Lymphadenitis

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

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).

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 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.