Morphology
Histoid leprosy with mycobacterial keratinous bullets after possible transepidermal elimination of bacilli Ashok Ghorpade, MD, MNAMS
Department of Dermatology and Venereology, JLN Hospital and Research Center, Bhilai Steel Plant, Bhilai, Chhattisgarh, India Correspondence Ashok Ghorpade, MD, MNAMS Department of Dermatology and Venereology JLN Hospital and Research Center Bhilai Steel Plant BK D-18, Sector 9 Bhilai, Chhattisgarh 490006 India E-mail: [email protected] Conflicts of interest: None.
Case report
1530
A 68-year-old Indian woman presented with multiple, asymptomatic skin lesions over the trunk and limbs of four months’ duration. There was no history of previous skin lesions or oral or topical treatment. There was hypoesthesia in the distal extremities (glove and stocking area), and the bilateral ulnar and lateral popliteal nerves were thickened and non-tender. Cutaneous examination showed shiny, circumscribed, skin-colored, and/or erythematous nodules, papules, and plaques on the breasts, abdomen, and back, and both arms, legs, and buttocks (Fig. 1). The subject’s family members did not have any skin problems. Routine hematology and liver and kidney function tests were normal; blood venereal disease research laboratory (VDRL) test and enzyme-linked immunosorbent assay (ELISA) for human immunodeficiency virus (HIV) 1 and 2 were negative. Systemic examination was normal. Slit smear examination from routine sites, including five papulonodular lesions and both ear lobes, was highly positive, with a bacterial index of 6 + (>1000 bacilli per oil immersion field) and a morphological index of 85%. A skin biopsy from a histoid nodule on the back showed a thin epidermis, a clear subepidermal grenz zone, and dermal granulomas of tightly packed, spindle-shaped histiocytes in bundles and whorls with foamy macrophages without the classical pseudoInternational Journal of Dermatology 2013, 52, 1530–1532
(a)
(b) Figure 1 (a) Shiny, skin-colored and erythematous nodules and papules on the breasts and abdomen of a 68-year-old woman. (b) Close-up of the shiny, skin-colored and erythematous nodules and plaques on the abdomen, arising abruptly on normal skin
capsule (Fig. 2). Ziehl–Neelsen staining of a section in this biopsy showed abundant lepra bacilli in the dermis. Equivalent staining of a section from a shiny nodule on the abdomen additionally revealed mild acanthosis with numerous, mostly solid-staining acid-fast bacilli arranged primarily in clumps inside the epidermis at various levels ª 2013 The International Society of Dermatology
Ghorpade A
Histoid leprosy with possible transepidermal elimination
Morphology
(b)
(a)
Figure 2 Histopathology in a nodule biopsy shows a thinned epidermis, a clear subepidermal zone and dermal granulomas of tightly packed, spindle-shaped histiocytes in bundles and whorls with foamy macrophages. (Hematoxylin and eosin stain; original magnification 9100)
and in the upper dermis (including the grenz zone) and a keratinous ball in which few solid-staining lepra bacilli were embedded, attached to the stratum corneum (Fig. 3a, b). A few other keratinous balls, in which numerous solid-staining lepra bacilli were embedded, were seen to be detached from the stratum corneum and lying free of the skin (Fig. 4a, b). These bacilli were longer than the lepra bacilli found in other forms of
(a)
Figure 4 One keratin ball in which numerous solid-staining lepra bacilli are embedded. (b) Close-up of the portion marked in (a), showing numerous solid-staining lepra bacilli inside the keratin ball. (Ziehl–Neelsen stain; original magnification [a] 9400, [b] oil immersion 91000)
leprosy. The patient’s diagnosis was confirmed as histoid leprosy, and treatment with rifampicin 600 mg/d and ofloxacin 400 mg/d for two months was initiated (to reduce the high bacillary load faster). This was followed by multibacillary multi-drug treatment with dapsone 100 mg/d, clofazimine 300 mg/month and 50 mg/d, and rifampicin 600 mg/month for two years. Monthly followup examinations showed the marked regression of skin lesions after eitht months and gradual reductions in slit
(b)
Figure 3 (a) Microphotograph showing numerous globi inside the prickle cell layer. (b) One keratin ball with few solid-staining lepra bacilli embedded inside, attached to the stratum corneum. (Ziehl–Neelsen stain; [a, b] oil immersion 91000) ª 2013 The International Society of Dermatology
International Journal of Dermatology 2013, 52, 1530–1532
1531
1532
Morphology
Histoid leprosy with possible transepidermal elimination
smear bacterial and morphological indices, which reached 2 + and 10%, respectively, after 24 months. The patient has been followed up for the last 18 months without any recurrence. Discussion The diagnosis of histoid leprosy was based on the patient’s history of asymptomatic skin lesions, cutaneous findings of shiny, skin-colored and/or erythematous nodules, papules and plaques arising abruptly from a normal skin surface, slit smear and fine needle aspiration cytology (FNAC) findings from the nodules, and histopathogical findings. Histoid leprosy is a variant of lepromatous leprosy, which is believed to occur after inadequate or irregular anti-leprosy treatment taken previously or as a result of dapsone-resistant mutation but which may also arise de novo.1 In a recent Indian report, histoid leprosy was found to constitute 1.8% of all leprosy cases and occurred de novo in 12.5% of patients.2 The lesions are shiny, skin-colored or erythematous papules, nodules, or plaques that arise abruptly from normal skin, mostly involving the buttocks, thighs, the posterior and lateral aspects of the arms, and the elbows, knees, and back.2,3 The presence of bacilli in the grenz zone, inside the epidermis at various levels, in the stratum corneum, and inside keratinous balls (bullets) suggests their movement with the maturation of epidermal cells. There are few reports of observation of epidermal Mycobacterium leprae in leprosy,4–7 which may indicate either that this is under-reported or that it is missed unless it is specifically sought.4 Okada et al.6 suggested that upper dermal lepra bacilli in multibacillary patients could be phagocytized by basal cells and gradually move up through the epidermis to be finally eliminated, possibly also from intact skin. Namisato et al.7 opined that rapidly growing dense granulomas in the upper dermis might contribute to the transepidermal elimination of M. leprae. Once eliminated, the bacilli might remain viable for several days or weeks.8 The scant reports of the phenomenon of transepidermal elimination of lepra bacilli may reflect under-reporting. Although this concept seems to be controversial, such transepidermal exit of lepra bacilli and their probable cutaneous inoculation, causing the occurrence of pseudoisomorphic Koebner phenomenon, in histoid leprosy has been previously reported by the present author.9,10 However, this is the first report of mycobacterial keratinous balls (bullets) in leprosy. Although the exact mode is uncertain, leprosy is believed to spread mostly through the respiratory route. The findings observed and referenced here, along with previous reports of leprosy occurring
International Journal of Dermatology 2013, 52, 1530–1532
Ghorpade A
after and at the sites of tattooing, trauma, and vaccination,11–13 suggest that skin could be a portal for both the exit and entry of the bacillus and contribute to its transmission. Untreated multibacillary cases have been aptly labeled as mobile factories of lepra bacilli10 as they offer safe houses for mycobacterial multiplication and dissemination. The presence of even a few such untreated, multibacillary leprosy patients with transepidermal mycobacterial elimination and mycobacterial keratinous bullets might pose some challenge to leprosy elimination. References 1 Sehgal VN, Aggarwal A, Srivastava G, et al. Evolution of histoid leprosy (de novo) in lepromatous (multibacillary) leprosy. Int J Dermatol 2005; 44: 576–578. 2 Kaur I, Dogra S, De D, et al. Histoid leprosy: a retrospective study of 40 cases from India. Br J Dermatol 2009; 160: 305–310. 3 Bhutani LK, Bedi TR, Malhotra YK, et al. Histoid leprosy in north India. Int J Lepr Other Mycobact Dis 1974; 42: 174–181. 4 Satapathy J, Kar BR, Job CK. Presence of Mycobacterium leprae in the epidermal cells of lepromatous skin and its significance. Indian J Dermatol Venereol Leprol 2005; 71: 267–269. 5 Seo VH, Cho W, Choi HY, et al. Mycobacterium leprae in the epidermis: ultrastructural study I. Int J Lepr Other Mycobact Dis 1995; 63: 101–104. 6 Okada S, Komura J, Nishiura M. Mycobacterium leprae found in epidermal cells by electron microscopy. Int J Lepr Other Mycobact Dis 1978; 46: 30–34. 7 Namisato M, Kakuta M, Kawatsu K, et al. Transepidermal elimination of lepromatous granuloma: a mechanism for mass transport of viable bacilli. Lep Rev 1997; 68: 167–172. 8 Noordeen SK. The epidemiology of leprosy. In: Hastings RC, Opromolla DV, eds. Leprosy, 2nd edn. Edinburgh: Churchill Livingstone, 1994: 36–37. 9 Ghorpade AK. Transepidermal elimination of Mycobacterium leprae in histoid leprosy: a case report suggesting possible participation of skin in leprosy transmission. Indian J Dermatol Venereol Leprol 2011; 77: 59–61. 10 Ghorpade A. Molluscoid skin lesions in histoid leprosy with pseudo-isomorphic Koebner phenomenon. Int J Dermatol 2008; 47: 1278–1280. 11 Ghorpade A. Inoculation (tattoo) leprosy: a report of 31 cases. J Eur Acad Dermatol Venereol 2002; 16: 494–499. 12 Ghorpade A. Inoculable leprosy. Int J Dermatol 2009; 48: 1267–1268. 13 Ghorpade A. Post-traumatic tuberculoid leprosy after injury with a glass bangle. Lepr Rev 2009; 80: 215–218.
ª 2013 The International Society of Dermatology
Histoid leprosy with mycobacterial keratinous bullets after possible transepidermal elimination of bacilli Ashok Ghorpade, MD, MNAMS
Department of Dermatology and Venereology, JLN Hospital and Research Center, Bhilai Steel Plant, Bhilai, Chhattisgarh, India Correspondence Ashok Ghorpade, MD, MNAMS Department of Dermatology and Venereology JLN Hospital and Research Center Bhilai Steel Plant BK D-18, Sector 9 Bhilai, Chhattisgarh 490006 India E-mail: [email protected] Conflicts of interest: None.
Case report
1530
A 68-year-old Indian woman presented with multiple, asymptomatic skin lesions over the trunk and limbs of four months’ duration. There was no history of previous skin lesions or oral or topical treatment. There was hypoesthesia in the distal extremities (glove and stocking area), and the bilateral ulnar and lateral popliteal nerves were thickened and non-tender. Cutaneous examination showed shiny, circumscribed, skin-colored, and/or erythematous nodules, papules, and plaques on the breasts, abdomen, and back, and both arms, legs, and buttocks (Fig. 1). The subject’s family members did not have any skin problems. Routine hematology and liver and kidney function tests were normal; blood venereal disease research laboratory (VDRL) test and enzyme-linked immunosorbent assay (ELISA) for human immunodeficiency virus (HIV) 1 and 2 were negative. Systemic examination was normal. Slit smear examination from routine sites, including five papulonodular lesions and both ear lobes, was highly positive, with a bacterial index of 6 + (>1000 bacilli per oil immersion field) and a morphological index of 85%. A skin biopsy from a histoid nodule on the back showed a thin epidermis, a clear subepidermal grenz zone, and dermal granulomas of tightly packed, spindle-shaped histiocytes in bundles and whorls with foamy macrophages without the classical pseudoInternational Journal of Dermatology 2013, 52, 1530–1532
(a)
(b) Figure 1 (a) Shiny, skin-colored and erythematous nodules and papules on the breasts and abdomen of a 68-year-old woman. (b) Close-up of the shiny, skin-colored and erythematous nodules and plaques on the abdomen, arising abruptly on normal skin
capsule (Fig. 2). Ziehl–Neelsen staining of a section in this biopsy showed abundant lepra bacilli in the dermis. Equivalent staining of a section from a shiny nodule on the abdomen additionally revealed mild acanthosis with numerous, mostly solid-staining acid-fast bacilli arranged primarily in clumps inside the epidermis at various levels ª 2013 The International Society of Dermatology
Ghorpade A
Histoid leprosy with possible transepidermal elimination
Morphology
(b)
(a)
Figure 2 Histopathology in a nodule biopsy shows a thinned epidermis, a clear subepidermal zone and dermal granulomas of tightly packed, spindle-shaped histiocytes in bundles and whorls with foamy macrophages. (Hematoxylin and eosin stain; original magnification 9100)
and in the upper dermis (including the grenz zone) and a keratinous ball in which few solid-staining lepra bacilli were embedded, attached to the stratum corneum (Fig. 3a, b). A few other keratinous balls, in which numerous solid-staining lepra bacilli were embedded, were seen to be detached from the stratum corneum and lying free of the skin (Fig. 4a, b). These bacilli were longer than the lepra bacilli found in other forms of
(a)
Figure 4 One keratin ball in which numerous solid-staining lepra bacilli are embedded. (b) Close-up of the portion marked in (a), showing numerous solid-staining lepra bacilli inside the keratin ball. (Ziehl–Neelsen stain; original magnification [a] 9400, [b] oil immersion 91000)
leprosy. The patient’s diagnosis was confirmed as histoid leprosy, and treatment with rifampicin 600 mg/d and ofloxacin 400 mg/d for two months was initiated (to reduce the high bacillary load faster). This was followed by multibacillary multi-drug treatment with dapsone 100 mg/d, clofazimine 300 mg/month and 50 mg/d, and rifampicin 600 mg/month for two years. Monthly followup examinations showed the marked regression of skin lesions after eitht months and gradual reductions in slit
(b)
Figure 3 (a) Microphotograph showing numerous globi inside the prickle cell layer. (b) One keratin ball with few solid-staining lepra bacilli embedded inside, attached to the stratum corneum. (Ziehl–Neelsen stain; [a, b] oil immersion 91000) ª 2013 The International Society of Dermatology
International Journal of Dermatology 2013, 52, 1530–1532
1531
1532
Morphology
Histoid leprosy with possible transepidermal elimination
smear bacterial and morphological indices, which reached 2 + and 10%, respectively, after 24 months. The patient has been followed up for the last 18 months without any recurrence. Discussion The diagnosis of histoid leprosy was based on the patient’s history of asymptomatic skin lesions, cutaneous findings of shiny, skin-colored and/or erythematous nodules, papules and plaques arising abruptly from a normal skin surface, slit smear and fine needle aspiration cytology (FNAC) findings from the nodules, and histopathogical findings. Histoid leprosy is a variant of lepromatous leprosy, which is believed to occur after inadequate or irregular anti-leprosy treatment taken previously or as a result of dapsone-resistant mutation but which may also arise de novo.1 In a recent Indian report, histoid leprosy was found to constitute 1.8% of all leprosy cases and occurred de novo in 12.5% of patients.2 The lesions are shiny, skin-colored or erythematous papules, nodules, or plaques that arise abruptly from normal skin, mostly involving the buttocks, thighs, the posterior and lateral aspects of the arms, and the elbows, knees, and back.2,3 The presence of bacilli in the grenz zone, inside the epidermis at various levels, in the stratum corneum, and inside keratinous balls (bullets) suggests their movement with the maturation of epidermal cells. There are few reports of observation of epidermal Mycobacterium leprae in leprosy,4–7 which may indicate either that this is under-reported or that it is missed unless it is specifically sought.4 Okada et al.6 suggested that upper dermal lepra bacilli in multibacillary patients could be phagocytized by basal cells and gradually move up through the epidermis to be finally eliminated, possibly also from intact skin. Namisato et al.7 opined that rapidly growing dense granulomas in the upper dermis might contribute to the transepidermal elimination of M. leprae. Once eliminated, the bacilli might remain viable for several days or weeks.8 The scant reports of the phenomenon of transepidermal elimination of lepra bacilli may reflect under-reporting. Although this concept seems to be controversial, such transepidermal exit of lepra bacilli and their probable cutaneous inoculation, causing the occurrence of pseudoisomorphic Koebner phenomenon, in histoid leprosy has been previously reported by the present author.9,10 However, this is the first report of mycobacterial keratinous balls (bullets) in leprosy. Although the exact mode is uncertain, leprosy is believed to spread mostly through the respiratory route. The findings observed and referenced here, along with previous reports of leprosy occurring
International Journal of Dermatology 2013, 52, 1530–1532
Ghorpade A
after and at the sites of tattooing, trauma, and vaccination,11–13 suggest that skin could be a portal for both the exit and entry of the bacillus and contribute to its transmission. Untreated multibacillary cases have been aptly labeled as mobile factories of lepra bacilli10 as they offer safe houses for mycobacterial multiplication and dissemination. The presence of even a few such untreated, multibacillary leprosy patients with transepidermal mycobacterial elimination and mycobacterial keratinous bullets might pose some challenge to leprosy elimination. References 1 Sehgal VN, Aggarwal A, Srivastava G, et al. Evolution of histoid leprosy (de novo) in lepromatous (multibacillary) leprosy. Int J Dermatol 2005; 44: 576–578. 2 Kaur I, Dogra S, De D, et al. Histoid leprosy: a retrospective study of 40 cases from India. Br J Dermatol 2009; 160: 305–310. 3 Bhutani LK, Bedi TR, Malhotra YK, et al. Histoid leprosy in north India. Int J Lepr Other Mycobact Dis 1974; 42: 174–181. 4 Satapathy J, Kar BR, Job CK. Presence of Mycobacterium leprae in the epidermal cells of lepromatous skin and its significance. Indian J Dermatol Venereol Leprol 2005; 71: 267–269. 5 Seo VH, Cho W, Choi HY, et al. Mycobacterium leprae in the epidermis: ultrastructural study I. Int J Lepr Other Mycobact Dis 1995; 63: 101–104. 6 Okada S, Komura J, Nishiura M. Mycobacterium leprae found in epidermal cells by electron microscopy. Int J Lepr Other Mycobact Dis 1978; 46: 30–34. 7 Namisato M, Kakuta M, Kawatsu K, et al. Transepidermal elimination of lepromatous granuloma: a mechanism for mass transport of viable bacilli. Lep Rev 1997; 68: 167–172. 8 Noordeen SK. The epidemiology of leprosy. In: Hastings RC, Opromolla DV, eds. Leprosy, 2nd edn. Edinburgh: Churchill Livingstone, 1994: 36–37. 9 Ghorpade AK. Transepidermal elimination of Mycobacterium leprae in histoid leprosy: a case report suggesting possible participation of skin in leprosy transmission. Indian J Dermatol Venereol Leprol 2011; 77: 59–61. 10 Ghorpade A. Molluscoid skin lesions in histoid leprosy with pseudo-isomorphic Koebner phenomenon. Int J Dermatol 2008; 47: 1278–1280. 11 Ghorpade A. Inoculation (tattoo) leprosy: a report of 31 cases. J Eur Acad Dermatol Venereol 2002; 16: 494–499. 12 Ghorpade A. Inoculable leprosy. Int J Dermatol 2009; 48: 1267–1268. 13 Ghorpade A. Post-traumatic tuberculoid leprosy after injury with a glass bangle. Lepr Rev 2009; 80: 215–218.
ª 2013 The International Society of Dermatology
