Lymphadenitis

Background
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.

Pathophysiology

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

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

History

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

Physical

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 Table 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

Causes
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]
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

Lymphadenitis Differential
Diagnoses
Diagnostic Considerations
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 lower extremities.
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
Sarcoidosis
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
Sarcoidosis
Intra-abdominal or retroperitoneal lymph nodes
Intra-abdominal or retroperitoneal lymph nodes
receive lymph drainage from local structures, which
is detected via 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)

Lymphadenitis Workup
Laboratory Studies

Differential Diagnoses

Acute Complications of Sarcoidosis

Brucellosis
Catscratch Disease
Cystinosis
Gaucher Disease
Gianotti-Crosti Syndrome
Group A Streptococcal Infections
Hemolytic Disease of Newborn
Histiocytosis
Hodgkin Lymphoma
Hyperimmunoglobulinemia E (Job)
Syndrome
Juvenile Idiopathic Arthritis
Kawasaki Disease
Lymphadenopathy
Neuroblastoma
Pediatric Chronic Granulomatous Disease
Pediatric Cytomegalovirus Infection

Pediatric Graft Versus Host Disease

Pediatric Mononucleosis and Epstein-Barr
Virus Infection
Pediatric Non-Hodgkin Lymphoma
Pediatric Plague
Pediatric Rhabdomyosarcoma
Pediatric Salmonella Infection
Pediatric Serum Sickness
Pediatric Thalassemia
Pediatric Tuberculosis
Sickle Cell Anemia
Sphingomyelinase Deficiency
Staphylococcus Aureus Infection
Thyroiditis
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
B henselae 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 interferongamma release assays (IGRA)
CBC count - Elevated WBC count may
indicate an infectious etiology
Erythrocyte sedimentation rate (ESR), Creactive 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

Imaging Studies
Ultrasonography may be useful for verifying lymph
node involvement and taking accurate
measurements of enlarged nodes. Ultrasound is
not able to differentiate between benign and
malignant forms of lymphadenopathy.
Chest radiography may be helpful in determining
pulmonary involvement or spread of
lymphadenopathy to the chest.

Procedures

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).

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 provide traction to
assist the removal.

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 atypical
mycobacterial lymphadenitis, neither incision and
drainage nor FNA should be performed as either of
these may increase the risk of fistula formation and
drainage.
A study reported on the accuracy and safety of
endobronchial ultrasound (EBUS) transbronchial
needle aspiration (TBNA) for the diagnosis of
tuberculous mediastinal lymphadenitis. The study
concluded that EBUS-TBNA is a safe and well
tolerated procedure in the assessment of patients
with suspected isolated mediastinal lymphadenitis.
The authors add that EBUS-TBNA should be
considered the procedure of choice for patients in
whom TB is suspected.[9]

Lymphadenitis Treatment
& Management
Medical Care
In patients with lymphadenitis, treatment depends
on the causative agent and may include expectant
management, antimicrobial therapy, or
chemotherapy and radiation (for malignancy).[10]

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.
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.
[11]
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

Consultations

Depending on the suspected etiology,

consultations with the following specialists may be
appropriate:
Infectious diseases specialist
Hematologist/oncologist
Dermatologist
Otolaryngologist
Surgeon
Interventional radiologist

Lymphadenitis Follow-up
Complications

The following complications may occur:

Cellulitis
Suppuration
Systemic involvement
Internal jugular vein thrombosis
Septic embolic phenomena
Carotid artery rupture
Mediastinal abscess
Purulent pericarditis

Prognosis
Prognosis depends on the etiology of the
lymphadenopathy and timing of intervention.