Update on the pathophysiology of psoriasis.

Psoriasis is a genetically programmed pathologic interaction among skin cells, immunocytes, and numerous biologic signaling molecules that is triggered by environmental stimuli. The immune response is a cellular one; type 1 (TH1) and type 17 (TH17) T cells are activated by IL-12 and IL-23 secreted by antigen-presenting cells (APCs) in the skin. Through various cytokines, such as tumor necrosis factor (TNF) α, these cells cause a chronic inflammatory state and alter epidermal hyperproliferation, differentiation, apoptosis, and neoangiogenesis that produce the cutaneous findings seen in this disease. The newer biologic therapies target the immunologic signaling pathways and cytokines identified in the pathogenesis of psoriasis and provide notable clinical improvement. Further study in the pathogenesis of psoriasis can help identify targets for future therapies.

Isotretinoin Monitoring Trends: A National Survey of Dermatologists.

BACKGROUND: Isotretinoin is an effective treatment for nodulocystic acne. Outside of required pregnancy testing, laboratory monitoring suggested by the manufacturers is vague. Dermatologists, therefore, monitor a variety of tests with variable frequency. Despite intense monitoring, the majority of patients do not have gross laboratory abnormalities that warrant changes in management.

OBJECTIVE: To survey US dermatologists regarding laboratory monitoring practices while prescribing isotretinoin.

METHODS: An online survey sent via e-mail to members of the American Academy of Dermatology.

RESULTS: 12,396 surveys were sent with a response rate of ~19%. At baseline >60% of responders check a CBC, LFTs, and a lipid panel. 74% check a monthly lipid panel and LFTs, while 57% check a monthly CBC. 75% report stopping isotretinoin when AST or ALT values reach 3 times normal; 89% report stopping at 4 times normal. When triglycerides reach 4 times normal, 72% stop the medication.

CONCLUSIONS: There is no consensus on isotretinoin monitoring tests and frequency, though the majority of dermatologists surveyed monitor a lipid panel and LFTs.

J Drugs Dermatol. 2017;16(6):557-564.

Zoon's balanitis.

Zoon's balanitis, is typically found in older, uncircumcised males and can be asymptomatic, pruritic, or cause dysuria. The typical appearance is erythematous, discrete, moist plaques with a "cayenne pepper" speckled appearance and an orange hue on the glans penis and sometimes prepuce, which may display "kissing lesions" on areas that are in direct contact with the lesions.These may eventually erode and leave a "rusty stain". Histologically, these have a dense lichenoid infiltrate in the upper and mid dermis with abundant plasma cells.

Sustained clinical resolution of acquired epidermodysplasia verruciformis in an immunocompromised patient after discontinuation of oral acitretin with topical imiquimod.

Increased cases of acquired epidermodysplasia verruciformis (EDV) have been reported in patients with human immunodeficiency virus (HIV). With regard to management, there are no randomized controlled trials in either immunocompetent or immunocompromised patients, and only a limited number of anecdotal treatment options. Systemic retinoids, either independently or in combination with other treatment modalities, have been used with limited success, demonstrating transient clinical response and recurrence of lesions after cessation of therapy. We report a case of an HIV-positive patient with acquired EDV who achieved sustained clinical resolution even after discontinuation of oral acitretin by applying topical imiquimod to prevent recurrence of his lesions.

Down-regulation of sfrp1 in a mammary epithelial cell line promotes the development of a cd44high/cd24low population which is invasive and resistant to anoikis.

BACKGROUND: The Wnt family of secreted proteins is implicated in the regulation of cell fate during development, as well as in cell proliferation, morphology, and migration. Aberrant activation of the Wnt/beta-catenin signaling pathway leads to the development of several human cancers, including breast cancer. Secreted frizzled-related protein 1 (SFRP1) antagonizes this pathway by competing with the Frizzled receptor for Wnt ligands resulting in an attenuation of the signal transduction cascade. Loss of SFRP1 expression is observed in breast cancer, along with several other cancers, and is associated with poor patient prognosis. However, it is not clear whether the loss of SFRP1 expression predisposes the mammary gland to tumorigenesis. RESULTS: When SFRP1 is knocked down in a non-malignant immortalized mammary epithelial cell line (76 N TERT), nuclear levels of beta-catenin rise and the Wnt pathway is stimulated. The SFRP1 knockdown cells exhibit increased expression of the pro-proliferative Cyclin D1 gene and increased cellular proliferation, undergo a partial epithelial-mesenchymal transition (EMT), are resistant to anchorage-independent cell death, exhibit increased migration, are significantly more invasive, and exhibit a CD24low/CD44high cell surface marker expression pattern. CONCLUSION: Our study suggests that loss of SFRP1 allows non-malignant cells to acquire characteristics associated with breast cancer cells.