Does imiquimod pretreatment optimize 308-nm excimer laser (UVB) therapy in psoriasis patients?

BACKGROUND/PURPOSE: Psoriasis continues to be a debilitating skin disease affecting 1-3% of the United States population. Although the effectiveness of several current biologic therapies have described this pathology as a IL-23, TNF-a and Th17-mediated disease, less invasive approaches are still in use and in need of refinement. One of these is the usage of narrow band-UVB (NB-UVB) therapy to deplete specifically intra-epidermal CD3+, CD4+ and CD8+ cells to clear psoriatic plaques. AIMS/OBJECTIVES: In order to improve NB-UVB therapy, we sought to determine whether skin pre-treatment with the TLR7 agonist imiquimod (IMQ) would help increase the efficiency of the former at resolving psoriatic plaques. MATERIALS AND METHODS: Eucerin® Original Moisturizing Lotion (topical vehicle) or Aldara® (imiquimod 5% topical cream) were applied for 5 days once daily to a maximum contiguous area of 25 cm2 (5 cm × 5 cm area). Patients were provided with sachets containing 12.5 mg of imiquimod each and were instructed to apply imiquimod (I) to two psoriasis plaques (5 sachets of imiquimod allotted to each plaque). A PHAROS excimer Laser EX-308 (Ra Medical Systems, Inc. Carlsbad, CA, USA) with an output of monochromatic 308-nm light and pulse width of 20-50 ns was used for all patients. Punch biopsies of psoriatic lesions (6 mm) were taken at 4 and 48 h after final application of topical treatment with or without excimer laser treatment. Real-time quantitative RT-PCR was performed according to manufacturer's instructions and Inmunohistochemistry was used as described before. RESULTS: Our results suggests that although IMQ seemed to activate the type I interferon pathway as previously described, its concomitant usage with NB-UVB for clearing psoriatic skin was ineffective. Although upregulation of genes MxA, GRAMD1A and DMXL2 suggested that IMQ treatment did induce skin changes in psoriasis patients, more optimal dosing of IMQ and NB-UVB might be necessary to achieve desired treatment responses. CONCLUSION: The observation that psoriasis involvement was not aggravated by usage of topical IMQ was encouraging. Additional observational studies might be necessary to further tailor the combination of IMQ with NB-UVB therapy to reliably improve the psoriatic pathology.

Subchondral insufficiency fractures and spontaneous osteonecrosis of the knee may not be related to osteoporosis.

UNLABELLED: The term insufficiency fracture implies inadequate bone and is applied to some subchondral knee magnetic resonance images. We reviewed bone mineral density, body mass index, meniscal extrusion, comorbidities, and demographics in 32 knee insufficiency fracture patients. Only five were osteoporotic. Meniscal extrusion was predominant. PURPOSE: The literature supports systemic osteoporosis as a risk fracture for spontaneous osteonecrosis of the knee (SONK). SONK is also called a subchondral insufficiency fracture. Recognizing that insufficiency fracture and SONK are related, we designed this retrospective study to determine if knee subchondral insufficiency fractures were associated with osteoporosis based on bone mineral density. METHODS: Based on magnetic resonance imaging findings, 32 patients were diagnosed as having an insufficiency fracture by an orthopaedic surgeon with magnetic resonance imaging confirmation by a musculoskeletal radiologist. We reviewed body mass index, age, sex, comorbidities, demographics, and bone mineral density using both T-scores and Z-scores. RESULTS: The average age was 70, and only five patients were osteoporotic. Twenty-six of the 32 patients were female. The average age-related Z-score was 1 standard deviation above normal. CONCLUSIONS: We conclude that osteoporosis is not the underlying cause of this disorder in the majority of patients.

Effect of botanicals on inflammation and skin aging: analyzing the evidence.

The skin and its immune system manifest a decline in physiologic function as it undergoes aging. External insults such as ultraviolet light exposure cause inflammation, which may enhance skin aging even further leading to cancer and signs of photoaging. There is a potential role for botanicals as an adjunct modality in the prevention of skin aging. Numerous over-the-counter anti-aging products are commercially available, many of which boast unverified claims to reduce stress, inflammation and correct signs of aging. In this article we reviewed the scientific literature for data on frequently published "anti-inflammaging" additives such as vitamins A, C and E and green tea. We also analyzed the evidence available on five promising ingredients commonly found in anti-aging products, namely, argan oil, rosemary, pomegranate, Coenzyme Q10, and Coffeeberry. Though there may be an increasing amount of scientific data on a few of these novel botanicals, in general, there remains a lack of clinical data to support the anti-aging claims made.

Silicon phthalocyanine 4 phototoxicity in Trichophyton rubrum.

Trichophyton rubrum is the leading pathogen that causes long-lasting skin and nail dermatophyte infections. Currently, topical treatment consists of terbinafine for the skin and ciclopirox for the nails, whereas systemic agents, such as oral terbinafine and itraconazole, are also prescribed. These systemic drugs have severe side effects, including liver toxicity. Topical therapies, however, are sometimes ineffective. This led us to investigate alternative treatment options, such as photodynamic therapy (PDT). Although PDT is traditionally recognized as a therapeutic option for treating a wide range of medical conditions, including age-related macular degeneration and malignant cancers, its antimicrobial properties have also received considerable attention. However, the mechanism(s) underlying the susceptibility of dermatophytic fungi to PDT is relatively unknown. As a noninvasive treatment, PDT uses a photosensitizing drug and light, which, in the presence of oxygen, results in cellular destruction. In this study, we investigated the mechanism of cytotoxicity of PDT in vitro using the silicon phthalocyanine (Pc) 4 [SiPc(OSi(CH3)2(CH2)3N(CH3)2)(OH)] in T. rubrum. Confocal microscopy revealed that Pc 4 binds to cytoplasmic organelles, and upon irradiation, reactive oxygen species (ROS) are generated. The impairment of fungal metabolic activities as measured by an XTT (2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxyanilide inner salt) assay indicated that 1.0 µM Pc 4 followed by 670 to 675 nm light at 2.0 J/cm(2) reduced the overall cell survival rate, which was substantiated by a dry weight assay. In addition, we found that this therapeutic approach is effective against terbinafine-sensitive (24602) and terbinafine-resistant (MRL666) strains. These data suggest that Pc 4-PDT may have utility as a treatment for dermatophytosis.

Single administration of lesion-limited high-dose (TURBO) ultraviolet B using the excimer laser: clinical clearing in association with apoptosis of epidermal and dermal T cell subsets in psoriasis.

BACKGROUND/PURPOSE: Development of effective therapy for psoriasis is confounded by numerous factors contributing to disease pathogenesis, including pathogenic immunocytes which appear to drive epidermal keratinocyte hyperproliferation. Our objective was to study clinical and biomarker effects of a single dose of TURBO laser UVB (308 nm) applied directly to psoriatic plaques. METHODS: Eighteen patients with chronic plaque psoriasis received a single dose of 10 minimal erythema dose (MED) UVB and were followed for 8 weeks. Keratome and punch biopsies were assessed for T cell depletion and apoptosis following a single 308-nm dose of UVB. RESULTS: Patients demonstrated clinical improvement as indicated by decreased global Psoriasis Area and Severity Index scores and reduced numbers of pathogenic memory/effector T cells infiltrating lesional epidermis and dermis. Consistent with apoptosis induction, caspase activation increased in lesional T cells after treatment. CONCLUSION: We conclude that a single 10 MED dose of TURBO UVB is effective at reducing the severity and extent of psoriatic lesions. We hypothesize that the reason a single treatment is sufficient to clear a psoriatic plaque is that the 10 MED dose is able to deliver sufficient photons to a microanatomic area of the lesion where susceptible pathogenic T cell mechanisms are operative.