Evaluation of Risk Factors Associated With Adult-Onset Acne in Patients Attending a Tertiary Care Center in East India: A Case-Control Study.

BACKGROUND: In recent years, the aesthetic appearance of the skin has emerged as a crucial factor influencing perceptions of beauty and contributing to self-confidence. The pursuit of flawless skin represents a prevalent focus within beauty regimens. Adult-onset acne (AOA) is the development of acne between the ages of 26 to 50 and it is emerging as a prevalent dermatological concern among this population. Individuals perceiving their skin as falling short of an 'ideal' standard may let it affect their quality of life. Significant gaps in our understanding persist regarding the contributing risk factors for AOA. OBJECTIVE: The study aims to assess both established and novel risk factors potentially influencing the onset of adult acne. Additionally, it seeks to calculate the odds ratio (OR) for AOA in both females and males exposed to the surveyed risk factors over a 24-month period. MATERIALS AND METHODS: Various risk factors were assessed, including stress, hormonal markers, psychological factors, environmental exposures, dietary habits, and cosmetic use. A total of 140 participants, consisting of 70 healthy individuals were selected. Discordant groups were analyzed for AOA. Detailed interviews were conducted to obtain a comprehensive medical history, focusing on potential risk factors, for patients diagnosed with acne. The OR was calculated to determine the likelihood of association between risk factors and the development of AOA. A proper protocol was devised, and statistical data was analyzed using Statistical Package for Social Sciences (SPSS; IBM Corp., Armonk, NY, USA). RESULTS: The most significant risk factors in the development of AOA in the Indian population based on OR and confidence interval (CI) were positive personal history of acne (OR 3.12 [95% CI 1.20 - 8.03]), positive family history of acne (OR 10.24 [95% CI 2.89 - 36.1]), overweight BMI (OR 6.16 [95% CI 2.56 - 14.76]), hormonal imbalance (OR 9.27 [95% CI 2.03 - 42.29]), menstrual irregularity in females (OR 12.94 [95% CI 3.59 - 46.53]), exposure to mineral oil or halogenated hydrocarbon use (OR 4.13 [95% CI 1.28 - 13.24]), less than six hours of sleep (OR 4.16 [95% CI 1.10 - 15.64]), chemical peels in females (OR 11.28 [95% CI 2.45 - 51.90]), diet consisting mainly of carbohydrates, high salt, saturated fats (OR 29.97 [95% CI 3.84 - 227.25]) and less than 2 liters of water intake in patients (OR 19.18 [95% CI 1.08 - 339.04]). Risk factors that were associated with a decreased likelihood of AOA included normal menstruation (OR 0.03 [95% CI 0.01 - 0.12]), healthy oral intake (OR 0.04 [95% CI 0.00 - 0.17]), no psychological stressors/depression/anxiety (OR 0.43 [95% CI 0.21 - 0.85]), no environmental factors (OR 0.07 [95% CI 0.02 - 0.24]), no associated cosmetic use (OR 0.45 [95% CI 0.22 - 0.90]), normal BMI (OR 0.18 [95% CI 0.07 - 0.39]), no history of acne (OR 0.12 [95% CI 0.05 - 0.26]). CONCLUSION: AOA is a complex and multifactorial condition, and most of the risk factors mentioned in this study on Indian skin type contribute to its development. The approach for AOA should be holistic. In addition to following a recommended treatment protocol, education should be provided about lifestyle modification, stress management, exercise, and environmental factors to help prevent and manage AOA.

Clinico-Epidemiological Profile of Allergic Contact Dermatitis and Its Correlation With Patch Testing in a Tertiary Care Center in Eastern India.

BACKGROUND: Allergic contact dermatitis (ACD) is one of the most common skin disorders seen among patients attending dermatology clinics in India. Patch testing is the gold standard for diagnosing ACD. The clinical-epidemiological pattern of ACD and the allergen-causing it may be different in different geographic locations. Finding the profile of allergens commonly causing ACD in a particular region will help to formulate prevention strategies for the development of ACD. AIM AND OBJECTIVE: The primary aim of the study was to find out the clinical-epidemiological distribution of allergic contact dermatitis and to identify the common allergens causing it by patch testing in this region of India. MATERIALS AND METHODS: A total of 111 cases of ACD were included in the study. Clinico epidemiological profiles of all patients were documented. The patch testing was performed in the outpatient department using the antigens of the Indian Standard Series kit (Systopic Laboratories Pvt. Ltd., New Delhi, India). Patches were removed after 48 hours (two days) of application. The first reading was taken 15 to 20 minutes after the removal of patches on day two. A second reading was taken on day four (96 hours of application) to confirm the presence of an allergic reaction.  Results: The patch test was found to be positive in 69% of cases. It was observed that male persons from lower socioeconomic status were getting ACD on most accounts. Potassium dichromate (PDC) was found to be the most common allergen (30.43%) followed by parthenium (26.08%), para-phenylenediamine (PPD) (21.73%), nickel sulfate (18.84%), chlorocresol (15.94%), black rubber (14.49%), cobalt sulfate (13.04%), and wool alcohols (7.24%) respectively. CONCLUSION: Our study showed potassium dichromate is the commonest allergen causing ACD in this part of the country. The importance of patch testing lies mainly in educating the patient regarding the avoidance of exposure to particular allergens to avoid the development of new ACD as well as an exaggeration of pre-existing ACD.

Author Correction: Micro RNAs upregulated in Vitiligo skin play an important role in its aetiopathogenesis by altering TRP1 expression and keratinocyte-melanocytes cross-talk.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Micro RNAs upregulated in Vitiligo skin play an important role in its aetiopathogenesis by altering TRP1 expression and keratinocyte-melanocytes cross-talk.

Translation of genes is regulated by many factors including microRNAs (miRNAs). miRNA profiling of lesional and non-lesional epidermal RNA from 18 vitiligo patients revealed significant upregulation of 29 miRNAs in the lesional epidermis, of which 6 miRNAs were transfected in normal human epidermal keratinocytes (NHEKs) to study their downstream effects using quantitative proteomics. Many proteins involved in oxidative stress, Vesicle trafficking, Cellular apoptosis, Mitochondrial proteins and Keratins were regulated after miRNA transfections in the keratinocytes. However, tyrosinase related protein-1 (TRP1/TYRP1), a melanogenesis protein, was consistently downregulated in NHEKs by all the six miRNAs tested, which was quite intriguing. TRP1 was also downregulated in lesional epidermis compared with non-lesional epidermis. Since melanocytes synthesize and transfer melanosomes to the surrounding keratinocytes, we hypothesized that downregulation of TRP1 in NHEKs may have a role in melanosome transfer, which was confirmed by our co-culture experiments. Downregulation of TRP1 in keratinocytes negatively affected the melanosome transfer from melanocytes to keratinocytes resulting in melanin accumulation which may be leading to melanin induced cytotoxicity in melanocytes. Regulation of key processes involved in aetiopathogenesis of vitiligo along with TRP1 suggests that miRNAs act in an integrated manner which may be detrimental for the loss of melanocytes in vitiligo.

Typing of Neisseria gonorrhoeae isolates by phenotypic and genotypic techniques in New Delhi, India.

BACKGROUND: The objective of this study is to investigate gonococcal isolates using phenotypic and genotypic methods. METHODOLOGY: Sixty gonococcal isolates obtained were examined. Strains were divided into 9 resistant phenotypes: Chromosomally mediated penicillin-resistant Neisseria gonorrhoeae (CMRNGP), penicillinase-producing NG (PPNG), chromosomally mediated tetracycline-resistant NG (CMRNGT), TRNG, PPNG and TRNG, CMRNGPT, quinolone resistant NG (QRNG), Azithro R, and decreased susceptibility (DS) to ceftriaxone. These isolates were also subjected to auxotyping and NG-multi-antigen sequence typing (MAST). RESULTS: Of 60 isolates, 32 (53.33%) PPNG and only one was CMRNGP; 16 (26.66%) were CMRNGT, while 18 (30%) were TRNG. Both PPNG and TRNG found in 13 (21.66%) and none were CMRNGPT. QRNG was seen in 93.33%, 5% Azithromycin R, and 6.66% were DS to ceftriaxone. Based on auxotyping, 24 (40%) nonrequiring, 16 (26.66%) were proline requiring, 13 (21.66%) arginine requiring while 7 (11.66%) belonged to others. The most common ST was 6058 (32.5%). The discriminatory indices of antibiogram, auxotyping and NG-MAST were 0.77, 0.72, and 0.95, respectively. CONCLUSIONS: NG-MAST is the method of choice for epidemiological studies.

An enhanced regimen as post-exposure chemoprophylaxis for leprosy: PEP+.

The ongoing transmission of Mycobacterium (M.) leprae reflected in a very slow decline in leprosy incidence, forces us to be innovative and conduct cutting-edge research. Single dose rifampicin (SDR) as post-exposure prophylaxis (PEP) for contacts of leprosy patients, reduces their risk to develop leprosy by 60%. This is a promising new preventive measure that can be integrated into routine leprosy control programmes, as is being demonstrated in the Leprosy Post-Exposure Programme that is currently ongoing in eight countries.The limited (60%) effectiveness of SDR is likely due to the fact that some contacts have a preclinical infection beyond the early stages for which SDR is not sufficient to prevent the development of clinical signs and symptoms of leprosy. An enhanced regimen, more potent against a higher load of leprosy bacteria, would increase the effectiveness of this preventive measure significantly.The Netherlands Leprosy Relief (NLR) is developing a multi-country study aiming to show that breaking the chain of transmission of M. leprae is possible, evidenced by a dramatic reduction in incidence. In this study the assessment of the effectiveness of an enhanced prophylactic regimen for leprosy is an important component. To define the so called PEP++ regimen for this intervention study, NLR convened an Expert Meeting that was attended by clinical leprologists, public health experts, pharmacologists, dermatologists and microbiologists.The Expert Meeting advised on combinations of available drugs, with known efficacy against leprosy, as well as on the duration of the intake, aiming at a risk reduction of 80-90%. To come to a conclusion the Expert Meeting considered the bactericidal, sterilising and bacteriostatic activity of the potential drugs. The criteria used to determine an optimal enhanced regimen were: effectiveness, safety, acceptability, availability, affordability, feasibility and not inducing drug resistance.The Expert Meeting concluded that the enhanced regimen for the PEP++ study should comprise three standard doses of rifampicin 600 mg (weight adjusted when given to children) plus moxifloxacin 400 mg given at four-weekly intervals. For children and for adults with contraindications for moxifloxacin, moxifloxacin should be replaced by clarithromycin 300 mg (weight adjusted).

An enhanced regimen as post-exposure chemoprophylaxis for leprosy: PEP++

The ongoing transmission of Mycobacterium (M.) leprae reflected in a very slow decline in leprosy incidence, forces us to be innovative and conduct cutting-edge research. Single dose rifampicin (SDR) as post-exposure prophylaxis (PEP) for contacts of leprosy patients, reduces their risk to develop leprosy by 60%. This is a promising new preventive measure that can be integrated into routine leprosy control programmes, as is being demonstrated in the Leprosy Post-Exposure Programme that is currently ongoing in eight countries.The limited (60%) effectiveness of SDR is likely due to the fact that some contacts have a preclinical infection beyond the early stages for which SDR is not sufficient to prevent the development of clinical signs and symptoms of leprosy. An enhanced regimen, more potent against a higher load of leprosy bacteria, would increase the effectiveness of this preventive measure significantly.The Netherlands Leprosy Relief (NLR) is developing a multi-country study aiming to show that breaking the chain of transmission of M. leprae is possible, evidenced by a dramatic reduction in incidence. In this study the assessment of the effectiveness of an enhanced prophylactic regimen for leprosy is an important component. To define the so called PEP++ regimen for this intervention study, NLR convened an Expert Meeting that was attended by clinical leprologists, public health experts, pharmacologists, dermatologists and microbiologists.The Expert Meeting advised on combinations of available drugs, with known efficacy against leprosy, as well as on the duration of the intake, aiming at a risk reduction of 80-90%. To come to a conclusion the Expert Meeting considered the bactericidal, sterilising and bacteriostatic activity of the potential drugs. The criteria used to determine an optimal enhanced regimen were: effectiveness, safety, acceptability, availability, affordability, feasibility and not inducing drug resistance.The Expert Meeting concluded that the enhanced regimen for the PEP++ study should comprise three standard doses of rifampicin 600 mg (weight adjusted when given to children) plus moxifloxacin 400 mg given at four-weekly intervals. For children and for adults with contraindications for moxifloxacin, moxifloxacin should be replaced by clarithromycin 300 mg (weight adjusted).

Mapping architectural and transcriptional alterations in non-lesional and lesional epidermis in vitiligo.

In vitiligo, chronic loss of melanocytes and consequent absence of melanin from the epidermis presents a challenge for long-term tissue maintenance. The stable vitiligo patches are known to attain an irreversible depigmented state. However, the molecular and cellular processes resulting in this remodeled tissue homeostasis is unclear. To investigate the complex interplay of inductive signals and cell intrinsic factors that support the new acquired state, we compared the matched lesional and non-lesional epidermis obtained from stable non-segmental vitiligo subjects. Hierarchical clustering of genome-wide expression of transcripts surprisingly segregated lesional and non-lesional samples in two distinct clades, despite the apparent heterogeneity in the lesions of different vitiligo subjects. Pathway enrichment showed the expected downregulation of melanogenic pathway and a significant downregulation of cornification and keratinocyte differentiation processes. These perturbations could indeed be recapitulated in the lesional epidermal tissue, including blunting of rete-ridges, thickening of stratum corneum and increase in the size of corneocytes. In addition, we identify marked increase in the putrescine levels due to the elevated expression of spermine/spermidine acetyl transferase. Our study provides insights into the intrinsic self-renewing ability of damaged lesional tissue to restore epidermal functionality in vitiligo.

Development of a potent invigorator of immune responses endowed with both preventive and therapeutic properties.

This article reviews briefly the making of an immunoprophylactic-cum-immunotherapeutic vaccine against leprosy. The vaccine is based on cultivable, heat-killed atypical mycobacteria, whose gene sequence is now known. It has been named Mycobacterium indicus pranii. It has received the approval of the Drug Controller General of India and the US Food and Drug Administration. Besides leprosy, M. indicus pranii has found utility in the treatment of category II ("difficult to treat") tuberculosis. It also heals ugly anogenital warts. It has preventive and therapeutic action against SP2/O myelomas. It is proving to be a potent adjuvant for enhancing antibody titers of a recombinant vaccine against human chorionic gonadotropin, with the potential of preventing pregnancy without derangement of ovulation and menstrual regularity in sexually active women.

IFN-γ signaling maintains skin pigmentation homeostasis through regulation of melanosome maturation.

Cellular homeostasis is an outcome of complex interacting processes with nonlinear feedbacks that can span distinct spatial and temporal dimensions. Skin tanning is one such dynamic response that maintains genome integrity of epidermal cells. Although pathways underlying hyperpigmentation cascade are recognized, negative feedback regulatory loops that can dampen the activated melanogenesis process are not completely understood. In this study, we delineate a regulatory role of IFN-γ in skin pigmentation biology. We show that IFN-γ signaling impedes maturation of the key organelle melanosome by concerted regulation of several pigmentation genes. Withdrawal of IFN-γ signal spontaneously restores normal cellular programming. This effect in melanocytes is mediated by IFN regulatory factor-1 and is not dependent on the central regulator microphthalmia-associated transcription factor. Chronic IFN-γ signaling shows a clear hypopigmentation phenotype in both mouse and human skin. Interestingly, IFN-γ KO mice display a delayed recovery response to restore basal state of epidermal pigmentation after UV-induced tanning. Together, our studies delineate a new spatiotemporal role of the IFN-γ signaling network in skin pigmentation homeostasis, which could have implications in various cutaneous depigmentary and malignant disorders.

HLA alleles and amino-acid signatures of the peptide-binding pockets of HLA molecules in vitiligo.

Vitiligo is a depigmenting disorder of the skin that is characterized by the loss of functional melanocytes from the lesional sites. Although the exact etiology is not understood, autoimmunity is thought to be a crucial deterministic factor. A recurring theme of several autoimmune disorders is the aberrant presentation of self-antigens to the immune system, which triggers downstream perturbations. Here we examine the role of alleles of HLA class I and class II loci to delineate vitiligo manifestation in two distinct populations. Our studies have identified three specific alleles, HLA-A*33:01, HLA-B*44:03, and HLA-DRB1*07:01, to be significantly increased in vitiligo patients as compared with controls in both the initial study on North Indians (N=1,404) and the replication study in Gujarat (N=355) cases, establishing their positive association with vitiligo. Both generalized and localized vitiligo have the same predisposing major histocompatibility complex alleles, i.e., B*44:03 and DRB1*07:01, in both the populations studied, beside the differences in the frequencies of other alleles, suggesting that localized vitiligo too may be an autoimmune disorder. Significant differences in the amino-acid signatures of the peptide-binding pockets of HLA-A and HLA-B α-chain and HLA-DR ß-chain were observed between vitiligo patients and unaffected controls.

A Comparison of Low-Fluence 1064-nm Q-Switched Nd: YAG Laser with Topical 20% Azelaic Acid Cream and their Combination in Melasma in Indian Patients.

BACKGROUND: Melasma is an acquired symmetric hypermelanosis characterised by irregular light to gray-brown macules on sun-exposed skin with a predilection for the cheeks, forehead, upper lip, nose and chin. The management of melasma is challenging and requires meticulous use of available therapeutic options. AIMS: To compare the therapeutic efficacy of low-fluence Q-switched Nd: YAG laser (QSNYL) with topical 20% azelaic acid cream and their combination in melasma in three study groups of 20 patients each. MATERIALS AND METHODS: Sixty Indian patients diagnosed as melasma were included. These patients were randomly divided in three groups (group A = 20 patients of melasma treated with low-fluence QSNYL at weekly intervals, group B = 20 patients of melasma treated with twice daily application of 20% azelaic acid cream and group C = 20 patients of melasma treated with combination of both). Study period was of 12 weeks each. Response to treatment was assessed using melasma area and severity index score. STATISTICAL ANALYSIS: The statistical analysis was done using Chi-square test, paired and unpaired student t-test. RESULTS: Significant improvement was recorded in all the three groups. The improvement was statistically highly significant in Group C as compared to group A (P < 0.001) and group B (P < 0.001). CONCLUSIONS: This study shows the efficacy of low-fluence QSNYL, topical 20% azelaic acid cream and their combination in melasma. The combination of low-fluence QSNYL and topical 20% azelaic acid cream yields better results as compared to low-fluence QSNYL and azelaic acid alone.

Transcriptional upregulation of Nrf2-dependent phase II detoxification genes in the involved epidermis of vitiligo vulgaris.

Oxidative stress is widely believed to be a contributing factor in vitiligo pathogenesis. To explore mechanisms by which epidermis responds to mounting oxidative stress, we investigated the involvement of phase II detoxification genes in vitiligo. Phase II detoxification pathways have recently been identified as being important in the regulation of epidermal skin homeostasis. In this study we show that the key transcription factor nuclear factor E2-related factor 2 (Nrf2) and the downstream genes NAD(P)H:quinone oxidase-1 (NQO-1), γ-glutamyl cystine ligase catalytic subunit (GCLC), and γ-glutamyl cystine ligase modifying subunit (GCLM) are upregulated in the lesional epidermal skin of subjects with vitiligo vulgaris. The differences between lesional and nonlesional skin were further investigated by studying the induced expression of Nrf2-dependent transcripts in skin punch biopsies using curcumin and santalol. Surprisingly, nonlesional skin showed induction of all transcripts while a similar effect was not observed for the skin punches from the lesional skin. The use of curcumin and santalol on epidermal cells showed that keratinocytes were more susceptible to apoptosis, whereas melanocytes induced phase II genes under the same concentrations with negligible apoptosis. Our studies provide new insights into the role of phase II detoxification pathway in maintaining skin homeostasis and sustaining redox balance in vitiligo patients.