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

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.

Leydig cell hyperplasia and the maintenance of bone volume: bone histomorphometry and testicular histopathology in 29 male leprosy autopsy cases.

This study was conducted to determine if osteoporosis in male leprosy patients is caused by testicular atrophy. Bone volume (BV/TV), trabecular number (TbN), trabecular thickness (TbTh), and trabecular separation (TbSp) were measured in two areas in decalcified paraffin sections of lumbar bones from 29 male leprosy and 6 male nonleprosy autopsy cases. We found significant differences in the average BV/TV measurements among the 7 patients with nodular Leydig cell hyperplasia (BV/TV 12.24%) and the 22 patients without hyperplasia (BV/TV 7.35%) and 6 patients without leprosy (BV/TV 12.98%). Bone volume was maintained in patients with nodular Leydig cell hyperplasia, and we determined no clinical factor other than the Leydig cell hyperplasia that reflected the bone volume. The osteoporosis of male leprosy patients was attributed to secondary gonadal dysfunction due to testicular atrophy, and Leydig cell hyperplasia appears to preserve bone volume.

Pseudoepitheliomatous hyperplasia in trophic ulcers in leprosy patients. A 28-case study.

Between 1984 and 1993, pseudoepitheliomatous hyperplasia developing in chronic ulcers were observed in 28 former Senegalese leprosy patients, which amounts to an annual frequency of 1.9 per 1000 ulcers. Correct diagnosis could only be made by histopathological examination of specimens taken from the depth of the lesion. Amputation was carried out on 17 patients and local excision on the other 10. Recurrence of growth was observed in 8 of the 10 patients treated by excision; in all of these 8 cases below knee amputation had to be subsequently performed. From our experience, it may be assumed that local excision should be carried out only in the case of small tumours. Since the aim of surgical procedure is to allow the patient to have physical autonomy, below knee amputation, followed by adaptation of prosthesis, should be the procedure chosen in the other cases.

Cauliflower growths in neuropathic plantar ulcers in leprosy patients

A clinical and histopathological review of thirteen cases of cauliflower growths occuring in neurophatic plantar ulcers in leprosy patients is presented. The majority of these lesions were found to be pseudo-epitheliomatous hyperplasias although a considerable number showed atypical histological features. Conservative surgical treatment by deep but limited local excision is advocated.