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Dupuytren contracture (DC) is predominantly an autosomal dominant disorder characterized by hypertrophy and contraction of the palmar fascia that results in tethered flexion of the affected digits. It has its highest prevalence in the North European population or in people of Viking descent, and its incidence is growing with age. DC shares a common inheritance mode, predisposing factors, comorbidities, pathophysiology, and evolution with Ledderhose disease, Garrod knuckle pads, and Peyronie disease. Nonmelanoma skin cancer also has a higher incidence in the population of North European phenotype and apparently a common genetic polymorphism. Psoriasis shares many risk factors and comorbidities with DC and has a higher prevalence in patients with DC. We suggest a close relationship among DC, some skin malignancies, and psoriasis. Regular monitoring for those skin diseases in all patients with DC is highly recommended.

Knuckle pads are benign painless papules and nodules that most commonly appear on the extensor surfaces of the proximal interphalangeal joints. Knuckle pads are frequently misdiagnosed due to their location overlying joints, which can lead to costly interventions and patient discomfort for a relatively harmless condition. We describe a 44-year-old woman who presented with mildly painful nodules on multiple bilateral proximal interphalangeal joints. The patient did not have a family history of fibromatosis and the rheumatoid factor was negative. Histology showed mild epidermal hyperkeratosis, papillomatosis, and acanthosis with a deep dermal, poorly circumscribed, proliferative nodule made of spindled myofibroblasts without cytological atypia. The diagnosis of knuckle pads was established based on the clinical and morphological presentation of the nodules. Treatment with intralesional triamcinolone acetonide injection produced significant clinical improvement. Our findings highlight the challenging diagnosis of knuckle pads and the importance of increasing the familiarity of knuckle pads in modern medical practice.

PLACK syndrome (OMIM 616295) is a form of generalized peeling skin syndrome (GPSS; OMIM 270300). It is an autosomal recessive genodermatosis caused by pathogenic mutations in CAST, which encodes calpastatin, an endogenous specific inhibitor of calpain, a calcium-dependent cysteine protease. We present a 5-year-old girl diagnosed with PLACK syndrome with typical clinical features and homozygosity for a novel variant.

Peeling skin syndrome is a heterogeneous group of rare disorders. Peeling skin, leukonychia, acral punctate keratoses, cheilitis and knuckle pads (PLACK syndrome, OMIM616295) is a newly described form of PSS with an autosomal recessive mode of inheritance. We report a 5.5-year-old boy with features of PLACK syndrome. Additionally, he had mild cerebral atrophy and mild muscle involvements. Whole exome sequencing was performed in genomic DNA of this individual and subsequent analysis revealed a homozygous c.544G > T (p.Glu182{*}) nonsense mutation in the CAST gene encoding calpastatin. Sanger sequencing confirmed this variant and demonstrated that his affected aunt was also homozygous. Real-time qRT-PCR and immunoblot analysis showed reduced calpastatin expression in skin fibroblasts derived from both affected individuals compared to heterozygous family members. In vitro calpastatin activity assays also showed decreased activity in affected individuals. This study further supports a key role for calpastatin in the tight regulation of proteolytic pathways within the skin.

Knuckle pads are benign subcutaneous and usually hyperkeratotic fibromas for which no specific treatments exist. Unspecific treatments are, most of the time, ineffective and a wait-and-see policy is often recommended to patients. However, especially in adolescents, knuckle pads are often poorly tolerated for cosmetic reasons, potentially causing embarrassment and social anxiety. Here we present the case of a young adult successfully treated with a combination of high-dose salicylic acid and urea topical keratolytics. In addition, we provide ideal diagnostic images obtained via high-resolution ultrasonography and histological features that can be used by medical practitioners to better distinguish knuckle pads from other proximal interphalangeal/ metacarpophalangeal joint diseases as also from other diseases inducing swelling of periarticular soft tissues.

We describe an 11-year-old girl with PLACK Syndrome (peeling skin, leukonychia, acral punctate keratosis, cheilitis, and knuckle pads), who was found to have a novel homozygous variant in CAST, the pathogenicity of which was confirmed using blood-derived RNA. There is no established treatment for PLACK syndrome. However, we demonstrate for the first time that this condition is associated with low levels of vitamin A and essential fatty acids, which prompted us to consider a potential treatment strategy. Indeed, we initiated this patient on intravenous lipid infusion (Vitalipid®; an emulsion of fat-soluble vitamins and lipofundin-MCT/LCT 20%) and the response was dramatic. Following the fourth monthly course of treatment, pruritis disappeared and the skin lesions showed remarkable objective improvement. PLACK syndrome is a very rare genodermatosis and only six families have been described to date with pathogenic CAST variants. This is the first report of an objective response to a therapeutic agent, which suggests that PLACK is a potentially treatable condition. The remarkable response we report and the relative safety of the intervention should prompt healthcare providers who care for PLACK syndrome patients to explore this as a potential treatment strategy in future studies.

Videogame controller–induced knuckle pads may present in a strikingly unique distribution. Successful paring without recurrence can be achieved when combined with removal of the original insult.

Knuckle pads or Garrod’s nodes are a rare, non-inflammatory condition. They consist of benign, well-circumscribed fibro-adipose tissue over the small joints of hands and feet. Knuckle pads may be under-diagnosed and mistaken for early arthritis. The rheumatologist should perform an accurate differential diagnosis in which he can be helped by ultrasound and by other colleagues, such as the dermatologist. Ultrasound is considered useful in the assessment of the thickening of the subcutaneous tissue, located usually on the extensor site of proximal interphalangeal and metacarpophalangeal hand joints. Dermoscopy may play a role in detecting epidermal and dermal changes. We hereby report the case of a female patient with knuckle pads mimicking psoriatic arthritis.

Background Epidermolytic palmoplantar keratoderma (EPPK) is characterized by hyperkeratotic lesions on palms and soles. The disorder is caused by mutations of keratin 9 (KRT9) or KRT1 gene. Methods Epidermolytic palmoplantar keratoderma was diagnosed by physical examination and histopathological analysis in a five‐generation Chinese family. Mutation was screened by Sanger sequencing. The palmar expression of multiple cytokeratins were analyzed by tape‐stripping and Real‐time PCR. Literatures of EPPK with additional symptoms were reviewed. Results Affected family members showed diffuse palmoplantar keratosis, with knuckle pads, friction‐related lesions and a novel additional symptom of palmar constriction. A heterozygous mutation of c.T491C (p.L164P) of KRT9 was found within the helix initiation motif. The hydrophobic effect was decreased and the initiation of coiled‐coil conformation was delayed. The KRT16/KRT6 expression were significantly increased in the patients, especially on the right, indicating activation of stress‐response and wound‐healing cytokeratins. There were also increased KRT9/KRT2, unchanged KRT10/KRT1, and undetectable KRT14/KRT5 expression. The genetic and phenotypic heterogeneity of EPPK with additional symptoms were summarized by literature review. Conclusion The p.L164P mutation of KRT9 caused EPPK with a novel symptom of palmar constriction. The expression of multiple cytokeratins was altered in EPPK patients.

Knuckle pads are thickening of the skin over the extensor surface of the proximal interphalangeal joints. Clinical picture, ultrasound imaging, and histopathological examination of the skin biopsy ascertain the diagnosis. In routine practice, two main differential diagnoses are important: knuckle pads vs. pseudo-knuckle pads and idiopathic vs. non-idiopathic forms of knuckle pads.

Dorsal lesions in Dupuytren’s disease are rare and data concerning their epidemiology and management are sparse. We conducted a systematic review to summarize reported cases of dorsal Dupuytren’s disease. Pubmed, Cochrane, and Embase databases were searched from 1893 to 2018, and 17 articles were selected (525 patients). The male to female ratio was 3.8:1. The dorsal disease was bilateral in 225 patients (50%). The index was the most commonly affected finger (48 patients). The proximal interphalangeal joint was the most commonly affected (484 cases). The most frequently reported lesions were knuckle pads (503 patients), dorsal nodules between interphalangeal joints (14 patients), boutonnière deformities (12 patients), and swan-neck deformities (2 patients). Nearly half of the included patients were treated surgically. Postoperative functional result depended on the treated lesion. Most of the included studies had a low level of evidence. Higher-quality studies are necessary to confirm our findings.

Fibromatoses are a group of benign connective tissue tumors characterized by the infiltrative, aggressive proliferation of well-differentiated fibroblasts, leading to frequent local recurrence. Within this heterogeneous disease group, superficial fibromatoses show slower growth and more benign infiltration of surrounding tissues than deep fibromatoses. Superficial fibromatoses relevant to dermatology include palmar, plantar, and penile fibromatosis, knuckle pads, pachydermodactyly and infantile digital fibromatosis. They present clinically with subcutaneous nodules or cords that lead to local infiltration and limited mobility of the affected areas. Treatment options vary from watchful waiting, non-invasive methods such as radiotherapy and intralesional corticosteroid/collagenase injections to radical surgical procedures. Early intervention may disrupt disease progression and may even restore functional ability. These disorders should therefore be recognized and treated early in the course of the disease.

Polyfibromatosis is a rare disease characterized by fibrosis manifesting in different locations. It is commonly characterized by palmar fibromatosis (Dupuytren’s contracture) in variable combinations with plantar fibromatosis (Ledderhose’s disease), penile fibromatosis (Peyronie’s disease), knuckle pads, and keloids. There are only three reported cases of polyfibromatosis and keloids with erosive arthritis. We report one such case and review the existing literature on this rare syndrome.

Background: Pachyonychia congenita (PC) is a rare autosomal dominant disease whose main clinical features include hypertrophic onychodystrophy and palmoplantar keratoderma. The new classification is based on genetic variants with mutations in keratin KRT6A, KRT6B, KRT6C, KRT16, KRT17, and an unknown mutation. Here, we present a case of PC with unusual clinical and histological features and a favorable response to oral acitretin. Case: A 49-year-old male presented with diffuse and striate palmoplantar keratoderma, thickened nails, knuckle pads, and pseudoainhum. Histology showed compact hyperkeratosis, prominent irregular acanthosis, and extensive epidermolytic hyperkeratosis, suggestive of Vörner's palmoplantar keratoderma. However, keratin 9 and 1 were not mutated, and full exome sequencing showed heterozygous missense mutation in type I keratin K16. Conclusion: To our knowledge, epidermolytic hyperkeratosis has not been previously described with PC. Our patient had an excellent response, maintained over the last 5 years, to a low dose of acitretin. We wish to emphasize the crucial role of whole exome sequencing in establishing the correct diagnosis.

Knuckle pads are hyperkeratotic, benign skin lesions that we commonly observe in obese patients. There is no study that investigates the association between metabolic syndrome (MetS) and knuckle pads. We aimed to investigate the frequency of MetS in patients with knuckle pads. Forty-seven patients with knuckle pads and 46 age- and sex-matched controls were enrolled. The presence of MetS was evaluated according to National Cholesterol Education Program-Adult Treatment Panel III criteria. In the patient group, waist circumference (P < 0.01), body mass index (BMI; P < 0.01), and systolic (P < 0.01) and diastolic blood pressure (P < 0.01) were higher than controls, and most of the patients had a history of hypertension (P < 0.01). The presence of MetS was found in 66% of the patients with knuckle pads and in 52.2% of the controls (P = 0.25). In the patient group, compared with controls, more patients had blood pressure above reference values or were on antihypertensive therapy (70.2% and 43.5%, P = 0.017, respectively), and had greater waist circumference value (93.6% and 76.1%, P = 0.038, respectively). The presence of the other three criteria were similar in both groups. Although we found similar MetS frequency in both groups, patients with knuckle pads should be examined for the presence of MetS components, especially abdominal obesity and hypertension.

Calpastatin is an endogenous specific inhibitor of calpain, a calcium-dependent cysteine protease. Here we show that loss-of-function mutations in calpastatin (CAST) are the genetic causes of an autosomal-recessive condition characterized by generalized peeling skin, leukonychia, acral punctate keratoses, cheilitis, and knuckle pads, which we propose to be given the acronym PLACK syndrome. In affected individuals with PLACK syndrome from three families of different ethnicities, we identified homozygous mutations (c.607dup, c.424A>T, and c.1750delG) in CAST, all of which were predicted to encode truncated proteins (p.Ile203Asnfs∗8, p.Lys142∗, and p.Val584Trpfs∗37). Immunohistochemistry shows that staining of calpastatin is reduced in skin from affected individuals. Transmission electron microscopy revealed widening of intercellular spaces with chromatin condensation and margination in the upper stratum spinosum in lesional skin, suggesting impaired intercellular adhesion as well as keratinocyte apoptosis. A significant increase of apoptotic keratinocytes was also observed in TUNEL assays. In vitro studies utilizing siRNA-mediated CAST knockdown revealed a role for calpastatin in keratinocyte adhesion. In summary, we describe PLACK syndrome, as a clinical entity of defective epidermal adhesion, caused by loss-of-function mutations in CAST.

Dermatological hand signs are common and can be benign (with or without treatment implications), linked to a change in patient's behaviour or herald more severe systemic conditions (dermatomyositis). Despite the peculiarity of underlying diseases, their visual appearances may overlap and sometimes be deceptive. It is therefore important for clinicians to be aware of the possible similarities in such diverse conditions, in order to make a correct diagnosis and target treatment. ### Which would be the most likely diagnosis for each image based on the cases below: 1. Gottron's papules 2. Psoriasis 3. Cutaneous T-cell lymphoma 4. Chewing pads 5. Knuckle calluses 6. Herpetic lesions 7. Idiopathic/familial knuckle pads 8. Cold burns (frost bites) 9. Common warts 10. Occupational lesions We evaluated a 17-year-old girl with dark phototype with an upper respiratory tract infection. Physical examination incidentally revealed plaque lesions located only at the extensor surface of her right hand, at the proximal interphalangeal joints (IJ) (figure 1A). Left hand was unharmed. The rest of the examination, apart from the concomitant respiratory infection, was negative. The girl also reported a recent school change as a current stressor. Figure 1 (A) Self-induced ‘chewing pads’, (B) Gottron’s papules, …

Epidermolytic palmoplantar keratoderma (EPPK), an autosomal-dominant genodermatosis, is the most frequently occurring hereditary palmoplantar keratoderma. EPPK is characterized by hyperkeratosis of the palms and soles. Approximately 90% of patients present with mutations in the KRT9 gene, which encodes for keratin 9. Many of these mutations are located within the highly conserved coil 1A region of the alpha-helical rod domain of keratin 9, an important domain for keratin heterodimerization. The objective was to assess the clinical and molecular characteristics of a Mexican family with EPPK. The clinical characteristics of members of this family were analyzed. The KRT9 gene of affected members was polymerase chain reaction amplified from genomic DNA and sequenced. All affected members of the family had hyperkeratosis of the palms and soles with knuckle pads. The R163W mutation in the KRT9 gene was present in all affected individuals who were tested. Although R163W is the most frequent KRT9 mutation in patients with EPPK, only two families have been reported with knuckle pads associated with this mutation. Our findings indicate that knuckle pads can be associated with EPPK and the R163W mutation in a family with a genetic background different from that described here.

Palmar fibromatosis and plantar fibromatosis, called Dupuytren disease and Ledderhose disease (DD, LD), respectively, are chronic inflammatory and hyperproliferative connective tissue disorders which involve the palmar fascia of the hand and the plantar fascia of the foot, where they produce nodules, cords, and contractures; in addition, the overlaying subcutaneous fat and skin layers can be affected. These digitopalmar and digitoplantar alterations are part of a deforming and progressive, irreversible condition and part of a systemic connective tissue disorder (Enzinger and Weiss 1995), which is characterized by typical biochemical changes and additional fibrous deposits located at the dorsal PIP joint (forming knuckle pads), on the ear helix, the hand wrist, the elbow, and the penis forming a penile angulation (Peyronie disease). Although the tissue changes appear to have some pathohistological similarities, many studies and research efforts to identify a single cause of this generalized disorder have failed so far (Tomasek et al. 1999; Rudolph and Vande Berg 1991). Although numerous hypotheses exist about the disease onset and progression, the specific role of mesenchymal stem cells, fibroblasts, and myofibroblasts and the correlation with the clinical development of DD and LD are still not conclusively answered (Rodel and Seegenschmiedt 2016).

Knuckle pads are benign subcutaneous fibrotic plaques. Clinically, these lesions present as slowly enlarging, painless and mobile nodules, typically located at the extensor site of the proximal interphalangeal (PIP) and metacarpophalangeal (MCP) joints. On ultrasound, knuckle pads present as subcutaneous hypoechogenic nodular thickenings. These lesions have a low to intermediate signal intensity on T1-WI and T2-WI MRI. Solely on the clinical presentation and the typical location, the diagnosis of knuckle pads can be made, however the radiologist has to be aware of the imaging features of knuckle pads to avoid misdiagnosis and potentially harmful treatment.