Lymph nodes - not lymphoma
Inflammatory disorders (noninfectious)
Drug hypersensitivity

Author: Jaya Balakrishna, M.D. (see Authors page)
Editorial Board Member Review: Genevieve M. Crane, M.D., Ph.D.
Deputy Editor Review: Debra Zynger, M.D.

Revised: 25 June 2018, last major update March 2018

Copyright: (c) 2003-2018, PathologyOutlines.com, Inc.

PubMed Search: "Drug hypersensitivity" lymph nodes[mh]

Cite this page: Balakrishna, J. Drug hypersensitivity. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/lymphnodesdrughypersensitivity.html. Accessed July 17th, 2018.
Definition / general
  • Certain drugs may give rise to soft lymph node enlargement, predominantly in the neck (J Pathol Bacteriol 1968;95:314)
  • Lymphadenopathy may occur alone or be associated with involvement of other organs (Neurology 1979;29:1480)
  • May resemble lymphoma by morphology
  • When the drug is stopped, the lymphadenopathy usually disappears in 1 - 2 weeks
  • Can present with lymphadenopathy or with a rare systemic disorder, DIHS / DRESS (Drug Induced Hypersensitivity Syndrome / Drug Reaction with Eosinophilia and Systemic Symptoms (Rev Assoc Med Bras 2016;62:227)
Essential features
  • History of drug exposure
  • Polymorphous infiltrate composed of immunoblasts, small lymphocytes, plasma cells, eosinophils and histiocytes
Terminology
  • Drug induced lymphadenopathy
  • Hydantoin lymphadenopathy
  • Pseudolymphoma syndrome
  • Drug induced hypersensitivity syndrome (DIHS)
  • Drug reaction with eosinophilia and systemic symptoms (DRESS)
ICD-10 coding
Epidemiology
  • Uncommon
  • Pediatric population
Sites
  • Predominantly cervical but all lymph node groups can be affected
  • Can be generalized
Pathophysiology
  • Different theories have been proposed:
Etiology
Clinical features
  • Isolated lymph node enlargement OR
  • Drug Induced Hypersensitivity Syndrome (DIHS) / Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) (Allergol Int 2016;65:432):
    • Fever, lymphadenopathy, facial edema, periorbital edema, conjunctival injection
    • Abdominal pain, diarrhea, hepatomegaly, splenomegaly
    • Skin rash (maculopapular rash, bullous, wheal and flare, plaque, patch, target lesion)
    • Internal organ involvement (liver - elevated alanine aminotransferase levels, kidney, lung); also brain (Turk J Pediatr 2015;57:541), heart, muscle, pancreas, thyroid (Int J Mol Sci 2017 Jun 9;18(6) pii: E1243)
    • Hematologic abnormalities (eosinophilia, atypical lymphocytes, lymphocytosis, lymphopenia, thrombocytopenia)
Diagnosis
  • Clinical history of drug exposure
  • Characteristic clinical and laboratory features
  • Biopsy of the affected lymph node (rarely done, not required for diagnosis)
Radiology description
  • Enlarged lymph nodes
Prognostic factors
  • Underlying disease conditions
  • Extent of drug exposure
  • Drug reaction with eosinophilia and systemic symptoms (DRESS) has 4% mortality (Acta Derm Venereol 2012;92:200)
Case reports
Treatment
  • Discontinuation of the offending drug
  • For severe cases, immunosuppressive drugs / corticosteroids, IV Ig, plasma exchange
Gross description
  • Enlarged lymph nodes
Microscopic (histologic) description
  • Polymorphous cellular infiltrate composed of lymphocytes, plasma cells, eosinophils and histiocytes, most often with architectural distortion
  • Focal hemorrhagic necrosis is usually seen without fibrosis or scarring
  • Typical multinucleated Reed-Sternberg cells are absent; however, cells resembling Hodgkin / Reed-Sternberg (HRS) cells may be seen
  • Blood vessels show endothelial hyperplasia
  • There is variable follicular and paracortical hyperplasia (Hum Pathol 1974;5:519)
Microscopic (histologic) images

Images hosted on other servers:

Various images



Carbamazepine hypersensitivity:

Small lymphoid
follicle with marked
interfollicular
edema

Polymorphous infiltrate
of immunoblasts,
macrophages and
plasma cells

Interfollicular
necrosis,
immunoblasts and
macrophages

Interfollicular Reed-Sternberg-like cell

Immunoblasts and mitotic figures

Reticulin stain
shows numerous
vascular
channels

Flow cytometry description
  • No aberrant immunophenotype
Molecular / cytogenetics description
  • No clonal cell populations
Differential diagnosis
  • For drug reaction with eosinophilia and systemic symptoms (DRESS) (Rev Assoc Med Bras 2016;62:227):
  • On lymph node biopsy (Hum Pathol 1974;5:519):
    • Angioimmunoblastic T cell lymphoma (AITL):
      • Presence of vascular proliferation, immunoblasts and polymorphous infiltrate cause confusion with angioimmunoblastic T cell lymphoma
      • AITL has characteristic T cells of T follicular helper (TFH) phenotype in perisinusoidal areas and T cell clones, not seen in drug hypersensitivity
    • Hodgkin lymphoma:
      • Presence of polymorphous inflammatory infiltrate and large Hodgkin / Reed-Sternberg-like cells may cause confusion
      • However, classic Hodgkin / Reed-Sternberg cells are not identified in drug hypersensitivity
Board review question #1
All of the following are proposed pathogenetic mechanisms for drug hypersensitivity, except:

  1. Direct toxicity
  2. Drug interactions with specific HLA types
  3. Hapten theory
  4. p-i concept
Board review answer #1
A. Direct toxicity. Drug molecules causing an immune reaction are proposed mechanisms of pathogenesis of drug hypersensitivity, including hapten theory (drug molecules bind to a protein and cause antigenicity), p-i concept (drug molecules bind to HLA and cause T cell response) and drug molecules interacting with certain HLA subtypes. Direct toxicity does not manifest as a drug reaction with eosinophilia and systemic symptoms (DRESS).