A hypomorphic Egfr allele does not ameliorate the palmoplantar keratoderma caused by SLURP1 deficiency.

Mutations in SLURP1, a secreted protein of keratinocytes, cause a palmoplantar keratoderma (PPK) known as mal de Meleda. Slurp1 deficiency in mice faithfully recapitulates the human disease, with increased keratinocyte proliferation and thickening of the epidermis on the volar surface of the paws. There has long been speculation that SLURP1 serves as a ligand for a receptor that regulates keratinocyte growth and differentiation. We were intrigued that mutations leading to increased signalling through the epidermal growth factor receptor (EGFR) cause PPK. Here, we sought to determine whether reducing EGFR signalling would ameliorate the PPK associated with SLURP1 deficiency. To address this issue, we bred Slurp1-deficient mice that were homozygous for a hypomorphic Egfr allele. The hypomorphic Egfr allele, which leads to reduced EGFR signalling in keratinocytes, did not ameliorate the PPK elicited by SLURP1 deficiency, suggesting that SLURP1 deficiency causes PPK independently (or downstream) from the EGFR pathway.

Sclerodermoid lesions in a patient with multiple transplants and porphyria cutanea tarda.

Patients with chronic graft versus host disease may exhibit a range of sclerotic features. Herein we present a patient with confirmed porphyria cutanea tarda who subsequently developed chronic graft versus host disease.

Nutrition: the future of melanoma prevention?

BACKGROUND: Melanoma is one of the deadliest forms of skin cancer, having a high metastatic potential and afflicting all age groups. The need for successful preventative measures is particularly urgent as metastatic melanoma is largely incurable. The beneficial role of nutrition and other natural compounds in the prevention and treatment of melanoma has been clearly demonstrated in the past, and is an exciting source for potential therapies in the future. OBJECTIVE: We sought to review updates in the current literature regarding new developments in the relationship between nutrition and melanoma risk and treatment. METHODS: Articles in the public domain regarding the impact of diet, grape seed proanthocyanidins, selenium, vitamin D, vitamin E, epigallocatechin-3-gallate, resveratrol, rosmarinic acid, lycopene, and fig latex on melanoma were included. RESULTS: Grape seed proanthocyanidins, epigallocatechin-3-gallate, resveratrol, rosmarinic acid, lycopene, and fig latex have demonstrated clear anticancer effects toward melanoma. The roles of selenium, vitamin D, and vitamin E, however, have been more controversial. LIMITATIONS: None. CONCLUSIONS: The role of natural compounds in the future of melanoma prevention and treatment is promising and one that is worthy of further exploration.

Aspirin use and melanoma risk: a review of the literature.

In view of the increasing incidence of melanoma, it is critical to find effective preventive approaches. Contradictory evidence has been reported with regard to the possible association of aspirin use and the risk of melanoma. We review these studies and seek to elucidate the mechanism by which aspirin may produce a chemoprotective effect against melanoma.

An unusual presentation and distribution of generalized eruptive syringomas.

A 19-year-old Caucasian man presented with numerous erythematous to flesh-colored papules that appeared in crops on his neck, axillae, buttocks, and lower back. The lesions started on his anterior neck at age 12. At 18 years, new crops of papules appeared on his axillae, back, and buttocks over several months. He reported pruritus in the lesions following exercise and perspiration. He denied any family history of similar lesions. His primary care physician treated him with topical triamcinolone 0.1% cream, which made the lesions smaller, less erythematous, and less pruritic; however, the papules never fully resolved. After discontinuation of the steroids, these erythematous pruritic papules gradually recurred in the same areas of his body. The patient denied any other medical complaints.

A case of lichen planus following Tdap vaccination.

Lichen planus (LP) is an inflammatory dermatosis of unknown etiology that is primarily associated with liver disease. Recently, there have been several reports of LP developing after administration of the hepatitis B, influenza and combined MMR-DTaP-IPV vaccines. Here we report the first case of LP developing on the lower extremities of an otherwise healthy adult male after administration of the Tdap vaccine. We present this case to draw awareness to this observation in light of recently updated Tdap vaccination recommendations.

Minocycline-induced pigmentation mimicking persistent ecchymosis.

We report an unusual case of minocycline-induced pigmentation mimicking persistent ecchymosis in a patient with persistent (20 months' duration) bluish black discoloration of the medial and lateral aspects of the left ankle following an avulsion fracture. We review the common presentations of minocycline-induced pigmentation as well as some of the more unusual presentations.

Rash on the thigh.

The patient's study habits led to the diagnosis in this case.

Poliosis overlying a nevus with blue nevus features.

Poliosis is a localized patch of gray or white hair. Because it can be seen with a variety of disorders and drugs, a full history and exam is indicated. Additionally, it can be associated with underlying benign and malignant tumors, necessitating histological identification. We review the lesions that are reported with poliosis. In addition, we will report a case of poliosis overlying an intradermal nevus with congenital as well as blue nevus features. To the best of our knowledge, blue nevus features associated with poliosis have not been previously described.

Porphyria cutanea tarda associated with Cys282Tyr mutation in HFE gene in hereditary hemochromatosis: a case report and review of the literature.

Porphyria cutanea tarda (PCT) typically presents with complaints of fragile skin, dorsal hand vesicles, erosions, and scars, and increased levels of uroporphyrins. A case of PCT caused by iron overload associated with hereditary hemochromatosis (HH) is reported. The laboratory workup revealed the patient was homozygous for the Cys282Tyr mutation in the HFE (hemochromatosis) gene. The associated diagnosis of HH was critical because without early treatment, damage to vital organs and premature death could occur. This report highlights the important association of PCT with HH and reviews the role of key genetic and hormonal factors in iron regulation.

Palmoplantar Keratoderma in Slurp2-Deficient Mice.

SLURP1, a member of the lymphocyte antigen 6 protein family, is secreted by suprabasal keratinocytes. Mutations in SLURP1 cause a palmoplantar keratoderma (PPK) known as mal de Meleda. SLURP2, another secreted lymphocyte antigen 6 protein, is encoded by a gene located ?20 kb downstream from SLURP1. SLURP2 is produced by suprabasal keratinocytes. To investigate the importance of SLURP2, we first examined Slurp2 knockout mice in which exon 2-3 sequences had been replaced with lacZ and neo cassettes. Slurp2(-/-) mice exhibited hyperkeratosis on the volar surface of the paws (i.e., palmoplantar keratoderma), increased keratinocyte proliferation, and an accumulation of lipid droplets in the stratum corneum. They also exhibited reduced body weight and hind limb clasping. These phenotypes are similar to those of Slurp1(-/-) mice. To solidify a link between Slurp2 deficiency and palmoplantar keratoderma and to be confident that the disease phenotypes in Slurp2(-/-) mice were not secondary to the effects of the lacZ and neo cassettes on Slurp1 expression, we created a new line of Slurp2 knockout mice (Slurp2X(-/-)) in which Slurp2 was inactivated with a simple nonsense mutation. Slurp2X(-/-) mice exhibited the same disease phenotypes. Thus, Slurp2 deficiency and Slurp1 deficiencies cause the same disease phenotypes.

Palmoplantar keratoderma along with neuromuscular and metabolic phenotypes in Slurp1-deficient mice.

Mutations in SLURP1 cause mal de Meleda, a rare palmoplantar keratoderma (PPK). SLURP1 is a secreted protein that is expressed highly in keratinocytes but has also been identified elsewhere (e.g., spinal cord neurons). Here, we examined Slurp1-deficient mice (Slurp1(-/-)) created by replacing exon 2 with ß-gal and neo cassettes. Slurp1(-/-) mice developed severe PPK characterized by increased keratinocyte proliferation, an accumulation of lipid droplets in the stratum corneum, and a water barrier defect. In addition, Slurp1(-/-) mice exhibited reduced adiposity, protection from obesity on a high-fat diet, low plasma lipid levels, and a neuromuscular abnormality (hind-limb clasping). Initially, it was unclear whether the metabolic and neuromuscular phenotypes were due to Slurp1 deficiency, because we found that the targeted Slurp1 mutation reduced the expression of several neighboring genes (e.g., Slurp2, Lypd2). We therefore created a new line of knockout mice (Slurp1X(-/-) mice) with a simple nonsense mutation in exon 2. The Slurp1X mutation did not reduce the expression of adjacent genes, but Slurp1X(-/-) mice exhibited all of the phenotypes observed in the original line of knockout mice. Thus, Slurp1 deficiency in mice elicits metabolic and neuromuscular abnormalities in addition to PPK.

Pox in the docks: varicella outbreak in an Australian prison system.

OBJECTIVES: 1. Describe an outbreak of varicella in a prison system. 2. Highlight the risks of disease transmission within the prison environment. 3. Promote infection control guidelines for high-risk sub-groups within the prison system, including the application of quarantine. SETTING: Four prisons, one prison hospital, the prison transport system, one courthouse. MAIN OUTCOME MEASURES: Number of cases of varicella infection; reported varicella immunity status of cases and contacts; immunity status of known HIV antibody positive inmates. RESULTS: Five cases of chickenpox were identified. There were 23 contacts of the Index Case occurring during transport between prison and court and whilst being held in the court holding cells. Two of these contacts developed chickenpox despite having given a prior history of infection. There were over 300 inmates exposed to varicella zoster virus (VZV) during the outbreak, including one HIV antibody positive inmate who had serologically confirmed immunity. This inmate developed shingles following exposure to VZV from one of the cases. CONCLUSIONS: There is an elevated risk of respiratory transmission of infections such as chickenpox in prisons. Clear guidelines should be in place to protect HIV antibody positive people, pregnant women, and others who are at increased risk of complications from such infections. In the case of varicella, all inmates and staff without documented immunity should be screened to determine immunity, and if non-immune, should be offered VZV vaccination. Every effort should be made to prevent HIV antibody positive inmates being exposed to varicella, regardless of their varicella immunity status. If an HIV antibody positive inmate, who is known to be non-immune is exposed to varicella, Varicella Zoster immunoglobulin should be given within 96 h.