Palmoplantar Keratoderma Research Articles

“Wood-Bark Sign” in Dermoscopy of Aquagenic Syringeal Acrokeratoderma

“Wood-Bark Sign” in Dermoscopy of Aquagenic Syringeal Acrokeratoderma

Sclerodermiform alterations in the hands of an adolescent

Objective Illustrate an typical presentation of a rare dermatosis. Methods Pityriasis rubra pilaris (PRP) is a rare inflammatory papulo-squamous dermatosis. Genetic factors, changes in vitamin A metabolism and infections have been proposed as triggering mechanism of the disease, but its etiology and pathogenesis are still unknown. It has been described in association with HIV, drugs, autoimmune disease and visceral neoplasms. It affects all races and genders equally, with a peak distribution in the first and fifth decades of life. Most case occur sporadically, but familial cases have been reported. Results Adolescent, 18 years old, with report of generalizes pruritic skin lesions since the age of 3 months, treatd only with antihistamines. He denied comorbidities, allergies or family history of skin diseases. On examination, follicular hyperkeratosis alternating with islands of healthy skin on the anterior and posterior trunk, ichthyosiform desquamation on the lower limbs, palmoplantar keratoderma and sclerodermiform alterations on the hands and feet were noted. A biposy of the lesion on the back was performed, which showed psoriasiform dermatitis with orhokeratosis and parakeratosis alternating horizontally. Considering the clinical-pathological correlation, the diagnosis was juvenile atypical PRP subtype. Conclusion The juvenile atypical subtype of PRP is the least frequent (5% of cases) and accounts for most familial cases. It appears in the first years of life and has a chronic course. It is characterized by follicular hyperkeratosis, erythema, ichthyosiform desquamation on the lower limbs, gross palmoplantar keratoderma and sclerodermiform alterations of the hands and feet.

Complete pachydermoperiostosis with diffuse keratoderma mimicking thyroid Acropachy: A case report and review of literature

Pachydermoperiostosis (PDP) is a rare genodermatosis with prominent cutaneous, soft tissue and skeletal manifestations. It can mimic secondary causes of hypertrophic osteoarthropathy such as thyroid acropachy. Cutaneous manifestations can be debilitating and constitute critical clues to formulating an accurate diagnosis. Palmoplantar keratoderma is a seldom reported manifestation of the disease hence, its significance as a phenotypic variant of pachydermoperiostosis is unknown. We describe a rare case of complete pachydermoperiostosis with diffuse palmoplantar keratoderma in a young African man presenting with hyperhidrosis, hyper-defecation and weight loss who had been previously misdiagnosed with thyroid acropachy. The aim is to provide a detailed clinical description of both common and unconventional features of this rare disease. Pachydermoperiostosis manifests with diverse genotypic and phenotypic characteristics that can mimic treatable, secondary causes of hypertrophic osteoarthropathy. Keratoderma and hyper-defecation are seldom reported manifestations that may represent unique variants of PDP. Awareness of characteristic dermatological manifestations of the disease can enhance early and accurate clinical diagnosis and prevent needless investigations.

Pityriasis rubra pilaris partially responsive to treatment with upadacitinib: A case report

Pityriasis rubra pilaris is a rare inflammatory dermatosis characterized by orange-red confluent plaques, hyperkeratotic follicular papules, palmoplantar keratoderma, and, in some cases, erythroderma. The etiology of pityriasis rubra pilaris is unclear. This condition is often treated with oral retinoids and topical corticosteroids, and more recently, biological agents have become the mainstay of treatment. However, there is a paucity of high-quality evidence on the safety and effectiveness of these agents, and the disease often remains refractory to therapy. Herein, we present a case of pityriasis rubra pilaris with a favorable response to treatment with upadacitinib, a Janus kinase inhibitor, which has not been previously reported in the literature for the management of this condition.

An Institution Based Cross-Sectional Observational Aetiological Study Correlating the Clinico-Pathological Findings in Patients Presenting with Acquired Palmoplantar Keratoderma.

Palmoplantar keratoderma (PPK) is a heterogeneous group of hereditary or acquired disorders characterised by excessive epidermal thickening of the palms and soles. Proper knowledge about the aetiology of the disease and clinico-demographic profile helps in planning management and predicting outcomes. To determine the prevalence of different dermatoses and describe their clinico-histological correlation in acquired palmoplantar keratoderma. An institution-based cross-sectional study conducted after obtaining Ethics-Committee permission and consent from participants. Patients of any age or gender presenting with acquired PPK were recruited. The calculated sample size was 67 by using the prevalence rate (p) of 22.2%, allowable error (L) of 10%, the confidence level of 95% (z = 1.96), and an infinite population size of 20,000. Patients were evaluated by taking demographic and clinical data in a pre-designed case record form, necessary laboratory investigations and histopathological examination that wereevaluated by three blinded experts. The pooled data were analysed with statistical software. Among the 67 participants, Psoriasis was diagnosed clinically in 39 (58.2%) and histologically in 7 (10.4%), Lichen planus (LP) clinically in 16 (23.9%) and histologically in 9 (13.4%), Pityriasis rubra pilaris (PRP) in 8 (11.9%) patients clinically and 7 (10.4%) histologically and Hyperkeratotic eczema (HKE) in 4 (6%) clinically and 43 (64.2%) histopathologically. There was very poor inter-rater agreement (Kappa = 0.148, SE 0.0047, 95% CI 0.057 to 0.24). The clinico-pathological correlation was found to be agreeable in 17.9% Psoriasis, 56.2% LP and 87.5% PRP. HKE was commonly misdiagnosed as Psoriasis in 65.1% of patients. Hyperkeratotic lesions of the palm and sole often present with overlapping clinical features and a skin biopsy has to be done to aid in diagnosis. Stratification of the clinical expertise of clinicians was done during the analysis.

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.

Atypical adult onset pityriasis rubra pilaris: a rare chronic form of pityriasis rubra pilaris

<p class="abstract">Pityriasis rubra pilaris (PRP) are a group of clinically similar papulo squamous dermatoses which present with erythematous, hyperkeratotic perifollicular papules which tend to coalesce to form plaques and may progress to erythroderma. We report a case of 46-year-old female patient who came with chief complaint of itching and burning sensation and scaly patches on extremities since one year. On dermatological examination well demarcated hyperkeratotic scaly plaques with follicular plugging and peripheral rim of erythema were seen over extensor and flexor aspects of elbows, knees, thighs, legs, dorsum of foot and gluteal region. Diffuse palmoplantar keratoderma, diffuse scaling and follicular plugging of the scalp, thickened brownish black nails were seen. On histopathology alternating layers of orthokeratosis and parakeratosis, follicular plugging with perifollicular parakeratosis, acanthosis with broad rete ridge, perivascular lymphocytic infiltration in upper dermis was seen, suggestive of PRP. Patient responded well to oral acitretin 25 mg once daily combined with oral methotrexate 10 mg once weekly along with topical emollients and corticosteroids after 6 weeks of treatment.</p>

Bothnian Palmoplantar Keratoderma: Further Delineation of the Associated Phenotype.

Bothnian palmoplantar keratoderma (PPKB, MIM600231) is an autosomal dominant form of diffuse non-epidermolytic PPK characterized by spontaneous yellowish-white PPK associated with a spongy appearance after water-immersion. It is due to AQP5 heterozygous mutations. We report four patients carrying a novel AQP5 heterozygous mutation (c.125T>A; p.(Ile42Asn)), and belonging to the same French family. Early palmoplantar swelling (before one year of age), pruritus and hyperhidrosis were constant. The PPK was finally characterized as transgrediens, non-progrediens, diffuse PPK with a clear delineation between normal and affected skin. The cutaneous modifications at water-immersion test, "hand-in-the-bucket sign", were significantly evident after 3 to 6 min of immersion in the children and father, respectively. AQP5 protein is expressed in eccrine sweat glands (ESG), salivary and airway submucosal glands. In PPKB, gain of function mutations seem to widen the channel diameter of ESG and increase water movement. Thus, swelling seems to be induced by hypotonicity with water entrance into cells, while hyperhidrosis is the result of an increased cytosolic calcium concentration.

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.

Hereditary keratoderma. Clinical case: Unna–Toast keratoderma and Buschke–Fischer–Brauer keratoderma

Palmoplantar keratoderma is a heterogeneous group of diseases, both hereditary and acquired, affecting, as a rule, the skin of the palms and soles in the form of focal or diffuse hyperkeratotic layers. Hereditary forms are characterized by a defect in the genes encoding certain structural components of keratinocytes, which leads to the corresponding clinical manifestations. The actual method of genomic sequencing has made it possible to identify the localization of defects in certain genes for specific types of hereditary palmoplantar keratoderma, however, despite the big step in diagnosis, therapy still remains complex and can only reduce the manifestations of the disease and improve the quality of life, and not cure it completely.
 The authors demonstrate a clinical case of UnnaToast keratoderma in a young patient with a long history of treatment of the disease, who showed a pronounced positive dynamics from the skin process against the background of the use of local agents, as well as the use of such a physiotherapeutic method as local PUVA therapy. In addition, the article provides a clinical case of hereditary keratoderma BuschkeFischerBrauer as an example of an accidentally diagnosed disease at a dermatologists appointment.

Proteomic profiling of sweat in patients with cystic fibrosis provides new insights into epidermal homoeostasis.

A high proportion of patients with Cystic Fibrosis (CF) also present the rare skin disease aquagenic palmoplantar keratoderma. A possible link between this condition and absence of a functional CF Transmembrane conductance Regulator protein in the sweat acinus and collecting duct remains unknown. In-depth characterization of sweat proteome profiles was performed in 25 CF patients compared to 12 healthy controls. A 20μL sweat sample was collected after pilocarpine iontophoresis and liquid chromatography tandem mass spectrometry (LC-MS/MS) proteomic analysis was performed. Sweat proteome profile of CF patients was significantly different from that of healthy subjects with 57 differentially expressed proteins. Cystic Fibrosis sweat proteome was characterized by an increase in 25 proteins including proteases (Kallikrein 7 and 13, Phospholipase B domain containing 1, Cathepsin A L2 and B, Lysosomal Pro-X carboxypeptidase); proinflammatory proteins (Annexin A2, Chitinase-3-like protein 1); cytochrome c and transglutaminases. Thirty-two proteins were downregulated in CF sweat including proteases (Elastase 2), antioxidative protein FAM129B; membrane-bound transporter SLC6A14 and regulator protein Sodium-hydrogen antiporter 3 regulator 1. This study is the first to report in-depth characterization of endogenous peptides in CF sweat and could help understand the complex physiology of the sweat gland. The proteome profile highlights the unbalanced proteolytic and proinflammatory activity of sweat in CF. These results also suggest a defect in pathways involved in skin barrier integrity in CF patients. Sweat proteome profile could prove to be a useful tool in the context of personalized medicine in CF.

“African” acral keratoderma: Further evidence for a single entity. A retrospective study of 42 patients

BackgroundSeveral phenotypes of non-inflammatory palmar and plantar keratoderma (PPK) have been described in patients of Sub-Saharan African descent. They include keratosis punctata of the palmar creases, marginal keratoderma, also known as acrokeratoelastoidosis or focal acral hyperkeratosis, knuckle pads, other forms of diffuse hyperkeratosis, the very rare “mosaic acral keratosis”, and ainhum. A previous survey has shown that these various forms of PPK are particularly frequent in patients of Sub-Saharan African descent and that they commonly occur concurrently, suggesting that they could form part of a single entity called “African” Acral Keratoderma (AAK). AimTo assess the validity of the concept of AAK and clarify its main characteristics. MethodsA retrospective, descriptive, monocenter study was carried out on patients with AAK seen at our institution between 2009 and 2020. ResultsThere were 42 patients (median age 38 years, range: 12–69 years), all of Sub-Saharan African descent. The male–female sex ratio was 0.3. Thirty-three (78%) had diffuse keratoderma, 25 (59%) had marginal keratoderma on their hands and/or feet, 20 (48%) had knuckle pads, 20 (48%) had keratosis punctata of the palmar creases, 3 had ainhum, and 2 had mosaic acral keratoderma. Mixed forms were seen in 76% of the patients (n = 32). Familial histories were reported by 17 patients (40%). Treatment was topical in over 90% of patients and systemic in 9 patients (21%). Ainhum was managed surgically. ConclusionThis retrospective study provides additional evidence for the concept of AAK. A genetic origin is suggested by the familial aggregation of cases.

259 KLF4 variants: a novel cause of palmoplantar keratoderma

A steadily growing number of hereditary palmoplantar keratodermas (PPKs) have been found to result from defective function of epidermal adhesion proteins such as desmoglein 1 (DSG1), a critical component of desmosomes which has been implicated in the pathogenesis of striate, diffuse and focal PPKs. Here we aimed at delineating the genetic basis of a novel dominant form of PPK. We studied three patients from two families diagnosed with PPK. Whole exome sequencing revealed causative pathogenic heterozygous variants in KLF4 gene in the three affected individuals.

173 A Model to Unravel Pathways Underpinning Palmoplantar Homeostasis and Disease

Tylosis with oesophageal cancer (TOC) is a rare syndrome associated with focal non-epidermolytic palmoplantar keratoderma (NEPPK), a high, lifetime risk of developing oesophageal squamous cell carcinoma (OSCC), and gain-of-function mutations in RHBDF2 (encoding iRhom2). To date, there is a lack of a useful and representative model to study the development of NEPPK and OSCC in vivo, which might aid our understanding of hyperproliferative skin disease and cancer predisposition. CRISPR-Cas9 was used to generate a novel mouse model of TOC that contains a heterozygous Rhbdf2I156T/+ mutation which mirrors the UK TOC family mutation, RHBDF2I186T/+.

188 CD44 functions as a novel interacting partner of Aquaporin 5 in keratinocytes

Dominant missense mutations in AQP5, encoding the water channel protein Aquaporin 5, underlie diffuse non-epidermolytic palmoplantar keratoderma (NEPPK), a rare skin condition characterized by thickening of the epidermis in palms and soles. Prior to this, AQP5 was only known to be expressed in sweat gland cells in the skin and the role of this water channel in the epidermis remains unclear. To study the role of AQP5 in skin, we have characterized two patient-derived keratinocyte cell lines expressing mutant AQP5Ile45Ser.

261 A novel skin phenotype resulting from heterozygous deletion of six keratin genes

The phenotypic spectrum of genodermatoses is continuously expanding. Three individuals were referred because of a highly unusual phenotype comprising sparse brittle hair, dystrophic nails, palmoplantar keratoderma and trauma-induced skin blistering. Whole exome sequencing analysis identified a heterozygous large genomic alteration of ∼116,0000 bp resulting in the deletion of the KRT9, KRT14, KRT15, KRT16, KRT19 genes as well as part of KRT17. This genomic change leads to the generation of a truncated KRT17 protein composed of the first 3 exons of the gene and part of intron 3.

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.

448 RSPO1-mutated keratinocytes from palmoplantar keratoderma display impaired differentiation, alteration of cell-cell adhesion, EMT-like phenotype and invasiveness properties

Secreted R-spondin (RSPO) proteins play a key role in reproductive organ development, epithelial stem cell renewal and cancer induction by reinforcing canonical Wnt signaling. We have previously reported that palmoplantar keratoderma (PPK), predisposition to cutaneous squamous cell carcinoma (SCC) development and sex reversal segregate as autosomal recessive trait in patients carrying RSPO1-mutations. Although our previous findings suggested that RSPO1 secreted from fibroblasts regulates keratinocyte growth or differentiation, the role of this protein in the epidermis remains largely unexplored.

206 KLICK syndrome is a hyperproliferative inflammatory skin disorder

Keratosis linearis with ichthyosis congenita and sclerosing keratoderma (KLICK) syndrome is an ultra-rare autosomal recessive genodermatosis. Clinical manifestations include linear hyperkeratotic papules in the flexures, palmoplantar keratoderma and pseudoainhum. To date, all affected individuals carry a homozygous mutation, c.-95delC in POMP, which encodes for proteasome maturation protein. Disease pathophysiology is not well understood and there are no approved therapies. However, literature indicates that KLICK syndrome, like some other ichthyoses, may involve uncharacterised inflammatory pathways.

263 EGFR signalling is overactive in Pachyonychia congenita: effective treatment with oral erlotinib

Pachyonychia congenita (PC) is a rare keratinizing disorder characterized by painful palmoplantar keratoderma (PPK), thickened nails and blistering for which there are no standard current treatment. PC is caused by dominant mutations in keratin 6A, 6B, 6C, 16 and 17 genes involved in stress, wound healing and epidermal barrier formation. Mechanisms leading to pain and PPK in PC remain elusive. To gain further insight into PC pathogenesis, we studied the human epidermal growth factor receptor (HER) pathway and transient receptor potential vanilloid-3 (TRPV3) expression in PC calluses in 3 patients.