Pseudoepitheliomatous hyperplasia and transepidermal elimination in lepromatous leprosy: Does T-cell plasticity play a role

Max K. Fischer, Kaley A. Myer, Syril T. Keena, Jonathan A. Harris, Frank T. Martiniuk, Shane A. Meehan, William R. Levis

Research output: Contribution to journalArticle

Abstract

Background: The longstanding concept of a Th1-Th2 dichotomy in leprosy, with Th1-predominant tuberculoid leprosy and Th2-predominant lepromatous leprosy (LL), has recently been challenged, and Cbl-b overexpression may emerge as an important factor in anergy and progression of LL. Moreover, Th17 and Th22 subsets have been identified as Th1-Th2 modulators in inflammatory skin diseases, most notably psoriasis, but their roles in leprosy have not yet been elucidated. The occurrence of pseudoepitheliomatous hyperplasia (PEH) with transepidermal elimination of mycobacteria in LL patients, which could theoretically be a portal for contact transmission, thus raises important immunological questions: Do Th17 and/or Th22 subsets mediate epidermal proliferation akin to Th1-driven psoriasis in supposedly Th2-predominant LL disease, and is the Th1-Th2 immunostat set systemically or locally? Furthermore, which microRNAs (miRs), signal transducers, and activators of transcription (STAT) proteins regulate this transition in leprosy, if any, and does differential Cb1-b expression play a role? Observation: A 71-year-old man presented with an infiltrative dermopathy characteristic of LL, as well as several hyperkeratotic plaques. Microscopic examination of the hyperkeratotic lesions demonstrated PEH with loss of the grenz zone and transepidermal elimination of acid-fast bacilli, whereas classic histopathologic features of LL were present at other sites. Hypotheses: We hypothesize that: Th17 and Th22 T-cell subsets act locally to induce T-cell plasticity in LL lesions, manifesting PEH; miR-181a is normal or increased in LL lesions with PEH compared to its expressional loss in classic LL lesions; miR-21 and STAT3 are increased in LL lesions with PEH, given their association with epithelial hyperproliferation; and Cbl-b is diminished in LL lesions with PEH compared to classic LL lesions. Conclusion: By understanding the factors that regulate T-cell and cytokine responses in leprosy, it should be possible to recognize these dynamic immunologic processes clinically and histopathologically and devise specific immunologic interventions.

Original languageEnglish (US)
Pages (from-to)1233-1235
Number of pages3
JournalJournal of Drugs in Dermatology
Volume11
Issue number10
StatePublished - Oct 1 2012

ASJC Scopus subject areas

  • Dermatology

Fingerprint Dive into the research topics of 'Pseudoepitheliomatous hyperplasia and transepidermal elimination in lepromatous leprosy: Does T-cell plasticity play a role'. Together they form a unique fingerprint.

  • Cite this

    Fischer, M. K., Myer, K. A., Keena, S. T., Harris, J. A., Martiniuk, F. T., Meehan, S. A., & Levis, W. R. (2012). Pseudoepitheliomatous hyperplasia and transepidermal elimination in lepromatous leprosy: Does T-cell plasticity play a role. Journal of Drugs in Dermatology, 11(10), 1233-1235.