Palmoplantar keratoderma (PPK) is a multi-faceted skin disorder characterized by the thickening of the epidermis and abrasions on the palms and soles of the feet. Among the genetic causes, biallelic pathogenic variants in the FAM83G gene have been associated with PPK in dogs and humans. Here, a novel homozygous variant (c.794G>C, p.Arg265Pro) in the FAM83G gene, identified by whole exome sequencing in a 60-year-old female patient with PPK, is reported. The patient exhibited alterations in the skin of both hands and feet, dystrophic nails, thin, curly and sparse hair, long upper eyelid eyelashes, and poor dental enamel. FAM83G activates WNT signalling through association with ser/thr protein kinase CK1α. When expressed in FAM83G-/- DLD1 colorectal cancer cells, the FAM83GR265P variant displayed poor stability, a loss of interaction with CK1α and attenuated WNT signalling response. These defects persisted in skin fibroblast cells derived from the patient. Our findings imply that the loss of FAM83G-CK1α interaction and subsequent attenuation of WNT signalling underlie the pathogenesis of PPK caused by the FAM83GR265P variant.

Arsenic is a natural element found in the earth\'s crust and is extensively present in various environmental components. Anthropogenic activities and a few natural events have generated contaminants that have led to massive environmental pollution, one form of which is arsenic contamination. Arsenic enters the human food chain via contaminated crops, water, seafood, and dairy products. In Pakistan, the increasing concentration of arsenic in the water is causing major health problems. Due to the serious health risks posed by arsenic, it is crucial to design and implement strategies for reducing and preventing the bioaccumulation of arsenic and its entry into the human food chain. There is a need for an institutional framework for arsenic mitigation, accountability, and systemic checks and balances. Targeted short- and long-term policies are required for effective and sustainable management.

The present study aimed to identify the possible effect of gentamicin (GEN) in Rats\' Cervi. Estradiol Valerate (EV) was used to induce cervical hyperkeratosis. GEN was administered in absence of EV. Serum and cervical GEN concentration were determined. Levels of malondialdehyde (MDA), total nitrites/nitrate (NOx), reduced glutathione (GSH), tumor necrosis factor-α (TNF-α), sirtuin type 1 (Sirt1) and nuclear factor (erythroid-derived 2)-like-2 factors (Nrf2) were measured in cervix tissue. Expression of BAX and Bcl2 were determined. Cervical histopathological examination was done. EV and GEN significantly increased MDA, NOx, TNF-α and BAX/Bcl2 ratio with decrease in GSH, Nrf2 and Sirt1 levels in cervical tissue. Histopathological picture of diffuse and marked hyperkeratosis was detected in EV and GEN groups. In conclusion, GEN-induced cervical hyperkeratosis via induction of oxidative stress, inflammation and apoptosis.

Sarcoptic mange was detected in five free-ranging raccoon dogs (Nyctereutes procyonoides) in the federal state of Schleswig-Holstein, Germany, during a health assessment study of invasive species, including raccoon dogs, carried out between 2021 and 2022. Four raccoon dogs showed severe lesions, including extensive alopecia with thickening and hyperpigmentation of the skin (lichenification). The fifth animal was less affected, showing only thinning of the hair coat in multiple body locations. Skin scrapings were performed and confirmed the presence of Sarcoptes scabiei. Histopathology of the skin revealed diffuse epidermal hyperplasia and hyperkeratosis, mild eosinophilic dermatitis, and varying amounts of intralesional mites. Staphylococcus pseudintermedius and Corynebacterium auriscanis were detected in the skin samples of the affected animals, indicating a secondary bacterial infection. The source of sarcoptic mange remains unclear; interspecies transmission via direct or indirect contact seems likely. Raccoon dogs are therefore a potential vector for sarcoptic mange, and their behaviour could contribute to disease spread and persistence.

OBJECTIVE: Recent literature highlights the potential of biologics in the management of inherited disorders of keratinisation. In this study, we conducted a systematic review of existing literature on treatment outcomes of inherited keratinisation disorders treated with biologics.
METHODS: Eligible records were retrieved through searches of the electronic databases MEDLINE, Embase, PubMed and Scopus. Databases were searched from inception to July 2023 for eligible records. A snowballing method was employed to search the references of the retrieved records for the identification of potentially relevant articles.
RESULTS: One hundred and four eligible studies consisting of a total of 166 patients with an inherited disorder of keratinisation were included. Patients had a median age of 19 years (range: 0.5 to 70 years). The most common disorders were Netherton syndrome (n = 63; 38%), autosomal recessive congenital ichthyoses (n = 27; 16%), CARD14-associated papulosquamous eruptions (n = 17; 10%) and familial pityriasis rubra pilaris (PRP) (n = 15; 9%).Of the 207 times biologics were employed, the three most frequently employed biologics were secukinumab (n = 47; 23%), dupilumab (n = 44; 21%) and ustekinumab (n = 37; 18%). Complete remission was observed in 10 (5%) instances, partial remission in 129 (62%), no or limited response to biologic therapy in 68 (32%) cases, and results are still pending in one case. A total of 33 adverse events were reported.
CONCLUSIONS: Whilst biologics may be considered in cases of inherited keratinisation disorders recalcitrant to standard therapy, definitive conclusions are prohibited by the low-level of evidence and substantial heterogeneity in methodology across the included studies. Establishment of consensus definitions, and randomised clinical trials may help ascertain the efficacy and safety of biologic therapy in this context and establish the best agent and dosing protocol for each disorder.

Clinical findings in many nail disorders are not usually pathognomonic. An accurate diagnosis therefore relies on inspection of the nail unit from different angles. We review clinical features of different nail disorders that can be observed during frontal examination of the distal edge of the nail plate and the hyponychium and correlate these with features observed when the nail is viewed from above. Frontal examination of the distal nail unit can help establish a clinical diagnosis in routine practice.

Genodermatoses are rare heterogeneous genetic skin diseases with multiorgan involvement. They severely impair an individual\'s well-being and can also lead to early death.
During the progress of this review, we have implemented a targeted research approach, diligently choosing the most relevant and exemplary articles within the subject matter. Our method entailed a systematic exploration of the scientific literature to ensure a compre-hensive and accurate compilation of the available sources.
Among genodermatoses, X-linked ones are of particular importance and should always be considered when pediatric males are affected. Regardless of other syndromic forms without prevalence of skin symptoms, X-linked genodermatoses can be classified in three main groups: keratinization defects, pigmentation defects, and inflammatory skin diseases. Typical examples are dyskeratosis congenita, keratosis follicularis spinulosa decalvans, hypohidrotic ectodermal dysplasia, chondrodysplasia punctata, hypohidrotic ectodermal dysplasia, incontinentia pigmenti, chronic granulomatous disease, CHILD syndrome and ichthyosis. In this field, genetic diagnosis of the specific disease is important, also considering that numerous clinical trials of orphan drugs and genetic therapies are being proposed for these rare genetic diseases.
Thus, this chapter starts from clinical to molecular testing and ends with a review of all clinical trials on orphan drugs and gene therapy for genodermatoses.

Ichthyoses are genetically determined cornification disorders of the epidermis characterized by the presence of different degrees of scaling, hyperkeratosis, and erythroderma often associated with palmoplantar keratoderma. Different classifications of these diseases have been proposed, often based upon the involved genes and/or the clinical presentation. The clinical features of these diseases present some overlap of phenotypes among distinct genetic entities, depending mainly on the penetrance of mutations. In this study, using a clinical, genetic, and molecular approach, we analyzed a family with two affected members who had clinical and histological features resembling erythrokeratodermia variabilis (EKV) or a type of erythrodermic hyperkeratosis with palmoplantar keratoderma. Despite of the clinical presentation, we demonstrated that the affected patients were genetically double heterozygous for two different mutations in the ABCA12 gene, known to be responsible for harlequin ichthyosis. To explain the mild phenotype of our patients, we performed a molecular characterization of the skin. In the upper layers of the epidermis, the results showed a patchy presence of the glucosyl-ceramides (GlcCer), which is the lipid transported by ABCA12, fundamental in contributing to skin impermeability. Indeed, the two mutations detected do not completely abolish ABCA12 activity, indicating that the mild phenotype is due to a partial loss of function of the enzyme, thus giving rise to an intermediate phenotype resembling EKVP, due to a partial depletion of GlcCer deposition.

Clinical findings in many nail disorders are not usually pathognomonic. An accurate diagnosis therefore relies on inspection of the nail unit from different angles. We review clinical features of different nail disorders that can be observed during frontal examination of the distal edge of the nail plate and the hyponychium and correlate these with features observed when the nail is viewed from above. Frontal examination of the distal nail unit can help establish a clinical diagnosis in routine practice.

BACKGROUND: Plantar hyperkeratosis (HK) is a very prevalent foot lesion formed due to an alteration in the keratinisation process, thereby increasing keratynocites and accumulating multiple layers of the stratum corneum that leads to plantar pain. As foot shape and plantar pressures is related with their appearance, the aim of this study is to examine how foot posture and plantar pressure influence the appearance of this keratopathy.
METHODS: On a sample of 400 subjects (201 men and 199 women), the plantar pressures were evaluated by the Footscan® platform in 10 zones. The clinical exploration consisted in the valuation of the Foot Posture Index (FPI), and the assessment of the appeerance (and location) or not of plantar calluses or hyperkeratosis.
RESULTS: 6.3% of the feet presented a highly supinated FPI, 15.5% were supinated, 57.3% corresponded to neutral, 17.3% were pronated and 3.8% were highly pronated. The participants with HK on the hallux, on the 1st, 2nd, 3rd or 5th MTH or on the lateral heel had a significantly higher pressure index (p < 0.001), ranging from 24.3 to 44% higher than those with no such alteration. Of the highly pronated feet, 66.7% presented HK in the hallux, while 32.3% of the supinated feet and 60% of the highly supinated feet presented it beneath the first MTH.
CONCLUSIONS: Foot posture influences the appearance of HK, though its association with plantar pressures. The participants with HK presented a mean foot pressure that was 32.3% higher than in those with no such condition. These values can be considered predictive for the appearance of HK and should be indicative of the need for preventive treatment.