Acrokeratosis paraneoplastica (Bazex syndrome) - a systematic review on risk factors, diagnosis, prognosis and management.

Acrokeratosis paraneoplastica Bazex (Bazex syndrome) is a rare paraneoplastic skin disease defined by erythematous, violaceous, scaly plaques on the hands and feet and on other acral locations such as nose and ears. Bazex syndrome is linked to a variety of underlying malignancies. Usually the skin lesions develop prior to the diagnosis of an internal malignant neoplasm with spontaneous remission after tumour removal. The objective of this study was to review the so far reported risk factors, diagnostic work-up, prognosis and treatment options for Bazex syndrome in a systematic manner. This systematic review is based on a search in MEDLINE, EMBASE and Cochrane Central Register for English and German articles from 1990 to 2015. Evidence on the diagnosis and treatment of Bazex syndrome is limited predominately to case reports or to small case series. There are no randomized controlled trials. A number of underlying tumour entities, predominately oropharyngeal neoplasms and tumours of the gastroenterological tract, but other malignancies were reported. Treatment modalities including topical and systemic corticosteroids, salicylic acid, topical vitamin D analogues, etretinate and PUVA therapy are often ineffective. Due to the small number of patients and the frequent misdiagnosis of this clinical entity, the aim of this systematic review was to call attention to this rare condition and to help clinicians to diagnose and treat Bazex syndrome effectively. Because of the good prognosis of the skin lesions and the tendency to resolve spontaneously if the underlying tumour is treated early, the differential diagnosis of Bazex syndrome should be taken into consideration when dealing with atypical psoriasiform cutaneous lesions. An early diagnosis may improve the patient's prognosis substantially.

[History of the radiation damage in occupations].

In the year following Röntgen`s discovery of X-rays in 1895, approximately 60 cases of hand dermatitis and hair loss induced by radiation were reported. People using X-rays in their occupation, including X-ray tube manufacturers, physicians, and engineers, experienced chronic radiation dermatitis and were the first to be diagnosed with occupational radiation exposure. Reports of later appearing disorders, including skin cancer, suffered by doctors and engineers, were regarded as serious occupational diseases. In the 1910's, blood disorders, including leukemia, in people with occupational exposure to radiation came into focus. Dial painters applying radium to watches with a luminous dial clock face suffered osteomyelitis from about 1914. Other radiation damage reports include radiation death and carcinogenesis in the Chernobyl nuclear power plant accident in 1986, and radiation death in the Tokai-mura JCO accident in 1999. The details of radiation damage in the Fukushima Daiichi Nuclear Power Plant in 2011 have not yet been reported, but must be followed in the future.

Keratin 71 mutations: from water dogs to woolly hair.

The study of rare genetic disorders of the hair follicle has resulted in the identification of many causative genes, leading to the potential for the development of novel therapeutic approaches for both inherited and acquired hair disorders. In this issue, Fujimoto et al. identify a missense mutation within the keratin 71 (KRT71) gene as the cause for autosomal dominant woolly hair/hypotrichosis in a Japanese family. This represents the first human mutation in KRT71 to be linked to a hair disorder, establishing this gene as an important determinant of mammalian hair texture. Moreover, this finding provides new insight into the relationship between similar phenotypes resulting from mutations in distinct regulatory pathways and underscores the role of the inner root sheath in human hair growth.

P-cadherin regulates human hair growth and cycling via canonical Wnt signaling and transforming growth factor-ß2.

P-cadherin is a key component of epithelial adherens junctions, and it is prominently expressed in the hair follicle (HF) matrix. Loss-of-function mutations in CDH3, which encodes P-cadherin, result in hypotrichosis with juvenile macular dystrophy (HJMD), an autosomal recessive disorder featuring sparse and short hair. Here, we attempted to recapitulate some aspects of HJMD in vitro by transfecting normal, organ-cultured human scalp HFs with lipofectamine and CDH3-specific or scrambled control siRNAs. As in HJMD patients, P-cadherin silencing inhibited hair shaft growth, prematurely induced HF regression (catagen), and inhibited hair matrix keratinocyte proliferation. In situ, membrane ß-catenin expression and transcription of the ß-catenin target gene, axin2, were significantly reduced, whereas glycogen synthase kinase 3 ß (GSK3ß) and phospho-ß-catenin immunoreactivity were increased. These effects were partially reversed by inhibiting GSK3ß. P-cadherin silencing reduced the expression of the anagen-promoting growth factor, IGF-1, whereas that of transforming growth factor ß 2 (TGFß2; catagen promoter) was enhanced. Neutralizing TGFß antagonized the catagen-promoting effects of P-cadherin silencing. In summary, we introduce human HFs as an attractive preclinical model for studying the functions of P-cadherin in human epithelial biology and pathology. This model demonstrates that cadherins can be successfully knocked down in an intact human organ in vitro, and shows that P-cadherin is needed for anagen maintenance by regulating canonical Wnt signaling and suppressing TGFß2.

A missense mutation within the helix initiation motif of the keratin K71 gene underlies autosomal dominant woolly hair/hypotrichosis.

Woolly hair (WH) is an abnormal variant of tightly curled hair, which is frequently associated with hypotrichosis. Non-syndromic forms of WH can show either autosomal-dominant WH (ADWH) or autosomal-recessive WH (ARWH) inheritance patterns. ARWH has recently been shown to be caused by mutations in either the lysophosphatidic acid receptor 6 (LPAR6) or lipase H (LIPH) gene. More recently, a mutation in the keratin K74 (KRT74) gene has been reported to underlie ADWH. Importantly, all of these genes are abundantly expressed in the inner root sheath (IRS) of human hair follicles. Besides these findings, the molecular mechanisms underlying hereditary WH have not been fully disclosed. In this study, we identified a Japanese family with ADWH and associated hypotrichosis. After exclusion of known causative genes, we discovered the heterozygous mutation c.422T>G (p.Phe141Cys) within the helix initiation motif of the IRS-specific keratin K71 (KRT71) gene in affected family members. We demonstrated that the mutant K71 protein led to disruption of keratin intermediate filament formation in cultured cells. To our knowledge, it is previously unreported that the KRT71 mutation is associated with a hereditary hair disorder in humans. Our findings further underscore the crucial role of the IRS-specific keratins in hair follicle development and hair growth in humans.

Genetic skin diseases predisposing to basal cell carcinoma.

Basal cell carcinoma (BCC) is the commonest cancer in humans. Predisposing factors reflect common genetic variations and environmental influences in most cases. However, an underlying Mendelian disorder should be suspected in a specific subset of patients, namely those with multiple, early onset lesions. Some specific conditions, including Gorlin, Bazex-Dupré-Christol and Rombo syndromes, and Xeroderma Pigmentosum, show BCC as a prominent feature. In addition, BCC may represent a relatively common, although less specific, finding in many other genodermatoses. These include disorders of DNA replication/repair functions (Bloom, Werner, Rothmund-Thomson and Muir-Torre syndromes), genodermatoses affecting the folliculo-sebaceus unit (Brooke-Spiegler, Schöpf-Schulz-Passarge and Cowden syndromes), immune response (cartilage-hair hypoplasia and epidermodysplasia verruciformis) and melanin biosynthesis (oculocutaneous albinism and Hermansky-Pudlak syndrome), and some epidermal nevus syndromes. Further conditions occasionally associated with BCCs exist, but the significance of the association remains to be proven.

Patterns of symptoms in women after gynecologic surgery.

PURPOSE/OBJECTIVES: To explore patterns of symptoms over time and the relationships between selected demographic and clinical characteristics. DESIGN: Secondary analysis of longitudinal data. SETTING: A hospital and comprehensive cancer center in the northeastern United States. SAMPLE: 66 women with gynecologic cancers, postsurgical, and scheduled to receive chemotherapy. METHODS: A secondary analysis using descriptive and general estimating equation statistical procedures was conducted on symptom and disease data in a subset of a larger nursing intervention study. MAIN RESEARCH VARIABLES: Demographic and clinical variables including cancer site, new diagnosis or recurrence, stage, treatment, comorbidities, emotional distress, use of a symptom management tool kit, and 10 symptoms over time. FINDINGS: Two patterns of symptoms were identified. The first pattern (pain, bowel dysfunction, disturbed sleep, depression, nausea, and lack of appetite) decreased, and the second pattern (fatigue, anxiety, hair loss, and numbness) remained constant over time. The total number of symptoms decreased over time. Factors associated with symptoms, such as the use of a tool kit and emotional distress, were identified. CONCLUSIONS: Tool kit use by women who experienced fatigue, bowel dysfunction, and anxiety suggests its usefulness as a self-care guide. Explanations for the two patterns of symptoms are discussed. IMPLICATIONS FOR NURSING: Postsurgical management should include management and monitoring of symptoms associated with treatment. Screening for emotional distress is recommended in this population. Use of the tool kit could be an effective postsurgical management strategy for women with gynecologic cancers.

A novel splice-acceptor site mutation in CDH3 gene in a consanguineous family exhibiting hypotrichosis with juvenile macular dystrophy.

Mutations in CDH3 gene, encoding P-cadherin, are responsible for hypotrichosis with juvenile macular dystrophy (HJMD), which is a rare autosomal recessive disorder. The HJMD is characterized by congenital sparse hair on scalp and progressive severe degenerative changes of the retinal macula which leads to variable degrees of blindness. The present study reports a large consanguineous Pakistani family with six individuals affected with HJMD. Genotyping using polymorphic microsatellite markers showed linkage of the family to CDH3 gene on chromosome 16q22.1. Sequence analysis of the CDH3 gene revealed a novel splice site mutation (c.IVS10-1 G â†’ A) in intron 10, which leads to skipping of exon 11 and probably synthesizing a non-functional premature truncated protein.

Hair restoration surgery in patients with pubic atrichosis or hypotrichosis: review of technique and clinical consideration of 507 cases.

BACKGROUND: Pubic atrichosis or hypotrichosis is a common condition in Korean women of Mongolian origin. This results in many patients receiving hair restoration surgery, which is currently thought to be the only definitive therapy. OBJECTIVE: To pursue more natural and realistic-appearing results, to define patient characteristics, and to estimate the survival rate of transplanted pubic hair through restoration surgery, we examined our cases of pubic hair restoration surgery with single-hair grafts. METHODS: We selected 507 patients with pubic atrichosis or hypotrichosis who visited for pubic hair transplantation between March 1, 2001, and February 28, 2005. We reviewed the medical charts of the 507 patients and performed statistical analysis. We also carried out a detailed evaluation of our surgical technique to 100 patients. In addition, 20 patients, who agreed to participate in the study for survival rate, had received transplantation of 40 hairs in a 1.5 x 1.5-cm area after the angular points were tattooed. The number of hairs grown after 1 year of transplantation was counted in each case. RESULTS: Among the 507 subjects, 169(33.3%) were in their 40s. The mean (+/-SD) patient age was 41.3+/-10.8 years. Of these, 115 patients (22.7%) had pubic atrichosis, and 392 patients (77.3%) had pubic hypotrichosis. In addition, 81.7% of atrichosis patients had a family history of atrichosis or hypotrichosis. Pubic atrichosis accompanied axillary atrichosis or hypotrichosis in 60.0 and 38.2% of the cases, respectively. The most common reason for the hair restorative procedure was the subject's sense of inferiority to the same sex (73.8%). The mean number of transplanted hairs was 929.3+/-76.6. The most common design pattern that we used was modified horizontal type (87.0%). The mean survival rate of single-hair grafts on the pubis was 73.6+/-7.6%. CONCLUSION: This study suggested that pubic hair transplantation surgery is a suitable cosmetic procedure to address the inferiority complex of patients with pubic atrichosis or hypotrichosis. Knowledge of natural pubic pattern and normal physiologic features is essential to create a natural and realistic appearance in a given subject.

Genetic hair and nail disorders.

Hair and nails are skin appendages that share with other ectodermal tissues a common developmental pathway. Inherited disorders affecting these two structures therefore very often involve other epithelial components and present with multiple anomalies, generating both physical and psychological distress among patients and their families. The present review briefly describes major recent advances in our understanding of hair and nail genodermatoses.

A gene for hypotrichosis simplex of the scalp maps to chromosome 6p21.3.

Hypotrichosis simplex of the scalp (HSS) is an autosomal dominant form of isolated alopecia causing almost complete loss of scalp hair, with onset in childhood. After exclusion of candidate regions previously associated with hair-loss disorders, we performed a genomewide linkage analysis in two Danish families and localized the gene to chromosome 6p21.3. This was confirmed in a Spanish family, with a total LOD score of 11.97 for marker D6S1701 in all families. The combined haplotype data identify a critical interval of 14.9 cM between markers D6S276 and D6S1607. Localization of the locus for HSS to 6p21.3 is a first step toward identification of the gene. The gene will give important insights into the molecular and cellular basis of hair growth on the scalp.

Flea species from dogs and cats in northern Greece: environmental and clinical implications.

Fleas were identified after being collected from 129 dogs and 38 cats of random breed, sex and age. All these animals, infested with fleas and admitted to the Clinic of Medicine of the Veterinary Faculty in Thessaloniki for routine procedures, were from different habitats and originated from various parts of northern Greece. Ctenocephalides canis was the most common species found on the dogs (71.3%). Conversely, its prevalence in the 14 cats was substantially lower (5.3%). Ctenocephalides felis was found on 97.4% of the cats and 40.3% of the dogs surveyed. Of the other flea species, with much lower prevalence, Pulex irritans (0.8%) and Xenopsylla cheopis (0.8%) were observed only on the dogs. Seventeen dogs (13.2%) and one cat (2.6%) had mixed infestations. Flea-associated dermatoses were observed in 26 dogs (20.2%) and four cats (10.5%). Flea-allergic dermatitis, with its typical manifestations, was seen in ten of the dogs (38.5%) with skin lesions. Three out of four flea-allergic cats presented miliary dermatitis and one symmetrical hypotrichosis.

Schöpf-Schulz-Passarge syndrome.

Three siblings, the children of a marriage between first cousins, are reported with the characteristic ophthalmological and cutaneous changes of the Schöpf-Schulz-Passarge syndrome. There have been only eight reported cases of this disorder, and it has not previously been described in Great Britain.