Palmoplantar Keratoderma Research Articles

Photogallery. Genodermatoses. Part II

Genodermatoses are a group of hereditary diseases primarily affecting the skin. To date, there are more than two hundred genetically determined dermatoses representing about 35% of all genetic diseases and 10% of all skin diseases. Genodermatoses can be caused by mutations in a single gene or the interaction of several genes and environmental factors. Hereditary diseases are characterized by a wide variety of phenotypic manifestations and the diagnostic complexity which represents a serious problem in modern dermatology.
 We present a gallery of hereditary dermatoses.
 Unna-Tost disease is a genodermatosis inherited in an autosomal dominant manner and characterized by diffuse excessive keratinization of the skin on the palms and soles, manifesting in the first to second year of life.
 Buschke-Fischer-Brauer punctate palmoplantar keratoderma is a late-developing focal dermatosis in which painful hyperkeratotic papules can occur when traumatized.
 Ehlers-Danlos syndrome is a condition demonstrating skin hyperextensibility and a number of typical symptoms of the skeletal and cardiovascular systems.
 Progeria manifests as premature skin aging, affecting the endocrine, skeletal, cardiovascular, and other systems of the body, as well as increasing the risk of developing malignant neoplasms of internal organs and skin.
 Congenital ichthyosiform erythroderma of Brocq is a severe chronic skin disease with autosomal recessive inheritance, which follows the pattern of lamellar ichthyosis but to a milder degree.
 X-linked ichthyosis, a hereditary "darkening" condition, occurs only in males and is characterized by impaired keratinization and the presence of gray-black scales on the skin.
 Lamellar ichthyosis is an autosomal recessive dermatosis characterized by generalized skin involvement.
 Netherton syndrome is a rare condition characterized by a combination of ichthyosis with structural anomalies of the hair shaft and atopy.

Case report: Area of focus of management of severe pityriasis rubra pilaris by dose optimization of adalimumab biosimilar in combination with acitretin and montelukast

Pityriasis rubra pilaris (PRP) is a rare inflammatory skin disorder characterized by hyperkeratotic follicular papules, orange-red scaling plaques with islands of sparing and palmoplantar keratoderma. While spontaneous resolution occurs in some cases, treatment can be challenging for others. The use of biologics in PRP management has gained attention in recent studies, although their high costs and potential side effects present limitations. We present a case of a 71-year-old patient with treatment-resistant PRP who showed significant improvement through optimized adalimumab treatment. Considering the emerging role of phospholipase A2 in PRP pathogenesis, montelukast was added, further enhancing the therapeutic response. By maintaining montelukast and prolonging the adalimumab interval to 3 and 4 weeks, effective dose optimization was achieved without PRP relapse. This case report highlights the potential for adalimumab dose optimization by shortening the initial treatment interval for increased effectiveness and lengthening the interval during the maintenance phase to conserve medication doses. Montelukast appears to assist in sustaining clinical outcomes during interval prolongation, necessitating further investigation through additional studies.

Clinical and Dermoscopic Study of Palmoplantar Keratodermas

Background: Palmoplantar keratodermas (PPK) represents a group of skin disorders characterized by excessive epidermal thickening of palms and soles. They are classically divided into inherited and acquired groups. Dermoscopy is a non-invasive procedure that can aid in the clinical diagnosis of PPK. Objectives: To study the clinical features and dermoscopic patterns of PPK caused by various dermatological conditions. Methods: Ninety-eight patients with various types of PPK were included in this cross-sectional observational study after obtaining informed consent. Symptoms, general systemic findings, and dermatological manifestations were recorded. The dermoscopic examination was performed by a single observer using Heine Delta 20+ and FotoFinder Medicam 1000. Diagnostically challenging cases were biopsied for histopathological examination. SPSS (Statistical Package for Social Sciences) version 20 [IBM SPSS statistics (IBM Corp. Armonk, NY, USA released 2011)] was used to perform statistical analyses. The chi-square test was applied to examine statistical associations between qualitative variables. The level of significance was set at 5%. Results: Out of 98 cases with PPK, 93 were acquired, and 5 were inherited. The commonest dermoscopy pattern included palmoplantar psoriasis (n = 48), showing a background light red color with yellow diffused white scales with regular dotted and glomerular vessels, followed by palmoplantar eczema (n = 39) (light red color with yellow patchy white background, yellow scales, and patchy dotted vessels). Light red/dull red background with diffuse white scaling and regular linear, dotted, or glomerular vessels were significantly in favor of palmoplantar psoriasis, while a yellow background, diffuse yellow scaling, patchy dotted vessels, and yellow crust were more in favor of palmoplantar dermatitis. Pityriasis rubra pilaris (PRP) (n = 3) showed a light red background, diffused white scales, and dotted and linear vessels with patchy distribution. Lichen planus (n = 2) revealed a light red color with a yellow background, diffused and peripheral white scales, and irregular linear (radial) and dotted vessels. Wickham’s striae were found on palms. Tinea manuum with pedis (n = 1) showed a dull red background and diffused white and yellow scales with the localization of the scales in the skin furrows. Palmoplantar keratodermas secondary to ichthyosis vulgaris (n = 3) revealed a light red background with diffused white and yellow patchy scaling and regular linear and patchy glomerular vessels. Greither’s disease showed a light red color with a yellow background, a diffused white scale pattern, and multiple dotted vessels arranged in an irregular pattern. Erythrokeratodermia variabilis showed a background color of light red and diffused white scales in a crisscross pattern. Conclusions: Dermoscopy can reveal characteristic but not pathognomonic dermoscopic patterns that can be useful in the clinical diagnosis of various types of PPK. More studies with larger sample sizes may help validate these findings and identify new patterns.

Unusual Presentation of Aquagenic Palmoplantar Keratoderma with Overlapping Clinical Features with Hereditary Papulotranslucent Acrokeratoderma in a Young Male.

Unusual Presentation of Aquagenic Palmoplantar Keratoderma with Overlapping Clinical Features with Hereditary Papulotranslucent Acrokeratoderma in a Young Male.

Queratodermia acuagénica: ¿una enfermedad rara en la era covid?

Queratodermia acuagénica: ¿una enfermedad rara en la era covid?

Basan syndrome in a family from South India: a novel SMARCAD1 variant.

Basan syndrome is a rare ectodermal dysplasia, characterised by adermatoglyphia, mottled acral pigmentation and various nail abnormalities; in addition to transient neonatal findings of acral blistering and facial milia. The genetic basis was established recently as heterozygous mutations affecting the skin specific isoform of the SMARCAD1 gene. It is now considered to be part of the spectrum of disorders resulting from haploinsufficiency of this isoform, which also includes Huriez syndrome and autosomal dominant adermatoglyphia. Here, we describe a family with Basan syndrome from South-India with a novel SMARCAD1 variant [SMARCAD1: c.-10 + 4_-10 + 7del] affecting the known mutational hotspot in non-coding exon 1.

236 Disrupted keratinocyte differentiation and increased chemokine and antimicrobial peptide expression in palmoplantar keratoderma due to keratin 9 mutation

236 Disrupted keratinocyte differentiation and increased chemokine and antimicrobial peptide expression in palmoplantar keratoderma due to keratin 9 mutation

The identification of a novel mutation (p.I223fs) in WRN associated with Werner syndrome.

Werner syndrome (WS) is a rare autosomal recessive genetic disease caused by mutations in the WRN gene, and it is characterized by multiple manifestations corresponding to early-onset aging. This study reports the case of a WS patient with a novel WRN mutation. A 36-year-old male patient with WS was evaluated after approval from the local ethics committee. The clinical and biochemical findings of the patient were described. Peripheral blood sample was collected to extract genomic DNA for WRN gene exome sequencing. The three-dimensional (3D) protein structural prediction analysis was performed via the AlphaFold 2.2 program and PyMol software. We report the case of a clinically diagnosed WS patient with consanguineous parents who presented with complex manifestations including early-onset diabetes mellitus, binocular cataracts, cerebral infarction, cerebral atherosclerosis, hypertension, dyslipidemia, hypothyroidism, and suspected meningioma, accompanied by short stature, gray hair, rough skin with subcutaneous fat atrophy, a high-pitched voice, palmoplantar keratoderma, bilateral flat feet, and an indolent deep ulceration on the foot. Exome sequencing identified a novel homozygous frameshift mutation in the WRN gene, c.666-669 del TATT, p.I223fs. The 3D structure prediction showed that premature termination and significant structural changes could occur in the mutant WRN protein. We identified a novel homozygous frameshift mutation, p.I223fs, in WRN in a Chinese patient with WS, expanding the spectrum of mutations in WS.

Lupus erythematosus comedonicus and vegetans: A challenging definition

AbstractA 39‐year‐old man presented with an acneiform facial eruption, bilateral vegetating erythematous plaques on the inguinal folds, focal palmoplantar keratoderma, keratotic violaceous plaques of the dorsum of both hands, and whitish striated lesions on the oral mucosa. Laboratory work‐up showed high titre of ANAs, anti‐SSA(Ro) and anti‐SSB(La) and hypocomplementemia (low C4). Three skin biopsies from different locations were suggestive of cutaneous lupus erythematosus (CLE). Treatment with hydroxychloroquine 400 mg/day plus topical and systemic corticosteroids led to significant clinical improvement after 2 months. Lupus erythematosus comedonicus is a form of discoid CLE and clinically characterized by acneiform lesions. Vegetating lesions, named as lupus erythematosus vegetans, are extremely rare in CLE. The combination of both manifestations in our patient may be better described as ‘lupus erythematous comedonicus and vegetans’.

Palmoplantar keratoderma climactericum successfully treated with topical oestrogen

AbstractKeratoderma climactericum is characterized by palmoplantar hyperkeratosis developing after the onset of menopause. Although rare, keratoderma climactericum can profoundly impact quality of life and may be refractory to prescription‐strength topical steroids and keratolytics. We report a 52‐year‐old female with a 1‐year history of palmoplantar keratoderma. She had a medical history of generalized anxiety disorder and had reached menopause 2 years before presentation. Previously failed treatments included clotrimazole 1% cream twice daily, triamcinolone 0.1% cream twice daily, and betamethasone 0.05% cream mixed with tazarotene 0.1% cream twice daily. She was diagnosed with keratoderma climactericum, and conjugated oestrogen 0.625 mg/g cream twice daily was initiated. After 4 weeks, she had dramatically reduced erythema and hyperkeratosis of her bilateral palms and soles. No adverse effects to treatment were reported. Although the utility of topical oestrogen for keratoderma climactericum has been debated, our case provides further evidence for its efficacy and safety.

Pityriasis rubra pilaris following administration of SARS‐CoV‐2 vaccine

Pityriasis rubra pilaris (PRP) is a rare, chronic, inflammatory dermatosis characterized by follicular, hyperkeratotic papules and palmoplantar keratoderma at any age. The exact etiology of the disease remains unknown, but it can be triggered by multiple factors and genetic backgrounds. Here, we describe a case of PRP occurring after SARS‐CoV‐2 vaccination. While the vaccination is generally safe, it should be kept in mind that PRP may be evoked by SARS‐CoV‐2 vaccination for early recognition of the cause and prognosis of the patients.

Differentiating Verruca Plana and Palmoplantar Keratoderma by Comparing Clinical Features

Background: Distinguishing verruca plana (VP) from certain types of palmoplantar keratoderma (PPK) can pose challenges as there are few prior investigations. Objective: This study aimed to enhance the differentiation between VP and PPK by analyzing their clinical characteristics. Methods: We conducted a retrospective study involving patients diagnosed with VP, or PPK based on biopsy results. Results: We identified 38 cases with VP/PPK-like lesions on their hands. Among them, ten (26.3%) were diagnosed with VP, while 15 (39.5%) were diagnosed with PPK. VP lesions predominantly manifested on the dorsum of the hand, whereas PPK was primarily observed on the palm, and dorsum. Erythematous, or brownish-colored lesions were more commonly associated with VP, while PPK lesions typically presented as flesh-colored. Conclusion: By comparing the clinical distinctions between VP, and PPK, we aim to provide valuable insights to facilitate the differentiation of these two conditions, which can sometimes be diagnostically challenging.

A novel SERPINA12 variant and first European patients with diffuse palmoplantar keratoderma.

Hereditary palmoplantar keratodermas (hPPKs) comprise a heterogeneous group of skin disorders characterized by persistent palmoplantar hyperkeratosis. Loss-of-function variants in a serine peptidase inhibitor, SERPINA12, have recently been implicated in autosomal recessive diffuse hPPK. The disorder appears to share similarities with another hPPK associated with protease overactivity, namely Nagashima-type PPK (NPPK) caused by biallelic variants in SERPINB7. The aim of this study was to enhance the understanding of the clinical and genetic characteristics of serine protease-related hPPKs caused by variants in SERPINA12 and SERPINB7. Whole-exome sequencing (WES) was performed for hPPK patients. Haplotype analysis was completed for the patients with identified recessive SERPINA12 variants and their available family members. In addition, the current literature of SERPINA12- and SERPINB7-related hPPKs was summarized. The phenotype of SERPINA12-related hPPK was confirmed by reporting three new SERPINA12 patients, the first of European origin. A novel SERPINA12 c.1100G>A p.(Gly367Glu) missense variant was identified confirming that the variant spectrum of SERPINA12 include both truncating and missense variants. The previously reported SERPINA12 c.631C>T p.(Arg211*) was indicated enriched in the Finnish population due to a plausible founder effect. In addition, SERPINA12 hPPK patients were shown to share a similar phenotype to patients with recessive variants in SERPINB7. The shared phenotype included diffuse transgradient PPK since birth or early childhood and frequent palmoplantar hyperhidrosis, aquagenic whitening and additional hyperkeratotic lesions in non-palmoplantar areas. SERPINA12 and SERPINB7 hPPK patients cannot be distinguished without genetic analysis. Recessive variants in SERPINA12 and SERPINB7 leading to protease overactivity and hPPK produce a similar phenotype, indistinguishable without genetic analysis. SERPINA12 variants should be assessed also in non-Asian patients with diffuse transgradient PPK. Understanding the role of serine protease inhibitors will provide insights into the complex proteolytic network in epidermal homeostasis.

Efficacy of Bath PUVA in the treatment of Palmoplantar hyperkeratosis

Background: Palmoplantar hyperkeratosis, or palmoplantar keratoderma, is a combination of skin conditions that are characterized by excessive thickening of the skin, mainly on the soles and palms. There are various treatment methods for keratoderma, and one of those methods are treatment through bathwater PUVA. It is a type of photochemotherapy. Objective of the study: The aim of the study was to observe the efficacy of bath PUVA treatment for palmoplantar hyperkeratosis. Methodology: This randomized clinical trial study was conducted at the Department of Dermatology and Venereology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh. The study duration was 6 months, from September 2007 to February 2008. A total of 30 patients presented with with palmoplantar hyperkeratosis were enrolled in this study through random sampling method following the inclusion and exclusion criteria. Results: Majority of participant (33.3%) were from the age group of 31-40 years. The mean ±SD age was 38.40±10.89 years, and the age range of the participants was 20-58 years. 70% of the participants were male, 83.3% were from low socioeconomic class, and 36.7% were businessmen respectively. Histopathological diagnosis revealed that 52% patients had psoriasis, 33% had nonspecific dermatitis, and 10% patients had chronic inflammatory dermatitis. Gradual improvement was observed from baseline to 8 weeks follow-up in regards to palmoplantar surface area involvement, erythema, and hyperkeratosis. 46.7% of the participants reported skin tenderness, and 93.3% have a burning sensation and no other side effects. Conclusion: Bath PUVA may be an effective option in the treatment palmoplantar keratosis particularly of psoriatic patients. A mild form of nonspecific dermatitis may be treated with bath PUVA. Mugda Med Coll J. 2022; 5(2): 76-81

Disruption of TUFT1, a Desmosome-Associated Protein, Causes Skin Fragility, Woolly Hair, and Palmoplantar Keratoderma

Desmosomes are dynamic complex protein structures involved in cellular adhesion. Disruption of these structures by loss-of-function variants in desmosomal genes leads to a variety of skin- and heart-related phenotypes. In this study, we report TUFT1 as a desmosome-associated protein, implicated in epidermal integrity. In two siblings with mild skin fragility, woolly hair, and mild palmoplantar keratoderma but without a cardiac phenotype, we identified a homozygous splice-site variant in the TUFT1 gene, leading to aberrant mRNA splicing and loss of TUFT1 protein. Patients' skin and keratinocytes showed acantholysis, perinuclear retraction of intermediate filaments, and reduced mechanical stress resistance. Immunolabeling and transfection studies showed that TUFT1 is positioned within the desmosome and that its location is dependent on the presence of the desmoplakin carboxy-terminal tail. A Tuft1-knockout mouse model mimicked the patients' phenotypes. Altogether, this study reveals TUFT1 as a desmosome-associated protein, whose absence causes skin fragility, woolly hair, and palmoplantar keratoderma.

Partial Loss of Function ABCA12 Mutations Generate Reduced Deposition of Glucosyl-Ceramide, Leading to Patchy Ichthyosis and Erythrodermia Resembling Erythrokeratodermia Variabilis et Progressiva (EKVP).

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.

Invisible palmar needles: thyroid disorder associated spiny keratoderma and the importance of proper light for visualization.

Spiny keratoderma is a rare skin condition that presents on the palmar and plantar surfaces of the hands and/or feet. This condition is difficult to appreciate under ambient lighting but can be both physically and emotionally distressing to patients. Furthermore, because of the association with various neoplasms and systemic diseases, timely diagnosis and appropriate follow-up is of importance. We evaluate a case of spiny keratoderma in a patient with recently diagnosed hypothyroidism and emphasize the importance of proper lighting during a dermatology-focused physical examination. The patient's palmar lesions were only appreciable under LED light and with physical examination. A biopsy of the lesions confirmed the diagnosis of spiny keratoderma.

Severe KIDAR syndrome caused by deletion in the AP1B1 gene: Report of a teenage patient and systematic review of the literature

Autosomal recessive keratitis-ichthyosis-deafness syndrome (KIDAR MIM #242150) is a very rare disorder caused by pathogenic loss-of-function variants in the AP1B1 gene. So far, nine patients have been reported in the literature and more clinical descriptions are essential to further delineate the phenotype of KIDAR. Here we report a new patient with KIDAR and compare the clinical findings with those from the other published cases with molecular confirmation.We describe a 14-year-old male born to non-consanguineous parents with unremarkable family history. The patient had fetal ascites, neonatal pancreatic insufficiency with consequent failure to thrive, feeding difficulties, recurrent infections and sepsis. The skin examination was remarkable for an ichthyosis with conspicuous palmoplantar keratoderma, sparse and brittle hair with alopecia on the vertex and slight bilateral ectropion. He had short stature, thin build, frontal bossing, small teeth and prominent abdomen. Additional features were congenital profound bilateral sensorineural deafness, photosensitivity and photophobia. Mild global developmental delay was noted. Persistent mild anemia, neutropenia, thrombocytopenia, and low serum copper, ceruloplasmin and growth hormone were also present. Brain magnetic resonance imaging (MRI) showed cerebral atrophy and thin corpus callosum. Genetic testing revealed a homozygous deletion in the AP1B1 gene, possibly including the same exons as a previously reported deletion.Comparing the phenotypes of all reported individuals, they are highly concordant and major features are enteropathy with feeding difficulties, failure to thrive, ichthyosis, palmoplantar keratoderma, sensorineural deafness and sparse and brittle hair. Here we report other features present in more than one patient that could be part of the phenotypic spectrum and suggest copy number variation analysis to be performed alongside sequencing of the AP1B1 gene in case of suspicion.

Incidence and Prevalence of 73 Different Genodermatoses: A Nationwide Study in Sweden.

This retrospective registry-based cohort study aimed to estimate the incidence and prevalence of genodermatoses in the Swedish population and to analyse associated healthcare usage. Patients diagnosed with genodermatoses were identified from the patient registry of Sahlgrenska University Hospital (Gothenburg, Sweden) between 2016 and 2020. Clinical data from medical records were used to verify diagnoses recorded in the National Patient Registry (NPR). The NPR was then searched for International Classification of Diseases, Tenth Revision (ICD-10) codes Q80-82 and Q84 from 2001 to 2020. The local cohort included 298 patients with 36 unique genodermatosis diagnoses. Verification of these diagnoses in the NPR showed positive predictive values of over 90%. The NPR search yielded 13,318 patients with 73 unique diagnoses, including ichthyoses (n = 3,341; 25%), porokeratosis (n = 2,277; 17%), palmoplantar keratodermas (n = 1,754; 13%), the epidermolysis bullosa group (n = 1011; 7%); Darier disease (n = 770; 6%), Hailey-Hailey disease (n = 477; 4%) and Gorlin syndrome (n = 402; 3%). The incidence and prevalence of each diagnosis were calculated based on the nationwide cohort and are reported. A total of 149,538 outpatient visits were registered, a mean of 4.6 visits per patient. This study provides a valuable resource for the epidemiology of genodermatoses by reporting on the incidence and prevalence of 73 different genodermatoses.

Genetic basis of a novel rare dominant form of palmoplantar keratoderma.

Genetic basis of a novel rare dominant form of palmoplantar keratoderma.