Laser and Lights in Psoriasis.

Psoriasis is a chronic inflammatory skin condition affecting millions of individuals worldwide. Over the years, various treatment modalities have been explored to alleviate the symptoms and improve the quality of life for patients with psoriasis. Among these treatment options, lasers and lights have emerged as promising non-invasive approaches with significant efficacy. This review aims to provide an overview of the current understanding and clinical applications of lasers and lights in the management of psoriasis. We have discussed the mechanisms of action behind different laser and light therapies and their impact on psoriatic plaques. Additionally, we discuss the various types of lasers and lights utilized, including excimer lasers, pulsed dye lasers, and narrowband ultraviolet B (NB-UVB) phototherapy, highlighting their unique properties and clinical outcomes. Moreover, we have addressed important considerations related to patient selection, treatment protocols, and potential side effects associated with lasers and lights. We emphasize the need for proper evaluation, monitoring, and customization of treatment plans to ensure optimal outcomes and minimize adverse events.

Bilastine in Refractory Chronic Spontaneous Urticaria: Disease Control and Cytokine Modulation in an Open-label Prospective Study.

Introduction: The treatment options for chronic spontaneous urticaria (CSU) primarily include second generation non-sedative antihistamine (SGAHs). Bilastine is a newer, nonsedating SGAH approved for urticaria in February 2019 by the Drugs Controller General of India. Its major advantages are in terms of superior efficacy, lack of drug interactions and adverse effects, including sedation, compared to conventional SGAHs. The role of cytokines in the pathogenesis of CSU is well known. However, there is a shortage of data regarding the change in serum levels of proinflammatory cytokines following H1 antihistamines. We conducted this trial to evaluate the role of bilastine in cytokine modulation and autoimmunity, thereby explaining its role in modifying the disease process in CSU. Materials and Methods: This prospective study was conducted in a tertiary institute in Kolkata on patients aged 12 years and above with a CSU >6 months. These patients had an unsatisfactory response, as per the Urticaria Activity Score 7 (UAS7), to previous antihistamine therapies in standard doses. Treatment effectiveness was determined by comparing the UAS7 at baseline with that at weeks 4, 8 and 12. Also, baseline serum interleukin-6 (IL-6) and IL-17 were compared with those at the end of the study, that is, 12 weeks. Results: Thirty patients who matched the inclusion criteria and signed informed consent were included in the study. At the end of 12 weeks, 10% of patients (n = 3) achieved a complete treatment response (UAS = 0), whereas 43.33% of patients (n = 13) were labelled as having well-controlled urticaria (UAS <6). At 12 weeks, the mean UAS7 score (6.47 ± 4.45) was statistically significant compared to the baseline score (25.47 ± 7.74). The mean values of serum IL-6 (pg/ml) and IL-17 (pg/ml) at baseline were 5.96 ± 5.24 pg/ml and 6.96 ± 5.97 pg/ml, respectively. At the end of treatment, that is, 3 months, the mean values were reduced to 4.61 ± 4.56 pg/ml and 5.08 ± 3.87 pg/ml. The reduction was statistically significant for both serum IL-6 (P < 0.001) and IL-17 (P < 0.0001). Conclusion: We conclude that bilastine at a once-daily continuous dose of 40 mg for 3 months is safe and effective in CSU patients who are refractory to treatment at the standard doses of SGAHs. Improved symptomatic control with bilastine was also associated with better control over the inflammatory process, as suggested by the lowering of mean cytokine levels in our study.

A Cross-Sectional Study to Evaluate the Role of the Nuclear Factor Kappa B (Nf-κB) Pathway in Regulating the Cytokine Cascade and as a Potential Therapeutic Target in Leprosy.

Pattern recognition receptors (PRRs), which are found in microorganisms but not in hosts, allow Leprae bacilli to be recognized as foreign. Several kinds of pattern recognition receptors, such as toll-like receptors (TLRs), NOD-like receptors (NLRs) and RIG-1-like receptors (RLRs), are present in the innate immune system. Sen and Baltimore (1986) discovered the transcription factor nuclear factor kappa-B (NF-B), employed by eukaryotic cells to regulate immunity, cell differentiation and proliferation. This study aimed to evaluate the role of the nuclear factor kappa B (NF-B) pathway in controlling the cytokine cascade in leprosy due to a lack of understanding of the link between cytokines and the severity of leprosy. Clinically suspected Hansen's patients were analysed for 4 years. Newly diagnosed leprosy patients were considered to have leprosy disease control (LDC). The cases with active or new lesions and an increase in BI by at least 2+, 12 months after completion of MDT were considered leprosy disease relapse (LDR) cases. Age- and sex-matched healthy individuals served as our control group (HC). An ELISA was performed to measure the concentration of five human cytokines. By qRT-PCR, the quantitative expression of receptor genes (NOD1 and NOD2), cytokine genes and the expression of the transcription factor NFκß were evaluated. This was followed by a transcription factor NFκß assay to see its expression in the monocytes of study subjects. Nuclear factor NF-κß was found to have a pronounced response in monocytes of HC and LDC patients and LDR cases when treated with NOD1 and NOD2 ligands. Our study concludes that the NF-kB pathway is involved in the induction and regulation of the cytokine cascade that contributes to chronic inflammation in leprosy.

Efficacy of Super-Bioavailable Itraconazole and Conventional Itraconazole at Different Dosing Regimens in Glabrous Tinea Infection - A Randomized Clinical Trial.

Introduction: Itraconazole follows non-linear pharmacokinetics and hence is recommended once daily, but in real-world practice, is commonly prescribed as twice daily. Hence, this study aimed to evaluate the efficacy and safety of super-bioavailable-itraconazole-130 mg (SB-130) and conventional-itraconazole-200 mg (CITZ-200) once daily compared with conventional-itraconazole-100 mg (CITZ-100) twice daily in glabrous tinea. Methods: A total of 261 eligible patients were enrolled in this prospective, randomized, clinical study from December-2021 to August-2022 at seven centers in India. Efficacy and safety assessments were done at week-3 and 6, with follow-up at week-10 for relapse. The primary objective was to assess the proportion of patients who achieved complete cure at week-6 following treatment in all itraconazole groups. The secondary outcomes were safety and clinical and mycological cure rates. Results: Of 261 patients, 240 were included in the analysis. At week-6, 140 patients were completely cured; thus, overall cure rate was 58.33%. Fifty-five patients (69%) in SB-130 while 47/77 (61%) and 38/83 (46%) patients were completely cured in CITZ-200 and CITZ-100 groups respectively (p<0.05; SB-130: CITZ-100, p=0.32; SB-130: CITZ-200, p=0.058; CITZ-200: CITZ-100). There was no statistical difference in the mycological cure rate and area clearance rate between any of the groups (p=0.14); however, a statistically significant difference was noted for OD dosing over BD dosing in achieving clinical cure rates (p<0.05). A total of 13/140 patients (9%) relapsed following complete cure, with no statistically significant difference between any of the groups (p=0.50). All treatments were safe and well-tolerated, with no discontinuation. Conclusion: In this clinical study, moderate efficacy with all doses of ITZ was reported but was better with OD dosing. Although there was no statistical difference between SB-130 and CITZ-200, SB-130 may be preferred over CITZ-200 owing to the advantage of SB over the conventional ITZ.

A Cross-Sectional Study of the Levels of Cytokines IL-6, TNF-α, and IFN-γ in Blood and Skin (Lesional and Uninvolved) of Vitiligo Patients and their Possible Role as Biomarkers.

Introduction: Vitiligo is a multifactorial disorder, most often explained by the autoimmune hypothesis. The objective of this study is to measure the levels of cytokines IL-6, TNF-α, and IFN-γ in the blood and skin (lesional and uninvolved) of vitiligo patients and to compare it with that of age-matched controls. Methods: IL-6, TNF-alpha, and IFN-gamma cytokines were measured with a BioRad 6110 ELISA reader. We compared the levels of these cytokines in generalized versus localized vitiligo and stable versus unstable vitiligo. We also correlated cytokine levels in blood/lesion/uninvolved skin with body surface area (BSA) involvement and Vitiligo Disease Activity (VIDA) scoring. Result: Forty-three participants, each with vitiligo and control, were analyzed. The values of TNF-α and IL 6 in sera were significantly higher in the vitiligo group compared with the controls (p < 0.001), whereas INF-γ was significantly lower in the vitiligo group than the control group. TNF-α, INF-γ levels when compared between blood, lesional skin, and normal skin in all vitiligo patients were found to be significant (p < 0.001). Conclusion: We conclude vitiligo is strongly associated with increased levels of TNF-α and IL 6.

A Cross-Sectional Study to Evaluate the Alteration of Cytokine Expression and Activation of Inflammatory Pathway in Response to NOD1 and NOD2 Signal in Leprosy.

Introduction: Leprae bacilli are identified as foreign by pattern recognition receptors (PRRs) present in the microbes but absent in the host. The Nucleotide oligomerization domain (NOD)-like receptor (NLR) family comprises the nucleotide-binding oligomerisation domain (NOD1 and NOD2) proteins, which are two well-known PRRs. The objectives of this study were to study the expression of cytoplasmic NOD1 and NOD2 in the pathogenesis of leprosy and the serum level of expressed cytokines and to measure the messenger Ribonucleic Acid (mRNA) expression. Methods: Clinically suspected Hansen's patients were analysed for 4 years. Newly diagnosed leprosy patients were considered leprosy disease control (LDC). The cases with active or new lesions and an increase in Bacteriological index (BI) by at least 2 + after 12 months of completion of Multidrug therapy (MDT) were considered leprosy disease relapse (LDR) cases. Age- and sex-matched healthy individuals served as our control group (healthy control (HC)). enzyme-linked immunosorbent assay (ELISA) was performed to measure the concentration of five human cytokines in serum, including three pro-inflammatory cytokines (Tumor necrosis factor (TNF)-α, Interferon gamma (IFN-γ) and IL-6), one anti-inflammatory cytokine (IL-10) and one chemokine (IL-8). Quantitative expression of receptor genes (NOD1 and NOD2) and cytokine genes (TNF-α, IFN-γ, IL-6, IL-10 and IL-8) was evaluated by quantitative real-time polymerase chain reaction (PCR) (qRT-PCR). We studied NOD1 and NOD2 expression in the tissues through fluorescence immunohistochemistry. Differential NLR intracellular expression on peripheral blood monocytes (PBMs) and their response to stimulation with specific ligands (lipopolysaccharide (LPS) and muramyl dipeptide (MDP)) were studied. Results: A significant difference in the expression of the NOD1 gene was observed in unstimulated monocytes of the LDC and LDR cases when compared to HC. The NOD2 transcript level was significantly higher in stimulated monocytes from LDC and LDR patients than in similarly stimulated cells from HC. The LDC patients had a significantly higher level of pro-inflammatory cytokines as compared to the HC. Conclusion: In conclusion, this study has demonstrated the expression of both cytokines and chemokines in response to NLR activation in the skin of leprosy patients.

Biologics Beyond Boundaries: Innovative Use of Biologics in Dermatology.

Several biologic agents have been approved for use in dermatology and other disciplines of medicine. However, based on the mechanism of action and a track record of the response, these agents are being increasingly used for off-label purposes to garner control of more remote and difficult disease processes. Herein, we present three difficult to treat patients where innovative uses of biologics beyond their approved indications have yielded good responses. Our first patient was a case of bullous pemphigoid, who showed excellent response to omalizumab. The second case was a patient of lepromatous leprosy with tenosynovitis and erythema nodosum leprosum, who was treated effectively with infliximab. Our third case was a treatment-resistant pyoderma gangrenosum, where infliximab showed a very good response. In the present study, we report the cases to highlight the usefulness of biologics that can expand much beyond the routine FDA approved indications.

Real-Life Experience of Efficacy and Safety of Bilastine in the Refractory Cases of Chronic Spontaneous Urticaria and its Effect on the Quality of Life of Patients.

INTRODUCTION: Second-generation H1-antihistamines (SGAHs) are the mainstay of treatment of chronic spontaneous urticaria (CSU). Bilastine, newer non-sedating SGAHs, was recently introduced in India after the approval of the Drugs Controller General of India. There is a paucity of evidence about the long-term efficacy and safety of Bilastine in Indian patients. We undertook this study to find the long-term efficacy and tolerability of Bilastine in patients with CSU in India. MATERIALS AND METHODS: This retrospective chart analysis was conducted by analyzing electronic medical records from May 1, 2019, to March 20, 2020, to identify patients of CSU who were prescribed Bilastine. Adult patients, with CSU >6 months were included, who had an unsatisfactory response as per Urticaria Activity Score 7 (UAS7) to previous antihistamine therapies, and who continued treatment for at least 6 months were included. Treatment effectiveness was determined by retrospectively reviewing their UAS7 scores from their medical records and evaluating their scores at weeks 4, 8, 12, 16, 20, and 24. Also, DLQI was assessed and compared at baseline and week 24. RESULT: Forty-nine patients were found to fulfill the criteria and included in the study. At the end of 24 weeks, 51% of patients (n = 25) achieved complete treatment response (UAS = 0), whereas 49% of patients (n = 24) were labeled as well-controlled urticaria (UAS<6). At 24 weeks, the mean UAS7 score (1.35 ± 1.61) was statistically significant compared to the baseline score (20.2 ± 5.73). The mean score of DLQI was also reduced to 1.63 ± 1.18 at 24 weeks from 8.39 ± 2.49 at baseline (P-value <0.001). CONCLUSION: The study showed that in patients who had an inadequate response with commonly used antihistamines at a double dose or combined use, switching over to Bilastine resulted not only in relieving the symptoms of CSU but also improved the quality of life of the patients with CSU.

Use of Artificial Intelligence in Dermatology.

Artificial intelligence (AI) has emerged as a major frontier in computer science research. Although AI has been available for some time and found its application in many fields of medicine, its use in dermatology is comparatively new and limited. A sound understanding of the concepts of AI is essential for dermatologists as skin conditions with their abundant clinical and dermatoscopic data and images can potentially be the next big thing in the application of AI in medicine. There are already a number of artificial intelligence studies focusing on skin disorders, such as skin cancer, psoriasis, atopic dermatitis and onychomycosis. This article presents an overview of AI and new developments relevant to dermatology, examining both its current applications and future potential.

Real-World Insight on Apremilast Therapy in Patients with Plaque Psoriasis: Indian Experience.

INTRODUCTION: Psoriasis is an immune-mediated inflammatory skin disorder, which follows a chronic course. Apremilast is a novel phosphodiesterase 4 (PDE4) inhibitor, approved by US-FDA for the treatment of moderate to severe plaque psoriasis and psoriatic arthritis. A majority of the data related to the effectivity and safety of apremilast use in psoriasis is extracted from clinical trials. The present study was planned to get an insight into real-world experience with the use of apremilast in patients with moderate-to-severe plaque psoriasis related to its effectiveness and safety in India. MATERIALS AND METHODS: The present study was a retrospective one, wherein a review of the medical records of patients with psoriasis was conducted at one center in Kolkata, who were prescribed apremilast for 16 weeks in a community dermatology practice, from December 2017 to May 2018. RESULTS: Out of 39 patients, two patients discontinued treatment due to diarrhea. Only three patients were treatment naïve; the rest had taken some form of systemic therapy before apremilast. At the end of 16 weeks of treatment with apremilast, PASI 100 was achieved in one patient (2.7%), PASI 90 in one (2.7%), PASI 75 in 18 patients (48%), while 14 patients (38%) achieved PASI 50. Eighteen (46%) experienced adverse events, diarrhea being the most common (29.7%). CONCLUSION: The findings of the present study indicate that apremilast is effective in a real-world setting, as compared with clinical trials in achieving certain endpoints like PASI 75, as was found in other real-world studies in other countries, as well.

A Quality of Life Study of Patients with Leprosy Attending the Dermatology OPD of a Tertiary Care Center of Eastern India.

BACKGROUND: Leprosy is a chronic infectious disease caused by Mycobacterium leprae affecting the skin, peripheral nervous system, and other tissues. The disease is associated with social stigma, and the patients sometimes suffer social discrimination because it often leads to visible physical deformities. Hence, leprosy may have severe impact on the quality of life (QoL) of patients. AIMS AND OBJECTIVES: The aim of this study was to assess the effect of leprosy on the QoL of the affected patients and to find out whether there is some association with certain demographic and clinical factors. MATERIALS AND METHODS: The Dermatology Life Quality Index (DLQI) questionnaire was used to assess the QoL of 114 patients with leprosy who attended dermatology outpatient department of a tertiary care center of eastern India. This was a cross-sectional study. RESULTS: Among a total of 114 patients, leprosy had no impact on the QoL of 15 (13.16%) patients. There was a mild impact in 23 (20.18%) of the patients. There was moderate impact in 37 (32.46%) of the patients. The disease had severe impact in the QoL of 39 (34.21%) patients. None of the patients had a very severe impact. Several of the clinical aspects such as nerve involvement, systemic features, deformity, disability grade, and type of leprosy have significant impact on QoL. Among the demographic factors, gender had some effects on QoL. CONCLUSION: Leprosy adversely affects the QoL of those affected. Although it is considered a social disease, at least in our part of the country, demographics have minimal effect on the QoL. Rather, important clinical aspects such as systemic features, nerve involvement, reaction, deformity, and disability have profound impact on the QoL of the patients.

Guidelines on Management of Atopic Dermatitis in India: An Evidence-Based Review and an Expert Consensus.

BACKGROUND: Atopic dermatitis (AD) is a common and chronic, pruritic inflammatory skin condition that affects all age groups. There was a dearth of consensus document on AD for Indian practitioners. This article aims to provide an evidence-based consensus statement for the management of AD with a special reference to the Indian context. This guideline includes updated definition, etiological factors, classification, and management of atopic dermatitis. METHODOLOGY: The preparation of guidelines was done in multiple phases. Indian Dermatology Expert Board Members (DEBM), recommended by the Skin Allergy Society of India, prepared 26 evidence-based recommendations for AD. An extensive literature search was done in MEDLINE, Google scholar, Cochrane, and other resources. Articles published in the past 10 years were reviewed and recommendations were graded based on the quality of evidence as per GRADE. After forming the initial structure, DEBM met in Mumbai and gave their decisions on an agree and disagree scale with an Indian perspective. Finally, their suggestions were compiled for preparing the article. After DEBM finalized the draft, a treatment algorithm was formulated for the management of AD. RESULTS: DEBM suggested a working definition for AD. The panel agreed that moisturizers should be used as mainstay of therapy and should be continued in all lines of therapy and in maintenance phase. Topical corticosteroids and topical calcineurin inhibitors should be considered as the first line of treatment. Among systemic therapies, cyclosporin should be considered first line, followed by azathioprine, methotrexate, and mycophenolate mofetil. Phototherapy can be an effecive alternative. Empirical food restriction was recommended against. CONCLUSION: These guidelines should form a reference for the management of patients with AD in an evidence-based manner.

Apremilast Coadministered with Secukinumab for Safe and Effective Control of Psoriasis with Resultant Reduction of Maintenance Dose of the Biologic.

Psoriasis is a chronic immune-mediated inflammatory condition, affecting 2-3% of the population. In recent years, advent of biologics, including secukinumab, have been a major advancement in the management of difficult-to-treat plaque psoriasis. However, high cost of biologics is often a deterrent, especially for Indian socioeconomic condition. Apremilast is an oral phosphodiesterase 4 inhibitor that is safe for use along with many other systemic therapies of psoriasis, including biologics. We report two cases of psoriasis on secukinumab therapy for long duration with good response to therapy. Later, addition of apremilast, allowed halving the dose of secukinumab with maintenance of improvement.

Clinicopathological Study of Primary Cutaneous Amyloidosis in a Tertiary Care Center of Eastern India Reveals Insignificant Association with Friction, Scrubbing, and Photo-Exposure: How valid is the "Keratinocyte Hypothesis"?

INTRODUCTION: Primary cutaneous amyloidosis (PCA) can be classified into four principal categories: macular amyloidosis, lichen amyloidosis, biphasic, and nodular amyloidosis. Some unusual variants such as widespread diffuse hyperpigmentation without papules, poikiloderma like involvement, lesions following Blaschko's line, etc., have also been reported. However, not much data are available regarding the demography, epidemiology, clinical patterns, and distribution and histopathological findings, especially from the eastern part of India. AIMS: We conducted a cross-sectional, institution-based study to evaluate clinicopathological pattern and factors of PCA in eastern India. MATERIALS AND METHODS: We recorded clinical and histopathological findings of 100 consecutive patients of PCA presenting to a tertiary care institution of Kolkata in eastern India. RESULTS: We found female patients of PCA outnumber male (M:F =1:1.9) with majority of patients being young adults (56%) between 20 and 40 years of age. More than half (54%) of the patients were pruritic. The severity of pruritus is significantly more associated with lichenoid and biphasic variants over macular amyloidosis. Positive family history was recorded in 17% of cases. Macular variant was the most common variant constituting 48% of the total PCA. We also found that the association with history of friction and scrubbing and photo-exposure were statistically insignificant. However, duration of the disease has statistically significant association with the disease morphology. Congo red stain showed these deposits as reddish orange substance in 28 patients out of 64 patients' samples on which Congo red could be performed. CONCLUSION: Our study revealed that many concepts of pathogenesis of PCA including friction and photoexposure might have lesser importance. However, morphological types were significantly associated with the duration of the disease and symptom severity.

Genomic Reduction at TTC Repeats in the Bacterial Genome of Treated Cases of Hansen's Disease: A Possible Survival Mechanism of Mycobacterium leprae.

INTRODUCTION: Mycobacterium leprae has a small genome and a tendency of persisting as a very low-grade infection. The authors have shown earlier, that the changes in TTC repeats, in M. leprae genome may contribute to the restriction of the pathogenicity of the bacterium and its survival strategy in case of pure neural Hansen's disease. We suspect, that a similar genomic reduction if happens in treated cases of Hansen's disease, can be a determining factor for developing persisters and relapse. AIM: The present study aimed to find out if there was any evidence of genomic reduction in treated cases of Hansen's disease that showed microbiological nonresponse. METHODS: Skin biopsies were taken from treated cases of Hansen's disease at tertiary centers in Kolkata and at Raipur who had bacterial index (BI) unchanged or increased compared to their pretreatment BI. Analysis for the mutation in rpoB gene and folP1 gene were done to rule out rifampicin and dapsone resistance, respectively. The entire TTC repeat region of the bacteria was amplified by polymerase chain reaction and was subjected to sequencing. The obtained sequences were then analyzed by CLUSTALW. RESULTS: A total of 127 patients were included in the study of which in 52 the BI remained same and 75 had an increase in BI, even after 6 months of completion of multidrug therapy. Among the samples, 2 had positive rpoB gene mutation. No mutation was found in the folP1 gene. The TTC repeat of both the rpoB-resistant samples was found to have 17 copies, which matched their pretreatment copy number. In other 125 cases, 60 cases showed no change from their pretreatment TTC number. Of those 65 samples that showed evidence of genomic reduction, 11 samples showed one copy, 41 showed 2 copies, and 13 showed 3 copies deletion. We also observed a significant regional variation. CONCLUSION: We concluded that there was evidence of genomic reduction, which might lead to microbiological nonresponse in treated cases of Hansen's disease. This indicated a possibility of future persistence and relapse.