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.

Coexistence of Lichen Planus Pemphigoides, Palmoplantar Keratoderma of Unna-Thost, and Atopic Dermatitis.

Lichen planus pemphigoides (LPP) is a very rare autoimmune blistering disease associated with lichenoid skin changes. Unna-Thost palmoplantar keratoderma (PKK) is a type of diffuse palmoplantar keratoderma that mostly affects the palms of the hands and soles of the feet. It usually begins in early childhood. We present a unique case of coexistence of LPP, Unna-Thost PPK, and atopic dermatitis (AD). To our knowledge, there are three reported cases of both LPP and Unna-Thost PPK and a few reports of coexistence of Unna-Thost PKK and AD.

Early Presentation of Pityriasis Rubra Pilaris Mimicking Tinea Corporis: Diagnostic Challenges of a Rare Skin Condition.

BACKGROUND Pityriasis rubra pilaris (PRP) is a rare chronic inflammatory skin condition characterized by follicular, papulosquamous, reddish-orange scaling, palmoplantar keratoderma, and erythema with islands of sparing. Its heterogeneous clinical presentation makes the diagnosis of PRP quite challenging, especially at the initial presentation, as it can mimic common skin conditions. CASE REPORT We present a case with an early presentation of PRP in a 61-year-old Malay woman with underlying uncontrolled diabetes, and discuss evolving clinical course of her disease. She presented to a primary care clinic with a 3-week history of itchy, ring-like skin lesions that started on her neck and chest but subsequently spread widely on her chest, back, and upper extremities. She was first treated as having extensive tinea corporis but responded poorly to multiple courses of antifungal treatment. An initial skin biopsy that was taken at the dermatology clinic revealed features suggestive of erythema annulare centrifugum. However, despite topical steroid treatment, her skin condition evolved further and she developed generalized erythroderma along with follicular hyperkeratosis and palmoplantar keratoderma. A repeat biopsy finally confirmed the diagnosis of PRP. CONCLUSIONS Making the diagnosis of PRP is challenging for clinicians. However, clinicians should approach any common skin problem that does not respond to treatment appropriately, with consideration of other uncommon skin disorders. A repeat skin biopsy may be considered if there are any doubts about the diagnosis. A clinical and histopathological correlation is important to aid in the diagnosis of PRP.

[Clinical Characteristics and Gene Mutations in 186 Cases of Kindler Syndrome].

Objective To investigate the clinical characteristics and genetic mutations in Kindler syndrome(KS)and provide a theoretical basis for the diagnosis and treatment of KS. Methods The clinical data of one case of KS from Peking Union Medical College Hospital and 185 cases reported in literature were collected. The gene mutation types,patient clinical data,and tumor characteristics were statistically analyzed. Results A total of 186 cases were enrolled,including 110 males and 76 females,with the mean age of(28±16)years. The data of gene mutation and specific clinical manifestations were available in 151 and 94 patients,respectively. The main clinical manifestations of KS included poikiloderma,occurrence of blister in childhood,and photosensitivity,and the secondary clinical manifestations included oral inflammation,palmoplantar keratoderma,webbing/pseudoainhum,dysphagia,urethral stricture and so on.Oral inflammation(r=0.234,P=0.023),palmoplantar keratoderma(r=0.325,P=0.001),webbing/pseudoainhum(r=0.247,P=0.016),dysphagia(r=0.333,P=0.001),urethral stricture(r=0.280,P=0.006)were significantly correlated with age,showing significantly higher incidence in the patients over 32 years old.Urethral stricture(χ2=11.292,P=0.001)and anal stenosis(χ2=4.014,P=0.045)were significantly correlated with sex,with higher incidence in males.Eighty different mutations were found in 151 patients,and the most common gene mutation was c.676C>T.Forty-one tumors occurred in 27 patients,among which squamous cell carcinoma accounted for 92.7%. The gene mutation site had no significant correlation with squamous cell carcinoma or patient country. Conclusions The c.676C>T in FERMT1 gene is the most common mutation in KS.The patients are prone to squamous cell carcinoma and mainly attacked at the exposure sites(hand and mouth).

A novel desmoplakin mutation causes dilated cardiomyopathy with palmoplantar keratoderma as an early clinical sign.

BACKGROUND: PPKs represent a heterogeneous group of disorders with hyperkeratosis of palmar and/or plantar skin. PPK, hair shaft abnormalities, cardiomyopathy and arrhythmias can be caused by mutations in desmosomal genes, e.g. desmoplakin (DSP). PPK should trigger genetic testing to reveal mutations with possible related cardiac disease. OBJECTIVES: To report a large multigenerational family with a novel DSP mutation associated with early-onset PPK and adult-onset cardiomyopathy and arrhythmias. METHODS: A custom-designed in-house panel of 35 PPK related genes was used to screen mutations in the index patient with focal PPK. The identified DSP mutation was verified by Sanger sequencing. DNA samples from 20 members of the large multigenerational family were sequenced for the DSP mutation. Medical records were reviewed. Clinical dermatological evaluation was performed, including light microscopy of hair samples. Cardiac evaluation included clinical examination, echocardiography, cardiac magnetic resonance imaging (CMR), electrocardiogram (ECG), Holter monitoring and laboratory tests. RESULTS: We identified a novel autosomal dominant truncating DSP c.2493delA p.(Glu831Aspfs*33) mutation associated with dilated cardiomyopathy (DCM) with arrhythmia susceptibility and focal PPK as an early cutaneous sign. The mutation was found in nine affected family members, but not in any unaffected members. Onset of dermatological findings preceded cardiac symptoms which were variable and occurred at adult age. CONCLUSIONS: We report a novel truncating DSP mutation causing focal PPK with varying severity and left ventricular dilatation and ventricular extrasystoles. This finding emphasizes the importance of genetic diagnosis in patients with PPK for clinical counselling and management of cardiomyopathies and arrhythmias.

A 45-year-old man with sudden cardiac death, cutaneous abnormalities and a rare desmoplakin mutation: a case report and literature review.

BACKGROUND: Arrhythmogenic cardiomyopathy (AC) is a rare, heritable myocardial disorder that is a leading cause of ventricular arrhythmia and sudden cardiac death (SCD) in young people. Desmoplakin (DSP) mutations account for 3-20% of AC cases. However, the number of patients with DSP mutations is extremely small in all published reports and genotype-phenotype correlations are scant and mostly non-gene-specific. CASE PRESENTATION: A 45-year-old man was admitted after an out-of-hospital cardiac arrest, with documented ventricular fibrillation. He had no previous history of heart disease or family history of SCD or cardiomyopathy. The cardiac magnetic resonance showed a mildly dilated left ventricle with an ejection fraction of 30% and a non-dilated right ventricle with mildly depressed systolic function, and extensive subepicardial late gadolinium enhancement. Genetic screening identified a heterozygote nonsense mutation in DSP (NM_004415.2: c.478 C > T; p.Arg160Ter). Cascade genetic screening of the relatives revealed a high prevalence of the genotype and cutaneous phenotype, but a very low penetrance of the cardiac phenotype. CONCLUSIONS: We report a case of SCD and an autosomal dominant mutation in DSP that causes arrhythmogenic dilated cardiomyopathy/AC. Like the recessive mutation in DSP known to cause Carvajal syndrome, Arg160Ter may be associated with cutaneous abnormalities.

Olmsted Syndrome: Case Report of Nursing Management of Premature Twins.

BACKGROUND: Olmsted syndrome is a rare and complex skin disorder affecting 46 (published) infants as of 2012. The infants affected in this case were born premature at 28 weeks' gestation. Infants affected by this syndrome demonstrate numerous plaques on several specific areas of the skin. Common treatments include exfoliation in addition to psoriasis treatments. The extremely fragile nature of the premature infants' skin complicates treatment modalities. CLINICAL FINDINGS: The progression of the infants' dermatologic findings and plaque formation is discussed in this case study. PRIMARY DIAGNOSIS: The primary diagnosis of Olmsted syndrome was made with the assistance of a multidisciplinary team to work through several differential diagnoses presenting with severe forms of palmoplantar keratoderma. INTERVENTIONS: The management of skin plaques in twin premature infants is presented in this case study. An evidence-based approach, utilizing the model of family-centered care, is presented with multidisciplinary involvement and an outline of the specific plan of care for the extensive skin care regimen used. OUTCOMES: An interdisciplinary skin care regimen was created to provide consistency in transition from hospital to home. Using a consistent approach, the plaques were able to be softened and many removed. Continual maintenance is required to manage continual buildup of skin plaques. PRACTICE RECOMMENDATIONS: Premature infants are at increased risk for infection due to the immaturity of their skin. The complexity of their skin complicates the ability to recognize and care for rare skin disorders. This case study illuminates the practicality of a consistent and evidence-based approach to a complex and rare skin disorder.

Clinical Characteristics and Gene Mutations in 186 Cases of Kindler Syndrome / 中国医学科学院学报

Objective To investigate the clinical characteristics and genetic mutations in Kindler syndrome(KS)and provide a theoretical basis for the diagnosis and treatment of KS. Methods The clinical data of one case of KS from Peking Union Medical College Hospital and 185 cases reported in literature were collected. The gene mutation types,patient clinical data,and tumor characteristics were statistically analyzed. Results A total of 186 cases were enrolled,including 110 males and 76 females,with the mean age of(28±16)years. The data of gene mutation and specific clinical manifestations were available in 151 and 94 patients,respectively. The main clinical manifestations of KS included poikiloderma,occurrence of blister in childhood,and photosensitivity,and the secondary clinical manifestations included oral inflammation,palmoplantar keratoderma,webbing/pseudoainhum,dysphagia,urethral stricture and so on.Oral inflammation(r=0.234,P=0.023),palmoplantar keratoderma(r=0.325,P=0.001),webbing/pseudoainhum(r=0.247,P=0.016),dysphagia(r=0.333,P=0.001),urethral stricture(r=0.280,P=0.006)were significantly correlated with age,showing significantly higher incidence in the patients over 32 years old.Urethral stricture(χ2=11.292,P=0.001)and anal stenosis(χ2=4.014,P=0.045)were significantly correlated with sex,with higher incidence in males.Eighty different mutations were found in 151 patients,and the most common gene mutation was c.676C>T.Forty-one tumors occurred in 27 patients,among which squamous cell carcinoma accounted for 92.7%. The gene mutation site had no significant correlation with squamous cell carcinoma or patient country. Conclusions The c.676C>T in FERMT1 gene is the most common mutation in KS.The patients are prone to squamous cell carcinoma and mainly attacked at the exposure sites(hand and mouth).

Generalized epidermolytic ichthyosis with palmoplantar hyperkeratosis.

Epidermolytic ichthyosis (EI, OMIM 113800) is a rare autosomal dominant keratinization disorder that is caused by keratin 1 or 10 gene mutation. It can be classified clinically based on the presence of palmoplantar hyperkeratosis involvement and extent of skin involvement. The diagnosis is made by clinical and histopathological examinations that can be confirmed by genetic testing. We present a 2-year-old girl who presented with erythematous and thick scaling skin. Her condition began at birth as multiple flaccid blisters that would easily break into erosions. There was no history of similar condition nor consanguinity within her family. Skin examination revealed diffuse erythematous skin covered with thick scales and erosion, predominantly on her face, extremities, palms, and soles. The skin histopathology examination showed diffuse parakeratosis with vacuolar and granular degeneration within granular and spinous layers along the epidermis. She was diagnosed with generalized EI with palmoplantar hyperkeratosis based on the clinical and histopathological examinations. Clinical improvement was observed after a one-month treatment with mupirocin cream, sodium bicarbonate bath, and moisturizer after bathing.

Hair Loss Caused by Gain-of-Function Mutant TRPV3 Is Associated with Premature Differentiation of Follicular Keratinocytes.

Gain-of-function mutations in the TRPV3 gene can cause Olmsted syndrome characterized by palmoplantar and periorificial keratoderma, itch, and hair loss. The mechanism underlying the hair loss remains unclear. In this study, we engineered an Olmsted syndrome mouse model by introducing the point mutation G568V to the corresponding Trpv3 locus in the mice. These mice developed fully penetrant hair loss. The hair loss was associated with premature differentiation of follicular keratinocytes characterized by precocious degeneration of trichohyalin and keratins, increased production of deiminated proteins, elevated apoptosis, and attenuation of transcription regulators (Foxn1, Msx2, Dlx3, and Gata3) known to regulate hair follicle differentiation. These abnormalities occurred in the medial‒proximal region of the inner root sheath and the hair shaft, where Trpv3 is highly expressed, and correlated with an impaired formation of the hair canal and the hair shaft. The mutant Trpv3 mice also exhibited increased proliferation in the outer root sheath, accelerated hair cycle, reduction of hair follicle stem cells, and miniaturization of regenerated hair follicles. Findings from this study suggest that precocious maturation of postmitotic follicular keratinocytes drives hair loss in patients with Olmsted syndrome.

Pterigión dorsal y onicólisis asociados a un penfigoide ampolloso / Dorsal Pterygium and Onycholysis Associated With Bullous Pemphigoid

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Spiny keratoderma.

Spiny keratoderma is a rare entity characterized by filiform keratotic lesions on palms and soles. Although there are some inherited cases the majority are acquired. This last variant can be idiopathic or associated with neoplasms and chronic systemic diseases. We report a new case of spiny keratoderma associated with endometrial carcinoma.

AAGAB Mutations in 18 Canadian Families With Punctate Palmoplantar Keratoderma and a Possible Link to Cancer.

BACKGROUND: Punctate palmoplantar keratoderma type 1 (PPPK1) presents in late childhood to adulthood with multiple small discrete hyperkeratotic papules on palms and soles. PPPK1 is an autosomal dominant skin disease caused by AAGAB mutations. It has been suggested that PPPK1 may be associated with an increased predisposition to systemic malignancies. OBJECTIVES: To evaluate the presence of AAGAB mutations in Canadian families with PPPK1 and the possible increased predisposition to systemic malignancies. METHODS: Eighteen unrelated Canadian families with PPPK1 were recruited for this study. Genomic DNA was extracted from saliva and PCR amplification was performed for all AAGAB exons and exon/intron junctions. PCR products were sequenced and analyzed for mutations. A family history of malignancy was obtained from the index case and, when possible, from other family members. RESULTS: We have identified 5 heterozygous AAGAB loss of function mutations in 11 families. The mutation c.370 C>T, p.Arg124* was the most prevalent and was identified in 6 families. A splice site mutation, c.451+3delAAGT, was identified in 2 families. The other mutations c.473delG, p.Gly158Glufs*0; c.550-551insAAT, p.Gly183*; and c.505-506 dupAA, p.Asn169Lysfs*6 were each identified in 1 family. Different cancers were reported in 11 families (Table 1 and Supplemental Figure S1). CONCLUSIONS: AAGAB mutations were found in 11 of 18 families with PPPK1. In some families there appears to be an association with cancer.

Acrokeratoelastoidosis: is there an association between asthma and sporadic cases in children?

Acrokeratoelastoidosis (AKE) is a rare, benign papular keratoderma that presents as keratotic papules on the lateral margins of the palms and soles. It is most commonly inherited in an autosomal dominant fashion, although sporadic cases are also described. We present a sporadic case of AKE in an 11-year-old girl with a past medical history significant for asthma. On literature review, we found three other cases presenting in children with a past medical history of asthma. We suggest a possible association between asthma and sporadic cases of AKE in children. Current understanding of the pathophysiology of AKE and its associated risk factors is limited and no effective treatment exists. Awareness of a possible association with asthma and atopy, careful history recording in young patients presenting with sporadic cases of AKE, and further research may help to delineate the likelihood of an association between AKE and asthma or atopy. Developing a better understanding of the associated factors that may contribute to the disease process may help guide more effective, targeted treatments in the future.