An Institution Based Cross-Sectional Observational Aetiological Study Correlating the Clinico-Pathological Findings in Patients Presenting with Acquired Palmoplantar Keratoderma.

Background: Palmoplantar keratoderma (PPK) is a heterogeneous group of hereditary or acquired disorders characterised by excessive epidermal thickening of the palms and soles. Proper knowledge about the aetiology of the disease and clinico-demographic profile helps in planning management and predicting outcomes. Aims and Objective: To determine the prevalence of different dermatoses and describe their clinico-histological correlation in acquired palmoplantar keratoderma. Materials and Methods: An institution-based cross-sectional study conducted after obtaining Ethics-Committee permission and consent from participants. Patients of any age or gender presenting with acquired PPK were recruited. The calculated sample size was 67 by using the prevalence rate (p) of 22.2%, allowable error (L) of 10%, the confidence level of 95% (z = 1.96), and an infinite population size of 20,000. Patients were evaluated by taking demographic and clinical data in a pre-designed case record form, necessary laboratory investigations and histopathological examination that wereevaluated by three blinded experts. The pooled data were analysed with statistical software. Results: Among the 67 participants, Psoriasis was diagnosed clinically in 39 (58.2%) and histologically in 7 (10.4%), Lichen planus (LP) clinically in 16 (23.9%) and histologically in 9 (13.4%), Pityriasis rubra pilaris (PRP) in 8 (11.9%) patients clinically and 7 (10.4%) histologically and Hyperkeratotic eczema (HKE) in 4 (6%) clinically and 43 (64.2%) histopathologically. There was very poor inter-rater agreement (Kappa = 0.148, SE 0.0047, 95% CI 0.057 to 0.24). The clinico-pathological correlation was found to be agreeable in 17.9% Psoriasis, 56.2% LP and 87.5% PRP. HKE was commonly misdiagnosed as Psoriasis in 65.1% of patients. Conclusion: Hyperkeratotic lesions of the palm and sole often present with overlapping clinical features and a skin biopsy has to be done to aid in diagnosis. Limitation: Stratification of the clinical expertise of clinicians was done during the analysis.

A Clinico-Demographic Profile and Sexual Behaviour Pattern in Attendees of Designated STI/RTI Clinic Having Sexually Transmitted Infections with Special Reference to HIV Seropositivity.

Introduction: The dynamics of sexually transmitted infections (STIs) are influenced by sexual behaviour (age of first sexual exposure, number of sexual partner/s, sexual orientation, mode of intercourse, addiction, occupation, correct and consistent use of condom). The presence of the human immunodeficiency virus (HIV) influences the clinical pattern of STIs and the course of disease too. Objective: Our study was conducted to find the prevalence of STIs among attendees of a designated STI/RTI clinic (DSRC) with the description of clinico-demographic profile and sexual behaviour and association of HIV seropositivity with STIs. Methods: Ours was an institution-based cross-sectional study conducted at DSRC after obtaining ethics committee approval and consent from patients. Clinical diagnosis, demographic profile and sexual history were obtained after maintaining audio-visual privacy. Statistical Analysis: Medcalc, version 10.2 was used. Results: Among 167 patients attending DSRC during the study period, 76 having sexual dysfunctions were excluded. The major STIs diagnosed were primary syphilis (6.59%), secondary syphilis (2.2%), herpes genitalis (42.86%), condyloma acuminata (26.37%), molluscum contagiosum (5.49%), genital candidiasis (7.69%), bowenoid papulosis (3.3%), genital scabies (4.4%) and chancroid (1.1%). Sexual orientations were heterosexual (64.83%), lesbian (1.1%), gay (12.1%), bisexual (17.58%) and with an animal partner (4.4%). Among the total study population, 8.8% was rapid plasma reagin (RPR) reactive and 12.1% was Integrated Counselling and Testing Centre (ICTC) reactive. Among the total patients who used condoms (n = 49), only 15 (16.4% of total participants) used condoms correctly and consistently. Peno-vaginal mode of intercourse (n = 78) was found to be most common followed by oro-insertive (n = 42), oro-receptive (n = 34), ano-insertive (n = 24), ano-receptive (n = 17) and digital insertion (n = 20). Conclusion: Sexual behaviour influences the disease outcome in patients with reproductive tract infection (RTI)/STI.

Dermatoses in the Elderly: Clinico-Demographic Profile of Patients Attending a Tertiary Care Centre.

BACKGROUND: Elderly population is vulnerable to develop a multitude of dermatological diseases, owing to comorbidities and polypharmacies. OBJECTIVE: To know the prevalence of dermatological conditions in elderly patients attending outpatient department, determine the pattern and relative frequency of skin diseases, and find the relation with associated comorbidities. MATERIALS AND METHODS: We performed a cross-sectional study on 250 patients, aged ≥60 years. Clinical diagnosis was done, followed by appropriate investigations when required. Descriptive data was analyzed on the parameters of range, mean ± S.D., frequencies, etc., Continuous variables were analyzed using unpaired t-test/Mann-Whitney U test and categorical data by Fisher's exact test/Chi-square test. Statistical software Medcalc version 10.2.0.0 for Windows vista was used. P value =0.05 was considered statistically significant. RESULTS: 250 patients were evaluated, 164 males (65.5%) and 86 females (34.4%). Mean age was 67.87 ± 7.29 years. Commonest disease category was infection (30%), followed by dermatitis (29.6%), papulo-squamous (18.4%), and immunobullous (6.4%). Difference in acute and chronic disease was significant (P = 0.0001). 30% had infections; fungal (50.66%), bacterial (32%), and viral (17.33%). 74 patients had dermatitis (29.6% of study population). Commonest systemic disease was hypertension (23.2%), followed by diabetes mellitus (19.6%). Association of diabetes mellitus was significant (P = 0.0014), more in infective dermatoses (P = 0.0007). All had signs of aging; idiopathic guttate hypomelanosis (51.2%), xerosis (45.2%), seborrheic keratosis (42.6%), cherry angioma (33.2%), senile acne (6.6%). Photoaging was noted as wrinkling (98.8%), freckles (35.6%), purpura (10.8%), telangiectasia (5.6%). People involved in outdoor activity had higher Glogau scale (3.01 ± 0.69) compared to those indoors (2.44 ± 0.74), statistically significant difference (P = 0.001). CONCLUSION: Our study is the first of its kind, in Eastern India, where we evaluated and explored the disease pattern and extent of geriatric dermatoses among patients attending dermatology OPD of a tertiary care hospital.

Iron trafficking in patients with Indian Post kala-azar dermal leishmaniasis.

BACKGROUND: During infections involving intracellular pathogens, iron performs a double-edged function by providing the pathogen with nutrients, but also boosts the host's antimicrobial arsenal. Although the role of iron has been described in visceral leishmaniasis, information regarding its status in the dermal sequel, Post Kala-azar Dermal Leishmaniasis (PKDL) remains limited. Accordingly, this study aimed to establish the status of iron within monocytes/macrophages of PKDL cases. METHODOLOGY/PRINCIPAL FINDINGS: The intramonocytic labile iron pool (LIP), status of CD163 (hemoglobin-haptoglobin scavenging receptor) and CD71 (transferrin receptor, Tfr) were evaluated within CD14+ monocytes by flow cytometry, and soluble CD163 by ELISA. At the lesional sites, Fe3+ status was evaluated by Prussian blue staining, parasite load by qPCR, while the mRNA expression of Tfr (TfR1/CD71), CD163, divalent metal transporter-1 (DMT-1), Lipocalin-2 (Lcn-2), Heme-oxygenase-1 (HO-1), Ferritin, Natural resistance-associated macrophage protein (NRAMP-1) and Ferroportin (Fpn-1) was evaluated by droplet digital PCR. Circulating monocytes demonstrated elevated levels of CD71, CD163 and soluble CD163, which corroborated with an enhanced lesional mRNA expression of TfR, CD163, DMT1 and Lcn-2. Additionally, the LIP was raised along with an elevated mRNA expression of ferritin and HO-1, as also iron exporters NRAMP-1 and Fpn-1. CONCLUSIONS/SIGNIFICANCE: In monocytes/macrophages of PKDL cases, enhancement of the iron influx gateways (TfR, CD163, DMT-1 and Lcn-2) possibly accounted for the enhanced LIP. However, enhancement of the iron exporters (NRAMP-1 and Fpn-1) defied the classical Ferritinlow/Ferroportinhigh phenotype of alternatively activated macrophages. The creation of such a pro-parasitic environment suggests incorporation of chemotherapeutic strategies wherein the availability of iron to the parasite can be restricted.

Decreased Frequency and Secretion of CD26 Promotes Disease Progression in Indian Post Kala-azar Dermal Leishmaniasis.

PURPOSE: Leishmania, the causative organisms for leishmaniasis, reside in host macrophages and survive by modulating the microbicidal pathways via attenuation of the oxidative burst and/or suppression of cell-mediated immunity. As post kala-azar dermal leishmaniasis (PKDL), the dermal sequela of visceral leishmaniasis, has no animal model, the underlying mechanism(s) that nullify the microbicidal effector mechanisms remain poorly understood. This study was aimed at assessing the status of dipeptidyl peptidase CD26, a co-stimulatory molecule that is essential for T-cell signal activation. METHODS: The frequency/expression of CD26 and CD45RO/RA was evaluated by flow cytometry, while levels of soluble CD26 (sCD26), CXCL-10, RANTES, IL-10 and TGF-ß along with adenosine deaminase (ADA) activity were measured using ELISA. RESULTS: In patients with PKDL vis-à-vis healthy individuals, there was a significant decrease in the frequency and expression of CD26 on CD3(+)CD8(+) T-cells, which was accompanied by a significant lowering of plasma levels of sCD26. Furthermore, these patients showed a significant decrease in the frequency of CD45RO(+)/CD8(+) T-cells, concomitant with a significant increase in the proportion of CD45RA(+)/CD8(+) T-cells. This could collectively translate into reduced formation of the immunological synapse of CD26, CD45RO, and ADA, and lead to an attenuation of the Th1 responses. The decreased levels of CD26 and sCD26 correlated negatively with raised levels of Th2 cytokines, IL-10, and TGF-ß along with the lesional parasite load, indicating disease specificity. CONCLUSIONS: Taken together, the decreased expression and secretion of CD26 in patients with PKDL resulted in impairment of the CD26-ADA interaction, and thereby possibly contributed to T-cell unresponsiveness, emphasizing the need to develop immunomodulatory therapies against PKDL and by extension, the leishmaniases.

M2 Polarization of Monocytes-Macrophages Is a Hallmark of Indian Post Kala-Azar Dermal Leishmaniasis.

The high level of functional diversity and plasticity in monocytes/macrophages has been defined within in vitro systems as M1 (classically activated), M2 (alternatively activated) and deactivated macrophages, of which the latter two subtypes are associated with suppression of cell mediated immunity, that confers susceptibility to intracellular infection. Although the Leishmania parasite modulates macrophage functions to ensure its survival, what remains an unanswered yet pertinent question is whether these macrophages are deactivated or alternatively activated. This study aimed to characterize the functional plasticity and polarization of monocytes/macrophages and delineate their importance in the immunopathogenesis of Post kala-azar dermal leishmaniasis (PKDL), a chronic dermatosis of human leishmaniasis. Monocytes from PKDL patients showed a decreased expression of TLR-2/4, along with an attenuated generation of reactive oxidative/nitrosative species. At disease presentation, an increased mRNA expression of classical M2 markers CD206, ARG1 and PPARG in monocytes and lesional macrophages indicated M2 polarization of macrophages which was corroborated by increased expression of CD206 and arginase-1. Furthermore, altered vitamin D signaling was a key feature in PKDL, as disease presentation was associated with raised plasma levels of monohydroxylated vitamin D3 and vitamin D3- associated genes, features of M2 polarization. Taken together, in PKDL, monocyte/macrophage subsets appear to be alternatively activated, a phenotype that might sustain disease chronicity. Importantly, repolarization of these monocytes to M1 by antileishmanial drugs suggests that switching from M2 to M1 phenotype might represent a therapeutic opportunity, worthy of future pharmacological consideration.

Decreased presence of Langerhans cells is a critical determinant for Indian Post kala-azar dermal leishmaniasis.

Post kala-azar dermal leishmaniasis (PKDL) is the dermal sequel of visceral leishmaniasis (VL) and occurs after apparent cure or alongside with VL. It is confined to South Asia (India, Nepal and Bangladesh) and East Africa (mainly Sudan), the incidence being 5-10% and 50-60% respectively. In South Asia, as the transmission of VL is anthroponotic, PKDL patients are the proposed disease reservoir, thus assuming epidemiological significance, its eradication being linked to the control of leishmaniasis. In the absence of an animal model and its low incidence, factors contributing towards the immunopathogenesis of PKDL remain an open-ended, yet pertinent question. This study delineated the lesional immunopathology in terms of granuloma formation, Langerhans cells, tissue macrophages along with mRNA expression of IL-12p40 and IL-10. Our study in Indian PKDL for the first time identified that the number of CD1a(+) /CD207(+) Langerhans cells are decreased and CD68(+) macrophages are increased along with the absence of an epitheloid granuloma. Importantly, this decrease in Langerhans cells was associated with decreased mRNA expression of IL-12p40 and increased IL-10. This was reverted with treatment allowing for elimination of parasites and disease resolution along with an increase in Langerhans cells and decrease in macrophages. Thus, in Indian PKDL, absence of a granuloma formation along with a decrease in Langerhans cells collectively caused immune inactivation essential for parasite persistence and disease sustenance.

A clinico-histopathological study of appendageal skin tumors, affecting head and neck region in patients attending the dermatology opd of a tertiary care centre in eastern India.

INTRODUCTION: Appendageal skin tumors (ATs) are those neoplasms that differentiate toward/arise from pilosebaceous apparatus, apocrine, or eccrine sweat glands. Pilosebaceous apparatus are concentrated in head-neck area; thus it is expected that ATs would account for a major fraction of skin tumors over this site. AIMS: This study aims at finding the clinico-histopathological correlation in cases ATs in head-neck region among attendees of dermatology OPD. MATERIALS AND METHODS: Cross-sectional descriptive study, conducted over 1-year period. All clinically suspected cases of ATs were evaluated and subjected to histopathological examination. Confirmed cases of ATs were finally analyzed. RESULTS: Among twenty eight thousand four hundred sixty six new patients attending OPD, 30 suspected cases of ATs underwent histopathological examination. Histopathology was confirmatory in only 23 (76.67%) cases. Out of 23, syringoma were found in 9 (39.13%), trichoepithelioma in 6 (26.08%), syringocystadenoma papilliferum in 4 (17.39%), sebaceous gland hyperplasia in 3 (13.04%), and vellous hair cyst in 1 (4.34 %). Females (65.21%) outnumbered males (34.78%) in our study population. CONCLUSIONS: ATs of head-neck region constitute a meager population (0.08%) attending dermatology OPD, and were more common among young population. Often it is over-diagnosed clinically thus necessitating histological confirmation. Young females being cosmetically more conscious are more eager to seek advice for this condition.

Enhanced lesional Foxp3 expression and peripheral anergic lymphocytes indicate a role for regulatory T cells in Indian post-kala-azar dermal leishmaniasis.

Indian post-kala-azar dermal leishmaniasis (PKDL) is a low-frequency (5-10%) dermal sequela of visceral leishmaniasis (VL) caused by Leishmania donovani; importantly, affected individuals are speculated to be parasite reservoirs. Insight into its immunopathogenesis could translate into rational immunomodulatory therapeutic approaches against leishmaniases. In patients with PKDL (n=21), peripheral lymphocytes were analyzed for surface markers, intracellular cytokines, and lymphoproliferative responses using flow cytometry. In lesional tissue biopsies (n=12), expression of counter-regulatory cytokines (IFN-gamma and IL-10) and the T-regulatory transcription factor forkhead box protein 3 (Foxp3) was analyzed using reverse transcriptase-PCR, along with immunohistochemical detection (n=8) of CD3 and Foxp3 positivity. In patients with PKDL, circulating CD8(+)CD28(-) and antigen-induced IL-10(+)CD3(+) lymphocytes were increased and receded with treatment. CD8(+) lymphocytes showed impaired proliferative responses to L. donovani antigen (LDA) and phytohemagglutinin, which were reinstated after treatment. At presentation, the upregulated lesional IFN-gamma and IL-10 messenger RNA (mRNA), Foxp3 mRNA, and protein were curtailed after treatment. In Indian patients with PKDL, increased frequency of the CD8(+)CD28(-) phenotype, enhanced antigen-specific IL-10 production, and accompanying anergy of circulating lymphocytes suggest their regulatory nature. Furthermore, the concomitantly elevated lesional expression of Foxp3 suggests their possible recruitment into the lesional site, which would sustain disease pathology.