What are the causes of lymphadenitis?

Causes of Lymphadenitis

Lymphadenitis is most commonly caused by acute bacterial infection (Staphylococcus aureus and Group A Streptococcus in 40-80% of cases), viral upper respiratory infections, or mycobacterial infections, with the specific etiology varying significantly by age, anatomic location, and acuity of presentation. 1, 2

Acute Bacterial Causes

• Staphylococcus aureus and Streptococcus pyogenes are the predominant pathogens in acute unilateral cervical lymphadenitis, accounting for 40-80% of cases in both children and adults 1, 2
• Methicillin-susceptible S. aureus (49%) and Group A Streptococcus (43%) dominate in culture-positive cases, while methicillin-resistant S. aureus represents only 6% in low-prevalence settings 3
• Suppurative lymphadenitis with abscess formation typically results from these bacterial pathogens and shows characteristic necrosis with abscess formation on histopathology 4, 5

Viral Causes

• Viral upper respiratory tract infections are the most common antecedent event, reported in 22-53% of lymphadenitis cases, and typically cause acute bilateral cervical lymphadenopathy 6, 1
• Epstein-Barr virus, Cytomegalovirus, Coxsackievirus, and Rubella are specific viral pathogens that cause mesenteric and cervical lymphadenitis 6
• Viral infections produce nonspecific follicular and/or paracortical hyperplasia on histopathology, distinguishing them from bacterial causes 4

Mycobacterial Causes

Nontuberculous Mycobacteria (NTM)

• Mycobacterium avium complex (MAC) causes approximately 80% of culture-proven NTM lymphadenitis, representing a dramatic shift from 30 years ago when M. scrofulaceum predominated 7
• NTM lymphadenitis primarily affects children aged 1-5 years (submandibular, submaxillary, cervical, or preauricular nodes) and rarely affects adults without HIV infection 7
• Geographic variation exists: M. scrofulaceum causes remaining cases in the United States and Australia, while M. malmoense and M. haemophilum predominate in Scandinavia and northern Europe 7
• The chlorination of tap water likely eliminated chlorine-sensitive M. scrofulaceum, explaining MAC's current dominance 7

Tuberculous Mycobacteria

• Mycobacterium tuberculosis causes more than 90% of culture-proven mycobacterial lymphadenitis in adults, making it the most critical diagnosis to exclude in this population 7, 8
• In children, only about 10% of culture-proven mycobacterial cervical lymphadenitis is due to M. tuberculosis 7
• Tuberculous lymphadenitis requires public health tracking and standard 4-drug anti-tuberculosis therapy, unlike NTM disease 8

Other Infectious Causes

• Cat-scratch disease (Bartonella henselae) is a common cause of subacute or chronic lymphadenitis in children 1, 2
• Toxoplasma gondii produces characteristic follicular hyperplasia, monocytoid B-cell hyperplasia, and clusters of epithelioid histiocytes 4
• Campylobacter jejuni can trigger mesenteric lymphadenitis, particularly in Asia 6

Non-Infectious Causes

• Inflammatory bowel disease, particularly ulcerative colitis, can present with mesenteric lymphadenitis 6
• Adult-onset Still's disease may present with abdominal pain and mesenteric lymphadenopathy 6
• Lymphoma and leukemia should be strongly considered in adults with persistent lymphadenopathy, as supraclavicular or posterior cervical nodes carry much higher malignancy risk than anterior cervical nodes 6, 2
• Autoimmune and noninfectious inflammatory disorders (including Kikuchi-Fujimoto lymphadenitis) can mimic infectious lymphadenitis and even lymphomas 4

Special Population Considerations

HIV-Infected Patients

• Disseminated MAC commonly causes suppurative lymphadenopathy in HIV patients with CD4 counts below 50 cells/μL, though most do not have active pulmonary disease 7
• Immune reconstitution inflammatory syndrome can cause paradoxical lymphadenitis (painful, swollen cervical, axillary, or inguinal nodes) after initiating antiretroviral therapy 7
• Cytomegalovirus colitis with mesenteric lymphadenitis carries high mortality if misdiagnosed in immunocompromised patients 6

Critical Diagnostic Pitfalls

• Distinguishing tuberculous from NTM lymphadenitis is essential: tuberculosis requires drug therapy and public health tracking, while NTM may be managed surgically 7, 8
• Tuberculin skin testing is mandatory in all suspected mycobacterial cases, though children with NTM can show reactions of 10 mm or more induration in up to one-third of cases 7
• History of TB exposure, foreign-born status, and chest radiograph findings (abnormal in 38% of TB cases) help differentiate etiologies 8
• Incisional biopsy or drainage alone for mycobacterial lymphadenitis frequently leads to sinus tract formation and chronic drainage—complete excision is preferred for NTM 8