Review on host-pathogen interaction in dermatophyte infections.

Dermatophytosis is a common superficial fungal infection of the skin and its appendages caused by dermatophytes. Recent times have witnessed a dynamic evolution of dermatophytes driven by their ecology, reproduction, pathogenicity and host immune response, influenced by population migration and socioeconomic status. Dermatophytes establish infection following successful adherence of arthroconidia to the surface of keratinized tissues. The proteolytic enzymes released during adherence and invasion not only ascertain their survival but also allow the persistence of infection in the host. While the cutaneous immune surveillance mechanism, after antigen exposure and presentation, leads to activation of T lymphocytes and subsequent clonal expansion generating effector T cells that differentially polarize to a predominant Th17 response, the response fails to eliminate the pathogen despite the presence of high levels of IFN-γ. In chronic dermatophytosis, antigens are a constant source of stimulus promoting a dysregulated Th17 response causing inflammation. The host-derived iTreg response fails to counterbalance the inflammation and instead polarizes to Th17 lineage, aggravating the chronicity of the infection. Increasing antifungal resistance and recalcitrant dermatophytosis has impeded the overall clinical remission. Human genetic research has the potential to generate knowledge to explore new therapeutic targets. The review focuses on understanding specific virulence factors involved in pathogenesis and defining the role of dysregulated host immune response against chronic dermatophytic infections for future management strategies.

Acrodermatitis Enteropathica Presenting with Recurrent Diarrhea and Vomiting in an Infant Reluctant to Breastfeed, and a Peculiar Erythemato-Eczematous Eruption around the Oral and Anogenital Regions.

A 6-month-old, 4-kg, dehydrated girl, an Indian native, was admitted with recurrent episodes of diarrhea that had occurred since age 2 months. She had stopped breastfeeding. She had also had concomitant vomiting and loss of appetite. Later, the mother noticed progressively increasing erythematous eruptions around the anogenital and the oral region. The baby had been born to a short-stature mother and was delivered by lower segment cesarean section. Regular antenatal follow-up was normal.

Nicolau Syndrome following Intramatricial Triamcinolone Injection for Nail Lichen Planus.

Nicolau syndrome (Embolia cutis medicamentosa) is a rare complication following parenteral administration of a drug. It has been reported in association with intramuscular, subcutaneous, intravenous and intra-articular injections. However, Nicolau syndrome following intramatricial injection has not been described to the best of our knowledge. We report the case of an 18-year-old male who developed this complication following 7th session of intramatricial injection. The patient was started on broad spectrum antibiotic coverage, vasodilator therapy, analgesics, and daily dressing. On day 21, the symptoms completely resolved with return of normal color of the digit. The case is being reported to make dermatologists aware of the possibility of Nicolau syndrome following intramatricial injection of triamcinolone acetonide.

Multifocal Tuberculosis Verrucosa Cutis: A Manifestation Extraordinary of Reactivation Secondary Tuberculosis.

A BCG (Bacillus Calmette-Guérin)-vaccinated 78-year-old man, a native Indian, reported with numerous asymptomatic, peanut-sized, dirty gray, elevated eruptions of 1 year's duration appearing over apparently normal skin on the upper and lower extremities (Figure 1). The onset of the eruptions had been sudden, but they had progressed slowly. A history of cough and/or expectoration, evening rise of temperature, night sweats, or loss of appetite and weight was denied.

Clinicopathologic spectrum of cutaneous tuberculosis: a retrospective analysis of 165 Indians.

BACKGROUND: Although cutaneous tuberculosis (CTB) is well described, it is wise to periodically revisit the prevailing clinical and epidemiological features, of this somewhat uncommon entity in developed nations that is also usually neglected in national tuberculosis control programs in countries where tuberculosis is a major health problem, to maintain heightened awareness as the HIV pandemic runs its course. METHODS: Medical records of 165 cases of CTB, diagnosed from 2007 to 2010, were studied. The diagnosis in each was made on the basis of well-conceived and described criteria. All patients had earlier been immunized with Bacillus Calmette-Guérin soon after birth. Patients were evaluated by routine hematology, Mantoux test, screening for HIV status in addition to fine-needle aspiration cytology, and/or histopathology of the lesion. RESULTS: Of the 165 cases (94 males and 71 females, male:female ratio of 1.32:1; age range, 1-64), 85 were lupus vulgaris, 11 tuberculosis verrucosa cutis (paucibacillary), and 39 scrofuloderma (multibacillary). The remaining 17 were tuberculids comprising 24 lichen scrofulosorum, 3 papulonecrotic tuberculid, 2 erythema induratum, and 1 erythema nodosum, afflicting children and young adults (age range, 0-10; 21-30). Fine-needle aspiration cytology was diagnostic in 39 cases, histopathology in 117, and their combination in 9. Clinicopathologic correlation and response to antituberculosis treatment were additional diagnostic adjuncts. CONCLUSIONS: CTB has a varied clinical and morphological spectrum. Cytology and histopathology play a key role in its diagnosis. An additional adjunct is the clinical response to antituberculosis treatment.

PARK2 and proinflammatory/anti-inflammatory cytokine gene interactions contribute to the susceptibility to leprosy: a case-control study of North Indian population.

OBJECTIVES: Cytokines and related molecules in immune-response pathways seem important in deciding the outcome of the host-pathogen interactions towards different polar forms in leprosy. We studied the role of significant and functionally important single-nucleotide polymorphisms (SNPs) in these genes, published independently from our research group, through combined interaction with an additional analysis of the in silico network outcome, to understand how these impact the susceptibility towards the disease, leprosy. DESIGN: The study was designed to assess an overall combined contribution of significantly associated individual SNPs to reflect on epistatic interactions and their outcome in the form of the disease, leprosy. Furthermore, in silico approach was adopted to carry out protein-protein interaction study between PARK2 and proinflammatory/anti-inflammatory cytokines. SETTING: Population-based case-control study involved the data of North India. Protein-protein interaction networks were constructed using cytoscape. PARTICIPANTS: Study included the data available from 2305 Northern Indians samples (829 patients with leprosy; 1476 healthy controls), generated by our research group. PRIMARY AND SECONDARY OUTCOME MEASURES: For genotype interaction analysis, all possible genotype combinations between selected SNPs were used as an independent variable, using binary logistic regression with the forward likelihood ratio method, keeping the gender as a covariate. RESULTS: Interaction analysis between PARK2 and significant SNPs of anti-inflammatory/proinflammatory cytokine genes, including BAT1 to BTNL2-DR spanning the HLA (6p21.3) region in a case-control comparison, showed that the combined analysis of: (1) PARK2, tumour necrosis factor (TNF), BTNL2-DR, interleukin (IL)-10, IL-6 and TGFBR2 increased the risk towards leprosy (OR=2.54); (2) PARK2, BAT1, NFKBIL1, LTA, TNF-LTB, IL12B and IL10RB provided increased protection (OR=0.26) in comparison with their individual contribution. CONCLUSIONS: Epistatic SNP-SNP interactions involving PARK2 and cytokine genes provide an additive risk towards leprosy susceptibility. Furthermore, in silico protein-protein interaction of PARK2 and important proinflammatory/anti-inflammatory molecules indicate that PARK2 is central to immune regulation, regulating the production of different cytokines on infection.

Anal cytology and p16 immunostaining for screening anal intraepithelial neoplasia in HIV-positive and HIV-negative men who have sex with men: a cross-sectional study.

Summary Akin to cervical cancer in sexually-active women, men who have sex with men (MSM) are predisposed to anal cancers, especially those with HIV co-infection. This cross-sectional study endeavored to assess the prevalence of anal dysplasia using Pap smears and p16 immunostaining amongst Indian MSM. A total of 31 consecutive HIV-positive and 34 HIV-negative MSM, from a cohort of sexually transmitted infection clinic attendees, underwent anal cytological evaluation with Pap smear and p16 staining. Chi square test and coefficient of correlation were used for comparison. Eighteen (27.7%) had abnormal anal cytology; increased in HIV-positive as compared to HIV-negative men (35% versus 20%, p = 0.180). Similarly, both low-grade (25.8% versus 17.6%) and high-grade lesions (8.3% versus 4.8%) were comparable in HIV-positive and HIV-negative group. Thirteen (20%) smears were p16-positive with a sensitivity and specificity for anal dysplasia of 72.3% and 100%, respectively. Anal cytology may be used to screen for anal dysplasia in MSM irrespective of HIV status. Furthermore, the addition of p16, with greater specificity for high-grade lesions, may improve diagnostic accuracy especially for high-grade lesions. A larger study to further corroborate these observations is warranted.

Lichen planus in childhood: a series of 316 patients.

Lichen planus (LP) is infrequently seen in children and the clinical presentation is often atypical. We conducted a retrospective analysis of clinical features and treatment response in childhood LP to date. The clinical profile and treatment response data of patients younger than 14 years old with LP (entered in a predesigned pro forma study) from January 1997 to June 2011 were analyzed. The treatment was administered according to a predetermined departmental protocol and was comprised of topical steroids with or without oral dapsone or corticosteroids. Patients were evaluated for response, adverse effects, and relapse. The study population consisted of 316 children (166 boys, 150 girls), or 18.7% of the total registered patients in the LP clinic. The mean age was 10.28 years (range 2-14 years). Cutaneous lesions were seen in 96.2%. Involvement of the oral mucosa was detected in 18%, nails in 13.9%, scalp in 8.2%, and genitalia in 4.4%. Classic LP was most prevalent (53.8%), followed by eruptive (16.5%), hypertrophic (8.2%), linear (6.9%), and lichen planopilaris (6.3%). LP pigmentosus, annular, and atrophic variants were encountered infrequently. Topical corticosteroids were the most common treatment used in 69.5% of patients, 28.8% of whom had excellent response at 6 months, although 38.8% failed to follow up. Dapsone was prescribed in 20% and systemic steroids in 9.8% of patients. We report the largest series to date of LP in childhood, with a more varied clinical presentation than in previous series. The course and response to treatment were similar to those in adults.

Mapping of PARK2 and PACRG overlapping regulatory region reveals LD structure and functional variants in association with leprosy in unrelated indian population groups.

Leprosy is a chronic infectious disease caused by Mycobacterium Leprae, where the host genetic background plays an important role toward the disease pathogenesis. Various studies have identified a number of human genes in association with leprosy or its clinical forms. However, non-replication of results has hinted at the heterogeneity among associations between different population groups, which could be due to differently evolved LD structures and differential frequencies of SNPs within the studied regions of the genome. A need for systematic and saturated mapping of the associated regions with the disease is warranted to unravel the observed heterogeneity in different populations. Mapping of the PARK2 and PACRG gene regulatory region with 96 SNPs, with a resolution of 1 SNP per 1 Kb for PARK2 gene regulatory region in a North Indian population, showed an involvement of 11 SNPs in determining the susceptibility towards leprosy. The association was replicated in a geographically distinct and unrelated population from Orissa in eastern India. In vitro reporter assays revealed that the two significantly associated SNPs, located 63.8 kb upstream of PARK2 gene and represented in a single BIN of 8 SNPs, influenced the gene expression. A comparison of BINs between Indian and Vietnamese populations revealed differences in the BIN structures, explaining the heterogeneity and also the reason for non-replication of the associated genomic region in different populations.

Lichen planus pigmentosus.

Lichen planus pigmentosus, a variant of lichen planus, is a disorder with conflicting taxonomy. Its worldwide recognition is still not fully understood because of insufficient contemporary evidence of the disease in the literature. The authors review the historical background, etiopathogenesis, clinical connotation, atypical variants, and histopathology to highlight its diversity.

A randomized, prospective study of efficacy and safety of oral tramadol in the management of post-herpetic neuralgia in patients from north India.

OBJECTIVE: To evaluate the safety and efficacy of oral tramadol therapy (50 to 200 mg/day) in the treatment for post-herpetic neuralgia (PHN). METHODS: The study was a prospective, single-blind, non-responder vs. responder, randomized trial conducted in 100 outpatients of PHN after oral administration of tramadol for 4 weeks. Those patients who had achieved 50% or greater pain relief after 14 days of oral tramadol treatment were categorized as responders and those reporting < 50% pain relief were categorized as non-responders. Rescue analgesia was provided by the topical application of a cream consisting of the combination of 3.33% doxepin and 0.05% capsaicin to the affected areas of PHN patients of both groups for at least 14 days, along with tramadol therapy. The rescue analgesia was extended to 4 weeks in patients of the non-responder group. The primary endpoints were measured using a numerical rating scale (NRS) at rest and with movement. Secondary endpoints included additional pain ratings such as global perceived effect (GPE), Neuropathic Pain Symptom Inventory scores (NPSI), daily sleep interference score (DSIS), quality of life (QOL) as per WHO QOL-BREF Questionnaire scores, patient and clinician ratings of global improvement. The 2 groups were compared on the basis of pain intensity scores, encompassing primary as well as secondary endpoints, and QOL after 28 days of the treatment regimen. RESULTS: Pain intensity scores measured by NRS (at resting and with movement), NPSI, and DSIS were consistently reduced (P < 0.001) over 28 days at varying intervals in both the groups, but the magnitude of reduction was higher in responders than non-responders. A concomitant improvement (P < 0.001) was observed in GPE on days 3, 14, and 28 as compared to the respective baseline scores in both the groups. Although the WHO QOL-BREF scores showed significant (P < 0.001) improvement in QOL of PHN patients at days 14 and 28 in both the groups, the magnitude of improvement was higher in responders as compared to non-responders. Significant improvement in pain intensity scores and QOL in non-responders is mainly attributed to the use of rescue analgesia for 28 days rather than recommended tramadol therapy. CONCLUSIONS: Treatment with tramadol 50 to 200 mg per day was associated with significant pain reduction in terms of enhanced pain relief, reduced sleep interference, greater global improvement, diminished side-effect profile, and improved QOL in PHN patients from North India. Further categorization of PHN patients may be helpful so that additional or alternative therapy may be prescribed to non-responders.

Familial reactive perforating collagenosis in a child: response to narrow-band UVB.

A favorable response to narrow-band ultraviolet B light treatment, a novel option, is illustrated in familial reactive perforating collagenosis, and its use is recommended. Its probable mode of action is outlined.

Sclerotherapy for the treatment of infantile hemangiomas.

Sclerotherapy is a simple, technically easy and effective mode of treatment for infantile hemangiomas (IH). It acts by blocking the growth of actively proliferating lesions, by targeting their vascularity accelerating their regression. Polidocanol is a commonly used sclerosant. We report two interesting cases of IH treated solely with polidocanol sclerotherapy and discuss the unique place this modality has in the armamentarium against IH. Sclerotherapy was found to be especially useful for large, exuberant and pedunculated lesions, producing rapid regression and preventing the disfiguring sequelae which are likely if large or pedunculated lesions are left to involute on their own.

Physiopathology of adverse cutaneous drug reactions--applied perceptions: part I.

Adverse cutaneous drug reactions are common, but their physiopathology is largely elusive. The authors assess various reactions to facilitate their diagnosis and treatment. Some of the common reaction patterns are included with the prime objective of highlighting their physiopathology.

Cutaneous tuberculosis: a diagnostic dilemma--laboratory inputs.

Bacterial cultures are the gold standard for diagnosing cutaneous tuberculosis, but there are limitations, despite the advances embracing the innovative technologies, including interferon yrelease assays, enzyme-linked immunoabsorbant assay, and molecular diagnostics, in addition to conventional skin tests and microscopic pathology. The results and their interpretation of cultures are reviewed for use in day-to-day practice.

Cutaneous tuberculosis: a diagnostic dilemma.

Cutaneous tuberculosis continues to be one of the most difficult conditions to diagnose. It is a challenge particularly in developing countries due to the lack of resources. The authors define the classification and clinical manifestations considered predictive of its diagnosis.

Fixed-drug eruption caused by ashwagandha (Withania somnifera): a widely used Ayurvedic drug.

A 28-year-old man with decreased libido received ashwagandha in the usual daily dosage of 5 g for 10 days. During this period, he experienced a burning and/or itching sensation as well as discoloration of the skin/mucous membrane confined to the penis. He had a similar type of eruption at the same site 6 months prior while taking ashwagandha. Examination of the skin surface was conspicuous and marked by the presence of a dusky, erythematous, oval, eroded plaque of 3 cm, affecting the glans penis and prepuce (Figure). The drug was withdrawn and topical 0.05% clobetasol propionate cream was administered along with cetrizine dihydrochloride, an H1-receptor blocker, 10 mg daily for 1 month. There was a perceptible amelioration of the lesion, resulting in residual greyish white pigmentation. He was prescribed oral drug provocation with 1 g of ashwagandha powder. Within 12 hours, a flare-up developed at the earlier site, confirming the causality.

Alterations in T-lymphocyte sub-set profiles and cytokine secretion by PBMC of systemic lupus erythematosus patients upon in vitro exposure to organochlorine pesticides.

Chronic exposure to organochlorine pesticides (OCP) has been suspected of causing immunoregulatory abnormalities that eventually lead to development and progression of systemic lupus erythematosus (SLE), but the role of these non-genetic stimuli has remained poorly understood. The objectives of the study were to quantify the levels of different OCP residues in the blood of SLE patients and to study the effects of in vitro treatment of peripheral blood mononuclear cells (PBMC) from these patients and healthy controls with OCP. Levels of different OCP residues in the blood were measured by gas-liquid chromatography. Isolated PBMC were treated in vitro with hexachlorocyclohexane (HCH), o,p'-dichlorodiphenyltrichloroethane (DDT), or phytohemagglutinin-M (PHA-M) for 72 h, then stained with different dye-labeled monoclonal antibodies to analyze alterations in T-lymphocytes using flow cytometry. Levels of different T(H)1 and T(H)2 cytokines were also estimated by ELISA. Significantly higher levels of p,p'-DDE and ß-HCH were detected in the blood of SLE patients than in healthy controls. HCH exposure markedly increased the percentages of CD3(+)CD4(+) T-lymphocytes and expression of CD45RO(+) on CD4(+) and CD8(+) T-lymphocytes, but decreased CD4(+)CD25(+) T-lymphocytes in SLE patients. DDT exposure increased the percentages of CD3(+)CD4(+) T-lymphocytes and decreased those of CD4(+)CD25(+) T-lymphocytes in SLE patients as compared to healthy controls. No significant responsiveness of patient PBMC to PHA-M stimulation was observed indicating suppression of T-lymphocytes by these OCP. Further, both HCH and DDT decreased the levels of IL-2 and IFNγ but had no effect on IL-4 levels in SLE patients. DDT also increased significantly the levels of IL-10 in patients. It is likely that higher levels and prolonged durations of exposure to HCH and DDT may significantly influence T-lymphocyte sub-sets and cytokine expression in vivo that could lead to the development or exacerbation of SLE.

Pathophysiology of adverse cutaneous drug reactions--applied perceptions: Part II.

Adverse cutaneous drug reactions are a group with common morphology. Much research has been performed on such reactions, but their pathophysiology is largely unknown. The authors provide a critical appraisal of the various aspects of their diagnosis and treatment. Some of the common reaction patterns are included with the prime objective of highlighting their pathophysiology.