Trans-epidermal extrusion of lepra bacilli from histoid lesions: a risk of continued transmission.

The current goal of Zero Leprosy focuses on the interruption of the transmission of infection within endemic regions. While the role of the skin in the transmission dynamics of leprosy has not been clearly delineated, recent research on the environmental presence of lepra bacilli brings this aspect back into focus. We present a case of lepromatous leprosy with perforated-appearing histoid lesions on the palms and soles, demonstrating the presence of lepra bacilli throughout the epidermis.

Clinical and histopathological spectrum of genital lichen sclerosus in 133 cases: Focus on the diagnosis of pre-sclerotic disease.

Background Early inflammatory lesions of lichen sclerosus are histopathologically difficult to diagnose until the hallmark of the disease i.e., papillary sclerosis becomes visible in histological sections. Pre-sclerotic and late or resolved phases of the disease have not been extensively studied. Methods We retrospectively reviewed all cases diagnosed as genital lichen sclerosus over a ten-year period from 2006 to 2016, correlating the clinical findings with the histological features. Results A total of 133 cases of genital lichen sclerosus (90 males and 43 females) were identified. Both genders demonstrated a similar histological spectrum. Fifty eight (44%) cases were identified as having pre-sclerotic lichen sclerosus, 64 (48%) as having progressive disease and 11 (8%) cases were classified as fully resolved with atrophy. Asymptomatic vitiligoid lesions were identified in 19 (14%) cases of which 12 were male. Low-grade squamous cell carcinoma was seen within the areas affected by long-standing lichen sclerosus, in four patients (3%, 2 male). Limitations We studied only haematoxylin and eosin stained sections. The presence of basement membrane thickening could have been better illustrated with the periodic acid-Schiff stain. Conclusion The pathogenesis of lichen sclerosus probably involves an immune reaction to the basement membrane at the epidermal interface and around the adnexa. The initial band of inflammation shifts gradually downwards from the epidermal interface into the dermis destroying the vascular channels and appendages, resulting in excessive deposition of altered extracellular matrix. Basilar infiltration of lymphocytes along with a grossly vacuolated or thickened basement membrane is proposed as the characteristic diagnostic feature of the pre-sclerotic stage. Greater awareness of the clinicopathological spectrum of lichen sclerosus should enable early diagnosis and treatment, thereby preventing structural damage and possible malignant transformation in chronic cases.

Lepromatous leprosy with dermatofibroma features: colonization or morphological variant of histoid leprosy with epidermal induction?

BACKGROUND: Leprosy is one of the main health problems in developing countries. It can show many different clinical presentations. CASE REPORT: A 37-yr-old woman with multiple reddish-brown papules on the lower and upper limbs, including the palms. The initial clinical impression was pityriasis lichenoides chronica. Biopsies were taken. The specimen from the left shin showed classical histological features of lepromatous leprosy. The specimen from the left thigh was similar to lipidized dermatofibroma showing epidermal hyperplasia with basal layer hyperpigmentation, a narrow Grenz zone, and spindle xanthomatous cells among dermal fibers. Fite-Faraco staining revealed many bacilli. DISCUSSION: No matter the clinical presentation, in the presence of lipidized macrophages, Fite-Faraco staining (an inexpensive method available worldwide) should be performed to rule out leprosy, even in nonendemic areas or associated with a tumor.

Histopathological Study of Skin Lesions in a Tertiary Care Hospital: A Descriptive Cross-sectional Study.

INTRODUCTION: Skin diseases are much common in developing countries. The spectrum varies according to geographic distribution, gender, age, and coexisting disorder. We conducted this study to find out the prevalence of different skin lesions and to evaluate their frequency and site of distribution. METHODS: A descriptive cross-sectional study was done in the pathology department of Kathmandu Medical college from June 2019 to November 2019 after ethical clearance. The skin biopsies were processed, sectioned and stained with Haematoxylin and eosin and evaluated. A convenience sampling method was used. Data was collected and entry was done in Statistical Packages for Social Services version 20.0, point estimate at 95% Confidence Interval was calculated along with frequency and proportion for binary data. RESULTS: Among 133 skin biopsies examined, noninfectious vesicobullous and vesicopustular disease were found in 42 (46.6%) cases followed by microbial disease in 22 (24.5%) and noninfectious erythematous papular and squamous disease in 21 (23.4%) cases. Spongiotic dermatitis was the most common vesicobullous disease seen in 26 (28.9%) cases. Leprosy was the commonest microbial disease found in 7 (7.8%) cases. The commonest noninfectious erythematous papular and squamous disease was erythema dyschromicum perstans seen in 7 (7.8%) cases. The commonest neoplastic lesion was keratinocytic tumor seen in 12 (32.5%) cases. The commonest tumor of the skin was intradermal nevus seen in 6 (16.3%) cases. CONCLUSIONS: Spongiotic dermatitis is a predominating non-neoplastic and overall skin lesion which was similar to the other studies done. Histopathological examination is the gold standard for the proper diagnosis as histomorphological features distinguish various skin lesions.

M2-Polarized Macrophages Determine Human Cutaneous Lesions in Lacaziosis.

Lacaziosis is a cutaneous chronic mycosis caused by Lacazia loboi. Macrophages are important cells in the host immune response in fungal infections. The macrophage population exhibits strong plasticity that varies according to the stimuli in the microenvironment of lesions M1 profile promotes a Th1 pattern of cytokines and a microbicidal function and M2 is related to Th2 cytokines and immunomodulatory response. We investigated the population of M1 and M2 polarized macrophages in human cutaneous lesions. A total of 27 biopsies from human lesions were submitted to an immunohistochemistry protocol using antibodies to detect M1 and M2 macrophages (Arginase-1, CD163, iNOS, RBP-J and cMAF). We could observe high number of cells expressing Arginase1, CD163 and c-MAF that correspond to elements of the M2 profile of macrophage, over iNOS and RBP-J (elements of the M1 profile). The results suggest a predominant phenotype of M2 macrophages, which have an immunomodulatory role and probably contributing to chronicity of Lacaziosis.

Autophagy links antimicrobial activity with antigen presentation in Langerhans cells.

DC, through the uptake, processing, and presentation of antigen, are responsible for activation of T cell responses to defend the host against infection, yet it is not known if they can directly kill invading bacteria. Here, we studied in human leprosy, how Langerhans cells (LC), specialized DC, contribute to host defense against bacterial infection. IFN-γ treatment of LC isolated from human epidermis and infected with Mycobacterium leprae (M. leprae) activated an antimicrobial activity, which was dependent on the upregulation of the antimicrobial peptide cathelicidin and induction of autophagy. IFN-γ induction of autophagy promoted fusion of phagosomes containing M. leprae with lysosomes and the delivery of cathelicidin to the intracellular compartment containing the pathogen. Autophagy enhanced the ability of M. leprae-infected LC to present antigen to CD1a-restricted T cells. The frequency of IFN-γ labeling and LC containing both cathelicidin and autophagic vesicles was greater in the self-healing lesions vs. progressive lesions, thus correlating with the effectiveness of host defense against the pathogen. These data indicate that autophagy links the ability of DC to kill and degrade an invading pathogen, ensuring cell survival from the infection while facilitating presentation of microbial antigens to resident T cells.

Histopathological comparison of lesional and perilesional skin in melasma: A cross-sectional analysis.

BACKGROUND: Melasma is a common acquired hyperpigmentary disorder of the sun exposed skin, especially the face. The pathogenesis is unclear but interplay between genetic factors, hormones and ultraviolet radiation is important. We have evaluated the histological characteristics of melasma and compared the findings with adjacent normal skin. METHODS: Skin biopsies were taken from both melasma and the surrounding perilesional normal skin in 50 Indian women. The sections were stained with hematoxylin and eosin, Fontana-Masson and Verhoeff-Van Gieson stains. RESULTS: Biopsy from melasma showed significant epidermal atrophy, basal cell hyperpigmentation and solar elastosis when compared with the perilesional skin. We found that the proportion of pendulous melanocytes was significantly higher in the lesional biopsy compared with the perilesional biopsy (76% vs 42%, P < 0.001). Similarly, pigmentary incontinence and features of solar elastosis were significantly higher in the lesional skin compared with the perilesional skin. CONCLUSION: The characteristic histopathological features such as epidermal atrophy, basal cell hyperpigmentation and solar elastosis suggest the role of chronic sun exposure in the pathogenesis of melasma. Presence of pendulous melanocytes is a characteristic feature of melasma. The presence of pendulous melanocytes may have prognostic implications in melasma.

Mast cell heterogeneity and anti-inflammatory annexin A1 expression in leprosy skin lesions.

Mast cells (MCs) have important immunoregulatory roles in skin inflammation. Annexin A1 (ANXA1) is an endogenous anti-inflammatory protein that can be expressed by mast cells, neutrophils, eosinophils, monocytes, epithelial and T cells. This study investigated MCs heterogeneity and ANXA1 expression in human dermatoses with special emphasis in leprosy. Sixty one skin biopsies from 2 groups were investigated: 40 newly diagnosed untreated leprosy patients (18 reaction-free, 11 type 1 reaction/T1R, 11 type 2 reaction/T2R); 21 patients with other dermatoses. Tryptase/try+ and chymase/chy + phenotypic markers and toluidine blue stained intact/degranulated MC counts/mm2 were evaluated. Try+/chy+ MCs and ANXA1 were identified by streptavidin-biotin-peroxidase immunostaining and density was reported. In leprosy, degranulated MCs outnumbered intact ones regardless of the leprosy form (from tuberculoid/TT to lepromatous/LL), leprosy reactions (reactional/reaction-free) and type of reaction (T1R/T2R). Compared to other dermatoses, leprosy skin lesions showed lower numbers of degranulated and intact MCs. Try+ MCs outnumbered chy+ in leprosy lesions (reaction-free/reactional, particularly in T2R), but not in other dermatoses. Compared to other dermatoses, ANXA1 expression, which is also expressed in mast cells, was higher in the epidermis of leprosy skin lesions, independently of reactional episode. In leprosy, higher MC degranulation and differential expression of try+/chy+ subsets independent of leprosy type and reaction suggest that the Mycobacterium leprae infection itself dictates the inflammatory MCs activation in skin lesions. Higher expression of ANXA1 in leprosy suggests its potential anti-inflammatory role to maintain homeostasis preventing tissue and nerve damage.

Histoid leprosy: a retrospective clinicopathological study from central Nepal.

BACKGROUND: Histoid leprosy is a rare variant of lepromatous leprosy characterized by varied morphological and histopathological appearance while having a high bacillary load. These factors contribute to an ominous threat to the elimination status of leprosy, whereby these patients may act as a reservoir of infection. OBJECTIVE: To identify the clinicopathological characteristics of histoid leprosy in Chitwan, Nepal. METHODS: A retrospective hospital-based study spanning a period of 6 years was carried out at our department. All cases clinically and histopathologically suggestive of histoid leprosy were included in our study, and all relevant data were recorded and analyzed as per standard protocol. RESULTS: Histoid leprosy comprised 2.9% of all leprosy cases. Mean age of 39.45 years and male:female ratio of 1.75:1 were seen. Previous history of leprosy was obtained in 72.7%, and de novo development of histoid leprosy took place in 27.3%. Papules were the most common lesion seen, and upper limbs were the most frequent site of involvement, and the ulnar nerve was enlarged in most cases. Mean bacillary index was 5.39. Histopathology showed epidermal atrophy, positive Fite-Faraco stain for lepra bacilli, spindle-shaped histiocytes arranged in various patterns, and a well-circumscribed area of cells in the dermis in all cases. Grenz zone and pseudocapsule were seen in the majority of patients. All cases responded well to multibacillary multidrug therapy (MB-MDT) of 2 years. CONCLUSION: A high index of suspicion is essential for diagnosing histoid leprosy, both clinically and histopathologically.

A morphometric and immunohistochemical study of melanocytes in periorbital hyperpigmentation.

BACKGROUND: An increase in number of melanocytes in the basal cell layer of the epidermis is an important feature in many disorders of hyperpigmentation. In this study, we attempted an objective evaluation of the linear density of melanocytes and keratinocytes, along with other epidermal characteristics, in periorbital hyperpigmentation using immunohistochemistry and morphometric techniques. METHODS: Melanocytes and epidermal parameters were assessed by digital morphometry in 30 newly diagnosed cases of periorbital hyperpigmentation and 14 controls from the post-auricular region. Melanocytes were labelled with the immunohistochemical stains, Melan-A and tyrosinase. We studied the linear keratinocyte density, mean linear melanocyte density, ratio of melanocytes to keratinocytes, the ratio between inner and outer epidermal length, maximum epidermal thickness and minimum epidermal thickness. RESULTS: Melan-A expression of melanocytes showed strong positive correlation (r=0.883) with the tyrosinase expression. Mean linear melanocyte density was 24/mm (range: 13-30/mm) in cases and 17/mm (13-21/mm) in controls and this difference was statistically significant (P<0.001). The mean ratio of melanocyte to keratinocyte was 0.22 (0.12-0.29) in cases and 0.16 (0.12-0.21) in controls; again, this difference was statistically significant (P<0.001). There was a mild negative correlation with linear keratinocyte density (r=-0.302) and the ratio between inner and outer epidermal length (r=-0.456). However, there were no differences in epidermal thicknesses. LIMITATIONS: There were fewer control biopsies than optimal, and they were not taken from the uninvolved periorbital region. CONCLUSION: Mean linear melanocyte density and the ratio of melanocytes to keratinocytes is increased in cases with periorbital hyperpigmentation. It is, therefore, likely that increased melanocyte density may be the key factor in the pathogenesis of periorbital hyperpigmentation.

Interface dermatitis.

Interface dermatitis includes diseases in which the primary pathology involves the dermo-epidermal junction. The salient histological findings include basal cell vacuolization, apoptotic keratinocytes (colloid or Civatte bodies), and obscuring of the dermo-epidermal junction by inflammatory cells. Secondary changes of the epidermis and papillary dermis along with type, distribution and density of inflammatory cells are used for the differential diagnoses of the various diseases that exhibit interface changes. Lupus erythematosus, dermatomyositis, lichen planus, graft versus host disease, erythema multiforme, fixed drug eruptions, lichen striatus, and pityriasis lichenoides are considered major interface diseases. Several other diseases (inflammatory, infective, and neoplastic) may show interface changes.

Morphometric study of microvessels, epidermal characteristics and inflammation in psoriasis vulgaris with their correlations.

BACKGROUND: Vascular proliferation, inflammation and epidermal changes are important features in the pathogenesis of psoriasis. AIMS: In this study we attempted an objective evaluation of these parameters using morphometry. METHODS: Inflammation, microvessels and epidermal parameters were assessed in 50 newly diagnosed cases of psoriasis vulgaris (between 01 Nov 2008 and 31 Oct 2011) by morphometry. Parameters studied were microvessel density, microvessel caliber, inflammatory cell density in dermis, ratio between inner and outer epidermal length, maximum epidermal thickness, minimum epidermal thickness and difference between maximum epidermal thickness and minimum epidermal thickness. RESULTS: Microvessel caliber showed moderate correlation (r = 0.645) and microvessel density, weak correlation (r = 0.226) with inflammatory cell density in dermis. Both these parameters also showed mild positive correlation with "ratio between inner and outer epidermal length". All parameters except minimum epidermal thickness showed mild positive correlation with inflammatory cell density in dermis. CONCLUSION: All microvessels and epidermal parameters showed positive correlation with dermal inflammation; and epidermal parameters exhibited positive correlation with micro-vascular dilation. It is likely that inflammation is a key factor in the pathogenesis of psoriasis.