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.

Alertas cutáneas en malignidades sistémicas (parte I) / Cutaneous alerts in systemic malignancy: Part 1

El objetivo de esta revisión es alertar al dermatólogo y a los clínicos en general de los signos y síntomas cutáneos que pueden contribuir al diagnóstico precoz de una neoplasia subyacente. Puesto que la piel es uno de los órganos más accesibles, nunca debe ser ignorada en las enfermedades sistémicas. Posee la ventaja de que su exploración no requiere técnicas agresivas y nos revela datos importantes de la situación del paciente. Habitualmente se abordan los síndromes paraneoplásicos clásicos, pero hay una gran variedad de procesos cutáneos no estrictamente paraneoplásicos, que en un determinado contexto sugieren la presencia de una malignidad o que tienen más riesgo de desarrollarla a lo largo de la vida. Se ha optado por enumerar las distintas dermatosis agrupándolas por su morfología clínica, siguiendo un orden aleatorio. Varios de los procesos comparten signos y síntomas múltiples, por lo que se ha recurrido al más notorio para incluirlo en un determinado grupo (AU)

The aim of this review is to familiarize dermatologists and clinicians in general with cutaneous signs and symptoms that can help lead to an early diagnosis of an underlying malignancy. Because the skin is one of the most accessible organs, it should never be overlooked in systemic disease. Examination of the skin has the advantage of revealing important information about the patient’s condition without requiring the use of invasive techniques. In the literature, most discussions of cutaneous manifestations of internal malignancy refer to classic paraneoplastic syndromes, but a wide variety of skin conditions, while not strictly paraneoplastic, can, in certain contexts, indicate the presence of malignancy or an increased risk of developing cancer later in life. In this review, various skin conditions that can signal malignancy or increased cancer risk are presented in randomly ordered groups based on clinical morphology. Conditions with multiple signs and symptoms have been classified on the basis of their most characteristic feature (AU)

Manifestation of diffuse yellowish keratoderma on the palms and soles in autosomal recessive congenital ichthyosis patients may be indicative of mutations in NIPAL4.

Ichthyosis is a heterogeneous disorder characterized by abnormal skin scaling over the whole body. Autosomal recessive congenital ichthyosis (ARCI) comprises various forms, the most important of which are lamellar ichthyosis (LI) and congenital ichthyosiform erythroderma (CIE). Seven genes have been identified to be causative of ARCI, and these account for disease in 60-80% of the patients. There is notable phenotypic overlap between the major forms of ARCI, and a strong genotype-phenotype correlation has not been found. Here, we initially aimed to identify the causative gene in a large Iranian ARCI pedigree, and subsequently performed genetic analysis on four other affected pedigrees. A genotype-phenotype correlation was sought. Whole genome homozygosity mapping using high-density single nucleotide polymorphism chips was performed on the large pedigree. Linkage to chromosome 5 and a mutation in NIPAL4 causing p.G297R were identified. The same mutation was also identified in two of the remaining four Iranian pedigrees. Two of the NIPAL4 mutation bearing pedigrees were classified as CIE and one as LI. Notably, all NIPAL4 mutation-bearing patients manifested diffuse yellowish keratoderma on the palms and soles. We provide evidence suggesting presentation of this diffuse yellowish keratoderma may be indicative of mutations in NIPAL4, providing an easily assessable genotype-phenotype correlation.

Vohwinkel syndrome: treatment of pseudo-ainhum.

BACKGROUND: Vohwinkel syndrome or keratoderma hereditaria mutilans is a rare autosomal dominant palmoplantar keratosis which manifests in infants and becomes more evident in adulthood. Patients with this mutation present hyperkeratosis of the palms and soles, constricting bands of the digits, usually at the fifth, and starfish-shaped hyperkeratosis on the dorsal aspects of the hands and feet. The disease mostly occurs in white women, where constricting fibrous bands appear on the digits and can lead to progressive strangulation and auto-amputation (pseudo-ainhum). AIM: The treatment of this keratoderma is very difficult and tends to be symptomatic: topical keratolytics and systemic retinoids have been used to treat hyperkeratosis, but without consistent results. Reconstructive surgery is utilized for the treatment of pseudo-ainhum. RESULTS AND CONCLUSION: In this study, we present an additional case of Vohwinkel syndrome in which constrictive bands of the fifth digit in the left hand were treated with a cross finger flap, with a favorable outcome after 18 months of follow-up.

Palmoplantar keratoderma as the initial sign in a peripheral T-cell lymphoma.

A 27-year-old male with an acquired severe, diffuse palmoplantar keratoderma as the initial sign of peripheral T-cell lymphoma is reported.

Caso clínico: Brote agudo de Psoriasis en un infectado por el VIH / Clinical case: severe attack of psoriasis in an hiv infected patient

La Psoriasis, que parece no tener una mayor prevalencia en infectados por el VIH, sí que presenta en su evolución en estos casos diferencias significativas ligadas no solo a la inmunodepresión, sino también a la propia acción del virus sobre los factores que influyen en la agudización de la psoriasis, como la estimulación de los queratinocitos, favorecer la presencia de infecciones en la piel, o la liberación de sustancia P que favorece igualmente el incremento queratinocítico. Se presenta un caso clínico y su expresión gráfica a través de las imágenes acompañantes(AU)

Psoriasis, which does not appear to have greater prevalence amongst HIV+ patients, does however present in its progress significant differences in these cases that are not only linked to immunodepression, but also to action of the virus itself on factors that aggravate psoriasis, such as the stimulation of keratinocytes, the favouring of skin infections, or the liberation of substance P, which also encourages growth in keratinocytes. A clinical case is presented along with explanatory images(AU)

Síndrome tilose hereditária e câncer de esôfago / Hereditary tylosis syndrome and esophagus cancer

A tilose palmo-plantar é um distúrbio autossômico dominante caracterizado por uma hiperceratose palmo-plantar. Em geral, desenvolve-se na segunda infância e se acentua em áreas de pressão. Existem duas formas familiares de tilose palmo-plantar: a não epidermolítica e a epidermolítica. Os pacientes com tilose palmo-plantar forma epidermolítica apresentam uma chance até 40 por cento maior de desenvolver carcinoma de células escamosas do esôfago. A associação de tilose palmo-plantar com neoplasia esofágica é denominada síndrome de Howel-Evans.

Tylosis palmoplantaris is an autosomal dominant disorder characterized by hyperkeratosis of palms and soles. Lesions start during childhood and are more evident in areas of pressure. Familial tylosis palmoplantaris comprises two forms: epidermolytic and non-epidermolytic. Patients with the epidermolytic variant have up to 40 percent higher chance of developing squamous cell carcinoma of the esophagus. The association of tylosis palmoplantaris with esophageal cancer is called Howel-Evans syndrome.

[Hereditary tylosis syndrome and esophagus cancer]. / Síndrome tilose hereditária e câncer de esôfago.

Tylosis palmoplantaris is an autosomal dominant disorder characterized by hyperkeratosis of palms and soles. Lesions start during childhood and are more evident in areas of pressure. Familial tylosis palmoplantaris comprises two forms: epidermolytic and non-epidermolytic. Patients with the epidermolytic variant have up to 40% higher chance of developing squamous cell carcinoma of the esophagus. The association of tylosis palmoplantaris with esophageal cancer is called Howel-Evans syndrome.

Transgrediens et progrediens palmoplantar keratoderma (Greither disease) and confluent and reticulated papillomatosis of Gougerot and Carteaud in the same patient: a coincidental finding?

A 13-year-old patient with typical findings of transgrediens et progrediens palmoplantar keratoderma that developed confluent and reticulated papillomatosis of Gougerot and Carteaud is presented. Although coexistence of the two disorders might be coincidental, the possibility of common pathogenetic pathways resulting in alterations of keratinization could be of investigational interest.

Genetics of gastroesophageal cancer: paradigms, paradoxes, and prognostic utility.

Hereditary diffuse gastric cancer and tylosis are autosomal dominant cancer susceptibility syndromes. Accumulating evidence also suggests a genetic contribution to Barrett's esophagus and adenocarcinoma, traditionally considered acquired disorders. In this article we review the current knowledge on the genetic mechanisms underlying hereditary diffuse gastric cancer, tylosis, and Barrett's esophagus. Hereditary diffuse gastric cancer is a paradigm for hereditary cancer susceptibility syndromes with E-cadherin implicated as the dominant oncogene in up to one-third of cases. Tylosis in contrast remains the paradox as whilst the putative abnormality has been localized to the long arm of chromosome 17, sequencing of this region has failed to reveal a disease causing mutation. In the case of Barrett's esophagus and adenocarcinoma, although a validated specific disease-associated gene is yet to be identified, the increasing body of evidence of a possible genetic link is paving the way for subsequent prognostic studies such as AspECT (Aspirin Esomeprazole Chemoprevention Trial). For the clinician these advances in understanding are already having implications for practice in terms of improved screening and the stratification of management strategies. As the mechanisms continue to be defined, there is the real possibility that these mechanisms could be exploited or subverted in the design of new therapies. In the meantime, however, clinicians should undertake rigorous biopsy programs to ensure early invasive lesions are detected.

An investigation of the tylosis with oesophageal cancer (TOC) locus in Iranian patients with oesophageal squamous cell carcinoma.

Oesophageal cancer is one of the ten leading causes of cancer mortality worldwide. Earlier loss of heterozygosity (or allelic imbalance) studies have implicated regions on chromosomes 3p, 5q, 9p, 13q, 17p, 17q, and 18q in the development of sporadic oesophageal cancer and recent data have linked the familial tylosis with oesophageal cancer (TOC) gene-containing region on chromosome 17q25 with this cancer. We have studied allelic imbalance (AI) at microsatellite markers both closely linked to and distant from the TOC gene locus in 60 sporadic squamous cell oesophageal cancers from Iran and have investigated the most likely candidate gene by mutation analysis in these tumours. Forty-four out of these 60 samples (73%) show allelic imbalance at one or more loci within or adjacent to the TOC minimal region, while the highest incidence of AI was observed at the D17S2244 and D17S2246 loci (almost 70% AI in informative cases), correlating with the TOC minimal region. Analysis of the coding regions of a candidate gene in these tumours failed to show an equivalently high incidence of mutation, although two mutations and one polymorphism were observed. These data support and extend previous observations that the TOC region of chromosome 17q25 may be involved in the aetiology of the sporadic form of oesophageal cancer from a number of different geographical populations and suggest that the causative gene may be epigenetically silenced rather than mutated.

Multiple myeloma in a patient with systemic lupus erythematosus, myasthenia gravis and non-familial diffuse palmoplantar keratoderma.

The coexistence of autoimmune diseases and malignancies including lymphoproliferative diseases is often reported in the literature. Here we report an unusual case with two autoimmune diseases--myasthenia gravis (MG) and systemic lupus erythematosus (SLE) associated with unique palmoplantar keratoderma (PK) which preceded the development of multiple myeloma (MM) for twenty and seven years respectively. MG associated with non-malignant thymoma developed in 1981 and was successfully treated with thymectomy and physostigmine. Thirteen years later SLE was diagnosed and until now it is also accompanied by skin lesions corresponding to non-familial, diffuse palmoplantar keratoderma which is resistant to treatment. In 2001 the patient revealed inguinal and abdominal lymphadenopathy first diagnosed as extramedullary plasmacytoma and then as multiple myeloma on the basis of bone marrow infiltration and monoclonal gammopathy. Therapy with VAD regimen achieved complete remission of the MM and significant improvement of the skin changes lasting for six months. We failed to collect sufficient numbers of CD 34+ cells for peripheral blood stem cell transplantation. Now the malignancy is in partial remission after CHOP therapy and the skin lesions have returned to their initial status. To our knowledge, this is the first case to be reported with coexistence of these four diseases.

Novel microsatellite markers and single nucleotide polymorphisms refine the tylosis with oesophageal cancer (TOC) minimal region on 17q25 to 42.5 kb: sequencing does not identify the causative gene.

Tylosis (focal non-epidermolytic palmoplantar keratoderma) is associated with the early onset of squamous cell oesophageal cancer in three families. Linkage and haplotype analyses have previously mapped the tylosis with oesophageal cancer ( TOC) locus to a 500-kb region on chromosome 17q25 that has also been implicated in sporadically occurring squamous cell oesophageal cancer. In the current study, 17 additional putative microsatellite markers were identified within this 500-kb region by using sequence data and seven of these were shown to be polymorphic in the UK and US families. In addition, our complete sequence analysis of the non-repetitive parts of the TOC minimal region identified 53 novel and six known single nucleotide polymorphisms (SNPs) in one or both of these families. Further fine mapping of the TOC disease locus by haplotype analysis of the seven polymorphic markers and 21 of the 59 SNPs allowed the reduction of the minimal region to 42.5 kb. One known and two putative genes are located within this region but none of these genes shows tylosis-specific mutations within their protein-coding regions. Alternative mechanisms of disease gene action must therefore be considered.

Hiperqueratosis digitada diminuta múltiple / Multiple minute digitate hyperkeratoses

Una mujer de 50 años presentaba cientos de pequeñas lesiones papulosas hiperqueratósicas distribuidas por el tronco y la zona proximal de extremidades, sin afectación palmoplantar ni de los anejos cutáneos. Al microscopio las lesiones mostraban hiperqueratosis ortoqueratósica. La hiperqueratosis digitada diminuta múltiple tiene varias formas de presentación: familiar (con inicio en la segunda y tercera década de la vida), esporádica y postinflamatoria. El estudio histopatólogico demuestra que las formas familiares y esporádicas tienen características semejantes, diferentes de las formas postinflamatorias. (AU)

Carcinoma of stomach in a patient with familial tylosis.

The association of tylosis with esophageal cancer has been extensively reported but association with gastric cancer is rare. We report a 55-year-old man with familial tylosis and carcinoma of the stomach for which radical gastrectomy was done. Repeat endoscopy 3 years later is normal.

To B or not to B: is tylosis B truly benign? Two North American genealogies.

Tylosis is a rare, autosomal dominant syndrome presenting with hyperkeratosis of the palms and soles of the feet. Two types have been identified. Late onset tylosis (type A) is reported to be associated with a high incidence of esophageal carcinoma, whereas early onset tylosis (type B) appears to be a benign disorder. This distinction has significant implications for surveillance and prognosis. We report two families exhibiting early onset type B tylosis, spanning five and seven generations, respectively, and believe these to be the first two extensive genealogies of tylosis type B reported in North America. They serve to verify the features of type B tylosis and its benign prognosis. The world literature is reviewed and clinical relevance is discussed. Recommendations for follow-up of afflicted individuals are proposed.