing prevalence of community-acquired methicillin-resistant S aureus (MRSA), empiric therapy with clindamycin should be considered.[13] Trimethoprim-sulfamethoxazole is often effective for MRSA infection, but it is not appropriate for GAS infections.
Chemotherapy and radiotherapy are used for treatment of malignancies.
For details on medical therapy, please refer to the Medscape Reference article that discusses the specific diagnosed condition, including the following:
Bronchiectasis
Brucellosis
Candidiasis
Catscratch Disease
Chronic Granulomatous Disease
Cystinosis
Cytomegalovirus Infection
Dental Abscess
Gaucher Disease
Gianotti-Crosti Syndrome
Graft Versus Host Disease
Hemolytic Disease of the Newborn
Histiocytosis
Histoplasmosis
Hodgkin Lymphoma
Hyperimmunoglobulin E (Job) Syndrome
Juvenile Rheumatoid Arthritis
Kawasaki Disease
Epstein-Barr Virus Infection or Mononucleosis
Neuroblastoma
Niemann-Pick Disease
Non-Hodgkin Lymphoma
Plague
Pharyngitis
Rhabdomyosarcoma
Rubella
Salmonella
Sarcoidosis
Serum Sickness
Sickle Cell Anemia
Sinusitis
Staphylococcus Aureus Infection
Group A Streptococcal Infection
Thalassemia
Thyroiditis
Toxoplasmosis
Tuberculosis
Tularemia
Yersinia Enterocolitica Infection
Depending on the suspected etiology, consultations with the following specialists may be appropriate:
Infectious diseases specialist
Hematologist/oncologist
Dermatologist
Otolaryngologist
Surgeon
Interventional radiologist
The following complications may occur:
Cellulitis
Suppuration
Systemic involvement
Internal jugular vein thrombosis
Septic embolic phenomena
Carotid artery rupture
Mediastinal abscess
Purulent pericarditis
Prognosis depends on the etiology of the lymphadenopathy and timing of intervention.
Overview
What causes increased lymph nodes in lymphadenitis?
Presentation
Which clinical history is characteristic of lymphadenitis?
What are the physical findings characteristic of lymphadenitis?
What should be included in the physical exam for lymphadenitis?
Which physical findings of lymphadenitis suggest malignancy?
Which physical findings of lymphadenitis suggest infection?
What are the manifestations of lymphadenitis by infectious agent?
Which immunologic or connective tissue disorders cause lymphadenitis?
Which primary diseases of lymphoid or reticuloendothelial tissue cause lymphadenitis?
Which immunodeficiency syndromes cause lymphadenitis?
Which metabolic and storage diseases cause lymphadenitis?
Which hematopoietic diseases cause lymphadenitis?
Which miscellaneous disorders cause lymphadenitis?
Which medications cause lymphadenitis?
DDX
What are diagnostic considerations for regional lymphadenitis?
What should be included in the differential diagnoses for cervical lymph nodes lymphadenitis?
What should be included in the differential diagnoses for axillary lymph nodes lymphadenitis?
What should be included in the differential diagnoses for supraclavicular lymph nodes lymphadenitis?
What should be included in the differential diagnoses for inguinal lymph nodes lymphadenitis?
What should be included in the differential diagnoses for hilar lymph nodes lymphadenitis?
What should be included in the differential diagnoses for generalized lymphadenitis?
What are the differential diagnoses for Lymphadenitis?
Workup
What is the role of lab studies in the workup of lymphadenitis?
What is the role of imaging studies in the workup of lymphadenitis?
Which procedures are indicated in the workup of lymphadenitis?
Treatment
What are the treatment options for lymphadenitis?
When is antimicrobial therapy indicated in the treatment of lymphadenitis?
What is the role of chemotherapy and radiotherapy in the treatment of lymphadenitis?
Which specialist consultations may be needed for the treatment of lymphadenitis?
Follow-up
What are possible complications of lymphadenitis?
What is the prognosis of lymphadenitis?