T-Regulatory Cells in Erythema Nodosum Leprosum: An Immunohistochemical and Image Morphometric Study.

ABSTRACT: Erythema nodosum leprosum (ENL) occurs as an immune-inflammatory complication of multibacillary leprosy (MBL), precipitated by an interaction between the host, bacilli, and the environment. This complication often causes significant morbidity due to systemic involvement and needs to be treated aggressively. T-regulatory cells (T-regs) are the immunomodulatory subset of T cells that are hypothesized to play a role in ENL. We have performed immunohistochemistry for FoxP3 (T-reg), CD3 (pan-T), CD4 (helper T), and CD8 (cytotoxic T) on 50 biopsy-proven cases of ENL along with 84 biopsy-proven cases of paucibacillary leprosy (PBL) (n = 49) and MBL (n = 35). Image morphometry was applied to objectively assess the relative preponderance of these subsets of T cells. The area fraction of T-regs showed a trend of reduction from PBL to MBL to ENL (P = 0.068), whereas the FoxP3:CD3 (T-reg: pan-T) ratio showed a significant reduction across these groups (P = 0.023). However, there was no significant difference of T-regs or FoxP3:CD3 ratio between MBL and ENL. The T-regs showed a significant positive correlation (P = 0.007) with the cytotoxic T cells in the skin biopsy. The presence of dermal eosinophils in ENL showed a trend association with the FoxP3:CD3 ratio (P = 0.05). Various histopathological parameters including epidermal spongiosis, dermal stromal edema, dermal ill-formed granuloma, and the presence of bacilli within the endothelium and vascular smooth muscle correlated with various T-cell subsets. Our study, one of the largest on this topic, objectively assessed the role of T-regs in the spectrum of leprosy. Nevertheless, the precipitation of ENL from MBL is probably not associated with the T-reg subset alone.

Image Morphometric Analysis of B Cells and Plasma Cells in Erythema Nodosum Leprosum With Clinicopathological Correlation.

ABSTRACT: Erythema nodosum leprosum (ENL) occurs as an immunological complication of multibacillary leprosy (MBL). The pathogenesis of ENL is long considered to be a T-cell-mediated process. The role of B cells and plasma cells in ENL is not well described in the literature. Therefore, we investigated the B-cell and plasma cell infiltrates in the skin biopsies of biopsy-proven cases of ENL by immunohistochemistry and image morphometry and compared the result with paucibacillary leprosy and MBL. Moreover, we sought a correlation of the B-cell and plasma cell infiltrates with different clinical, hematological, histopathological, and bacteriological parameters as well as the T-cell subsets in the skin biopsies. Our study highlighted a significant reduction in the number of B cells from paucibacillary leprosy to MBL to ENL, although there was no significant variation in the plasma cell infiltrate. The plasma cell infiltrate correlated with absolute neutrophilia in the blood and the presence of eosinophils in the ENL lesions. Both B cells and plasma cells positively correlated with CD4-positive T-helper cells and the CD8-positive cytotoxic T cells. Besides, the B cells also correlated positively with the CD3-positive pan T cells in the biopsy and negatively correlated with the T-regulatory:T-cell ratio. Our results suggested the role of B cells and plasma cells even at the tissue level in the pathobiogenesis of ENL.

Dermoscopic features of acute cutaneous lupus erythematosus: A retrospective analysis from a tertiary care centre of East India.

BACKGROUND: The cutaneous features of acute cutaneous lupus erythematosus (ACLE) can be confused with other dermatoses. The dermoscopic features of ACLE have rarely been reported. AIMS: We aimed to study the dermoscopic features of ACLE, malar rash, and generalized ACLE. MATERIALS AND METHODS: The dermoscopic features of all biopsy and direct immunofluorescence confirmed ACLE cases were analysed retrospectively between May 2019 and May 2020. RESULTS: A total of 21 patients with skin phototypes III, IV, or V were included in the analysis. A pinkish-white to reddish-white homogenous area (94.1%), brown dots, globules and peppering (76.4%), and keratotic follicular plugging (64.7%) were the common dermoscopic features observed in the case of generalized ACLE. Similarly, in the case of malar rash, a pinkish-white to reddish-white homogenous area (77.8%) was the most common dermoscopic feature, followed by keratotic follicular plugging (66.7%), scales (44.5%), and brown dots, globules, and peppering (44.5%). In both variants, vascular structures were dominated by linear vessels with or without branching. CONCLUSIONS: A multicomponent pattern comprising white scales, homogenous pinkish-white to the reddish-white area, brown dots/globules/peppering, keratotic follicular plugging, and linear vessels with or without branching were the common dermoscopic features observed in our study and may indicate the diagnosis of both localized and generalized ACLE. In addition, a paucity of dotted vessels may serve as an additional clue.

A fleshy papule on the eyelid.

Angiolymphoid hyperplasia with eosinophilia is an uncommon tumor affecting the head and neck region. It usually presents as solitary or multiple erythematous or brownish papules and nodules. It is considered a reactive angioproliferative disorder by some, whereas others believe it to be a neoplastic growth. Involvement of the eyelid is a rare occurrence. We report an instance of angiolymphoid hyperplasia with eosinophilia involving the eyelid in a 19-year-old woman with review of literature.

Proportionate growth of congenital nevi: Blow a balloon to explain.

Any form of congenital nevus in a child is a cause of parental anxiety. Parents are often worried about the future course of the lesion. Some of these lesions grow in extent with the child's growth and involve other body areas; others grow proportionate to the involved body part, giving an impression of apparent growth of the lesion. We use an illustrative "blowing a balloon" technique to explain the apparent growth pattern of some congenital nevi.

An Innovative Cooling Jacket to Combat Heat Intolerance in Children with Anhidrosis.

Hyperthermia and heat intolerance are distressing symptoms in patients with anhidrosis. Body cooling devices are an integral part of management of these patients. A cooling jacket made from easily available materials has been invented for a girl with congenital insensitivity to pain and anhidrosis with severe heat intolerance. This innovative cooling jacket may be helpful for anhidrotic children in resource-poor situations.

Childhood leprosy in India over the past two decades.

OBJECTIVES: Clinico-epidemiological pattern of childhood leprosy in India over the past two decades were analysed from the Indian studies conducted during the years 1990-2009. RESULTS: Twelve studies on childhood leprosy were included. Ten were conducted in health institutions and one was a community-based survey. Voluntary reporting was the principal method of case detection; community survey was adopted in two studies. Occurrence of childhood leprosy in tertiary care hospitals varied from 5.1-11.43%, in one urban clinic and the three leprosy referral hospitals it was 9.81-31.3% and peripheral surveys recorded 7.06-35.5% cases. History of familial contact was present in 0.66-47% cases. Borderline tuberculoid was the commonest clinical type, majority with single lesion. Other types were indeterminate (3.48-10.1%), borderline lepromatous (1.9-19.4%), lepromatous (0.1 to 9.38%), and pure neuritic (3.48-10.1%). Single peripheral nerve trunk was involved in 13.63-40-62% cases and multiple nerve involvement was recorded in 4.54-59.38% cases. The majority of cases were paucibacillary (43.28-98%). Multibacillary (MB) cases ranged from 2-56.6%. Slit-skin smear positive cases ranged from 5.42-25%. Lepra reactions occurred in 0-29.7% cases. Relapse rate varied between 1.16-7.1%. Deformity occurred in 0-24% cases. CONCLUSIONS: Multibacillary cases were common among Indian children, some of whom were smear positive. Probably these cases were the source of many new cases. Pure neuritic leprosy was frequent among Indian children, so also the lepra reactions and deformities. The presence of familial and extra-familial contact with leprosy cases may be a cause of concern, as it implies continuing transmission of the disease.

Childhood leprosy in the post-elimination phase: data from a tertiary health care hospital in the Karnataka state of south India.

OBJECTIVE: Children with leprosy attending a tertiary care hospital during the post-elimination period, in the Karnataka state of south India, have been studied. Data on childhood leprosy collected by the field health workers from district leprosy office during the same period through community survey was also analysed. RESULTS: In the hospital, 61 new childhood cases were diagnosed, 19.7% of the total leprosy cases (n = 309) examined during that period. Borderline tuberculoid leprosy was the commonest presentation in children. Twenty four (39.34%) were paucibacillary and 37 (60.65%) were multi-bacillary. Positive slit skin smear was obtained in 8.19%. Household contacts were identified in 18.2%. Reactions were seen in 16.4% (type 1 and 2) and 8.19% children had visible deformity. Analysis of the data collected by the field health workers showed 223 (21.25%) childhood cases (paucibacillary 69.50% and multi-bacillary 30.49%). Type 1 reaction was recorded in 4.93%. Deformities were seen in 5.82%, and 1.79% had WHO Grade 2 deformities. CONCLUSION: More multi-bacillary cases were recorded in the hospital as compared to higher number of pauci-bacillary cases by the community survey. Cases with reactions and deformities were also higher in hospital. Type 2 reaction was not recorded in community survey and WHO Grade 2 deformities were low. Patients with more severe disease might have attended the hospital by choice, resulting in the difference in data. The results indicate that transmission of leprosy is continuing in India even in this state with low endemicity. Presence of household contacts, children with multi-bacillary disease and smear positivity in childhood cases are the aspects requiring special attention.

Incidental detection of Cladosporium in cytology.

BACKGROUND: Fungal infection incidental detection is a common encounter in cytopathology practices. Detection of the fungal organisms and awareness of the morphological features are challenges for the cytopathologist. CASE PRESENTATION: We report a case of incidental detection of a fungal organism in a 67-year-old male patient with complaints of bilateral elbow joint swellings. Cytology was done and showed a fungal organism (Cladosporium sps.). CONCLUSION: Fine needle aspiration cytology (FNAC) along with Rapid on-site evaluation (ROSE) is a rapid, minimally invasive technique used for the diagnosis and detection of various fungi / parasites leading to early and definitive treatment.

Clinicodermoscopic and immunopathological profile of non-infectious non-eczematous inflammatory tattoo reactions: A retrospective study from a tertiary care centre of East India.

Introduction Tattoo-associated complications are on the rise due to the popularity of decorative tattoos in recent years. The exact pathogeneses of various tattoo reaction patterns are still unclear, and their dermoscopic details are sparsely reported. Aim We aimed to retrospectively study the clinical, dermoscopic and immunopathological details of patients with non-infectious, non-eczematous inflammatory tattoo reaction patterns in a tertiary care centre of East India. Method The clinical, dermoscopic and pathological details of all the patients who had non-infectious, non-eczematous inflammatory tattoo reactions were collected. In all the cases, immunohistochemistry was done for CD1a, CD3, CD4, CD8, FoxP3, CD20 and CD56. Results A total of five patients of skin phototypes IV and V and six tattoo reactions were analysed. Five lesions had reactions at the site of a black tattoo, and one at the site of red tattoo. Clinically, the patients presented with erythematous or blue-grey flat-topped to verrucous papules and plaques. Dermoscopic features were dominated by a central white to pink-white structureless area, a peripheral grey-white to bluish-white structureless area, white scales, comedo-like opening with keratotic plugging, milia-like cysts and shiny white structures. Pathologically, except for one lesion that only showed a lichenoid reaction pattern in the red tattoo, all had a combination of reaction patterns. Immunohistochemistry showed increased epidermal and dermal Langerhans cells, predominantly CD8 positive T cells in the epidermis and dermis, sparse dermal B cells and CD4 positive T cells, reduced T regulatory cells and a complete absence of CD56 positive NK cells. Limitations Small sample size was the limitation of the study. Conclusion The clinical morphology and dermoscopy may not differentiate between various types of non-infectious non-eczematous inflammatory tattoo reactions. The immunological profile supports a delayed hypersensitivity reaction due to contact sensitisation to tattoo pigment, and CD8 positive T cells play a central role in executing various pathological reaction patterns, both in the epidermis and dermis.

RASopathies: Dermatologists' viewpoints.

Ras/mitogen-activated protein kinase pathway dysregulation results in a group of disorders, collectively termed as RASopathies. Neurofibromatosis type 1, Noonan syndrome, Noonan syndrome with multiple lentigines, Noonan syndrome/loose anagen hair, Legius syndrome, Costello syndrome, cardio-facio-cutaneous syndrome and capillary malformation-arteriovenous malformation are the well-recognized RASopathies. These are characterized by multi-organ tumours and hamartomas. Some other features in common are facial dysmorphism, skeletal abnormalities, congenital heart disease, neurocognitive abnormalities and risk of various solid-organ and haematological malignancies. Some of the RASopathies are heterogeneous, caused by several gene mutations resulting in variations in phenotypes and severity ranging from mild to fatal. Significant phenotypic overlaps among different disorders, often makes it difficult to pinpoint a clinical diagnosis. Specific cutaneous manifestations are present in some of the RASopathies and are often the earliest clinical signs/symptoms. Hence, dermatologists contribute significantly as primary care physicians by identifying disorder-specific cutaneous lesions. However, diagnostic work-up and management of these disorders are often multidisciplinary. Confirmation of diagnosis is possible only by genetic mapping in each case. Genetic counseling of the patients and the affected families is an important component of the management. The aim of this review is description of cutaneous manifestations of RASopathies in the background of multi-system involvement to enable dermatologists a comprehensive and logical approach to work up and diagnose such patients in the absence of facility for specific molecular testing.

A Cross-Sectional Study to Correlate Serum Complement C3 and C4 Levels With Clinical and Pathological Severity in Cutaneous Small-Vessel Vasculitis.

Introduction The role of serum C3 and C4 levels as a marker of disease activity in cutaneous small-vessel vasculitis (CSVV) has been sparsely studied, especially in India. The primary objective was to determine the correlation between clinico-histopathological severity and serum C3 and C4 levels in CSVV. The secondary objective was to determine the association between direct immunofluorescence (DIF) findings and serum C3 and C4 levels and clinico-histopathological findings. Method This prospective cross-sectional study included all the clinically diagnosed cases of CSVV that satisfied the pathological criteria for CSVV. A clinical disease activity grade and a histopathological severity grade were calculated in all patients (N=50). Results Serum C3 and C4 levels (n=44) were diminished in 4.5% of cases. There was no significant correlation between the serum C3 and C4 levels and the clinical and histopathological severity. DIF was positive in 60.0% of cases (n=45), and IgA was the predominant immune deposit (46.7%). No significant association was detected between the DIF findings and the serum C3 and C4 levels, histopathological severity, and clinical disease activity grade. Positive DIF findings were significantly associated with palpable purpura and cutaneous necrosis. A significant association was detected between gastrointestinal involvement and IgA positivity. Conclusion In CSVV, serum C3 and C4 may not be used as markers of disease severity, and a positive DIF finding may indicate an underlying gastrointestinal involvement.

Dermoscopic Analysis of Vascular Malformations and Tumors Based Upon Dominant Vascular Dermoscopic Features: A Retrospective Analysis From a Tertiary Care Center of East India.

Background Cutaneous vascular malformations and tumors comprise a vast group of conditions with variable clinical presentations. It is imperative to differentiate them from nonvascular lesions and from each other as their management and prognosis differ significantly. There is only sparse literature on dermoscopic features of various vascular malformations and tumors, especially from India. Aim We aimed to retrospectively study the dermoscopic findings of various vascular malformations and tumors based on their dominant vascular dermoscopic feature. Method All the vascular malformations and tumors for which clinical details and clinical and dermoscopic images were available were included in the analysis. The dominant vascular feature(s) was defined as a single or combination of two or more vascular features (in case a single vascular feature does not satisfy the criteria) that constitute more than 75% of the lesions' vascular features. These included red, purple, blue, black (or any combination) dots, globules, lacunae, structureless area, linear, linear irregular, hairpin, comma, and arborizing vessels. Results A total of 52 patients with 68 vascular lesions (22 vascular malformations and 46 vascular tumors) were analyzed. Port-wine stain showed linear irregular vessels with sharp border with or without intervening white structureless area; unilateral nevoid telangiectasia had red dots and globules; angiokeratoma displayed red, reddish-purple to brown lacunae; blue color was seen in venous and glomuvenous malformation and venous lake; a mixed pattern was noted in infantile hemangioma and verrucous hemangioma; a red to reddish-white structureless area was observed in pyogenic granuloma and cherry angioma, and a subungual ill-defined pink structureless area was spotted in subungual glomus tumor. Conclusion The dermoscopic features observed in various vascular lesions may overlap; however, the dominant dermoscopic feature along with its color may point to the diagnosis.

Clinico-Dermoscopic-Pathological Features of a Rare Case of Locally Invasive Multifocal Primary Cutaneous Diffuse Large B Cell Lymphoma-Leg Type Over the Face and Scalp.

Primary cutaneous diffuse large B-cell lymphoma-leg type (PCDLBCL-LT) is characterized by diffuse monotonous proliferation of centroblasts and immunoblasts. It commonly presents as erythematous to violaceous nodules on one or both the legs and has a poor prognosis. We report the clinico-dermoscopic-pathological features and therapeutic response of a rare case of PCDLBCL-LT in a 62-year-old diabetic man, who presented with multifocal plaques, one lobulated and two arcuate-shaped, on the face and scalp. During the investigation, one of the plaques had eroded the underlying bone without any evidence of malignant cells in the cerebrospinal fluid. He was successfully treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) along with intrathecal methotrexate.

Knuckle lesions in inherited and acquired disorders.

Skin lesions occurring over the knuckles can be a primary or characteristic manifestation of a disorder. Characteristic knuckle lesions may also be important cutaneous features of various internal disorders when they serve as useful clinical pointers, as well as may speak of the disease severity in certain instances. Furthermore, knuckle lesions also speak of various external factors as the underlying cause of the disease/lesions, such as trauma - occupational or otherwise, and contact dermatitis. Although knuckles essentially imply dorsal aspect of the metacarpophalangeal joints, many of the lesions described as those 'involving the knuckles' are seen over the proximal and/or less frequently, the distal interphalangel joints as well. This review presents a compilation of various inherited and acquired dermatoses and dermatological manifestations of various internal disorders associated with different forms of knuckle lesions.