Stress and skin diseases can be negatively associated with each other, as the stigma due to skin diseases could worsen the psychological burden, forming a harmful cycle of psychological stress attributed to skin diseases.¹

Figure 1: Harmful cycle between psychological stress and skin disease.

Adapted from: Zhang H, et al, Brain Behav Immun. 2024

Stress mechanism

Stress can be classified as follows:¹

Table 1: Classification of stress

The circuit of body response to stress is explained below:¹

Data reveals psychological stress could augment the release of cortisol, thereby disrupting the skin barrier function, damaging keratinocyte differentiation, raising the risk of skin infections, and significantly worsening atopic dermatitis (AD) and chronic urticaria (CU).¹

Stress and AD

Keratinocytes release proinflammatory cytokines that amplify skin inflammation in AD. Cortisol suppresses neutrophil responses that compromise antimicrobial defence against secondary infections in AD lesions.¹

Stress and CU

CU could arise due to interactions between the immune and nervous systems. Stress induces the release of substance P and calcitonin gene-related peptide causing pruritis. Proinflammatory cytokines trigger the association of psychological factors and mood changes with urticaria.¹

Stress and psoriasis

Psychological stress can induce the onset and exacerbation of psoriasis since stress can alter the NEI network, leading to increased levels of catecholamines, glucocorticoids (GCs), and opioids.¹

Stress and skin tumours

Under stress, the HPA axis and nerve system are triggered and release epinephrine, which results in a tumour response.¹

Stress and hair disorders

Stress is involved in the process of grey hair and hair loss via the HPA axis and the sympathetic nervous system. Activation of sympathetic nerves, mediating melanocyte stem cell proliferation, and oxidative damage to melanocytes cause grey hair. Regulation of metabolic pathways and mitochondrial functions impact hair colour.

Chronic stress causes increased corticosterone levels, affects the expression of growth-arrest specific 6 protein in dermal mastoid cells, and inhibits hair follicle stem cell activity.¹

• The impact of stress on the immune system, involving the HPA axis, sympathetic nervous system, and neuropeptides, has been discussed about skin diseases.¹
• Recent studies have extensively examined the influence of stress on gut microbiota, particularly in patients with skin conditions.¹
• Establishing connections within the stress-gut microbiota-skin axis can advance our comprehension of the intricate brain-gut–skin relationship, offering insights for future research directions. Presently, investigations have unveiled central inflammation affecting the periphery through the blood-brain barrier.¹

Key takeaway

Stress disrupts skin immunity, exacerbating diseases like psoriasis and acne by affecting immune balance and barrier function.¹

Introduction

Skin cancer is the second-most misdiagnosed cancer, after breast cancer, which profoundly affects the patient’s likelihood of survival. This demands early, decisive, precise, quantitative diagnostic tools for skin cancer.¹

Overview of biosensors

Biosensors are analytical devices for skin cancer diagnostics consisting of three main components.¹

Bioreceptors are immobilised biological systems that estimate the specificity of the biosensors and are classified into four major categories.¹

Based on the transduction techniques, the four categories of biosensors utilise components (mass, electrochemical, magnetic, and optical) with effective applications in detecting skin cancer. To enhance detection, secondary elements such as fluorophores are sometimes used. Lately, nanomaterials and nanoparticles have been utilised to further improve biosensing properties such as reproducibility, response time, and sensitivity for skin cancer diagnosis.¹

Biomarkers associated with skin cancer

A summary of melanoma skin cancer biomarkers along with their clinically relevant characteristics is presented below.¹

Adapted from: Chatzilakou E, et al. Biosens Bioelectron. 2024.

^{ISF: Interstitial fluid; LDH: Lactate dehydrogenase; MART-1: Melanoma antigen recognised by T-cells–1; MC1R: Melanocortin 1 receptor; MIA: Melanoma inhibitory activity; MITF: Microphthalmia-associated transcription factor; NA: Not available; PMEL: Premelanosome protein; S100B: S100 calcium-binding protein B; VEGF: Vascular endothelial growth factor}

Optimal biosensors for skin cancer

The three prime sensors for melanoma detection biosensing technologies include optical biosensors, electrochemical sensors, and piezoelectric sensors. An overview of melanoma detection biosensing technologies for each of these sensors is provided.¹

Optical bisensors¹

Adapted from: Chatzilakou E, et al. Biosens Bioelectron. 2024.

BRAF: B-Raf; CDK: Cyclin-dependent kinases; DNA: Deoxyribonucleic acid; EGFR: Estimated glomerular filtration rate; IL6R: Interleukin 6 receptor; NA: Not available; S100B: S100 calcium-binding protein B; VEGF: Vascular endothelial growth factor.

Electrochemical biosensors¹

Bio-FET: Biologically coupled gate field-effect transistor; CTC: Circulating tumour cells; S100B: S100 calcium-binding protein B.

BRAF: B-Raf.

Is biosensor design safe to implement for skin cancer?

AI: Artificial intelligence

• This review study compiled some breakthrough studies implying that biosensing technologies could play a potential role in public health benefits.¹
• Biosensing methods may significantly improve early detection precision economically and effectively.¹
• However, there is a need for further research to understand the clinical relevance of biosensors in melanoma diagnosis and treatment.¹

Key takeaways

• Globally, skin cancer is a critical health concern. Recent evidence imply that biosensors would be a promising candidate for skin cancer diagnosis due to their rapid detection accuracy and reliability.¹

Extracellular vesicles (EVs) are lipid-enveloped nanoparticles formed naturally by cells that act in the intercellular transfer of biological material, such as proteins, ribonucleic acids, and metabolites.

Pre-clinical data suggest the use of EVs in regenerative processes such as:¹

Advantages of EVs over stem cell therapies

EVs tend to show the following benefits over stem cell therapies:¹

Applications of EVs in regenerative dermatology

Multiple features of EVs have made them promising candidates for various therapeutic approaches, including recent applications in regenerative dermatology. Some of the positive outcomes of mesenchymal (MSC) EVs are attributed to their effects on fibroblasts and their capacity to modulate the local inflammatory environment.¹

The therapeutic efficacy of MSC-EVs seems to be inversely related to the donor’s developmental maturity from which they are obtained. On increasing passage, a reduction was observed in the pro-vascularising activity of MSC-EVs. While developing EVs therapeutically, basic parameters must be carefully considered. These parameters are related to the cell source, the method of culture (e.g., 2-dimensional vs. 3-dimensional), frequency and timing of EV collection, the method of EV isolation applied (e.g., ultracentrifugation, size-exclusion chromatography, and tangential flow filtration), and the addition of exogenous priming agents to cell cultures (e.g., hypoxia or stimulation with inflammatory cytokines). However, if these theories are autologously developed, the consequence of donor maturity on MSC-EV potency could prove to be a limiting factor.¹

Figure 1: Production criteria overview and their impact on the final preparation.

Post-production parameters required for standardisation
Transparency and standardisation must be considered w.r.t reporting of bioavailability, dosage, and purity for EV preparations as shown in Figure 2.¹

Moreover, as the use of EVs is limited to topical administration in future, one should consider their application using full-thickness human skin models. Combining EVs with conventional skin-puncturing treatments (FDA unapproved for subdermal injection adminstration), such as micro-needling (FDA approval of topical with adjunct administration is unclear), could be a chance for the enhanced delivery of EVs.¹
Data suggest that compared to micro-needling alone, the addition of EVs could augment collagen density and organisation.¹

However, currently, injectable EV therapy has not been approved by the Food and Drug Administration, with the application of EVs in general dermatological practice confined solely to topical administration.
To date, no specific regulatory guidelines have been published concerning EV therapies, and EVs are expected to be regulated as drugs and biological products under section 351 of the Public Health Service Act and the Federal Food Drug & Cosmetics Act because more evidence is required for establishing the safety, efficacy, purity, and potency properties.¹

Conclusion:

• Although EV formulations demonstrated positive effects on the epidermal barrier by decreasing the rates of inflammatory cytokines and inducing de novo production of ceramides after injection in an AD model, these formulations reduced dupilumab facial redness, and were toxicologically safe when tested in rats. But the effects of lyophilisation on the long-term integrity and potency of EV formulations are currently in the nascent stages only, with storage buffer and pH having a significant impact.¹
• An observation in animal models implies that EVs derived from a younger organism can lead to the rejuvenation of older cells. Though the availability of EV formulations is getting frequent in private aesthetics clinics, at present, no EV therapy has been approved for public usage by the Food and Drug Administration or European Medicines Agencies (EMA). Hence, private aesthetic practitioners must exercise caution while combining EV therapies with adjunct treatments in their clinics.¹
• However, chances are that EVs will be regulated as drugs and biological products under section 351 of the Public Health Service (PHS) Act and the Federal Food Drug & Cosmetics & (FD&C) Act. This implies that more studies are required to demonstrate the safety, efficacy, purity, and potency of a product for a given application.¹

Key takeaways

• EVs are extremely complex and heterogenous biological products that are considered beneficial; however, more studies are required to establish its clinical and long-term safety data.¹
• This article showcased the therapeutic and commercial landscape of EVs in regenerative dermatology and cosmetic science.¹

Typically, atopic dermatitis (AD) is a skin disease that is defined as a common, chronic, inflammatory dermatosis characterised by frequent itchiness. This review examines the possible reasons that AD could result in multiple diseases, such as autoimmune, cardiovascular, neurological, and psychiatric diseases.¹

Co-occurring conditions with AD
There seems to be a bidirectional association between AD and comorbidities that are depicted in Figure 1.¹

Figure 1: Diagrammatic representation of atopic disease and its probable comorbidities.

Th: T helper cells.

Probable factors that increase comorbidity prevalence in AD patients

A couple of behavioural changes are reported in patients with AD, such as:¹

• Regular physical activity helps in the primary and secondary prevention of several chronic diseases such as obesity, depression, and cardiovascular diseases. AD in adults is often associated with reduced moderately to vigorous and overall physical activity in the USA.¹
• In certain cases, patients with eczematous skin lesions on their palms and soles might find it difficult to participate in a variety of activities, furthermore increased skin temperature and perspiration are known to flare up triggers.¹
• Sleep interruption and depression, which could be present in AD patients, may worsen the ability to continue regular exercise schedule.¹
• Sleeplessness and social shame due to scarring skin lesions may influence the origin of depression and anxiety among AD patients.¹
• A positive correlation exists between AD and food allergy; however, obesity could be due to prenatal and earlylife antibiotic exposure.¹
• AD is also associated with an increased incidence of eating disorders, with bulimia nervosa and binge eating disorder being the most dominant. Evidence suggests that binge eating disorder is related to a high incidence of obesity.¹
• Incorrect administration of systemic treatment for AD could be a triggering factor. For example, glucocorticosteroids could have side effects such as weight gain, sleep disturbance, mood changes, and hyperglycaemia, or cyclosporine A could have side effects such as renal impairment and high blood pressure.¹
• Regular AD patient interaction with physicians, would facilitate the recognition of diseases that are usually difficult to detect.¹

Cardiovascular diseases and AD connection
When the critical T helper cells are activated in AD, there is a rise in cardiovascular biomarkers in the blood serum, including T helper (Th)1, interferon-gamma (INF-γ), tumour necrosis factor-alpha (TNF-α), and Th17 (C-C motif chemokine ligand 20 (CCL20)) as shown in Figure 2.

Figure 2: Plausible interrelation between atopic disease and cardiovascular diseases.

CXCL: C-X-C motif ligand; CCL: C-C motif chemokine ligand; INF-γ: Interferon gamma; Il: Interleukin; PPI3/elafin: Peptidase inhibitor 3/elafin; S100A12: Calgranulin C, S100A8/A9 (=MRP8/14): Myeloid-related protein 8/14; TNF-β: Tumour necrosis factor-beta.

Older AD patients tend to show more levels of cardiovascular indications as there exists a positive association between cardiovascular indicators and age.¹

However, data on paediatric AD revealed increased levels of multiple cardiovascular markers, such as E-selectin, an endothelial cell adhesion molecule, and several matrix metalloproteinases (MMPs).¹ Moreover, there is no clear evidence to indicate that patients with AD require more extensive cardiovascular monitoring or therapy than is suggested for the general population.¹

Neuropsychiatric diseases and AD connection
The onset and maintenance of the atopic itch are interdependent with the neurological system, cutaneous immune response, and keratinocytes.¹

Epilepsy and AD

• Neuroinflammation–involved in the pathogenesis of epilepsy.¹
• Microglia and astrocytes–main factors involved in neuroinflammation.¹
• Microglial activation–response to pro-inflammatory mediators released from immune cells, containing mast cells.¹
• In the neuroinflammation process, excess levels of inflammatory mediators might influence neurogenesis, neurodegeneration, and permeability of the blood–brain barrier, which could result in an imbalance in neurotransmission, leading to neurological disorders, including epileptic seizures.¹
• The association between AD and neuropsychological comorbidities could be due to genetics: for instance, deletion of chromosome 22q13.2 is a common manifestation among AD, epilepsy, mental retardation, and autism spectrum disorder (ASD).¹

Autism and AD

• A correlation exists between ASD and AD, suggesting that individuals with ASD have a higher risk of developing AD.¹
• Furthermore, comorbid AD is interlinked with an increase in the severity of ASD symptoms.¹
• Neuroinflammation–one of the environmental factors in the pathogenesis of ASD.¹
• Abnormal high levels of IL-1β, IL-6, IL-8, and IL-17 are observed in patients with ASD of all ages.¹
• According to studies on a mouse model, exposure to lipopolysaccharide, IL-17, and polyinosine polycytidylic acid during pregnancy resulted in ASD behaviour in the mice offspring.¹

• Neural cellular adhesion molecule (NCAM) 1 regulates nuclear factor kappa B (NF-κB) transcription in neurons, which alters pro-inflammatory signalling.¹
• Furthermore, according to a mouse model study, as both the epidermis and neural tissues originate from the embryonic neuroectoderm, the presence of neuro- and epidermal toxicity at the onset of AD and ASD could be due to the shared susceptibility of the brain and epidermis in the pathogenesis of both AD and ASD.¹

Attention deficit hyperactivity disorder and AD

• Data shows that attention deficit hyperactivity disorder (ADHD) has a higher prevalence in children with AD.¹
• More the number of atopic diseases in a patient, the more severe their ADHD.¹
• A possibility for a higher risk of atopic disease development among siblings of children with ADHD exists due to common genetic factors.¹
• Sleeping problems in infancy and early exposure to sedative H1-antihistamines that can cross the BBB were suspected as possible contributors to the development of ADHD in later childhood.¹

Depression and AD

• AD could be related to an increased risk of depression, parental depression, suicidality, and anti-depressant use.¹
• A positive but weak correlation between AD and depression in children was also found.¹
• One of the most widely recognised mechanisms to describe the association between AD and psychiatric disorders are the overactivity of the hypothalamic–pituitary–adrenal (HPA) axis and the sympathetic nervous system (SNS).¹
• Increased corticotropin-releasing hormone (CRH) and glucocorticoid receptor resistance result in the upregulation of inflammatory cytokines and the continuance of inflammation, while the activation of brain microglia by the same cytokines is a suggested mechanism of concomitant depression.¹

• Notable associations with hypercortisolaemia were found with certain subtypes of depression.¹
• Some studies demonstrated hypothalamic–pituitary–adrenal responses arising from IgE-mediated degranulation of mast cells via centrally released histamine could result in increased CRH and cortisol levels on AD patients.¹
• Data suggests the occurrence of behavioural and emotional disorders, mental retardation, memory impairment, and psychological development disorders among AD children.¹

Autoimmune diseases and AD connection

• Both AD and autoimmune diseases, such as rheumatoid arthritis, have common immunopathogenesis wherein cytokines play vital roles.¹
• Epigenetic changes along with gene variations could likely increase the susceptibilities to both rheumatoid diseases and AD.¹
• Patients with early onset alopecia areata (AA) could have a higher risk for AD.¹
• AD patients are likely to have a higher vitiligo prevalence possibly due to either genetic abnormalities or melanocyte destruction.¹
• However, the occurrence of both AD and type I diabetes (T1D) is found to be inconclusive, suggesting a mostly negative association between these diseases.¹

Conclusion:

• AD appears to be associated with multiple comorbid allergic, cardiovascular, mental health, neurologic, autoimmune, and metabolic conditions and other comorbidities depending on the risk factor exposure, genes, and immune dysregulations.¹
• Identification and management of the immunological causes behind chronic inflammation would help to prevent the development of other comorbidities.¹

Key takeaway

• AD can exist with other medical conditions such as allergies, cardiovascular disorders, mental health disorders, neurologic disorders, autoimmune disorders, metabolic conditions due to a similarity between the causal factors.¹

Melanoma is considered to be the third most common cutaneous malignancy after basal cell carcinoma and squamous cell carcinoma. The incidence of melanoma has increased rapidly compared to other cancers, especially in women of Caucasian race. Some of the treatment regimens used at present for metastatic melanoma include surgery, immunotherapy, targeted therapy, and chemotherapy.¹

Metastatic melanoma patients reported better survival upon introduction of targeted therapy with v-RAF murine sarcoma viral oncogene homolog B1/ mitogen-activated extracellular signal-regulated kinase (BRAF/MEK) inhibitors and immunotherapy. The loss of the tumour suppressant gene cyclin dependent kinase inhibitor 2A (CDKN2A) acts as a major factor for worsening melanoma. Some of the properties of CDKN2A are as follows:²

Most frequently inactivated tumour suppressor gene in melanoma2

Location: Adjacent to the CDKN2B gene on chromosome 9p21²

Role: Encodes two tumour suppressor proteins: p16 and p14. These proteins are transcribed from different exons (exon 1a for p16 and exon 1b for p14), causing distinct reading frames in the shared exons 2 and 3²

Loss of p16 in melanoma could increase proliferation, slow down ageing, and introduce invasion, ultimately leading to melanoma.² Figure 1 describes the various therapeutic approaches used for the loss of CDKN2A in melanoma.²

Figure 1: Six therapeutic strategies for targeting loss of CDKN2A especially p16 in melanoma.

ANRIL: Antisense noncoding RNA in the INK4; AURK: Aurora kinase; CDK: Cyclin-dependent kinase: CDKN2A: Cyclin dependent kinase inhibitor 2A; CHK1: Checkpoint kinase 1; E2F: Transcription factor; G1: Growth 1 phase; G2: Growth 2 phase; JAK2: Janus kinase 2; IFN: Interferons; M: Mitosis; MHC: Major histocompatibility complex; MK2: Mitogen-activated protein kinase-activated protein kinase 2; MTA: Metastatic associated proteins; MTAP: S-methyl-5'-thioadenosine phosphorylase; mTORC1: Mammalian target of rapamycin complex 1; NOX4: NADPH oxidase 4; PD-1: Programmed cell death protein; PDL-1: programmed cell death ligand; PRC: Protein regulator of cytokinesis; PRMT5: Protein arginine methyltransferases 5; Rb: Retinoblastoma; ROS: Reactive oxygen species; RPIA: Ribose 5-phosphate isomerase A; RRM2: Ribonucleotide reductase regulatory subunitM2; TCR: T-cell receptor; TYMS: Thymidylate Synthetase; S: Synthesis; SASP: SASP: Senescence-associated secretory phenotype; WEE1: Protein kinase;

Target metabolic rewiring

• As in Fig 1c. p16 has a role in metabolism and consequent metabolic reprogramming; therefore, p16 loss may provide opportunities for therapy.²
• Evidence suggests that increased nucleotide metabolism could be vulnerable to p16-deficient cancers, as knockdown of p16 was associated with an increase in nucleotide metabolism.²
• Deficit of p16 is associated with increased levels of reactive oxygen species, independently of the CDK4‒ retinoblastoma protein pathway.²

Epigenetic reactivation and collateral lethality

• In Fig 1e. after targeting the alterations in cell cycle regulation and metabolism from CDKN2A loss, restoration of CDKN2A expression could help when CDKN2A is inactive because of the epigenetic mechanism.²
• Collateral lethality can occur when alternatively, CDKN2A is lost by deletion of the 9p21 locus, and co-deletion of nearby genes would result in vulnerabilities.²

Boost immune responses

CDKN2A can be a biomarker for immune checkpoint inhibitors’ sensitivity, as the loss in CDKN2A results in increased levels of neoantigens, which result in increased immune responses shown in Fig 1d.²

Conclusion

• With advancements in screening techniques applied to melanocytic cells, the innovation of therapeutic approaches directed at CDKN2A loss in melanoma would be further improvised.²
• Therapeutic targeting of CDKN2A loss can be beneficial for precision medicine in melanoma beyond targeting oncogenes.²

Key takeaways

• The third most common cutaneous malignancy is melanoma.¹
• Adopting strategies such as CDKN2A loss could be promising in melanoma treatment.²

The European guidelines (EuroGuiDerm) on atopic eczema (AE) have proposed certain recommendations on non- systemic treatment for special populations such as pregnant women, lactating women, and paediatric patients.¹

Pregnancy

AE is one of the most frequently occurring general skin diseases in pregnancy. It may be:¹

(i) worsening in women with a chronic condition or
(ii) reactivated in patients with a past AE history or
(iii) occur in women with no AE history (atopic eruption of pregnancy)

Table 1: EuroGuiDerm recommendations for pregnant women¹

E: Atopic eczema; NB: Newborn; TCI: Topical calcineurin inhibitors; TCS: Topical corticosteroid; UVB: Ultraviolet B.

Lactating women
The below table provides a list of recommendations for breastfeeding mothers.¹

Table 2: EuroGuiDerm recommendations for lactating women¹

AE: Atopic eczema; TCS: Topical corticosteroid.

Paediatric population
AE can show up quite early in life, and most of the patients show symptoms of AE before the age of 5 years.¹

Treatment includes:¹

• Bathing of AE infants without harsh soaps and detergents and using bath emollients to aid skin hydration and emollients as soap substitutes to aid barrier function. This also gives essential psychological advantages between parent and child.
• Use of wet wraps for additional skin hydration, particularly in young children.
• Use of topical corticosteroids about two to three times a week.
• Some topical calcineurin inhibitors are approved down to 3 months of age.

Occupational aspects

AE patients portray a significant risk of developing occupational contact dermatitis, as atopy worsens the effects of irritant and allergen exposure in several professions.¹

For such patients, the guidelines suggest individual pre-employment counselling on the choice of profession, including risk assessment, avoidance strategies, and protective measures.¹

Conclusion

The EuroGuiDerm guidelines recommend separate guidelines for the non-systemic treatment of AE in special patient populations which includes pregnant women, lactating mothers, paediatric population, and people with occupational hazard risk to develop AD.¹

Key takeaway

EuroGuiDerm guidelines recommend safe and personalised administration of topical treatment for the four patient categories.¹

AD seems to be affecting other organs than the skin and there seems to be an increased risk of major depression and anxiety disorders involved with AD. Another concern is that behavioural and emotional factors can have an impact on AD symptoms. Hence, the treatment of AD should also focus on the educational and psychological types of support for people with AD.¹

Hanifin and Rajka criteria are two diagnostic criteria that are being used for the diagnosis of atopic dermatitis for many years. However, the disadvantage of the diagnostic criteria is its exhaustive nature.²

Results:

• Among the criteria, 4 major and 21 minor criteria were taken into consideration.²
• The study found that pruritus was the most common major criteria reported in about 94.2% of patients.²
• The study found that majority of the patients demonstrated minority criteria, such as xerosis, Dennie Morgan fold early age of onset (Refer Table 1).²
• Additionally, the study found that peri-follicular-accentuation was lesser in Indian patients as compared to other Asian studies.²

Table 1. Minor criteria seen in the present and other Indian studies

One of the therapeutic strategies for combatting the behavioural and emotional aspects of AD includes internet-delivered cognitive behavioural therapy (ICBT). As the name suggests, ICBT is a psychological treatment provided over the internet instead of a conventional face-to–face CBT. Over ICBT, the therapist supports patients through a protected online communication platform. Participants are provided with some reading materials along with constructive exercises to do for 12 weeks. Although the reading material is the same for all the participants, they are asked to develop individual exercises based on their specific circumstances. During the 12-week period, the participants can reach out to the therapist when required.¹

Another strategy is via digital self-care, which differs from the guided approach in the following ways:¹

• Shorter duration (approximately 8 weeks)
• Participants receive detailed instructions and guidance and can select exposure exercises from a list of examples.
• A coordinator would supervise the process and could contact inactive participants.

Conclusion

• The minor criteria included xerosis, early age of onset, Dennie–Morgan fold, aggravation because of emotional/environmental factors, palmar hyper‑linearity/ichthyosis vulgaris/keratosis pilaris, pityriasis alba, and orbital darkening.²
• Therapeutic strategies such as ICBT with a therapist or via digital self-care can improve the behavioural and emotional aspects related to AD.¹

Key takeaways

• AD can have an aftereffect on the mental health of the patients.¹
• AD symptoms can have an impact due to the behavioural and emotional factors associated with mental health.¹
• Apart from the conventional strategy, there are online tools to record a patient’s mental health status such as guided CBT or self-guided CBT.¹
• Differences among the frequency of different Hanifin and Rajka minor criteria exist among different study populations.²

Atopic dermatitis is a highly complex, heterogenous, chronic inflammatory skin disease. It is characterised by a pruritic, erythematous rash with an unknown immunological mechanism. Even though many paediatric cases are temporary, atopic dermatitis is commonly the first stage of the atopic march and chronic, active disease. Up to 75% of atopic dermatitis patients claim that it is first manifested in their childhood.¹

Objectives

In a study, potential signalling nodes, that contribute to disease heterogeneity and progression as well as circulating inflammatory patterns in atopic dermatitis-affected children, were characterised and identified.¹
In another study, it was investigated whether specific skin biomarkers in stratum corneum tape strips collected at 2 months of age from infants with clinically normal skin are different in children who develop atopic dermatitis compared to children who do not develop it.²

Methods

IgE: Immunoglobulin E; NMF: Natural moisturising factor; PBMC: Peripheral blood mononuclear cell; SB: Sphingoid base; SCORAD: SCORing Atopic Dermatitis.

Results

CASP-8: Caspase-8; CD4: Clusters of differentiation 4; EASI: Eczema area and severity index; IL: Interleukin; MMP-10: Matrix remodelling proteins; NMF: Natural moisturizing factor; TARC/CCL17: Thymus and activation-regulated chemokine/ CC chemokine ligand 17; AD: Atopic Dermatitis; NMF: Natural moisturizing factor; SB: Sphingoid base; SCORAD: SCORing Atopic Dermatitis.

Figure 1: Visual representation of cytokine correlations to each other (thickness of connecting line) and to SCORAD (size of circle) across all time points of the study.¹

Adapted from: Engle SM, et al. Clin Exp Immunol. 2022.

CASP-8: Caspase-8; CCL19: Chemokine ligand 19; CD5: Clusters of differentiation 5; CXCL12: C-X-C motif chemokine 12; IL: Interleukin; Eotaxin-2: CC chemokine ligand 24; TNFRSF9: Tumour necrosis factor-receptor superfamily member 9; TRAIL: Tumour necrosis factor-related apoptosis-inducing ligand; TRANCE: Tumour necrosis factor-related activation-induced cytokine; SCORAD: SCORing Atopic Dermatitis.
Purple colour denotes correlations ≥0.35. Dark blue colour denotes correlations ≤0.35.¹

Conclusions

SB: Sphingoid base; TARC/CCL17: Thymus and activation-regulated chemokine/CC chemokine ligand 17.

Acne vulgaris is a common skin condition. Acne-causing hormones such as insulin, insulin-like growth factor 1, and androgens are influenced by diet and metabolism. It has been known for many years that increased dairy consumption and foods with high glycaemic index affect the levels of hormones associated with acne aetiology.¹

Objectives

The researchers performed a systematic assessment of high-quality evidence on the association between the dietary glycaemic index and dairy intake with acne genesis.¹

Methods

• Using the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a thorough search of the MEDLINE database was conducted.¹
• The quality of the evidence was evaluated using the Newcastle–Ottawa Quality Evaluation Scale.¹
• After being screened for inclusion and exclusion criteria, 34 articles were included in the final data and the level of evidence (LOE) assessment.¹

Results

• Most of the included studies (82.4%) were observational, while the remaining studies were interventional controlled trials.¹
• 17.9% of the observational studies exclusively assessed the association between glycaemic index/glycaemic load and acne.¹
• 35.7% exclusively commented on the association between dairy and acne and 46.4% described the association of dairy products and glycaemic index/glycaemic load with acne.¹
• All the interventional trials included in the study examined the effect of glycaemic index/glycaemic load on acne.¹
• There were no randomized controlled trials (RCT) on the link between dairy consumption and acne, conclusions were made on observational studies.¹

Conclusions

The number of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases has been increasing worldwide and numerous dermatologic manifestations associated with SARS-CoV-2 infection have been reported. Estimated rates of coronavirus disease 2019 (COVID-19) related cutaneous manifestations range from 4% to 20.4%.¹

Objectives

The study's objective was to review various skin manifestations brought on by SARS-CoV-2 infection.¹

Methods

• The researchers used specific key words to conduct searches on PubMed.¹
• In the narrative review, articles that were published between September 2014 and August 2021 were included.¹

Results

CBLL: Chilblain-like lesions; CD3: Cluster of differentiation 3; CD4: Clusters of differentiation 4; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; T cells: T lymphocyte.

Adapted from Huynh T, et al. Am J Clin Dermatol. 2022.

Images captured from Huynh T, et al. Am J Clin Dermatol. 2022.

Conclusions

CBLL: Chilblain-like lesions; COVID-19: Coronavirus disease 2019; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2.

• Actinic keratosis is a prevalent precancerous cutaneous neoplasm that develops on skin that has been exposed to the sun for an extended period.¹
• Although a few susceptibility loci, including interferon regulatory factor 4 (IRF4), tyrosinase gene (TYR), and melanocortin 1 receptor (MC1R), have been identified, there is a moderate genetic component to actinic keratosis susceptibility.¹

A genome-wide association study (GWAS) of actinic keratosis was conducted in non-Hispanic white participants of the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort (n=63,110, discovery cohort), with validation in the Mass-General Brigham (MGB) Biobank cohort (n=29,130).¹

Figure 1:Manhattan plot of GWAS meta-analysis of actinic keratosis combining results of GERA and MGB Biobank cohorts (n=92,240).¹

Adapted from Kim Y, et al. Commun Biol. 2022.

BNC2: Basonuclin 2; DEF8: Differentially expressed in FDCP 8 Homolog; FOXP: Forkhead Box P; HERC2: Homologous to the E6-AP carboxyl terminus And RLD Domain Containing E3 Ubiquitin Protein Ligase 2; HLA-DQA1: Human leukocyte antigen -major histocompatibility complex, class II DQ alpha 1; RALY: RNA binding protein; MMP24: Matrix metalloproteinase-24; SLC45A: Solute carrier family 45 members 2; TYR: Tyrosinase gene; TRPS1: Trichorhinophalangeal syndrome type I.

The Y-axis represents log-scale p-values, and loci with the smallest p obtained from the logistic regression are labelled with the nearest or corresponding gene’s name. Known loci are in dark blue triangles and newly identified loci in discovery analysis are in purple triangles and newly identified loci in meta-analysis are in light blue triangles.¹

In summary, this study found seven novel loci that contribute to the pathophysiology of actinic keratosis and provided independent replication of three previously reported actinic keratosis susceptibility loci.¹

Atopic dermatitis (AD) is one of the most frequently encountered chronic inflammatory skin condition in the UK.^1,2 It affects both, children and adults; however, the paediatric population is predominantly affected.^3,4 The overall prevalence of diagnosed AD in European paediatric population was found to be the lowest in Germany (8.4%), while the highest prevalence was observed in the Southern European countries of Spain (18.6%) and Italy (17.6%). Figure 1 depicts the prevalence of AD in children, across different regions of the globe.⁵ The Global Burden of Disease 2017 data highlights that this chronic condition is highly prevalent in Asian countries, particularly in the high-income territories.⁶

The burden of this disease is substantially high⁷ and the quality of life of AD patients may be significantly reduced.^7,8 Several studies have highlighted the need for psychological support for patients with AD as well as their caregivers to help them cope with the disturbed sleep, disruption of daily life activities, depression, anxiety, and difficulty in maintaining social life.^7,8 Also, AD patients are always prone to infections owing to the defective skin barrier, dysregulated immune system, and altered skin microbiome, which may cause complications in these patients.^9-11 Health care utilization is significantly increased in AD patients, which also results in significant financial burden.¹² Recent developments have promulgated the role of keratinocytes, as a component of the innate and adaptive immune system, in regulating the release of several key molecules triggering inflammatory reactions and immune responses in AD. A better understanding of the pathogenesis would help formulate appropriate treatments to improve the quality of life in these patients and to prevent allergic disorders associated with AD.¹³

AD has been found to be genetically inheritable.^14,15 AD patients express distinct immune and barrier signs, as detected by RNA-sequencing tape strip profiling, which is a minimally invasive technique. Recent studies propose the use of this technique as an alternative to the regular biopsies for detection of AD (both lesional and non-lesional) biomarkers, although further studies are warranted to establish this fact.^16,17 With the development of more targeted therapies, AD biomarkers are valuable sources to understand patient-specific molecular dysregulations differing between the several AD subtypes,¹⁷ contributing to more tailored treatment and may help to predict which patients are most likely to benefit from the specific targeted therapies.¹⁸

A short time ago, treatment for AD mainly targeted emollients, topical steroids, and topical calcineurin inhibitors. Patients who were severely affected by the disease were encouraged to take systemic immunosuppressants. Novel therapeutic strategies, including biologics, aiming at different molecular events involved in the development of AD, have been developed recently.^19,20 These options mainly target the type 2 immune pathway and have been found to control the disease effectively and are well-tolerated.^1,2,21 The emerging systemic therapies include monoclonal antibodies targeting IL-4,²² IL-¹³,23 IL-31,²⁴ IL-33, thymic stromal lymphopoietin,^9,25 and OX40.²⁶ Latest advances on some probiotic preparations have been shown to be beneficial in decreasing allergic symptoms of AD in children; yet further studies with larger sample sizes are warranted to elude the robustness of this evidence.²⁷ Treatment of a pregnant patient for AD, using systemic drugs, may pose a challenge as it can affect the unborn child. Recent studies advocate that treatment with topical agents should be considered in pregnancy.^28,29 The European task force on atopic dermatitis recommends the use of UV radiations in addition to topical corticosteroids. It also adds that moderate sun exposure may be used in such patients.²⁹ Although there have been many promising treatment options for AD, which particularly affects the high-income countries of Asia, further planned prospective studies involving the long-term follow-up of AD patients and cost-effective analyses are warranted to aid clinical decisions in the application of these novel drugs for its treatment.

Source:
1. Plant A, Ardern-Jones MR. Clin Med (Lond). 2021;21(3):177-81. 2. Cork MJ, et al. Journal of Dermatological Treatment. 2020;31(8):801-9. 3. NHS.Available from: https://www.nhs.uk/conditions/atopic-eczema/. 4. Kowalska-Olędzka E, etal. Journal of Drug Assessment. 2019;8(1):126-8. 5. Silverberg JI, et al. Ann Allergy Asthma Immunol. 2021;126(4):417-28.e2. 6. Urban K, et al. JAAD International. 2021;2:40-50. 7. Ražnatović Ðurović M, et al. Ital J Dermatol Venerol. 2021;156(1):29-35. 8. Capozza K, et al. Dermatitis. 2020;31(3):223-7. 9. Wang V, et al. Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology. 2021;126(1):3-12. 10. Ong PY,Leung DY. Clin Rev Allergy Immunol. 2016;51(3):329-37. 11. Cai SC, et al. Br J Dermatol. 2012;166(1):200-3. 12. Sandhu JK, et al. Pediatr Dermatol. 2019;36(3):303-10. 13. Chieosilapatham P, et al. Clin Exp Immunol. 2021;204(3):296-309. 14. Brown SJ. J InvestDermatol. 2021;141(1):19-22. 15. Mucha S, et al. Journal of Allergy and Clinical Immunology. 2020;145(4):1208-18. 16. He H, et al. J Allergy Clin Immunol. 2021;147(1):199-212. 17. Renert-Yuval Y, Thyssen, J. P., Bissonnette,R., Bieber, T., Kabashima, K., Hijnen, D., & Guttman-Yassky, E. Journal of Allergy and Clinical Immunology. 2021;147(4):1174–90.e1. 18. Bakker DS, et al. J Allergy Clin Immunol. 2021;147(1):189-98. 19. Ramamoorthy R. Journal of Skin and Sexually Transmitted Diseases.0. 20. Katoh N. J Dermatol. 2021;48(2):152-7. 21. Puar N, et al. Ann Allergy Asthma Immunol. 2021;126(1):21-31. 22. Hajar T, et al. An Bras Dermatol. 2018;93(1):104-7. 23. Furue K, et al. Immunology. 2019;158(4):281-6. 24. Ruzicka T, et al. N Engl J Med. 2017;376(9):826-35. 25. Newsom M, et al. Drugs. 2020;80(11):1041-52. 26. Guttman-Yassky E, et al. J Allergy Clin Immunol. 2019;144(2):482-93.e7. 27. Tan-Lim CSC, et al. Pediatr Allergy Immunol. 2021;32(1):124-36. 28. Napolitano M, et al. Dermatol Ther. 2021;34(1):e14475. 29. Vestergaard C, et al. Journal of the European Academy of Dermatology and Venereology. 2019;33(9):1644-59.

NON-2022-9857-N

Further, randomised controlled trials are warranted to assess the efficacy of these dietary modifications in patients with various skin ailments.

Source:
1. Svoboda SA, Christopher M, Shields BE. Reexamining the Role of Diet in Dermatology. Cutis. 2021;107(6):308-14. 2. Castaldo G, Rastrelli L, Galdo G, Molettieri P, Rotondi Aufiero F, Cereda E. Aggressive weight-loss program with a ketogenic induction phase for the treatment of chronic plaque psoriasis: A proof-of-concept, single-arm, open-label clinical trial. Nutrition. 2020;74:110757. 3. Drago F, De Col E, Agnoletti AF, Schiavetti I, Savarino V, Rebora A, et al. The role of small intestinal bacterial overgrowth in rosacea: A 3-year follow-up. J Am Acad Dermatol. 2016;75(3):e113-e5. 4. Afifi L, Danesh MJ, Lee KM, Beroukhim K, Farahnik B, Ahn RS, et al. Dietary Behaviors in Psoriasis: Patient-Reported Outcomes from a U.S. National Survey. Dermatol Ther (Heidelb). 2017;7(2):227-42. 5. Song MS, Farber D, Bitton A, Jass J, Singer M, Karpati G. Dermatomyositis associated with celiac disease: response to a gluten-free diet. Can J Gastroenterol. 2006;20(6):433-5. 6. Egan CA, Smith EP, Taylor TB, Meyer LJ,Samowitz WS, Zone JJ. Linear IgA bullous dermatosis responsive to a gluten-free diet. Am J Gastroenterol. 2001;96(6):1927-9. 7. Son JH, Chung BY, Kim HO, Park CW. A Histamine-Free Diet Is Helpful for Treatment of Adult Patients with Chronic Spontaneous Urticaria. Ann Dermatol. 2018;30(2):164-72. 8. Maintz L, Benfadal S, Allam JP, Hagemann T, Fimmers R, Novak N. Evidence for a reduced histamine degradation capacity in a subgroup of patients with atopic eczema. J Allergy Clin Immunol. 2006;117(5):1106-12. 9. Korovesi A, Dalamaga M, Kotopouli M, Papadavid E. Adherence to the Mediterranean diet is independently associated with psoriasis risk, severity, and quality of life: a cross-sectional observational study. Int J Dermatol. 2019;58(9):e164-e5. 10. Barrea L, Fabbrocini G, Annunziata G, Muscogiuri G, Donnarumma M, Marasca C, et al. Role of Nutrition and Adherence to the Mediterranean Diet in the Multidisciplinary Approach of Hidradenitis Suppurativa: Evaluation of Nutritional Status and Its Association with Severity of Disease. Nutrients. 2018;11(1). 11. Skroza N, Tolino E, Semyonov L, Proietti I, Bernardini N, Nicolucci F, et al. Mediterranean diet and familial dysmetabolism as factors influencing the development of acne. Scand J Public Health. 2012;40(5):466-74.

NON-2022-9863-N

With increasing awareness about the role of dietary modifications in skin care treatment, dermatologists play an imperative role in recommending modified diets to their patients.¹ Gluten-free (GF) diet is becoming immensly popular worldwide. Besides celiac disease and wheat allergic patients, GF diets are frequently adapted by other patients as well, including those with non-celiac gluten sensitivity (NCGS).^2-4

Patients with NCGS

Although these patients do not have celiac disease or wheat allergy, they show intestinal as well as extra-intestinal manifestation on ingestion of gluten. GF diet may prove beneficial for some NCGS patients.¹

GF diets may prove to be beneficial beneficial for patients suffering from various skin ailments, yet, more high-quality studies are warranted to elucidate these benefits in patients without celiac disease and wheat allergy.

Source:
1. Bell KA, Pourang A, Mesinkovska NA, Cardis MA. The effect of gluten on skin and hair: a systematic review. Dermatol Online J. 2021;27(4). 2. Hietikko M, Hervonen K, Salmi T, Ilus T, Zone JJ, Kaukinen K, et al. Disappearance of epidermal transglutaminase and IgA deposits from the papillary dermis of patients with dermatitis herpetiformis after a long-term gluten-free diet. Br J Dermatol. 2018;178(3):e198-e201. 3. Graziano M, Rossi M. An update on the cutaneous manifestations of coeliac disease and non-coeliac gluten sensitivity. Int Rev Immunol. 2018;37(6):291-300. 4. Sapone A, Bai JC, Ciacci C, Dolinsek J, Green PHR, Hadjivassiliou M, et al. Spectrum of gluten-related disorders: consensus on new nomenclature and classification. BMC Med. 2012;10:13-.

NON-2022-9861-N