Limfadenitis

01Pathophysiology

Lymph nodes serve as immunologic filtration stations positioned along lymphatic drainage pathways. Afferent lymphatic vessels carry antigens, microorganisms, and immune cells from peripheral tissues into the node, where they encounter resident macrophages, dendritic cells, and lymphocytes within the cortex and paracortex. Lymphadenitis occurs when this filtration process triggers an inflammatory response within the node itself, either because the pathogen is directly proliferating in the nodal tissue or because the immune response to a drained infection is vigorous enough to cause nodal swelling and tenderness.

In acute bacterial lymphadenitis, organisms such as S. aureus or Group A Streptococcus spread from a primary site of infection (e.g., impetigo, pharyngitis, dental abscess) via afferent lymphatics into the draining node. The bacterial load overwhelms local macrophage clearance, triggering a neutrophilic inflammatory infiltrate. This is why you see rapid nodal enlargement, warmth, erythema, and tenderness. If the infection is not controlled, the center of the node undergoes liquefactive necrosis, forming a fluctuant abscess. This explains the clinical progression from a firm, tender node to a soft, fluctuant mass.

In cat-scratch disease, Bartonella henselae is inoculated through a scratch or bite from an infected kitten. The organism travels via lymphatics to the regional draining node (axillary from upper extremity inoculation, cervical from facial scratches). Here, the immune response forms stellate (star-shaped) granulomas with central microabscesses, a hallmark histologic pattern. The slow granulomatous process explains the subacute timeline (weeks, not days) and the characteristically indolent course.

In tuberculous lymphadenitis (scrofula), M. tuberculosis seeds the lymph node either through primary infection (via the lungs and hematogenous spread) or through reactivation of latent bacilli within the node. The hallmark pathologic finding is the caseating granuloma, a collection of epithelioid histiocytes and multinucleated Langhans giant cells surrounding a core of cheese-like (caseous) necrosis. This caseation is what distinguishes TB from other granulomatous causes. Over time, the caseous center may liquefy and form a cold abscess, which is non-tender and non-erythematous because the inflammatory response is granulomatous rather than pyogenic. The abscess can eventually erode through the skin, creating a draining sinus tract.

In nontuberculous mycobacterial (NTM) lymphadenitis, particularly caused by M. avium complex in immunocompetent children aged 1 to 5 years, the organism is typically acquired through oral mucosal inoculation (the child puts contaminated soil or water in their mouth). The submandibular and preauricular nodes are most commonly affected. The pathology shows non-caseating or poorly formed granulomas. The overlying skin develops a characteristic violaceous (purple-blue) discoloration, a finding that is nearly pathognomonic on the exam and distinguishes NTM from TB.

02Classification and Clinical Manifestation

By Duration and Course

By Location and Drainage Pattern

By Etiology

03Diagnostic Workup

The approach begins with a thorough history and physical examination. Key questions include the duration and rate of growth, associated symptoms (fever, weight loss, night sweats), animal exposures, travel to TB-endemic areas, dental health, and recent infections. On exam, note the size, location (unilateral vs. bilateral), tenderness, mobility, skin changes, and whether nodes are matted.

For a child presenting with an acute, unilateral, tender cervical node with fever and overlying erythema, the best initial step is empiric antibiotic therapy directed at S. aureus and GAS, without immediate imaging or biopsy. This is a common exam point: do not jump to biopsy for a straightforward acute presentation in a child.

If the node does not respond to antibiotics after 48 to 72 hours or if it becomes fluctuant, the next step is ultrasound. Ultrasound is the preferred initial imaging modality because it differentiates cellulitis/phlegmon from a drainable abscess, avoids radiation, and can guide needle aspiration. On ultrasound, an abscess appears as a hypoechoic collection with posterior acoustic enhancement and peripheral vascularity.

When cat-scratch disease is suspected (subacute adenopathy, kitten exposure, visible inoculation papule), order Bartonella henselae IgM and IgG serology. This is the confirmatory test for cat-scratch disease. Biopsy is rarely needed but, if performed, shows stellate granulomas with central microabscesses and organisms visible on Warthin-Starry silver stain.

When mycobacterial lymphadenitis is on the differential, PPD (tuberculin skin test) or IGRA (interferon-gamma release assay) is a key branching point:

• A strongly positive PPD (induration >15 mm) with risk factors favors TB.

• A weakly positive (5 to 10 mm) or negative PPD in a young child with a unilateral submandibular node and violaceous skin favors NTM.

• For TB, also obtain a chest X-ray and send sputum for AFB stain and culture if pulmonary disease is suspected.

FNA with cytology, AFB stain, and culture can provide rapid information but has limitations: it cannot assess nodal architecture, so it cannot reliably distinguish reactive hyperplasia from lymphoma. For this reason, excisional biopsy remains the gold standard when the diagnosis is uncertain after 4 to 6 weeks, when malignancy is suspected (hard, fixed, non-tender, supraclavicular node, constitutional symptoms), or when NTM is the suspected etiology (where excision is both diagnostic and therapeutic).

A critical exam principle: never perform incision and drainage on a suspected NTM node. I&D leads to chronic draining sinus tracts. Complete surgical excision is the correct approach.

04Management and Treatment

Acute Bacterial Lymphadenitis

The initial step in a child with an acutely inflamed, unilateral cervical node is empiric oral antibiotics covering S. aureus and Group A Streptococcus. Cephalexin is appropriate for uncomplicated cases in areas with low MRSA prevalence. In communities with high MRSA rates, clindamycin is preferred because it covers both MRSA and streptococci. If the child is systemically ill (high fever, toxic appearance, unable to tolerate oral medications), admit for IV antibiotics such as clindamycin 40 mg/kg/day IV divided q8h or vancomycin 15 mg/kg IV q6h if severe MRSA is suspected.

Reassess at 48 to 72 hours. If the node is not improving, obtain an ultrasound. If ultrasound reveals a drainable abscess (>2 to 3 cm), the next best step is incision and drainage (or ultrasound-guided needle aspiration for smaller collections). Always send aspirated material for Gram stain, aerobic and anaerobic culture, and AFB stain/culture.

Cat-Scratch Disease

In immunocompetent patients with mild disease, the standard approach is observation and reassurance. The lymphadenopathy is self-limited and resolves over 2 to 4 months, though some nodes may suppurate. Needle aspiration of a tense, suppurative node can be performed for symptomatic relief but is not required.

Antibiotic therapy with azithromycin is reserved for patients with moderate to severe lymphadenopathy (nodes >5 cm), systemic symptoms, or immunocompromised status. Azithromycin has the strongest evidence from a randomized trial showing accelerated resolution of lymphadenopathy. In immunocompromised patients (particularly HIV), cat-scratch disease can progress to bacillary angiomatosis or peliosis hepatis, which requires prolonged antibiotic therapy with doxycycline or erythromycin for weeks to months.

Tuberculous Lymphadenitis

The treatment mirrors pulmonary TB: the standard four-drug RIPE regimen for 2 months of intensive therapy, followed by 4 months of continuation therapy with rifampin and isoniazid. An important exam point is the phenomenon of paradoxical reaction: after starting anti-TB therapy, nodes may transiently enlarge or new nodes may appear due to immune reconstitution. This does not indicate treatment failure, and the correct step is to continue therapy, not to switch regimens. Surgical excision is reserved for nodes that do not respond after adequate treatment or those causing compressive symptoms.

NTM Lymphadenitis

This is where management diverges from TB and is a favorite exam topic. The treatment of choice for NTM cervical lymphadenitis in children is complete surgical excision of the affected node(s). This approach is curative in over 90% of cases and provides tissue for definitive histopathologic and microbiologic diagnosis. Standard anti-TB drugs are ineffective against most NTM species. If surgical excision is not feasible (proximity to the facial nerve, for instance), a course of macrolide-based combination therapy (clarithromycin plus ethambutol with or without rifabutin) can be considered, though cure rates are lower. The critical teaching point: never perform I&D on a suspected NTM node, as this leads to chronic draining sinus tracts that are extremely difficult to manage.

05Differential Diagnosis and Distractors

06Traps and High-Yield Pearls

The most common way students answer lymphadenitis questions incorrectly falls into three patterns.

First, they biopsy too early. When the vignette describes an acutely inflamed, unilateral cervical node in a febrile child, the next best step is empiric antibiotics and reassessment, not biopsy. Excisional biopsy is reserved for nodes that persist beyond 4 to 6 weeks, fail antibiotic therapy, or have red-flag features for malignancy (non-tender, fixed, supraclavicular, constitutional symptoms). Jumping to biopsy on an acute presentation is a classic distractor.

Second, they confuse NTM management with TB management. This is heavily tested. TB lymphadenitis is treated medically with RIPE. NTM lymphadenitis is treated with complete surgical excision. Performing I&D on an NTM node is wrong and leads to chronic sinus tracts. If the vignette describes a child aged 1 to 5 with a unilateral submandibular node and violaceous overlying skin, the answer is surgical excision, not anti-TB drugs.

Third, they miss the paradoxical reaction in TB treatment. A node that enlarges after starting anti-TB therapy is not a sign of treatment failure or drug resistance. It is an expected immune reconstitution phenomenon, and the correct response is to continue therapy. Switching to second-line agents or adding empiric antibiotics in this scenario is incorrect.

The core competency being tested in lymphadenitis questions is the ability to match the clinical timeline and presentation to the correct etiology, select the appropriate diagnostic step based on the stage of workup, and know the etiology-driven differences in management, particularly the surgical excision rule for NTM and the observation-first approach for cat-scratch disease in immunocompetent patients.