#dermpathJC February 2021 summary

#dermpathJC February 2021:

Thursday, February 25th, 9pm EST

Article discussed:  Erythema Migrans and Interface Changes: More Than a Fortuitous Association

Authors: Tekin, Burak MD; Song, Yali MD; DiCostanzo, Damian MD; Lee, Bonnie A. MD

Temporary free access courtesy of The American Journal of Dermatopathology: https://journals.lww.com/amjdermatopathology/pages/articleviewer.aspx?year=2020&issue=10000&article=00004&type=Fulltext

Summary prepared by: Shaymaa Ashi, MD (@shaymaloh)

Journal Club Summary:


  • This article reviewed the histopathologic characteristic of erythema chronicum migrans (ECM), with emphasis on the classical features and observation of new patterns.
  • ECM represents the cutaneous manifestation of early Lyme disease. It typically presents with polycyclic targetoid rash with erythematous border and central clearing. Fully developed lesions usually measure >5 cm.  It is usually localized; but can be disseminated (25%).
  • Diagnosis is made based on clinical findings (characteristic clinical lesions, history of tick bite) and response to treatment. Serology has low sensitivity in early Lyme disease.  PCR can be used for confirmation.
  • Biopsy is warranted when the clinical presentation is atypical (vesicular, bullous, or hemorrhagic/purpuric rash, no history of tick bite) to confirm ECM and exclude other entities in the differential diagnosis (viral exanthems, arthropod bite reaction, erythema nodosum, drug eruption, gyrate erythema, dermatitis, and tinea).
  • Classic histopathologic features are superficial to deep perivascular inflammatory infiltrate, mainly of lymphocytes, associated with plasma cells and eosinophils.
  • Some studies state that variations in histomorphology can occur, including interface dermatitis, spongiosis, necrotic keratinocytes, absence of plasma cells.

Summary of current study methodology and results:

  • The aim of this study is to detect the frequency of variable histopathologic findings in ECM lesions to increase the diagnostic sensitivity of biopsy, usually performed to establish the diagnosis in cases with atypical clinical presentations.
  • Two dermatopathologists evaluated biopsies from a cohort of 14 cases with clinically and/or serologically confirmed Lyme disease from the archives of 2 institutions located in Lyme disease endemic area (Ackerman Academy of Dermatopathology and Dermpath Diagnostics in New York). The most prominent histopathological changes detected are summarized as follows:
  • All 14 cases demonstrated a superficial perivascular lymphocytic infiltrate.
    • 5/14 cases (36%) did not have any additional changes
    • 11/14 cases (64%) showed additional interstitial and/or deep perivascular lymphocytic infiltrate
    • The density of the infiltrate was variable (sparse to markedly dense). Nodular or pseudolymphomatous infiltrates were not identified as opposed to other studies
    • 12/14 cases (86%) showed interface changes, ranging from focal to diffuse
    • 2/14 cases (14%) showed necrotic keratinocytes
    • 2/14 cases (14%) showed mild spongiosis
    • 7/14 cases (50%) showed eosinophils
    • 10/14 case (71%) showed plasma cells
    • 3/14 cases (21%) showed extravasated RBCs
A-C Focal interface dermatitis, papillary dermal edema and extravasated RBCs. D: lymphocyte exocytosis to basal layer. Arrows in A-D: elongated squiggly lymphocytes

Summary of literature review:

  • Berger et al (1983): Some cases (24%) show lymphocytes blurring of the dermo-epidermal junction (44%) and extend to epidermis (21%)
  • de Koning (1983): Some cases have lymphocytes disrupting the dermo-epidermal junction and the basement membrane
  • Böer et al (2007): Vacuolar degeneration seen in 8/34 cases, lymphocytes seen in basal layer (15/34), and in suprabasal epidermal levels (7/34)
  • Wilson et al (2012): Interface/vacuolar change seen in 2/4 cases (50%)
  • Miraflor et al (2016): Interface change seen in 3/8 cases (38%)

Discussion points:

  • Interface dermatitis, focal to diffuse, with sparse perivascular lymphocytic infiltrates, is seen in a high percentage of ECM biopsies, and scrutiny is needed in examining the tissue to look for subtle/focal interface changes, to avoid missing ECM cases in the earlier phase when serology tends to be negative.
  • This study has higher percentage of ECM cases with interface dermatitis (86%) compared to the other studies mentioned in the literature review.  
  • More than 50% of the cases in this study had only focal interface changes.
  • The density of the dermal infiltrates is variable.
  • The center of early lesions has more eosinophils, while the periphery has more plasma cells. This study had comparable results to those of Miraflor et al study regarding plasma and eosinophils percentage, while Wilson et al indicated absence of plasma cells in his case cohort and Boer et al indicated plasma cells were unreliable criterion for ECM diagnosis.
  • A new observation in this study is that reactive lymphocytes seen in biopsies from infections are elongated and squiggly, correlating with findings of ultrastructural studies of reactive T lymphocytes.
  • The limitation of this study: retrospective study design, diagnosis was not uniformly confirmed in all cases by serology or PCR, site of biopsies (center versus periphery) was not indicated.
  • ECM can have variable histopathologic manifestations and should be included in the differential diagnosis of sparsely inflamed biopsies and those with subtle/focal interface dermatitis.

Memorable Tweets:

And now a SPECIAL interview with Dr Bonnie Lee (senior author of ECM paper) on the ASDP YouTube channel: Dr Silvija Gottesman and Dr Jisun Cha’s #DermpathJC​ Q&A session with Dr Bonnie Lee about the histologic findings of Erythema Chronicum Migrans, a characteristic cutaneous eruption that appears in the early stages on Lyme disease.

Until next month #dermpathJC, stay safe!

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