Cardiovascular Considerations and Implications for Treatment in Psoriasis: An Updated Review.

Psoriasis, a prevalent chronic inflammatory skin disorder affecting 2-3% of the global population, has transcended its dermatological confines, revealing a profound association with cardiovascular diseases (CVD). This comprehensive review explores the intricate interplay between psoriasis and cardiovascular system, delving into genetic links, immune pathways, and adipose tissue dysfunction beyond conventional CVD risk factors. The pathophysiological connections unveil unique signatures, distinct from other inflammatory skin conditions, in particular psoriasis-specific genetic polymorphisms in IL-23 and TNF-α have consistently been linked to CVD. The review navigates the complex landscape of psoriasis treatments, addressing challenges and future directions in particular relevance to CVDs in psoriasis. Therapeutic interventions, including TNF inhibitors (TNFi), present promise in reducing cardiovascular risks, and methotrexate could constitute a favourable choice. Conversely, the relationship between IL-12/23 inhibitors and cardiovascular risk remains uncertain, while recent evidence indicates that Janus kinase inhibitors may not carry CVD risks. Emerging evidence supports the safety and efficacy of IL-17 and IL-23 inhibitors in patients with CVDs, hinting at evolving therapeutic paradigms. Lifestyle modifications, statins, and emerging therapies offer preventive strategies. Dedicated screening guidelines for CVD risk assessment in psoriasis are however lacking. Further, the impact of different disease phenotypes and treatment hierarchies in cardiovascular outcomes remains elusive, demanding ongoing research at the intersection of dermatology, rheumatology, and cardiology. In conclusion, unraveling the intricate connections between psoriasis and CVD provides a foundation for a holistic approach to patient care. Collaboration between specialties, advancements in screening methodologies, and a nuanced understanding of treatment impacts are essential for comprehensive cardiovascular risk management in individuals with psoriasis.

Psoriasis is a skin condition that not only affects the skin but is also linked to issues in the body's fat tissue, which can lead to inflammation and heart problems. The fat tissue in people with psoriasis contains various immune cells, contributing to obesity and insulin resistance. Research has found a strong connection between inflammation in fat tissues and cardiovascular problems in people with psoriasis. Specific substances released by fat tissue, like leptin, resistin, and adiponectin, can impact inflammation and cardiovascular health. Psoriasis patients often show increased levels of these substances. Treatment for psoriasis may influence cardiovascular health. Some studies suggest that certain medications, like methotrexate or TNF inhibitors, may lower the risk of heart events. However, there are also concerns about potential adverse effects, and further research is needed to fully understand how psoriasis treatments affect cardiovascular outcomes. To manage the cardiovascular risks associated with psoriasis, regular screening for heart-related issues is recommended. Lifestyle changes, such as a healthy diet, stress management, and smoking cessation, are also essential. Additionally, specific medications, like statins and metformin, may be beneficial in controlling cardiovascular risk factors in people with psoriasis. Despite advancements in understanding the relationship between psoriasis and cardiovascular health, there are still challenges. Research is ongoing to develop better screening guidelines and treatment strategies. Collaboration between dermatologists, rheumatologists, and cardiologists is crucial to address the complex nature of this condition and its impact on the heart.

Ocular Cicatricial Pemphigoid in Young Patients.

PURPOSE: The purpose of this study is to report ocular cicatricial pemphigoid (OCP) occurring in young patients. Relevant literature is also reviewed. METHODS: Medical records of patients aged 30 years or younger who were treated for OCP between August 2021 and May 2023 at a tertiary care eye institute were reviewed. The most common differential diagnoses of cicatrizing conjunctivitis, such as Stevens-Johnson syndrome sequelae, chemical injury, chronic topical/systemic drug use, autoimmune connective tissue disorders, or allergic eye diseases, were ruled out based on clinical history, examination, and the Cicatrizing Conjunctivitis Score described by Shanbhag et al. The diagnosis of OCP was confirmed by positive direct immunofluorescence of oral mucosal and/or conjunctival biopsy in a majority of the patients. RESULTS: Seven patients fulfilled the criteria for a diagnosis of OCP. The mean age at presentation was 21.86 ± 5.25 years (13-28 years). Some of the patients presented with relatively atypical features for OCP such as corneal immune ring infiltrate and bilateral corneal perforation. Six patients exhibited systemic mucosal lesions, and the direct immunofluorescence yield was 85.71%. All patients required aggressive immunosuppressive treatment. CONCLUSIONS: OCP is classically described as a rare disease that occurs in old age. This case series highlights the importance of a higher index of suspicion for diagnosing OCP at a younger age. Early administration of immunosuppressive agents can potentially control severe ocular surface inflammation and its sequelae.

A challenging case of borderline lepromatous leprosy non-responsive to WHO-MDT: exploring approaches beyond WHO-MDT.

Just as we prioritize personalized medicine for various other medical conditions, we should also include a neglected disease like leprosy, ensuring that patients receive the best care possible and improving their quality of life. Our case highlights the importance of instituting an alternate therapeutic regimen in a scenario where there is a lack of clinical response to multidrug therapy, even in the absence of documented drug resistance of the currently available molecular diagnostics. The search for the perfect regimen tailored for each individual leprosy patient should continue. Alternate anti-leprosy therapy is highly useful in cases with confirmed drug resistance or clinically non-responsive cases; however, their misuse should also be strictly avoided to prevent the development of resistance to them.

Assessing the impact of childhood and adolescent chronic plaque psoriasis on parents/caregivers using the Family Dermatology Life Quality Index (FDLQI): A cross-sectional study.

Background Chronic childhood diseases are a burden for paediatric patients and their caregivers. Limited data are available on the effect of paediatric psoriasis on the caregiver's well-being and quality of life. Objective To assess the impact of childhood and adolescent chronic plaque psoriasis on parents/caregivers quality of life. Methods A single-centre cross-sectional study was performed which included 102 children with psoriasis and their caregivers. Clinico-demographic data of children and socio-demographic details of primary caregivers were collected. Out of pocket expenditure for treatment was calculated for all the patients. The quality of life of children was assessed using the Children's Dermatology Life Quality Index (CDLQI) and the caregiver's quality of life was assessed using the Family Dermatology Life Quality Index (FDLQI). Results CDLQI was impaired in 85.29 % of children with a median score of 7. The item 'symptoms' was most commonly affected (87.2%), followed by 'self-conscious' (70.5%) and 'treatment' (65.6%). FDLQI was impaired in 96.1% of caregivers with a median value of 11. The most affected FDLQI items were 'emotional' in 95%, followed by 'time-spent' in 78.4%. Almost 40% of patients had catastrophic health expenditure (CHE) and their FDLQI was significantly higher (p-0.014) compared to caregivers who did not experience catastrophic health expenditure. FDLQI had a positive relationship with the involvement of exposed body sites (p-0.003), CDLQI (p-0.000), treatment expense (p-0.031) and a negative correlation with duration of illness (p-0.04). Conclusion Childhood psoriasis has a negative impact on the quality of life of the children and caregivers highlighting the need for intervention strategies for both.

Role of FoxO1 in Acne and Effect of Isotretinoin on FoxO1 Expression.

Background: Nodulocystic acne is a severe type of acne that is known to improve after treatment with isotretinoin. Melnik has hypothesized a unifying concept on the mechanism of acne pathogenesis involving altered expression of Forkhead box O transcription factor (FoxO1) and role of isotretinoin in improving acne via modulating this pathway. Aim: To evaluate the pathway proposed by Melnik in acne pathogenesis by analysing the difference in the expression of FoxO1, peroxisome proliferator-activated receptor (PPARγ), and androgen receptor (AR) between acne patients and non-acne controls and the effect of treatment with isotretinoin on change in expression of these genes in acne patients. Results: The gene expression of FoxO1 was non significantly higher in acne patients as compared to controls. After treatment with isotretinoin, a significant decrease in FoxO1 expression in acne patients at mRNA (P = 0.05) level was observed. There was a significant decrease in grade 3 positivity of FoxO1 at protein level (P = 0.0009). A decrease in androgen receptor positivity (P = 0.055) at protein level was also observed. Conclusion: Reduction in FoxO1 expression appears to be an important mechanism of action of isotretinoin in acne.

Increased prevalence of metabolic syndrome and non-alcoholic fatty liver disease in children with atopic dermatitis: A case-control study from northern India.

BACKGROUND/OBJECTIVES: Atopic dermatitis (AD) is a chronic inflammatory skin disorder that affects children worldwide, with potential associations to metabolic syndrome (MetS) and non-alcoholic fatty liver disease (NAFLD). Limited research exists on the interplay between AD, MetS, and NAFLD in the pediatric population. This study aimed to investigate the prevalence and potential relationships among AD, MetS, and NAFLD in children. METHODS: A case-control study design was employed, recruiting 50 children with AD (median age: 9.5 years) and 50 age- and sex-matched healthy controls (median age: 11.5 years, p = .051). Data on demographic characteristics, clinical features, disease severity, treatment history, anthropometric measurements, and laboratory evaluations were collected. MetS and NAFLD were diagnosed based on established criteria. RESULTS: The prevalence of MetS was significantly higher in children with AD compared with controls (24% vs. 2%, p = .002). Significant differences for systolic blood pressure (p < .001), diastolic blood pressure (p = .012), and waist circumference (p = .040) were observed between AD patients and controls. Children with AD had higher triglyceride levels (p = .005). NAFLD was exclusively seen in moderate to severe AD cases (6% vs. 0%, p = .242). AD severity showed associations with increased body mass index (p = .020). CONCLUSION: This study highlights the increased prevalence of MetS and the potential association with NAFLD in children with AD. The findings suggest that AD may contribute to the development of metabolic abnormalities at an early age. Further research is needed to elucidate the underlying mechanisms and explore preventive strategies for these interconnected conditions.

Case report: Interleukin-17 targeted biological therapy in netherton syndrome.

Netherton syndrome (NS) is rare and multisystemic congenital skin disorder classically distinguied as a triad of congenital ichthyosiform erythroderma, trichorrhexis invaginata (TI), and an atopic diathesis. Recent advances in pathogenesis have explored the role of IL-23/Th17 pathway in NS. Herein, we present a 17 years old girl harbouring homozygous four base pair deletion in exon 26 of the SPINK5 gene, presented with pruritus, scaling, dry skin and generalized eczematous lesions. She was administered anti IL17A (subcutaneous secukinumab) therapy. The treatment was well tolerated and resulted in a favourable clinical response, reduction of the IL17A gene expression and CD4 + Th17 cell population after 6 months which revealed an abrogation of Th17-skewing during therapy.

Accuracy of serration pattern analysis by direct immunofluorescence in subepidermal autoimmune blistering diseases.

Background Direct immunofluorescence (DIF) is essential for the diagnosis of sub-epidermal immunobullous diseases (SIBD). Bullous pemphigoid (BP), a sub-epidermal immunobullous disease, shows linear IgG and C3 deposition along the dermo-epidermal junction by DIF. However, similar histological and DIF findings are also seen in epidermolysis bullosa acquisita (EBA). High-power examination of antibody deposition by DIF in a "u" or "n" serrated pattern can help differentiate these two entities. Aims/Objectives The aim of this study was to determine the diagnostic accuracy of serration patterns in IgG-mediated sub-epidermal immunobullous disease. Methods All cases of IgG-mediated sub-epidermal immunobullous disease diagnosed over the past 2 years and 9 months period and confirmed serologically, were included. Examination of the serration pattern in DIF was assessed on oil emersion. Salt split skin indirect immunofluorescence (SSS IIF), BP180 enzyme-linked immunosorbent assay (ELISA), profile ELISA and BIOCHIP mosaic were performed, wherever available. Results This study included 74 cases of bullous pemphigoid, eight cases of mucus membrane pemphigoid (MMP) and one case of epidermolysis bullosa acquisita. The characteristic zigzag "n" pattern was visualised in 66 out of 82 cases (80.5%) of the pemphigoid group (BP + MMP); the single epidermolysis bullosa acquisita case showed the "u" serrated pattern. No statistical correlation was seen between serration pattern and BP180 positivity by ELISA (P = 0.05). Limitations The study is limited by the single case of epidermolysis bullosa acquisita (which could be due to rarity of this disease in north Indian population due to genetic variation), lack of detailed serological investigations and immunoblot in all cases. Conclusion Serration pattern analysis is an easy-to-interpret and highly useful technique for characterisation of sub-epidermal immunobullous diseases.

Contact hypersensitivity to Indian standard patch test series correlates with disease severity among children with atopic dermatitis.

Background There is emerging evidence of a relationship between atopic dermatitis (AD) and allergic contact dermatitis (ACD), though the data available are scarce with conflicting viewpoints. We explored the occurrence of contact hypersensitivity among children with atopic dermatitis by patch testing them with the Indian standard series and tried to correlate the presence of contact hypersensitivity with the clinical severity of AD in these children. Methods In this single-centre, cross-sectional study, children between 6 months and 12 years diagnosed with atopic dermatitis were included and patch tested with the Indian standard series. Outcome parameters were the proportion of patients having positive patch-test reactions, the proportion of positive patch-test reactions for each allergen and factors associated with patch test positivity in atopic dermatitis. Results Of the 136 patients, 80 were boys. The mean age of the study population was 5.6 ± 3.2 years. Twenty-eight (20.6%) patients had patch test positivity at 96 h. Fragrance mix was the commonest allergen, followed by potassium dichromate, cobalt chloride hexahydrate and nickel. SCORing atopic dermatitis (SCORAD) was significantly higher in patients with positive patch tests as compared to patients with negative patch tests (P = 0.009). Conclusion Greater disease severity in atopic dermatitis was found to be associated with patch test positivity. Limitations Inability to establish relevance in about 50% of the patients was a limitation of our study. Follow-up data regarding the impact of allergen avoidance is not available.

Utility of C3d and C4d immunohistochemical staining in formalin-fixed skin or mucosal biopsy specimens in diagnosis of bullous pemphigoid and mucous membrane pemphigoid.

Bullous pemphigoid (BP) and mucous membrane pemphigoid (MMP) sometimes have overlapping clinical, histopathological, and direct immunofluorescence (DIF) features in the early stages. Complement deposition is an intrinsic component of the patho-mechanism of BP in contrast to MMP. Hence immunohistochemistry (IHC) for C3d and C4d may be helpful in differentiating the two disorders. Seventy-four patients of BP and 18 patients of MMP along with 10 negative controls were enrolled in this study. C3d and C4d IHC was performed in formalin-fixed skin biopsy specimens. C3d IHC staining in BP/MMP had a sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 59.2%/41.2%, 100%/100%, 100%/100%, 25.6%/50.0%, respectively. C4d IHC staining in BP/MMP had a sensitivity, specificity, PPV and NPV of 26.8%/17.6%, 100%/100%, 100%/100% and 16.1%/41.7%, respectively. Receiver operator analysis showed utility of C3d in diagnosing both BP [Area under curve (AUC) = 0.8, p = 0.0001] and MMP (AUC = 0.71; p = 0.001). C4d was useful in diagnosis of BP (AUC = 0.5; p = 0.0001), but not MMP (AUC = 0.6; p = 0.064). Hence, C3d is a better diagnostic modality for BP as compared to C4d, whereas C3d and C4d have lower diagnostic importance in MMP. C3d IHC can be employed in diagnosing BP when a second biopsy for direct immunofluorescence (DIF) is not possible or where a facility for IF microscopy does not exist.

A prospective study to estimate the incidence and pattern of adverse drug reactions to first-line antiretroviral therapy (tenofovir, efavirenz, and lamivudine).

Background: Antiretroviral drugs are efficacious but are associated with long-term toxicities, drug interactions, and emergence of drug resistance. Objective: To study the incidence and pattern of adverse drug reactions in human immunodeficiency virus (HIV) patients receiving first-line antiretroviral therapy (ART) (tenofovir, efavirenz, and lamivudine (TEL) which was introduced by NACO in 2013. Materials and Methods: A prospective, single-center observational study that included 135 treatment-naive HIV patients who were started on fixed drug once-daily regimen (TEL). At baseline, detailed clinical history, body weight, waist-hip ratio, complete blood count, liver and renal function test, CD4 cell count were performed. Clinical monitoring for cutaneous, neuropsychiatric, and gastrointestinal side effects was done every month along with laboratory monitoring and anthropometric measurement for every 6 months. CD4 counts were measured at baseline and end of the study at 12 months. Results: Out of 135 participants, 89 (65.9%) were males and 46 (34%) were females. The mean age and the mean duration of illness at inclusion were 35.10 ± 8.97 years and 1.2 ± 0.6 years, respectively. The mean increase in weight at baseline and at 12 months (57.55 ± 6.56 to 64.04 ± 8.2) was statistically significant (95% confidence interval [CI]: 4.35-8.62, P < 0.001). The mean CD4 counts at baseline were 309.73 ± 118.44 and increased after 12 months of treatment to 421 ± 129.4 which was statistically significant (95% CI: 81.54-140.99, P < 0.001). The mean difference in platelet count was statistically significant between baseline and 12 months (95% CI: 10.32-46.13, P = 0.002). The mean difference in serum urea levels at baseline and at 6 months (95% CI: 0.60-1.61, P < 0.001) as well as 12 months were statistically significant (95% CI: 0.08-1.03, P = 0.02). The mean increase in serum creatinine at baseline (0.75 ± 0.12) and at 12 months (0.97 ± 0.16) was also significant (95% CI: 0.21-0.28, P < 0.001). There was a significant difference between mean creatinine clearance at baseline and at 12 months (109.9 ± 13.75 to 99.33 ± 12.52, P < 0.0001). One patient discontinued treatment due to adverse effects while two patients were shifted to second-line antiretroviral treatment. Limitations: Small sample size, single-center study and short follow-up period, long-term toxicities were not appreciated. Conclusion: Fixed drug combination with TEL as a first-line ART for HIV is a safe regime as we observed minimal side effects with current regimen.