Causes of reactive lymphadenitis

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Here is a comprehensive summary of the causes of reactive lymphadenitis, drawn from authoritative pathology and clinical textbooks.

Causes of Reactive Lymphadenitis

Reactive lymphadenitis is lymph node enlargement triggered when immune cells within the node are activated by foreign antigens - either infectious or non-infectious. The causes are best understood by examining the three main histological reaction patterns they produce.

1. Acute Nonspecific Lymphadenitis

This occurs either locally (draining a regional infection) or systemically. The node becomes swollen, gray-red, and engorged, with large germinal centers and neutrophilic infiltrates. With pyogenic organisms, abscess formation may follow.

Common causes:

Bacterial infections - streptococci and staphylococci are the most frequent culprits
Tonsillitis, dental infections, and bacterial pharyngitis (common causes of acute cervical lymphadenitis)
Any regional pyogenic infection draining into a node group

2. Chronic Nonspecific Lymphadenitis - Three Patterns

A. Follicular Hyperplasia (B-cell driven)

Activated B cells migrate into follicles, creating enlarged, reactive germinal centers with tingible body macrophages.

Causes:

Rheumatoid arthritis (and other autoimmune diseases)
Toxoplasmosis
Early HIV infection

B. Paracortical Hyperplasia (T-cell driven)

Activated parafollicular T cells transform into large immunoblasts, which can efface B-cell follicles.

Causes:

Viral infections, especially Epstein-Barr virus (EBV) / infectious mononucleosis
Vaccinations (post-immunization lymphadenopathy)
Drug reactions, especially phenytoin (and other anticonvulsants)

C. Sinus Histiocytosis

Distension of lymphatic sinusoids by hypertrophied endothelial cells and infiltrating macrophages.

Causes:

Lymph nodes draining carcinomas (represents an anti-tumor immune response)

3. Other Named Causes (Specific / Granulomatous)

Cause	Key Features
Cat-scratch disease (Bartonella henselae)	Granulomatous or suppurative cervical adenopathy; history of cat scratch
Tuberculosis	Granulomatous lymphadenitis with caseating necrosis
Atypical mycobacteria (M. avium)	Subacute; violaceous overlying skin; common in children
Toxoplasmosis	Follicular hyperplasia with epithelioid histiocyte clusters blurring germinal centers; monocytoid B cells
EBV (infectious mononucleosis)	Generalized lymphadenopathy, paracortical pattern
CMV (cytomegalovirus)	Rare; chronic lymphadenopathy
Syphilis	Generalized or regional reactive adenopathy
Rubella	Generalized lymphadenopathy
HIV	Early: follicular hyperplasia; late: lymph node depletion
Kikuchi histiocytic necrotizing lymphadenitis	Benign self-limited; necrotizing without neutrophils
Kawasaki disease	Febrile illness with cervical lymphadenitis in children
Rosai-Dorfman disease	Massive sinus histiocytosis
Castleman disease	Benign lymph node hyperplasia

4. Non-infectious / Non-microbial Causes

Autoimmune diseases - rheumatoid arthritis, SLE, and others
Drug reactions - phenytoin is classic; also other anticonvulsants
Post-vaccination response
Reaction to draining malignancy (sinus histiocytosis pattern)

Histological Summary

Photomicrograph of reactive lymphadenitis showing a hyperplastic germinal center (GC) with pale-staining B lymphocytes and macrophages, surrounded by a darker mantle zone of T lymphocytes. x120.

Reactive lymphadenitis: hyperplastic germinal center (GC) with B lymphocytes and macrophages inside; T lymphocyte mantle zone surrounding it. - Histology: A Text and Atlas (Pawlina)

Sources:

Robbins & Kumar Basic Pathology (Robbins Pathology), pp. 2198-2230
Histology: A Text and Atlas with Correlated Cell and Molecular Biology (Pawlina), pp. 1224-1225
Henry's Clinical Diagnosis and Management by Laboratory Methods, p. 2776
Cummings Otolaryngology Head and Neck Surgery, pp. 3889-3899

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