Andrew Blauvelt, Angela Williams, Kimberly M. Deininger
et al.
Abstract Introduction Atopic dermatitis (AD) is a chronic, inflammatory skin disease with a hallmark symptom of pruritus. We developed Worst Pruritus Numeric Rating Scale (NRS)—a single-item, patient-reported outcome measure—to assess itch severity in clinical trial populations of adults with moderate-to-severe AD. The objective of this study was to evaluate the psychometric properties of Worst Pruritus NRS and determine its appropriateness for use in clinical trials assessing the efficacy of treatments among adults with moderate-to-severe AD. Methods We used data from a subset of 267 participants in a phase 2 clinical trial of rocatinlimab (NCT03703102; N = 274) to confirm reliability, validity, and ability to detect change in Worst Pruritus NRS. We estimated and confirmed a meaningful within-patient change (MWPC) threshold using anchor- and distribution-based methods. Results All intraclass correlation coefficients (ICCs) were ≥ 0.86, providing robust evidence for test–retest reliability. Evidence supported construct validity, including known-groups validity (all P < 0.0001). There were moderate, positive correlations between scores on Worst Pruritus NRS and supportive measures at week 16, including Dermatology Life Quality Index (DLQI) question 1 (itch item) (r = 0.78), DLQI (r = 0.66), Eczema Area and Severity Index (EASI) (r = 0.50), Investigator’s Global Assessment (IGA) (r = 0.46), Body Surface Area of Involvement (BSA) (r = 0.40), and SCORing Atopic Dermatitis (SCORAD) itch item (r = 0.97). On average, patients with better DLQI question 1 scores, EASI, and IGA classifications achieved better (i.e., lower) scores on Worst Pruritus NRS at week 16 (P < 0.0001). Ability to detect change was supported with moderate-to-strong and positive correlations between Worst Pruritus NRS change scores and changes in supporting measures. MWPC estimates confirmed the commonly applied 4-point threshold value and a range of 3 to 4 points as indicative of meaningful within-patient change. Conclusions Worst Pruritus NRS is a reliable and valid patient-reported outcome measure to assess itch severity in clinical trial settings among adults with moderate-to-severe AD.
Alberto Di Caro, Maria Elisabetta Greco, Francesca Paola Sasso
et al.
Dear Editor,
Vitiligo is an acquired, chronic depigmenting disorder characterized by the progressive loss of epidermal melanocytes. Leukotrichia, present in approximately 10% to 60% of cases, results from the loss of melanocytes within the hair follicles. Clinically, it manifests as well-demarcated, nonscaling depigmented macules that may coalesce and expand over time. [...]
Recent studies have shown that local injection of secukinumab can achieve positive therapeutic effects when applied in the treatment of nail psoriasis. At present, there have been no other studies on the use of biological agents in the treatment of pediatric nail psoriasis. Three children were included in the study to evaluate the efficacy and safety of periungual injection and long-term injection of secukinumab in the treatment of nail psoriasis in children. It was found that local injection did not achieve a remarkable therapeutic effect. The nail lesions were improved continuously by subcutaneous injection once a month.
The tricarboxylic acid (TCA) cycle is capable of providing sufficient energy for the physiological activities under aerobic conditions. Although tumor metabolic reprogramming places aerobic glycolysis in a dominant position, the TCA cycle remains indispensable for tumor cells as a hub for the metabolic linkage and interconversion of glucose, lipids, and certain amino acids. TCA intermediates such as citrate, α-ketoglutarate, succinate, and fumarate are altered in tumors, and they regulate the tumor metabolism, signal transduction, and immune environment to affect tumorigenesis and tumor progression. This article provides a comprehensive review of the modifications occurring in tumor cells in relation to the intermediates of the TCA cycle, which affects tumor pathogenesis and current therapeutic strategy for therapy through targeting TCA cycle in cancer cells.
BackgroundOrally administered small-molecule drugs including tyrosine kinase 2 (TYK2) inhibitors and phosphodiesterase 4 (PDE4) inhibitors are new candidates for systemic therapy in plaque psoriasis. However, no previous articles evaluated the benefit and risk profile of TYK2 and PDE4 inhibitors in psoriasis.ObjectivesThe objective of this study was to compare the efficacy and safety of oral small-molecule drugs, including TYK2 and PDE4 inhibitors, in treating moderate-to-severe plaque psoriasis.MethodsPubMed, Embase, and Cochrane library were searched for eligible randomized clinical trials (RCTs). Response rates for a 75% reduction from baseline in Psoriasis Area and Severity Index (PASI-75) and Physician’s Global Assessment score of 0 or 1 (PGA 0/1) were used for efficacy assessment. Safety was evaluated with the incidence of adverse events (AEs). A Bayesian multiple treatment network meta-analysis (NMA) was performed.ResultsIn total, 13 RCTs (five for TYK2 inhibitors and eight for PDE4 inhibitors) involving 5274 patients were included. The study found that deucravacitinib at any dose (except for 3 mg QOD), ropsacitinib (200 and 400 mg QD), and apremilast (20 and 30 mg BID) had higher PASI and PGA response rates than placebo. In addition, deucravacitinib (3 mg BID, 6 mg QD, 6 mg BID, and 12 mg QD), and ropsacitinib (400 mg QD) showed superior efficacy than apremilast (30 mg BID). In terms of safety, deucravacitinib or ropsacitinib at any dose did not lead to a higher incidence of AEs than apremilast (30 mg BID). The ranking analysis of efficacy revealed that deucravacitinib 12 mg QD and deucravacitinib 3 mg BID had the highest chance of being the most effective oral treatment, followed by deucravacitinib 6 mg BID and ropsacitinib 400 mg QD.ConclusionsOral TYK2 inhibitors demonstrated satisfactory performance in treating psoriasis, surpassing apremilast at certain doses. More large-scale, long-term studies focusing on novel TYK2 inhibitors are needed.Systematic review registrationPROSPERO (ID: CRD42022384859), available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022384859, identifier CRD42022384859.
Georgi Tchernev, Simona Kordeva, Heily Kirilova
et al.
Post-vaccinal and parainfectious activation of the immunity with subsequent development of a certain immunological/skin-immunological disease isn’t rare in the clinical practice. This concept is mentioned in relation to molecular/antigenic mimicry. To this day, the pathogenesis of sarcoidosis and sarcoid-type reactions remains a mystery. Moreover, they can be a warning sign of changes in tissue homeostasis, whether it is infectious, non-infectious-immunological, tumor-related, etc. We present a rare form of erythrodermic sarcoidosis with massive systemic involvement (pericarditis, supraventricular tachycardia, hepatitis, iritis/iridocyclitis, pulmonary fibrosis/bihilar lymphadenopathy, and arthritis) developed after receiving the ChadOx1-S vaccine for Covid-19. Systemic immunosuppressive therapy with Methylprednisolone was introduced according to a scheme (in a reduction mode with an initial dose of 40 mg/day intravenously) in combination with: topical Pimecrolimus 1% cream twice a day. Rapid improvement of the symptoms was observed within the first two days of treatment. According to the references in the scientific literature, the presented patient turns out to be the first case of erythrodermic sarcoidosis (with systemic involvement), described as a side effect after vaccination and/or administration of a certain medicinal form.
Michał Abendrot, Lilianna Chęcińska, Joachim Kusz
et al.
The multifunctional profile of Zn<sup>2+ </sup>has influenced its great popularity in various pharmaceutical, food, and cosmetic products. Despite the use of different inorganic and organic zinc derivatives, the search for new zinc-containing compounds with a safer skin profile still remains an open issue. The present paper describes the synthesis, structural characterization, and antibacterial activity of zinc(II) complexes with proteinogenic amino acids as potential candidates for dermatological treatments. The obtained complexes are of the general formula [Zn(AA)<sub>2</sub>], where AA represents an amino acid (L-Glu, Gly, L-His, L-Pro, L-Met, and L-Trp). Their synthesis was designed in such a way that the final bis(aminoacidate) zinc(II) complexes did not contain any counter-ions such as Cl<sup>−</sup>, NO<sub>3</sub><sup>−</sup>, or SO<sub>4</sub><sup>2−</sup> that can cause some skin irritations. The chemical structure and composition of the compounds were identified by <sup>1</sup>H NMR spectroscopy and elemental analysis, and four were also characterized by single-crystal X-ray diffraction. The Hirshfeld surface analysis for the Zn<sup>2+</sup> metallic center helped to determine its coordination number and geometry for each complex. Finally, the antibacterial properties of the complexes were determined with respect to three Gram-positive strains, viz. <i>Staphylococcus aureus</i> ATCC 6538, <i>Staphylococcus epidermidis</i> ATCC 12228, and <i>Streptococcus pyogenes</i> ATCC 19615, and two Gram-negative bacteria, viz. <i>Escherichia coli </i>ATCC 25992 and<i> Pseudomonas aeruginosa </i>ATCC 27853, and were compared with the activity of zinc 2-pirrolidone 5-carboxylate (ZnPCA), commonly applied in dermatology. It was found that the Zn(II) complexes with methionine and glycine exhibited a higher antibacterial activity than the tested standard, and the antimicrobial properties of complex with Trp were satisfactory. The results of the antimicrobial activity examination allow us to postulate that the obtained zinc complexes might become new active substances for use in dermatological products.
The pathogenesis of rosacea remains unclear but has been reported to correlate with skin barrier function. The objective of this study was to elucidate the skincare habits of Chinese adolescents and determine the relationship between skincare habits and rosacea. A university-based cross-sectional investigation included 310 rosacea cases and 3,129 healthy controls who underwent health examinations and completed a questionnaire about daily skincare habits. Fitzpatrick skin phototype IV is a protective factor against rosacea (adjusted adds ratio (aOR) 0.40; 95% confidence interval (CI) 0.22–0.72). Long bath duration (> 11 min, aOR 2.60; 95% CI 1.01–6.72) and frequent use of facial cleansers (> 2 times/day, aOR 1.70; 95% CI 1.17–2.36) were positively associated with rosacea, but bath frequency (p = 0.22), water temperature (p = 0.53), and sun protection (p = 0.65) were not associated with rosacea. Inappropriate skincare habits, including extended bath durations and frequent use of facial cleansers, significantly increase the risk of rosacea in Chinese adolescents.
Aikaterini Patsatsi, MD, PhD, Cybill Dianne C. Uy, MD, Dedee F. Murrell, MD, PhD
Background: Milia are superficial keratinous cysts seen as pearly white, dome-shaped lesions 1–2 mm in diameter. Milia are associated with diseases that cause subepidermal blistering, such as hereditary forms of epidermolysis bullosa, epidermolysis bullosa acquisita, bullous pemphigoid, bullous lichen planus, and porphyria cutanea tarda. Multiple eruptive milia are rare and more extensive in number than primary milia. Objective: The aim of this study was to search the literature for cases of blistering diseases with multiple milia formation, especially in areas of the skin where there was no evidence of blistering or trauma, and review the interpretations of their pathogenesis. Methods: We performed a literature search with the terms multiple milia and bullous diseases, pemphigoid, and pemphigus. Results: Very few studies have investigated the origin of milia. Primary milia are thought to originate from the sebaceous collar of vellus hairs, and secondary milia are believed to derive from eccrine ducts more commonly than from overlying epidermis, hair follicles, or sebaceous ducts. Milia secondary to blisters or trauma are speculated to be produced through the regeneration process of disrupted sweat glands or hair follicles. Immunological predisposition, aberrant interaction between the hemidesmosomes, and the extracellular matrix components beneath the hemidesmosomes have been described with regard to the formation of numerous milia during recovery. Multiple milia could be a primary manifestation of dystrophic epidermolysis bullosa in skin areas without evidence of blistering. Conclusion: The exact etiology of multiple milia remains unknown. Immunological predisposition and improper interaction between hemidesmosomes and extracellular matrix components are speculated to play a role in the formation of milia during recovery of bullous lesions in blistering diseases. Still, further studies on the triggering mechanisms of keratinocyte dysfunction in cases of multiple milia formation without evidence of prior blistering are needed.
Maria Rosaria Sapienza, Francesco Abate, Federica Melle
et al.
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy for which there is still no effective therapy. In order to identify genetic alterations useful for a new treatment design, we used whole-exome sequencing to analyze 14 BPDCN patients and the patient-derived CAL-1 cell line. The functional enrichment analysis of mutational data reported the epigenetic regulatory program to be the most significantly undermined (P
Loose anagen hair syndrome is an uncommon hair disorder, particularly in non-Caucasian children. We report the case of a 13-year-old Thai boy who presented with a single patch of hair thinning on the frontal scalp with excessive shedding, and the hairs did not grow long. Microscopic examination showed naked anagen bulbs with ruffling of the cuticle, which is compatible with loose anagen hair syndrome. To our knowledge, there is no reported case in Southeast Asian children.
Aryan Maleki, Noorulain Khalid Faculty of Medicine, Barts and The London School of Medicine and Dentistry, London, UKWe read with great interest the paper by Zari and Alrahmani1 investigating the relationship between stress and acne among female medical students. These findings are relevant as around 20% of young people are affected by moderate-to-severe acne, and indeed acne severity is associated with increased risks of anxiety, depression and suicidal ideation.2 The authors identified that “stress severity strongly correlated with an increase in acne severity,” and suggested that stress likely has an important role in the pathogenesis of acne.1 However, the paper could have been taken further to better establish the true extent of this relationship, and ultimately whether certain patients will benefit from clinical interventions based on their perceived stress scale. View the original paper by Zari and Alrahmani.
Acute generalised exanthematous pustulosis (AGEP) is a severe cutaneous adverse reaction and is attributed to drugs in more than 90% of cases. It is a rare disease, with an estimated incidence of 1–5 patients per million per year. The clinical manifestations characterised by the rapid development of sterile pustular lesions, fever and leucocytosis. Number of drugs has been reported to be associated with AGEP, most common being the antibiotics. Histopathologically there is intraepidermal pustules and papillary dermal oedema with neutrophilic and eosinophilic infiltrations. Systemic involvement can be present in more severe cases. Early diagnosis with withdrawal of the causative drug is the most important step in the management. Treatment includes supportive care, prevention of antibiotics and use of a potent topical steroid.
Background: Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease. Objective: We report the profile and outcome of 100 cases of BP seen at our center. Patients and Methods: This was a retrospective study of patients with BP seen at Changi General Hospital, Singapore from 2004 to 2012. Results: There were 57 female and 43 male patients. Other than the usual comorbidities such as diabetes mellitus and neurological diseases, there were a high incidence of osteoporosis (29%), hypothyroidism (6%), malignancy (6%), and hepatitis B carrier (3%). Peripheral blood eosinophilia is seen in almost half of the patients. The study results showed the higher sensitivity of direct immunofluorescence (93.5%) as compared to indirect immunofluorescence (89.1%). Topical and systemic corticosteroids were the standard treatment (96%). The duration to remission ranged from 2 weeks to 34 months, with a mean age of 7 months. Doxycycline and nicotinamide were effective for localized BP. The mortality rate was 35%. Conclusion: In Singapore, BP is associated with significant morbidity and mortality. High mortality of BP is related to the advanced age of the patients, associated medical conditions and complications from the treatment.
S. V. Koshkin, T. V. Chermnyh, G. A. Zajceva
et al.
Sixty patients with different clinical symptoms of secondary syphilis (ulcer chancres, pustular syphilis, hypertrophic papules, widespread leukoderma and alopecia) were examined in order to study the distribution pattern of histocompatibility antigens of the first class in patients with secondary syphilis of the skin and mucous membranes. As a result of the study, the presence of an associative relationship between the distribution pattern of histocompatibility antigens of the first class and various clinical manifestations in patients with secondary syphilis was established.
Santwana Mahar, Khushbu Mahajan, Swati Agarwal
et al.
Introduction: Irrational use of Topical Corticosteroid (TC) is quite
common in India due to unrestricted availability and use of TC
not only by general public but also by physicians and chemists
due to quick relief of symptoms in different dermatological
conditions.
Aim: The present study was conducted to evaluate and analyse
the prevalence of misuse of TC and the causes behind misuse
of TC among patients in a dermatology outpatient department
in New Delhi.
Materials and Methods: This was a cross-sectional
observational questionnaire based study conducted over
a period of 5 months (1st June 2015 to 30th November 2015).
Patients were questioned and assessed for misuse of TCs in
terms of indication, dose, frequency, duration and source of
recommendation of TC.
Results: During the study period, 256 (11.77%) patients
presented with inappropriate use of TC out of 2174 patients
attending OPD of dermatology unit of a government hospital.
A total of 250 patients presented with adverse effects of TC
resulting from the misuse of these drugs. There were 60%female
patients and 20-29 years (38%) was the most common age
group affected. We found fungal infection (38%) was the most
common reason of abuse followed by facial acne (29%) and
lightening of skin colour (8.4%). Friends and family (33.2%)
were found to be the most influencing factors for misuse of
TC. Betamethasone (72.8%) was the most commonly used TC
preparation and tinea incognito (26.4%) followed by facial acne
(25.6%) were the most common side effect experienced.
Conclusion: Outcome of the misuse of TC could be dreadful and
the cause for same lies at all levels- patients, family, physicians
and the regulatory authorities.