Disorders Of Keratinization Research Articles

The impact of physical activity, diet and stress on acne vulgaris. Pathogenesis and therapeutic procedures

Introduction Acne vulgaris is the most common skin disease that affects the majority of the population. Concepts on the pathogenesis of this disease have been changing over the years, as evidenced by the current indication of the precedence of inflammatory or immunological processes over disorders of keratinization of the outlets of hair and sebaceous units during the formation of acne lesions. Due to the complexity of the etiopathogenesis of acne vulgaris, the selection of appropriate therapeutic management is sometimes complicated. In addition, the process of treating the disease is multifaceted and time-consuming. Purpose The purpose of this review is to present the current state of knowledge on the effects of physical activity, diet and stress on acne vulgaris, as well as on the pathogenesis of acne vulgaris and the therapeutic management of patients suffering from this disease. Methods Literature was searched in PubMed and Google Scholarship databases. Publicly available books were searched. Results There is a proven precedence of inflammatory or immune processes over disorders of the keratinization of the estuaries of hair and sebaceous units during the formation of acne lesions. Conclusions Specialists should delve into the mechanism of the problem visible on the patient's skin to effectively and permanently cure the disease.

Pachyonychia Congenita: Clinical Features and Future Treatments.

Pachyonychia congenita (PC) is a rare, autosomal dominant inherited disorder of keratinization that is characterized by a triad of focal palmoplantar keratoderma, plantar pain, and hypertrophic nail dystrophy. It can be debilitating, causing significantly impaired mobility. PC is diagnosed clinically alongside identification of a heterozygous pathogenic mutation in one of five keratin genes: KRT6A, KRT6B, KRT6C, KRT16, or KRT17. Each keratin gene mutation is associated with a distinct clinical phenotype, with variable age of onset and additional features, which has allowed classification by genotype. Additional features include pilosebaceous cysts, follicular hyperkeratosis, natal teeth, oral leukokeratosis, hidradenitis suppurativa, itching, and neurovascular structures. Although classed as rare, the prevalence of PC is likely to be underestimated. There is no cure or specific treatment for PC at present. Current treatments are limited to conservative measures to reduce plantar friction and trauma, mechanical debridement, topical treatments, and treatments for associated features or complications, most commonly infection. However, through active research in collaboration with PC Project, a patient-advocacy group, and the International PC Research Registry, a global registry of PC patients, there are now many new potential therapeutic options on the horizon. This review summarizes the clinical features associated with PC and highlights the current and future treatment of its manifestations.

A case of squamous cell carcinoma arising in a giant porokeratosis previously diagnosed as psoriasis.

Porokeratosis (PK) is a disorder of keratinization with a clinical presentation of an atrophic center surrounded by a hyperkeratotic border. Lesions of porokeratosis carry a risk of malignant transformation with giant porokeratosis (GPK) being a high-risk variant. We report a case in which a single, large, erythematous, scaly plaque in an immunocompromised patient showed initial histopathological features consistent with psoriasis and subsequent histological features consistent with GPK. This plaque underwent malignant transformation to squamous cell carcinoma on three occasions. This case highlights that specimens taken from central portions of porokeratosis may resemble a variety of dermatoses histologically, including psoriasis, resulting in misdiagnosis as seen in our patient. When a patient presents with a diagnosis previously made that isn't responding to therapy as expected, repeat biopsy is appropriate.

A Review on Palmoplantar keratodermas

A palmoplantar keratoderma is a group of hereditary, keratinization disorders characterised by hyperkeratotic thickening of the palms and soles. PPK presents in three forms namely diffuse, focal & punctate. The aetiological factors of Palmoplantar keratoderma are drug-related, chemical-related, systemic disease-related, infection-related, & idiopathic. Palmoplantar keratodermas are diagnosed based on their clinical manifestations and forms. Tiny raindrop-shaped lesions, which are relatively uncommon in nature are one of the clinical symptoms of Type-I PPK. The papules are round and hyperkeratotic and the lesions are yellow to flesh-coloured, well-circumscribed, and firm to the touch. Type-II usually presents with small spines to protrude from the palms and soles whereas Type-III is characterised by tiny flat or umbilicated keratotic shining papules to form along the palms, soles, and digits borders. The prevalence of PPK is less among Indian populations hence managing these conditions might be more challenging due to limited treatment options. However, managing these conditions is based on the classifications and their presentation.

Retinoid-induced skeletal hyperostosis in disorders of keratinization.

For disorders of keratinization, topical treatment alone may be ineffective, and systemic retinoid therapy may be indicated. Treatment with systemic retinoids (acitretin, isotretinoin and alitretinoin) has been shown to be effective in reducing disease severity; however, potentially rare adverse effects (AEs) may occur, including hyperostotic skeletal changes. The true prevalence of this AE in adult patients administered life-long therapy is unknown. We identified 3 of 127 (2.4%) patients (with ichthyosis or Darier disease) who had been prescribed isotretinoin with or without acitretin, and who developed radiological signs and clinical symptoms of hyperostosis and ligamentous ossification. This clinical review highlights the significance of retinoid-induced skeletal hyperostosis in patients prescribed long-term, high-dose retinoid therapy for disorders of keratinization. Patients commencing systemic retinoid therapy, particularly women of childbearing age, should be counselled about this important and potentially serious AE, especially if long-term treatment is indicated.

308 A case report illustrating the problem of VUS identification in the genetic diagnosis of congenital ichthyosis

NGS gene panel screening significantly improves diagnosis of congenital ichthyoses, a genetically heterogeneous group of keratinization disorders with more than 60 causative genes. However, it can occur that variants of uncertain significance (VUS) are detected and therefore no definitive diagnosis could be established. We report the case of a female patient with congenital ichthyosis and palmoplantar keratoderma, born to healthy caucasian non-consanguineous parents without any family history of ichthyosis.

Clinical and molecular characteristics of autosomal recessive congenital ichthyosis in Thailand.

Autosomal recessive congenital ichthyosis (ARCI) is a heterogenous group of rare keratinization disorders. To date, more than 13 causative genes have been identified. However, data on clinical and molecular characteristics including genotype-phenotype correlation are lacking in Thailand. We collected cases diagnosed with non-syndromic ARCI and syndromic recessive congenital ichthyosis at the Institute of Dermatology from 2011 to 2021 and performed genetic testing with next-generation sequencing and assessed clinical details. Baseline demographic data, birth history, family history, skin manifestations at birth, current cutaneous manifestations, comorbidities, and response to treatments were assessed. DNA was screened for mutations using targeted gene sequencing of 45 genes related to congenital ichthyosis. A total of 33 patients were analyzed with an average age of 23.8± 13.9 years. Congenital ichthyosiform erythroderma (CIE) was most common (60.6%), followed by lamellar ichthyosis (18.2%), self-improving congenital ichthyosis (6.1%), Netherton syndrome (6.1%), ichthyosis prematurity syndrome (3%), Sjögren-Larsson syndrome (3%) and bathing suit ichthyosis (3%). Eight genes were found with pathogenic variants in our cohort as follows: ABCA12 42.4% (14/33), NIPAL4 24.2% (8/33), TGM1 15.2% (5/33), SPINK5 6.1% (2/33), ALDH3A2 3% (1/33), SLC27A4 3% (1/33), CYP4F22 3% (1/33), and ST14 3% (1/33). Clinically, 79% of patients with ABCA12 pathogenic variants in this study had CIE, 79% of w had novel biallelic pathogenic compound heterozygous variants, whereas 21% had homozygous missense variants. This is the first study to describe clinical and molecular findings of ARCI in a cohort from Thailand. Our findings demonstrate the clinical spectrum of the diseases and expand the molecular findings in a Southeast Asian population.

An automatic feature extraction technique from the images of granular parakeratosis disease

The largest and most vital part of the human body is skin and any change in the features of skin is termed as a skin lesion. The paper considers granular parakeratosis lesion that is an epidermal reaction occurring due to the disorder of keratinization, and mainly seen in intertriginous areas. The manual inspection of the lesion features is a bit cumbersome due to which an automated system is proposed in this paper. The main goal is to determine the size and depth of granular parakeratosis lesions using the proposed ensemble algorithm, partition clustering and region properties method. As a flow of the proposed model, segmentation is done using U-net with binary cross entropy, features are extracted using partition clustering and region properties method, and classification is done using SVM 10-fold model. The proposed feature extraction method estimates the depth and absolute size of K lesions in each image by predicting the absolute height and width of the lesion in terms of pixel square. After extracting the features, classification is done, thereby obtaining an accuracy of 95%, sensitivity and specificity of 100%. The proposed model provides better performance compared to state-of-the-art models. The main application of this automated system is in dermatology field where some skin lesions have same features which makes the experts to diagnose the disease incorrectly. If the proposed system is incorporated, diagnosis can be done in an effective manner considering all the relevant features.

Reporte de un colibrí oreja blanca (Hylocharis leucotis) afectado por el trastorno de queratina aviar

El trastorno de la queratina aviar ocasiona un crecimiento anormal del pico y afecta a varias especies de aves en América y Europa. Sin embargo, hasta la fecha, no se había registrado en el grupo de los colibríes. En este trabajo reportamos a un individuo de Hylocharis leucotis con dicho trastorno, el cual fue capturado en la localidad de San Bernardino Lagunas, Vicente Guerrero, Puebla. Es posible que esta alteración afecte la alimentación y polinización de los colibríes que la padecen.

Autoinflammatory keratinization diseases

As predisposing factors and pathogenic mechanisms of inflammatory keratinization disorders of the skin have become increasingly elucidated in recent years, a number of inflammatory keratinization disorders are now known to have the excessive activation of innate immunity as their pathogenesis. Autoinflammation-associated pathogeneses have been clarified in patients with generalized pustular psoriasis (GPP), pityriasis rubra pilaris (PRP) type V, and familial keratosis lichenoides chronica (KLC). Thus, based on these findings, in 2017, we proposed the clinical entity “autoinflammatory keratinization disease (AiKD),” which comprehensively includes inflammatory keratinization disorders with pathogenic mechanisms related to autoinflammation (the excessive activation of innate immunity). In 2017, GPP and associated diseases, PRP type V, and familial KLC came to be considered as AiKDs. In addition to these diseases, hidradenitis suppurative, porokeratosis, keratosis linearis with ichthyosis congenita and sclerosing keratoderma syndrome, and AiKDs with hepatitis and autism have been newly recognized as AiKDs. The concept of AiKD may contribute to the selection of novel treatment methods. For example, recognizing hidradenitis suppurativa precisely as an AiKD has resulted in the application of adalimumab, an anti-tumor necrosis factor alpha antibody, as a treatment. The concept of AiKD is thought to be useful toward our accurate understanding of the pathogeneses of inflammatory keratinization disorders and our choice of appropriate treatment methods. As the pathogenic mechanisms of inflammatory keratinization disorders are further elucidated, it is presumed that the number of keratinization diseases whose pathogeneses are associated with autoinflammation will increase and that the number of diseases recognized as AiKDs will grow more and more.

Spinular follicular keratosis of Siemens associated with wooly hair in two sisters: Trichoscopic description and anatomopathological correlation

Spinular follicular keratosis (SFK) is a rare X-linked inherited disorder of keratinization characterized by diffuse follicular hyperkeratosis and progressive scarring alopecia of the scalp, eyebrows, and eyelashes. Trichoscopy is a non-invasive dermatological tool that has improved the differential diagnosis of hair pathologies. In fact, dermoscopic models have been developed for several entities of scalp diseases, allowing early diagnostic confirmation and rapid action without the need for histopathology, as well as good follow-up for patients and signs of pathological activity. To date, the specific trichoscopic signs of KFSD have not been developed. Herein, we report the case of KFSD of Siemens in two sisters associated with wooly hair. We employed trichoscopy as a highly useful tool for diagnosis, then performed an anatomopathological study to confirm the diagnosis and explain the signs found on trichoscopy.

Porokeratosis is one of the most common genodermatoses and is associated with an increased risk of keratinocyte cancer and melanoma.

Porokeratosis is a clinically heterogeneous group of keratinization disorders with a genetic background mainly affecting the mevalonate pathway, which is involved in the synthesis of cholesterol, an essential component for the formation of the extracellular lipid lamellae in the stratum corneum. Porokeratosis is reportedly associated with an increased risk of keratinocyte cancer, but to date, no large epidemiological studies have been conducted to further address this association. The first objective was to characterize a cohort of patients diagnosed with porokeratosis at the Department of Dermatology and Venereology, Sahlgrenska University Hospital (SU), Gothenburg, Sweden. The second objective was to conduct a nationwide registry-based cohort study to investigate the association, if any, between porokeratosis and the cutaneous malignancies squamous cell carcinoma (SCC), basal cell carcinoma (BCC) and melanoma. For the SU cohort, the hospital registry was searched for patients with a diagnosis of porokeratosis recorded between 2016 and 2020. Clinical data were extracted from the records of the identified patients. For the nationwide cohort, national registries were searched to identify patients with a diagnosis of porokeratosis between 2001 and 2020. A tenfold control cohort was formed by Statistics Sweden. The data was cross-referenced with the Swedish Cancer Register to study the associations between porokeratosis and SCC, BCC and melanoma. Disseminated superficial actinic porokeratosis was the most common clinical type among the 108 patients in the SU cohort. In the nationwide search, 2277 patients with porokeratosis were identified (prevalence 1/4132). Porokeratosis was associated with an increased risk for SCC, BCC and melanoma with hazard ratios (95% CI) of 4.3 (3.4-5.4), 2.42 (1.97-2.98) and 1.83 (1.18-2.82), respectively, in the patient cohort, compared to the matched control group. Porokeratosis is a common genodermatosis, and it is associated with an enhanced risk of skin cancer.

Inherited ichthyosis as a paradigm of rare skin disorders: Genomic medicine, pathogenesis, and management

Great advances have been made in the field of heritable skin disorders using next-generation sequencing (NGS) technologies (ie, whole-genome sequencing, whole-exome sequencing, whole-transcriptome sequencing, and disease-targeted multigene panels). When NGS first became available, the cost and lack of access to these technologies were limiting factors; however, with decreasing sequencing costs and the expanding knowledge base of genetic skin diseases, fundamental awareness of NGS has become prudent. The heritable ichthyoses comprise a genotypically and phenotypically heterogeneous group of monogenic keratinization disorders characterized by persistent scaling, with at least 55 distinct genes currently implicated in causing nonsyndromic and syndromic forms of the disease. By providing a simplified overview of available NGS techniques and applying them in the context of ichthyosis, one of the most common genodermatoses, we hope to encourage dermatologists to offer, when appropriate, genetic testing earlier in patients with unsolved presentations. With the aid of NGS, dermatologists can provide diagnostic certainty in cases of suspected genodermatoses and offer potentially life-changing genome-guided and targeted therapies as they become available.

Comparative study of the efficacy of fractional Er: YAG 2940 nm laser and Q-switched Nd: YAG 1064 nm laser in keratosis pilaris.

Keratosis pilaris is a common keratinization disorder of the extensor surfaces of the proximal extremities. Various treatment modalities reduce symptoms, but their efficacy is limited. The aim of this study is to compare the efficiency of Q-Switched Nd: YAG laser and fractional Er: YAG laser. The lesions in both arms were randomly divided into areas A and B. Fractional Er: YAG 2940 nm laser performed to area A 1.5J/cm2 , spot size 7 mm, frequency 3Hz and three passes and Q-Switched Nd: YAG 1064 nm laser performed to Area B, 4-6J/cm2 spot size 4 mm, 8Hz frequency, and as a single pass. Both lasers were performed in 4 sessions at 3-week intervals. The global improvement scale evaluated treatment responses in dyspigmentation and skin texture. Twenty patients completed the study, and the mean age of a total of 20 patients was 22.9. There was no significant difference in dyspigmentation and skin texture with global improvement scale between Area A and Area B, respectively (p=0.078, p=0.638). In addition, there was no significant difference between patient satisfaction levels after treatment in Area A and Area B (p=0.868). The efficiency of the fractional Er: YAG 2940 nm laser was found equal to the Q-switched Nd: YAG 1064 nm laser. Fractional Er: YAG 2940 nm laser may be a new treatment option in the treatment of keratosis pilaris.

Oral manifestation of pachyonychia congenita type 1: Jadassohn lewandowsky syndrome

Pachyonychia congenital (PC), is a rare genetic disorder, autosomal dominant, disorder of keratinization. This condition is characterized by cutaneous manifestation mainly hyperkeratosis of skin and mucosae and hypertrophy of nails. In this condition, almost 50% of the patients will have oral leukokeratosis. The case report here is of a 15 years old girl, presented with dystrophic, thickened fingernails and toenails with subungual hyperkeratosis, palmoplantar keratoderma, hyperkeratotic plaques in buccal mucosae. Histological examination shows acanthosis, parakeratosis and ballooning of epithelial cells, these features were consistent leukokeratosis, and has been diagnosed as Pachyonychia Congenita type 1. This is a rare condition hence, has been reported.

Clinical and Dermoscopic Evaluation of Trichloroacetic Acid 20% Versus Long-Pulsed 1064-nm Nd-YAG Laser in the Treatment of Keratosis Pilaris.

Keratosis pilaris (KP) is a common disorder of keratinization with different therapeutic modalities; however, none of them is completely satisfactory. Assess and compare the efficacy of trichloroacetic acid (TCA) 20% and long-pulsed 1,064-nm Nd:YAG laser in the treatment of KP. Twenty patients with symmetrically distributed areas of KP were enrolled in this study. In each patient, 2 symmetrical KP areas were randomly assigned to receive 4 sessions of either long-pulsed Nd:YAG laser or TCA 20%. Clinical evaluation by Investigator Global Assessment (IGA) was done by 2 blinded physicians after treatment. Dermoscopic assessment was done at baseline and at the end point of the study. Investigator Global Assessment of laser-treated area showed that 2 patients (10%) had moderate improvement, 10 patients (50%) had marked improvement, and 8 patients (40%) had excellent improvement. Investigator Global Assessment of TCA-treated area showed that 9 patients (45%) had marked improvement and 11 patients (55%) had excellent improvement. Dermoscopic score of KP showed a significant reduction with both modalities. The IGA and reduction in dermoscopic scores were comparable between the 2 modalities. Both long-pulsed 1,064-nm Nd:YAG laser and 20% TCA are effective in the treatment of KP. Name of the trial register: clinicaltrial.gov . Registration number: NCT04797663.

PP2 protects from keratin mutation-associated liver injury and filament disruption via SRC kinase inhibition in male but not female mice.

Hepatocyte keratin polypeptides 8/18 (K8/K18) are unique among intermediate filaments proteins (IFs) in that their mutation predisposes to, rather than causes, human disease. Mice that overexpress human K18 R90C manifest disrupted hepatocyte keratin filaments with hyperphosphorylated keratins and predisposition to Fas-induced liver injury. We hypothesized that high-throughput screening will identify compounds that protect the liver from mutation-triggered predisposition to injury. Using A549 cells transduced with a lentivirus K18 construct and high-throughput screening, we identified the SRC-family tyrosine kinases inhibitor, PP2, as a compound that reverses keratin filament disruption and protects from apoptotic cell death caused by K18 R90C mutation at this highly conserved arginine. PP2 also ameliorated Fas-induced apoptosis and liver injury in male but not female K18 R90C mice. The PP2 male selectivity is due to its lower turnover in male versus female livers. Knockdown of SRC but not another kinase target of PP2, protein tyrosine kinase 6, in A549 cells abrogated the hepatoprotective effect of PP2. Phosphoproteomic analysis and validation showed that the protective effect of PP2 associates with Ser/Thr but not Tyr keratin hypophosphorylation, and differs from the sex-independent effect of the Ser/Thr kinase inhibitor PKC412. Inhibition of RAF kinase, a downstream target of SRC, by vemurafenib had a similar protective effect to PP2 in A549 cells and male K18 R90C mice. PP2 protects, in a male-selective manner, keratin mutation-induced mouse liver injury by inhibiting SRC-triggered downstream Ser/Thr phosphorylation of K8/K18, which is phenocopied by RAF kinase inhibitor vemurafenib. The PP2/vemurafenib-associated findings, and their unique mechanisms of action, further support the potential role of select kinase inhibition as therapeutic opportunities for keratin and other IF-associated human diseases.

Treatment of keratosis pilaris rubra with 577-nm pro-yellow laser.

Keratosis pilaris rubra (KPR) is a rare group of idiopathic hereditary disorders of keratinization, and it is considered as variants of keratosis pilaris. It is characterized by a well-defined erythema and small, keratotic follicular papules that are seen on the cheeks and preauricular area. Keratosis pilaris rubra is an aesthetically distressed situation, and especially vascular erythema is the most common complaint. In recent years, pro-yellow (577 nm) laser, laser system with yellow light wavelength, has been used as an alternative for seeking more effective treatment especially in vascular lesions. However, in the literature, pro-yellow laser therapy has never been used before in keratosis pilaris rubra. Therefore, we wanted to evaluate the effectiveness of the pro-yellow laser in keratosis pilaris rubra patients. In our study, four patients with keratosis pilaris rubra treated with pro-yellow laser in our Cosmetology Unit between December 2017 and March 2019 were evaluated. The first session was started with 20 j/cm2 and the dose increased 2 j/cm2 at each session. The dose was increased up to 26 j/cm2 , a total of four sessions (20-22-24-26 j/cm2 ) was applied in treatment. All the sessions were used in treatment scanner mode. Objectifying a clearance of erythema >75% was clinically evident in three patients, in the fourth patient, erythema regressed approximately 50%. There has been no recurrence of the lesions after a minimum three months follow-up. There was no permanent side effect in any patient. Pro-yellow laser is a well option for the treatment of keratosis pilaris rubra, and we think that it could be a safety choice therapy. In addition, a well tolerance to treatment and a low incidence of serious side effects make it a very reliable therapy. Further clinical studies are needed to improve our findings.

Use of retinoids in dermatology

Background: Retinoid, whose existence was first known in the 20th century, was initially referred to as a naturally occurring substance with vitamin A action. However, now it has become a generic term for all substances exhibiting an active action through the retinoid receptor located in the nucleus of the cells. Retinoids are biologically important substances involved in many functions, including reproduction, embryonic morphogenesis, regulation of epithelial proliferation and differentiation, reduction of sebaceous gland, immune and anti-inflammatory effects, tumor prevention, and effects on extracellular matrix components.Current Concepts: Topical retinoids are used to treat several conditions, including acne, photoaging, and psoriasis. Their side effects are dose-related skin irritations, while teratogenicity risk is rare to non-existent. Systemic retinoids are a treatment of choice for acne and keratinization disorders. They are also useful for the treatment of psoriasis, pityriasis rubra pilaris, cutaneous T-cell lymphoma, and chronic hand eczema. Systemic retinoid therapy requires the careful patient selection and monitoring due to associated teratogenicity. Other important side effects are hypertriglyceridemia, dryness of lips, blepharoconjunctivitis, bone pain, increased muscle tone, myopathy, hypothyroidism, and neutropenia.Discussion and Conclusion: Awareness of the side effects and proper use of retinoids are important for successful treatment outcomes of the above-mentioned dermatological conditions.

Dermoscopic furrow ink test of the palmar lesion in loricrin keratoderma.

Palmoplantar keratodermas (PPK) comprise a heterogeneous group of keratinization disorders that gradually progress during childhood, resulting in difficulties to establish a diagnosis and to identify a candidate gene for sequencing. Dermoscopic examination with staining of palmoplantar skin using a whiteboard marker, so-called "furrow ink test", could be a useful tool for differentiation between furrow and ridge in understanding the morphological characteristics of PPK. One of the striking features in autosomal dominant loricrin keratoderma (LK) is diffuse PPK with honeycomb pattern. In this study, we performed dermoscopic furrow ink test in a Japanese family of LK with the most frequent mutation c.684dup, p.Ser229Valfs*107 in the loricrin gene. The severe lesion revealed that irregular circular hyperkeratoses were aggregated and normal structures of furrows and ridges were disrupted. To accurately describe the nature of this dermoscopic patterned skin surface, we suggest that the condition could be termed as "irregular cobblestone appearance" rather than "honeycomb pattern". Regular cobblestone appearance to maintain parallel furrow structure was observed in early or mild hyperkeratotic lesions. Eccrine sweat glands that open on the surface of ridges nearly disappeared, resulting in hypohidrosis.