Early intervention of extracorporeal photopheresis for advancing/progressing cutaneous T-cell lymphoma.

Patients with cutaneous T-cell lymphoma with progressive disease typically undergo a series of skin-directed and systemic therapy regimens during cycles of response and relapse. Extracorporeal photopheresis (ECP) is an effective and safe systemic treatment option, often reserved for later stages of disease and typically employed after failure of several other therapies. ECP has benefits in response rate, time to next treatment, and tolerability that may support its use earlier in the treatment cycle for advancing/progressing disease.

Vitamin K2 Awareness in Sun-Protected Patients Supplementing With Vitamin D.

Dermatologists often recommend vitamin D for sun-protected patients. Most patients are not aware of the key role vitamin K2 plays in vitamin D metabolism and do not receive sufficient dietary vitamin K2. A survey of 50 sun-protecting patients shows 4/50 understood the role of vitamin K2 and 1/50 was supplementing vitamin K2. Therefore, counseling on vitamin K2 supplementation may be of benefit to sun-protected dermatology patients. J Drugs Dermatol. 2021;20(2):228-229. doi:10.36849/JDD.5829.

Formulation and preclinical evaluation of a toll-like receptor 7/8 agonist as an anti-tumoral immunomodulator.

The toll-like receptor 7 and 8 (TLR7/8) agonist Resiquimod (R848) has been recognized as a promising immunostimulator for the treatment of cutaneous cancers in multiple clinical trials. However, systemic administration of R848 often results in strong immune-related toxicities while having limited therapeutic effects to the tumor. In the present study, a prodrug-based nanocarrier delivery system was developed that exhibited high therapeutic efficiency. R848 was conjugated to α-tocopherol to constitute an R848-Toco prodrug, followed by formulating with a tocopherol-modified hyaluronic acid (HA-Toco) as a polymeric nano-suspension. In vitro evaluation showed that the delivery system prolonged the release kinetics while maintaining TLR agonist activities. When administered subcutaneously, the nano-suspension formed a depot at the injection site, inducing localized immune responses without systemic expansion. This formulation also suppressed tumor growth and recruited immune cells to the tumor in a murine model of head and neck cancer. In a preclinical canine study of spontaneous mast cell tumors, the treatment led to a 67% response rate (three partial remissions and one complete remission).

75% Complete Response and 15% Partial Response to Extracorporeal Photopheresis Combined With Other Therapies in Resistant Early Stage Cutaneous T-Cell Lymphoma.

INTRODUCTION: Extracorporeal photopheresis (ECP) has been used for the treatment of advanced stage or treatment refractory cutaneous T-cell lymphoma (CTCL) since 1987, and more recently has also been shown to be of benefit for earlier stage resistant CTCL. Complete response rates in prior studies of ECP in early CTCL have ranged from 0% to 40%. METHODS: We reviewed electronic medical records of all CTCL patients seen in the University of Kansas Cancer Center between June 2007 and May 2011. International review board approval was obtained. Inclusion criteria were (1) early stage CTCL and (2) ECP treatment. Data included demographics, type of intravenous access employed, CTCL subtype, cytogenetic features, adverse events, adjuvant treatments, and survival time in years. Treatment response was assessed via a modified severity weighted assessment tool (mSWAT). Primary outcome measures were response rates to ECP at 6 months and 12 months after beginning treatment. RESULTS: Of 20 patients (13 female; 7 male), 7 were Stage 1A, 11 were 1B, and 2 were 2A. Seven patients with stable disease and 2 patients with progression at 6 months received adjuvant therapy (PUVA/systemic retinoids/metotrexate/interferon) in addition to ECP. Twelve-month response to ECP was 90%: 15 patients (75%) had complete responses, 3 (15%) had partial responses, 1 had stable disease, and 1 progressed. CONCLUSION: Used alone or in combination with adjuvant treatments, ECP can be an effective treatment method in early stage CTCL.

J Drugs Dermatol. 2016;15(10):1212-1216.

Scurvy in the present times: vitamin C allergy leading to strict fast food diet.

Scurvy results from a deficiency of vitamin C, a nutrient otherwise known as ascorbic acid. Today, scurvy is rare yet emerges in select patients. The patient reported herein developed scurvy secondary to deliberate avoidance of vitamin C-rich foods. Classic cutaneous manifestations of scurvy include follicular hyperkeratosis and perifollicular hemorrhage encompassing coiled "corkscrew" hairs and hairs bent into "swan-neck" deformities. Ecchymoses, purpura, and petechiae are also characteristically prominent. Classic oral abnormalities include erythematous, swollen gingivae that hemorrhage from subtle microtrauma.Subungual linear splinter hemorrhages may also manifest as a sign of the disease. To establish the diagnosis requirements include characteristic physical exam findings, evidence of inadequate dietary intake, and rapid reversal of symptoms upon supplementation. Although unnecessary for diagnosis, histological findings demonstrate perifollicular inflammation and hemorrhage, fibrosis, and hyperkeratosis, amongst dilated hair follicles and keratin plugging. Although citrus fruit allergies have been historically documented, ascorbic acid has not been previously reported as an allergen. Although lacking absolute certainty, this report suggests a presumed case of ascorbic acid allergy based on patient history and favorable response to ascorbic acid desensitization therapy.

Safe and efficacious use of intralesional steroids for the treatment of focally resistant mycosis fungoides.

Cutaneous T-cell lymphoma is a cancer of skin-homing T cells, of which mycosis fungoides (MF) is the most common variant. MF treatments range from topical steroids to systemic chemotherapy. Resistant cutaneous MF nodules can present a special challenge in that typical topical therapies may not penetrate thick lesions, and increasing systemic therapy brings added risk of side effects. We report successful use of intralesional steroids (ILS) for treatment-resistant MF, including tumor-stage plaques and nodules in 4 consecutive patients with focally resistant MF. ILS have been widely used to treat a broad range of cutaneous conditions such as alopecia areata and keloids. Side effects of ILS include hypopigmentation, atrophy, telangiectasias, lilac discoloration, acne, and striae. Rarely, and in circumstances involving unusually large doses, ILS may cause Cushing's syndrome, hypothalamus-pituitary-adrenal axis suppression, and reduced bone mineral density. The MF patients tolerated treatment well without any of the above side effects other than local hypopigmention in a single patient. These results point toward further exploration into ILS as a treatment for focally resistant MF.

Consumption of polyphenol plants may slow aging and associated diseases.

Slowing aging is a widely shared goal. Plant-derived polyphenols, which are found in commonly consumed food plants such as tea, cocoa, blueberry and grape, have been proposed to have many health benefits, including slowing aging. In-vivo studies have demonstrated the lifespan-extending ability of six polyphenol-containing plants. These include five widely consumed foods (tea, blueberry, cocoa, apple, pomegranate) and a flower commonly used as a folk medicine (betony). These and multiple other plant polyphenols have been shown to have beneficial effects on aging-associated changes across a variety of organisms from worm and fly to rodent and human.

Potentiation of dietary restriction-induced lifespan extension by polyphenols.

Dietary restriction (DR) extends lifespan across multiple species including mouse. Antioxidant plant extracts rich in polyphenols have also been shown to increase lifespan. We hypothesized that polyphenols might potentiate DR-induced lifespan extension. Twenty week old C57BL/6 mice were placed on one of three diets: continuous feeding (control), alternate day chow (Intermittent fed, IF), or IF supplemented with polyphenol antioxidants (PAO) from blueberry, pomegranate, and green tea extracts (IF+PAO). Both IF and IF+PAO groups outlived the control group and the IF+PAO group outlived the IF group (all p<0.001). In the brain, IF induced the expression of inflammatory genes and p38 MAPK phosphorylation, while the addition of PAO reduced brain inflammatory gene expression and p38 MAPK phosphorylation. Our data indicate that while IF overall promotes longevity, some aspects of IF-induced stress may paradoxically lessen this effect. Polyphenol compounds, in turn, may potentiate IF-induced longevity by minimizing specific components of IF-induced cell stress.

A review of photodynamic therapy (PDT) for the treatment of acne vulgaris.

BACKGROUND: Photodynamic therapy (PDT) is increasing in dermatology. Antibiotic resistance and the challenges of isotretinoin therapy have led to investigation of PDT in the treatment of acne vulgaris. OBJECTIVE: To review the results of clinical trials and case series with respect to light source, topical photosensitizing agent, adverse events, efficacy and skin type. METHODS: A non-critical review is presented of a PubMed search for studies examining PDT in the treatment of acne vulgaris. RESULTS: The authors found 21 clinical trials and case series of various designs. Eight studies employed a split-face design comparing photosensitizer to placebo, no treatment or another photosensitizer. Two trials used three test spots and one control spot per patient. Three studies utilized control subjects receiving no photosensitizer with or without light therapy. All 21 studies reported a reduction in inflammatory lesions and/or a significant improvement in acne. The light sources utilized included blue light, pulsed-dye laser (PDL), intense pulsed light (IPL) and red light. Studies comparing the use of PDT to light therapy alone demonstrated greater improvement in treatment groups pretreated with a photosensitizer. CONCLUSION: All studies reported reduction in inflammatory lesions or significant improvement in acne. Several studies confirm a light source combined with photosensitizer is superior to light alone. Adverse reactions including photosensitivity, pustular eruptions, and crusting varied among photosensitizers and light sources. PDT appears to be a useful therapeutic option for acne patients who are recalcitrant to standard treatments and poor candidates for systemic retinoids. Further studies are still needed before a consensus protocol can be established. Additional investigations are needed to establish optimal incubation time, activating light source and frequency of treatment.