Pseudoepitheliomatous Hyperplasia and Transepidermal Elimination in Lepromatous Leprosy: Does T-cell Plasticity Play a Role?
October 2012 | Volume 11 | Issue 10 | Case Reports | 1233 | Copyright © October 2012
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?
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.
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.
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.
J Drugs Dermatol.
JFAP Miller discovered the thymic education of T-cell clones in 1961. In 1962, the British leprologists classified leprosy according to the thymus as intact cell-mediated immunity (CMI) tuberculoid and anergic lepromatous leprosy, with several
in between forms.1 Numerous articles have pointed out the “lessons of leprosy” that have taught us about the human immune system.2,3,4,5 In the 1980s, it was discovered that the anergic lepromatous form lacked gamma-interferon. Nathan and colleagues injected IFN-γ into lepromatous lesions to activate
the flaccid macrophages of LL patients to kill intracellular Mycobacterium leprae bacilli.7 Unexpectedly, this resulted in a psoriasis-like proliferation of the epidermis with micaceous scaling. In 1986, Mosman and Coffman introduced the concept of the Th1-Th2 cytokine dichotomy.8 Subsequently, Krueger and Gottlieb discovered the T helper (Th) 1 cell to be at the center of psoriasis,9 while Freedberg discovered the induction of Keratin 17 (K17) by activation of the interferon (IFN)-γ receptor on keratinocytes.
10 Keratin 17 is not present in normal mature, healthy epidermis, but can be found in certain disease states, such as psoriasis and squamous cell carcinomas. The current case study extends our knowledge of the human immune system and raises still unanswered questions, such as whether the Th1-Th2 immunostat is set predominantly centrally or peripherally.
REPORT OF A CASE
A 71-year-old man born in the Dominican Republic who had been living in the United States for the past 44 years and had last traveled outside the United States 11 years previously, presented with multiple
asymptomatic facial nodules. Physical examination revealed an infiltrative dermopathy with multiple skin-colored plaques and nodules on the bilateral forehead, arms, trunk, and thighs, as well as a few hyperkeratotic plaques with rupioid scale on the nasal tip and right forearm (Figure 1). Multiple punch biopsies of both the nodules lacking surface changes and the hyperkeratotic plaques all revealed a diffuse histiocytic dermal infiltrate with numerous
Fite-positive bacilli, diagnostic of multibacillary leprosy. The nodules without surface changes demonstrated the classic histomorphology of lepromatous leprosy, with a grenz zone and no epidermal atrophy. The hyperkeratotic plaques demonstrated focal loss of the grenz zone in areas of pronounced pseudoepitheliomatous
hyperplasia, where transepidermal elimination of acid-fast bacilli was apparent (Figure 2).