Novel X-linked syndrome of cardiac valvulopathy, keloid scarring, and reduced joint mobility due to filamin A substitution G1576R.

Filamin A (FLNA) is known to be involved in intracellular actin binding, cell migration, scaffolding, and signaling. We report a novel X-linked syndrome characterized by cardiac valvular disease, keloid scarring and reduced joint mobility in male second cousins due to a previously unreported mutation in FLNA. Whole exome sequencing was performed using standard methods and segregation analysis was performed in affected and non-affected family members. A novel hemizygous c.4726G>A (p.G1576R) mutation in FLNA was detected. Segregation analysis performed on multiple maternal family members showed c.4726G>A (p.G1576R) segregated with disease in an X-linked inheritance pattern. The findings in these cases are distinct from previously described FLNA related disorders by virtue of decreased joint mobility and spontaneous keloid scarring. They occur in association with a novel mutation and represent a novel genetic syndrome.

Off-label uses of biologics in dermatology: rituximab, omalizumab, infliximab, etanercept, adalimumab, efalizumab, and alefacept (part 2 of 2).

Recently, dermatologists have witnessed a revolution in our therapeutic armamentarium with the development of several novel biologic immunomodulators. Although psoriasis remains the only condition in dermatology for which the use of biologic immunomodulators has been approved by the Food and Drug Administration, these drugs have the potential to significantly impact the treatment of several inflammatory conditions in dermatology. This article includes a review of the mechanism of action, dosing, and side-effect profile, as well as a review of the current literature on off-label uses of the CD20-positive B-cell antagonist rituximab, the IgE antagonist omalizumab, the tumor necrosis factor-alpha antagonists infliximab, etanercept, and adalimumab, and the T-cell response modifiers efalizumab and alefacept.

A single-center, open-label, prospective pilot study of subcutaneous efalizumab for oral erosive lichen planus.

OBJECTIVE: To evaluate the efficacy of efalizumab in the treatment of oral erosive lichen planus. DESIGN: A single-center, open-label, prospective pilot study. The primary efficacy outcome measure was the change in oral mucosal surface area involvement after 12 weeks of treatment. Secondary outcome measures included the 100-mm visual analog scale (VAS) for pain and a modified Oral Health Impact Profile (OHIP-14) questionnaire. RESULTS: Four adult patients with oral erosive lichen planus were enrolled and treated with efalizumab 0.7 mg/kg subcutaneously at week 0 followed by 1.0 mg/kg weekly from week 1 to week 11. The mean reduction in the affected mucosal surface area was 71.1% (range 57.3% to 96.8%). The mean improvement in the 100-mm VAS for pain was 82%. The mean improvement in the OHIP-14 questionnaire was 69.3%. Significant adverse events included hospitalization for urticaria and a staphylococcal abscess of an artificial hip joint in one patient and drug-induced subacute cutaneous lupus in another patient.

Skin cancer examination teaching in US medical education.

OBJECTIVE: To determine physician preparation for performing the skin cancer examination (SCE). DESIGN: We evaluated medical students' observation, training, and practice of the SCE; hours spent in a dermatology clinic; and self-reported skill level for the SCE by a self-administered survey. PARTICIPANTS: Graduating students at 7 US medical schools during the 2002-2003 academic year. MAIN OUTCOME MEASURES: Percentages of students reporting SCE skill observation, training, and practice. RESULTS: Of 934 students, 659 (70.6%) completed surveys. Twenty-three percent of students had never observed an SCE, 26.7% had never been trained to perform an SCE, and 43.4% had never examined a patient for skin cancer. Only 28.2% rated themselves as somewhat or very skilled in the SCE. This rate dropped to 19.7% among 553 students who had not completed a dermatology elective. Compared with students without training, students who had been trained at least once in the SCE were 7 times more likely to rate themselves as being somewhat or very skilled in the SCE. Sixty-nine percent of students agreed that insufficient emphasis in their medical training was placed on learning about the SCE. CONCLUSIONS: This survey documents the need for more consistent training of medical students in SCE. Even brief curricular additions would augment students' perceived skill levels and improve practice patterns and competencies of future physicians. More frequent and improved SCEs might result in earlier detection of melanoma and nonmelanoma skin cancers by nondermatologists, with significant public health benefits.

Nonscarring inflammatory alopecia associated with the epidermal growth factor receptor inhibitor gefitinib.

Gefitinib (ZD1839, Iressa, AstraZeneca, Wilmington, Del) is a novel oral anticancer agent that acts by blocking the function of the epidermal growth factor receptor. Gefitinib and other drugs that block epidermal growth factor receptor function have been associated with a similar and interesting pattern of cutaneous adverse effects, including follicular acneiform eruptions, xerosis, desquamation, seborrheic dermatitis, chronic paronychia, and hair texture changes. These effects appear to reflect the significance of epidermal growth factor receptor signaling in the skin. Here we present a case of a woman who developed an extensive nonscarring inflammatory alopecia after 2 years of gefitinib therapy.

Off-label uses of biologic agents in dermatology: a 2006 update.

The introduction of a number of biologic therapies into the market has revolutionized the practice of dermatology. These therapies include adalimumab, alefacept, efalizumab, etanercept, infliximab, IVIg, omalizumab, and rituximab. Most dermatologists are familiar with the indications of these medications that have been approved by the Food and Drug Administration; however, numerous off-label uses have evolved. To update the reader on more recent uses of the biologics for off-label dermatologic use, this article will emphasize more recent published data from 2005 through the date of submission in May 2006.