Infections in the era of immunobiologicals.

Immunobiologicals represent an innovative therapeutic option in dermatology. They are indicated in severe and refractory cases of different diseases when there is contraindication, intolerance, or failure of conventional systemic therapy and in cases with significant impairment of patient quality of life. The main immunobiologicals used in dermatology basically include inhibitors of tumor necrosis factor-alpha (anti-TNF), inhibitors of interleukin-12 and -23 (anti-IL12/23), inhibitors of interleukin-17 and its receptor (anti-IL17), inhibitors of interleukin-23 (anti-IL23), rituximab (anti-CD20 antibody), dupilumab (anti-IL4/IL13) and intravenous immunoglobulin. Their immunomodulatory action may be associated with an increase in the risk of infections in the short and long term, and each case must be assessed individually, according to the risk inherent to the drug, the patient general condition, and the need for precautions. This article will discuss the main risks of infection associated with the use of immunobiologicals, addressing the risk in immunocompetent and immunosuppressed patients, vaccination, fungal infections, tuberculosis, leprosy, and viral hepatitis, and how to manage the patient in the most diverse scenarios.

Janus-kinase inhibitors in dermatology: A review of their use in psoriasis, vitiligo, systemic lupus erythematosus, hidradenitis suppurativa, dermatomyositis, lichen planus, lichen planopilaris, sarcoidosis and graft-versus-host disease.

Recent studies on molecular pathways have elucidated novel therapeutic approaches in inflammatory and autoimmune skin disorders. Specifically, the dysregulation of the Janus kinase signal transducer and activator of transcription (JAK-STAT) cascade plays a central role in the pathogenesis of many skin conditions. JAK inhibitors, with their ability to selectively target immune responses, are potential treatment options. Using the National Library of Medicine, we provide a comprehensive review of the use of United States Food and Drug Administration (FDA)-approved and emerging JAK or tyrosine kinase 2 (TYK2) inhibitors in a wide range of dermatologic conditions, including psoriasis, vitiligo, systemic lupus erythematosus, hidradenitis suppurativa, dermatomyositis, lichen planus, lichen planopilaris, sarcoidosis and graft-versus-host disease. In patients with psoriasis, oral deucravacitinib (TYK2 inhibitor) has been approved as a once-daily therapy with demonstrated superiority and efficacy over apremilast and placebo and tolerable safety profiles. In patients with vitiligo, topical ruxolitinib (JAK1 inhibitor) is approved as a twice-daily treatment for repigmentation. The efficacy of several other JAK inhibitors has also been demonstrated in several clinical trials and case studies for systemic lupus erythematosus, hidradenitis suppurativa, dermatomyositis, lichen planus, lichen planopilaris, sarcoidosis and graft-versus-host disease. Further investigations with long-term clinical trials are necessary to confirm their utility in treatment and safety for these diseases.

Preparation and characterization of solid lipid nanoparticles encapsulated noscapine and evaluation of its protective effects against imiquimod-induced psoriasis-like skin lesions.

Psoriasis is a chronic inflammatory skin disease characterized by thickening the epidermis with erythema, scaling, and proliferation. Noscapine (NOS) has several anti-inflammatory, anti-angiogenic, and anti-fibrotic effects, but its low solubility and large size results in its lower efficacy in the clinic. In this regard, solid lipid nanoparticles (SLN) encapsulated NOS (SLN-NOS) were fabricated using the well-known response surface method based on the central composite design and modified high-shear homogenization and ultrasound method. As a result, Precirol® was selected as the best lipid base for the SLN formulation based on Hildebrand-Hansen solubility parameters, in which SLN-NOS 1 % had the best zeta potential (-35.74 ± 2.59 mV), average particle size (245.66 ± 17 nm), polydispersity index (PDI, 0.226 ± 0.09), high entrapment efficiency (89.77 %), and ICH-based stability results. After 72 h, the SLN-NOS 1 % released 83.23 % and 58.49 % of the NOS at pH 5.8 and 7.4, respectively. Moreover, Franz diffusion cell's results indicated that the skin levels of NOS for SLN and cream formulations were 46.88 % and 13.5 % of the total amount, respectively. Our pharmacological assessments revealed that treatment with SLN-NOS 1 % significantly attenuated clinical parameters, namely ear thickness, length, and psoriasis area and severity index, compared to the IMQ group. Interestingly, SLN-NOS 1 % reduced the levels of interleukin (IL)-17, tumor necrosis factor-α, and transforming growth factor-ß, while elevating IL-10, compared to the IMQ group. Histology studies also showed that topical application of SLN-NOS 1 % significantly decreased parakeratosis, hyperkeratosis, acanthosis, and inflammation compared to the IMQ group. Taken together, SLN-NOS 1 % showed a high potential to attenuate skin inflammation.

Review of the reasons for and effectiveness of switching biologics for psoriasis treatment in Korea.

Background Switching of biologics in patients has become common in clinical practice. Objectives This study investigated the reasons for and effectiveness of switching biologic agents during the treatment of psoriasis. Methods We retrospectively reviewed patients with psoriasis who were treated with biologics at Pusan National University Hospital and Chosun University Hospital from March 2012 to June 2020. We assessed their demographics and treatment characteristics (reasons for switching biologics and efficacy of the first- and second biologic agents). Results Of the 162 psoriatic patients treated with biologic agents for more than 52 weeks, 35 required a switch to another biologic agent. The reasons for switching biologic agents were inefficacy (n = 30), adverse events (n = 2) and others (n = 3). The mean psoriasis area and severity index (PASI) score was 12.1 at the start of the second biologic and 3.4 at 14-16 weeks later. Patients were more likely to switch to another biologic agent when they exhibited a high initial psoriasis area and severity index score and concomitant psoriatic arthritis. Limitations As a retrospective study, there were some limitations such as lack of a placebo control group and the time point of 14-16 weeks being somewhat early to judge the effect of the biologics. Conclusions The most common reason for switching biologic agents in Korea was treatment inefficacy, especially secondary failure. Despite the inefficacy of previous biologic agents, switching to a different agent may be an efficacious approach.

Methotrexate monotherapy versus methotrexate and apremilast combination therapy in the treatment of palmoplantar psoriasis: A prospective, randomised, assessor-blinded, comparative study.

BACKGROUND: Palmoplantar psoriasis is a chronic debilitating condition which significantly impairs quality of life. OBJECTIVES: To assess the efficacy and safety of the combination of apremilast and methotrexate compared with methotrexate monotherapy in the treatment of palmoplantar psoriasis. Also, to study the impact on treatment on the Dermatology Life Quality Index and Palmoplantar Quality of Life Index. METHODS: A total of 64 patients were randomised to two groups in a 1:1 ratio - Group A received both methotrexate and apremilast in combination, while Group B received only methotrexate, for 16 weeks. The primary endpoints were the mean score of Modified Palmoplantar Psoriasis Area and Severity Index at week 16, the proportion of patients achieving modified palmoplantar psoriasis area severity index-75 and/or Palmoplantar Psoriasis Physician Global Assessment score 0/1 at week 16. RESULTS: A significantly higher proportion of patients in Group A achieved Modified Palmoplantar Psoriasis Area and Severity Index-75 at week 16 (43% in Group A vs 30% in Group B). The Modified Palmoplantar Psoriasis Area and Severity Index score was significantly lower in the combination group at week 16 (4.03 ± 2.05 in Group A and 5.89 ± 2.31 in Group B, P-value = 0.002). About 80% of patients in the combination group with baseline Palmoplantar Psoriasis Physician Global Assessment ≥3 achieved Palmoplantar Psoriasis Physician Global Assessment 0/1 compared to 60% in Group B. The combination group showed a significantly higher reduction in Dermatology Life Quality Index and Palmoplantar Quality of Life Index scores compared to the methotrexate alone group (P-value = 0.025). No notable adverse events were observed. LIMITATION: The limitations of the study were single blinding, small sample size and a lack of longer follow up to assess the rate of relapse. We did not account for attrition during sample size calculation. Also, due to the paucity of data regarding the use of apremilast in palmoplantar psoriasis, definitive comparisons could not be made with previous studies. CONCLUSION: The combination of apremilast and methotrexate has superior efficacy and a similar safety profile as compared to methotrexate monotherapy for the treatment of moderate to severe palmoplantar psoriasis.

The use of medicinal plants for the treatment of psoriasis: A systematic review and meta-analysis.

Background Psoriasis is a chronic inflammatory disease that presents as scaly patches on the skin that affects about 3% of the world's population. Adherence to treatment and discrimination against people are common problems, adversely impacts quality of life. Objectives The aim of this study was to investigate the use of medicinal plants as therapeutic adjuvants in the treatment of plaque psoriasis through a systematic review and meta-analysis. Methods A systematic review and meta-analysis of randomized controlled trials in patients with plaque psoriasis was carried out, comparing the efficacy of herbal treatments alone or in association with other therapies. The search was performed in the databases of The Cochrane Library, Lilacs, Medline via PubMed and Embase, only including studies published from 2016 to 2020.The certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework. A systematic review and meta-analysis of randomized controlled trials (RCT) in patients with plaque psoriasis was carried out, comparing the efficacy of herbal treatments alone or in association with other therapies. We comprehensively searched the MEDLINE, Embase, Lilacs and Cochrane Library databases, only including studies published from 2016 to 2020. The certainty of evidence was assessed using the GRADE approach. Results Out of 2,268 articles evaluated, only seven RCT were eligible for final analysis. Five of these studies evidenced low risk of bias and a high level of evidence. Limitations Few RCT of medicinal plants. Conclusion This meta-analysis indicates that medicinal plants may be used as topical or oral products, either alone or combined with other forms of treatment. These products have the potential to greatly improve the quality of life of the patient.

Correlation of IL36RN and CARD14 mutations with clinical manifestations and laboratory findings in patients with generalised pustular psoriasis.

Background Generalized pustular psoriasis (GPP) is a chronic disease associated with genetic factors related to mutations of the interleukin 36 receptor antagonist gene (IL36RN) and the caspase recruitment domain 14 gene (CARD14). However, the relevance of these mutations to the clinical features and severity of GPP remains unclear. Aims Our objective was to correlate the presence of IL36RN and CARD14 mutations with the clinical and laboratory findings in patients with GPP. Methods This cross-sectional descriptive study was conducted in 64 subjects with GPP. Clinical manifestations were recorded and the severity was graded as mild, moderate, or severe. Routine laboratory tests were performed and blood samples were collected for Sanger sequencing. The clinical data of patients were compared among the different mutation groups. Results The two main variants of IL36RN were c.115+6T > C (p.Arg10ArgfsX1) and c.227C > T (p.Pro76Leu). The major CARD14 mutations were c.2458C > T (p.Arg820Trp), c.1641C > T (p.Arg547Ser), and c.1753G > A transitions. Provocative factors were uncommon in the group with both IL36RN and CARD14 mutations. Drugs (unspecified), especially herbals, were the most common triggers. A history of psoriasis was frequent in patients with only CARD14 mutations, but fever was uncommon. The c.1641C > T mutation was associated with leukocytosis > 15000/mm3 and the c.1753G > A mutation was associated with hypoalbuminemia <3.8g/dL. Both the c.115+6T > C and c.227C > T variants of IL36RN were associated with fever ≥38.5°C while the c.115+6T > C variant was also associated with geographic tongue. No gene mutations were associated with the total severity and severity grades. Limitations Four patients without the two major IL36RN mutations were excluded from the study. Conclusion The presence of IL36RN and CARD14 mutations were associated with a history of psoriasis, various provocative factors, fever, leukocytosis, hypoalbuminemia, and geographic tongue. Further studies to explore the role of these mutations in therapeutic efficacy and disease outcomes are necessary.

The Use of Bakuchiol in Dermatology: A Review of In Vitro and In Vivo Evidence.

The plant Psoralea corylfolia contains compounds such as psoralens that are useful for the treatment of psoriasis and vitiligo, and the plant is used in Chinese and Indian traditional medicine for diseases such as psoriasis and leprosy. Bakuchiol, a meroterpene phenol in Psoralea corylfolia, has similar functional properties to topical retinoids, which are commonly used to treat acne, post-inflammatory hyperpigmentation, and wrinkles. Bakuchiol’s anti-inflammatory and anti-proliferative properties also may lead to improvement in psoriasis and skin cancers, yet more clinical evidence is needed to elucidate these effects. Notably, bakuchiol does not cause common adverse effects seen with topical retinoids such as burning and scaling, permitting wider use in patients with sensitive skin. This review will detail the current evidence for bakuchiol as an alternative treatment in dermatologic conditions. J Drugs Dermatol. 2022;21(6):624-629. doi:10.36849/JDD.6740.

Coronavirus disease 2019 vaccination in patients with psoriasis: A position statement from India by SIG psoriasis (IADVL Academy).

Coronavirus disease 2019 (COVID-19) pandemic has affected every sphere of life including management of psoriasis. The availability of COVID-19 vaccines has given rise to hope and at the same time some apprehensions as well. With the general population becoming eligible for vaccination, there is some confusion, on the eligibility of patients with different medical conditions and patients on immunosuppressive or immunomodulating medications for COVID-19 vaccination. Dermatologists treating psoriasis patients frequently face questions from them, whether they can undergo coronavirus disease 2019 vaccination. A PUBMED search was performed using the following strategy: 'COVID-19' AND 'Vaccine' AND 'Psoriasis'. We also performed a PUBMED search using the following strategy: 'SARS-CoV-2' AND 'Vaccine' AND 'Psoriasis'. All articles irrespective of language and publication date were included to arrive at this position statement. This position statement deals with the safety, eligibility and modifications of treatment, if needed among psoriasis patients with regards to the coronavirus disease 2019 vaccines currently available in India.

Pattern of use of biologics in psoriasis among Indian dermatologists - A cross sectional survey.

Background and Aims Biologics are a relatively new class of highly effective drugs in the management of psoriasis. They act on specific immune processes, achieve rapid and sustained clearance and do not cause target organ damage unlike conventional systemic therapy. It appears that their use in our country is not as widespread as in developed nations despite these benefits ; their prohibitive cost may be a major factor for the limited usage. This survey aimed to find out the extent of use and factors hindering usage of biologics for the management of psoriasis by Indian dermatologists. Methods It was a cross-sectional questionnaire based study. The questionnaire was designed after a focussed group discussion, followed by validation. The survey was sent in the form of a link to Indian dermatologists. The responses were recorded in excel-sheet and the data was analyzed by SPSS ver 25. Results Of the 310 participants who took part, 287 completed the survey. Two hundred (70%) were users of biologics, while 87 (30%) had never used them. Cost was the major factor which prevented biologic use. Majority of the respondents used biologics in less than 2 cases per month. Secukinumab was the most common biologic used followed by etanercept. The factors which determined choice of biologics were convenience, cost, previous experience, co-morbid conditions and recommendations by an expert. Limitations A small sample size was the limitation of the study. Dermatologists who do not use biologics may be under-represented in the study. Conclusions Biologics are not used optimally by Indian dermatologists for management of psoriasis. The cost, fear of adverse effects, lack of awareness and inadequate felt need are major factors which prevent their regular use.

Management practice, quality of life and associated factors in psoriasis patients attending a dermatological center in Ethiopia.

BACKGROUND: Psoriasis is a chronic inflammatory disease characterized by keratinocyte hyperproliferation and aberrant differentiation with great negative impact on patients' quality of life (QoL). This study aimed at assessing factors influencing management practice, and QoL and its associated factors among ambulatory psoriatic patients visiting All Africa Leprosy, Tuberculosis and Rehabilitation Training (ALERT) Center in Addis Ababa, Ethiopia. MATERIALS AND METHODS: A cross sectional study was conducted in 207 patients with psoriasis attending the dermatology clinic of ALERT Center in Addis Ababa, Ethiopia. Data were collected using structured questionnaire and patients' chart review. Dermatology Life Quality Index (DLQI) was used to measure patients' QoL. Patients' characteristics were summarized using descriptive statistics and predictors of QoL were identified by binary logistic regression. RESULTS: Among 207 study participants, 122 (58.9%) were females. The mean age of the study population was 37.92 (SD = 14.86) years (ranging from 16 to 68 years). The mean age at which diagnosis of psoriasis made was 32 (SD = 13.7) years ranging from 10 to 62 years. The duration of the disease in 112 (54.1%) patients were more than or equal to 5 years. Majority of study participants 145 (70.0%) had plaque psoriasis followed by sebopsoriasis, 24 (11.6%). The majority of plaque psoriasis (80%) cases were managed by topical corticosteroids with or without salicylic acid or coal tar and only 21 (14.5%) treated by methotrexate alone. The mean DLQI was 6.25 corresponding to a moderate effect. Symptoms and feelings were the most affected domains of QoL. Factors associated with poor QoL were female [AOR = 0.17 (95%CI: 0.06, 0.48)], low, above average and high family income ([AOR = 0.12 (95% CI: 0.02, 0.56)], [AOR = 0.06 (95% CI:0.01, 0.32)], and [AOR = 0.03 (95% CI: 0.01, 0.22)]), respectively, and primary education level [AOR = 0.14 (95% CI: 0.03, 0.64)] while being on systemic therapy [AOR = 4.26 (CI: 1.18, 15.35)] was predictor of better QoL. Poor QoL was predominant in females [AOR = 0.17 (95%CI: 0.06, 0.48)], low income [AOR = 0.12 (95% CI: 0.02, 0.56] patients, and patients with primary education level [AOR = 0.14 (95% CI: 0.03, 0.64)]. Patients on systemic therapy [AOR = 4.26 (CI: 1.18, 15.35)] had good QoL. CONCLUSION: Our study identified that topical corticosteroids were the mainstay of psoriasis treatment in the dermatology clinic of ALERT Center in Addis Ababa, Ethiopia. Moderate effect QoL was achieved by study participants based on DLQL score.

Azathioprine weekly pulse versus methotrexate for the treatment of chronic plaque psoriasis: A randomized controlled trial.

BACKGROUND: Methotrexate is the most commonly used drug in the treatment of psoriasis with good efficacy and safety. Recently, weekly azathioprine pulse has been shown to be effective in this disease. AIM: The aim of this study is to compare the effectiveness and safety of weekly pulse doses of azathioprine and methotrexate for the treatment of chronic plaque psoriasis. METHODS: In this randomized controlled trial, 80 patients with chronic plaque psoriasis were recruited. After detailed clinical and laboratory evaluation, patients were randomized to 2 groups to receive either weekly 300 mg azathioprine (n = 40) or 15 mg methotrexate every week (n = 40) for 20 weeks, following which the response to treatment and adverse effects were assessed. The patients were then followed up every 4 weeks for 3 months to determine any relapse. RESULTS: Overall, 48 (60%) patients achieved PASI 75, while 36 (45%) and 59 (73.8%) patients achieved PASI 100 and 50, respectively. On intention to treat analysis, PASI ≥ 75 was achieved in 47.5% (19/40) patients in group 1 compared to 85% (34/40) patients in group 2 (p < 0.001). However, on per protocol analysis, PASI ≥ 75 was achieved in 86% (19/22) patients in group 1 and 92% (34/37) patients in group 2 (p = 0.497). Minor clinical and biochemical adverse effects were noted in both the groups, which were comparable. One (7.7%) patient in group 1 and 4 (17.4%) in group 2 relapsed during follow-up. LIMITATIONS: Limitations of study include small sample size and short follow-up. CONCLUSION: Weekly azathioprine pulse appears to be beneficial in the management of chronic plaque psoriasis. However, it is less effective than weekly methotrexate. It can thus be of use as a therapeutic option in patients with contraindication to methotrexate or other similar agents in this disease.

Safety and efficacy of methotrexate (0.3 mg/kg/week) versus a combination of methotrexate (0.15 mg/kg/week) with cyclosporine (2.5 mg/kg/day) in chronic plaque psoriasis: A randomised non-blinded controlled trial.

BACKGROUND: Psoriasis is a chronic, inflammatory, relapsing and remitting disease with no cure till date. There is a paucity of trials using a combination of methotrexate (MTX) and cyclosporine (CsA) in chronic plaque psoriasis, due to fear of added toxicity, although they are time tested treatment options for monotherapy. AIMS: The study aimed to compare the efficacy and adverse effect profile of the standard recommended dose of MTX (i.e. 0.3mg/kg/week) versus a combination of reduced doses of MTX and CsA (i.e. MTX 0.15 mg/kg/week with CsA 2.5mg/kg/day) in patients with chronic plaque psoriasis. METHODS: Study design was a non-blinded randomised controlled trial. Patients of chronic plaque psoriasis with PASI more than 10 were randomised in 1: 1 allocation to receive either 0.3 mg/kg/week of intramuscular MTX injection or a combination of 0.15 mg/kg/week of intramuscular MTX injection and 2.5 mg/kg/day of CsA rounded off to the nearest 25 mg. Patients were followed up at every 2 weeks for 12 weeks. The doses were kept fixed throughout the study period. RESULTS: A total of 66 patients received MTX monotherapy, whereas 67 patients received the combination. At baseline, both groups were comparable in their BSA (P = 0.105, Student t-test) and PASI (P = 0.277, Student t-test), which reduced significantly at 12 weeks in both groups (P < 0.001, paired t-test). The achievement of PASI-75 (P = 0.005), PASI-90 (P < 0.001) and PASI-100 (P = 0.001) was more in the combination group (Chi square test). Intention to treat analysis using Chi square test also showed better outcomes for PASI-75 (P = 0.027), PASI-90 (P < 0.001) and PASI-100 (P = 0.001) in the combination group. Combination group also had earlier onset of action (P = 0.001, Chi square test). There was no significant difference between the groups in terms of laboratory and clinical adverse events. LIMITATIONS: Non-blinded, no comparison with CsA monotherapy arm, no follow up beyond 12 weeks. CONCLUSION: The combination of reduced doses of MTX and CsA is more efficacious with earlier onset of action and similar adverse effects as with MTX monotherapy.