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.

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.

Prevention of transmission of leprosy: The current scenario.

With the worldwide implementation of WHO multidrug therapy in the 1980s, the global burden of leprosy has decreased. However, the annual new case detection rate around the world has remained nearly static over the past decade with India, Brazil, and Indonesia contributing the majority of these new cases. This has been attributed to the ongoing transmission of Mycobacterium leprae from existing untreated cases and partly to the intensive new case detection programs operative in endemic areas. The WHO has called for a "global interruption of transmission of leprosy by 2020". Targeted chemoprophylaxis of contacts may help bring down the number of new cases. The single-dose rifampicin currently in use for post-exposure prophylaxis (PEP) has limitations and so newer antileprosy drugs and regimens have been trialed for chemoprophylaxis. BCG re-vaccination in combination with chemoprophylaxis for the prevention of leprosy transmission has not been very encouraging. The use of the anti-phenolic glycolipid-1 (PGL-1) antibody test to detect subclinical cases and administer targeted chemoprophylaxis was unsuccessful owing to its low sensitivity and technical difficulties in a field setup. There is a pressing need for newer multidrug chemoprophylactic regimens using second-line antileprosy drugs. The Netherlands Leprosy Relief has proposed an enhanced PEP++ regimen. A simple but highly sensitive and specific serological test to detect subclinical cases at the field level needs to be developed. Although there are a number of challenges in the large-scale implementation of strategies to halt leprosy transmission, it is important to overcome these in order to move towards a "leprosy-free world."

Anticoagulants in dermatology.

Anticoagulants are the cornerstone of treatment of venous thromboembolism associated with various medical conditions and surgical procedures. They act on different steps of the coagulation pathway and are broadly categorized into heparins, vitamin K antagonists, and inhibitors of thrombin and factor Xa. The classification is evolving as newer and better oral and parenteral anticoagulants are being added. Anticoagulants in dermatology are important not only for their therapeutic application in cutaneous thrombotic dermatoses such as livedoid vasculitis, purpura fulminans, superficial and deep venous thrombosis and others but also for their use in non-thrombotic dermatoses such as lichen planus, recurrent oral aphthosis, chronic urticaria and several others. Further, the use of anticoagulants for any indication is associated with various adverse effects with dermatologic manifestations including specific reactions such as warfarin-induced skin necrosis, heparin-induced thrombocytopenia and anticoagulant-associated cholesterol embolization syndrome.

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.

Sensitive skin: an overview.

Sensitive skin is less tolerant to frequent and prolonged use of cosmetics and toiletries. It is self-diagnosed and typically unaccompanied by any obvious physical signs of irritation. With the change in lifestyle and also with increased opportunity to use many new brands of cosmetics and toiletries, there has been an increase in females complaining of unique sensation in their facial skin. Sensitive skin presents as smarting, burning, stinging, itching, and/or tight sensation in their facial skin. The condition is found in more than 50% of women and 40% of men, creating a sizable demand for products designed to minimize skin sensitivity. Good numbers of invasive and non-invasive tests are designed to evaluate and predict the sensitive skin. Management includes guidelines for selecting suitable cosmetics and toiletries in sensitive skin individuals.

Nails: diagnostic clue to genodermatoses.

Nails are cutaneous appendages mostly involved in mechanical functions. However, nails may reflect presence of various systemic disorders evidenced by alteration of their shape, size, color or texture. Genodermatoses are multisystem disorders with cutaneous involvement. Many of the genodermatoses present with nail changes and some of these may be the clinical pointers to the diagnosis. Diagnostic clues to various genodermatoses derived from nail findings have been discussed.