Sara Moradi Tuchayi

Assessment of rosacea severity: A review of evaluation methods used in clinical trials

BACKGROUND Novel rosacea treatments are needed. Assessment methodologies for clinical trials of rosacea treatments are not standardized and are relatively inadequate. To determine the efficacy of new treatments, a valid and reliable assessment methodology is needed. OBJECTIVE We sought to determine the assessment methodologies used in clinical trials for rosacea treatments, to demonstrate the need for a valid and reliable assessment tool, and to describe the relevant properties of such a tool. METHODS PubMed and MEDLINE were searched for clinical trials of rosacea treatments since January 1, 1985. RESULTS In all, 32 clinical trials met inclusion criteria. Assessment methodologies were highly variable, and standardized assessment methodologies were used in only 3 studies. The various manifestations of rosacea were assessed inconsistently. LIMITATIONS Eighteen articles could not be included as a result of lack of access to the full text. CONCLUSIONS The diverse methodologies make the assessment of novel treatments and comparison of treatments difficult. A valid and reliable assessment tool is needed to properly assess novel treatments to improve the management of rosacea.

Thymic stromal lymphopoietin blocks early stages of breast carcinogenesis

Advances in the field of cancer immunology, including studies on tumor-infiltrating CD8+ cytotoxic T lymphocytes (CTLs), have led to new immunotherapeutics with proven efficacy against late-stage cancers. However, the antitumor potential of the immune system in targeting early-stage cancers remains uncertain. Here, we demonstrated that both genetic and chemical induction of thymic stromal lymphopoietin (TSLP) at a distant site leads to robust antitumor immunity against spontaneous breast carcinogenesis in mice. Breast tumors exposed to high circulating levels of TSLP were arrested at an early adenoma-like stage and were prevented from advancing to late carcinoma and metastasis. Additionally, CD4+ Th2 cells mediated the antitumor effects of TSLP, challenging the notion that Th2 cells only promote cancer. We also discovered that TSLP is expressed by the breast tumor cells themselves and acts to block breast cancer promotion. Moreover, TSLP-induced immunity also blocked early stages of pancreatic cancer development. Together, our findings demonstrate that TSLP potently induces immunity directed against early stages of breast cancer development without causing inflammation in the normal breast tissue. Moreover, our results highlight a previously unappreciated function of the immune system in controlling the early development of cancer and establish a fundamental role for TSLP and Th2 cells in tumor immunity against early-stage cancers.

Randomized trial of calcipotriol combined with 5-fluorouracil for skin cancer precursor immunotherapy

BACKGROUND. Actinic keratosis is a precursor to cutaneous squamous cell carcinoma. Long treatment durations and severe side effects have limited the efficacy of current actinic keratosis treatments. Thymic stromal lymphopoietin (TSLP) is an epithelium-derived cytokine that induces a robust antitumor immunity in barrier-defective skin. Here, we investigated the efficacy of calcipotriol, a topical TSLP inducer, in combination with 5-fluorouracil (5-FU) as an immunotherapy for actinic keratosis. METHODS. The mechanism of calcipotriol action against skin carcinogenesis was examined in genetically engineered mouse models. The efficacy and safety of 0.005% calcipotriol ointment combined with 5% 5-FU cream were compared with Vaseline plus 5-FU for the field treatment of actinic keratosis in a randomized, double-blind clinical trial involving 131 participants. The assigned treatment was self-applied to the entirety of the qualified anatomical sites (face, scalp, and upper extremities) twice daily for 4 consecutive days. The percentage of reduction in the number of actinic keratoses (primary outcome), local skin reactions, and immune activation parameters were assessed. RESULTS. Calcipotriol suppressed skin cancer development in mice in a TSLP-dependent manner. Four-day application of calcipotriol plus 5-FU versus Vaseline plus 5-FU led to an 87.8% versus 26.3% mean reduction in the number of actinic keratoses in participants (P < 0.0001). Importantly, calcipotriol plus 5-FU treatment induced TSLP, HLA class II, and natural killer cell group 2D (NKG2D) ligand expression in the lesional keratinocytes associated with a marked CD4+ T cell infiltration, which peaked on days 10–11 after treatment, without pain, crusting, or ulceration. CONCLUSION. Our findings demonstrate the synergistic effects of calcipotriol and 5-FU treatment in optimally activating a CD4+ T cell–mediated immunity against actinic keratoses and, potentially, cancers of the skin and other organs. TRIAL REGISTRATION. ClinicalTrials.gov NCT02019355. FUNDING. Not applicable (investigator-initiated clinical trial).

Tolerability of Topical Retinoids: Are There Clinically Meaningful Differences Among Topical Retinoids?

Background: Topical retinoids are first-line treatment options for acne vulgaris. These drugs, however, produce varying degree of cutaneous irritation within the first few weeks of treatment. Objective: Our purpose was to examine differences in tolerability of topical retinoids and assess whether these differences would be clinically meaningful. Methods: A PubMed search was performed for sources on topical retinoids in acne vulgaris treatment. Thirty-four clinical studies were analyzed. Results: Thirteen studies had statistically significant results on tolerability of retinoid based on retinoid, vehicle, concentration, or skin type. All studies classified most of skin reactions as mild-moderate. Large differences in the number of dropouts due to irritation were not identified. Conclusion: Irritation studies did not show a high frequency of clinically significant irritation with topical retinoids. We anticipate that the large variation in patient use of topical retinoids would likely account for more variation in response than differences between drug formulations.

Rosacea patients seeking advice: Qualitative analysis of patients’ posts on a rosacea support forum

Abstract Background: Social media have become outlets for patients to voice opinions and ask questions. Since suffering from rosacea is an isolating experience and the disease is poorly understood, patients use social media to expand their knowledge about the condition. Objective: To understand rosacea patients’ online health information seeking habits to obtain a better insight of their educational needs. Methods: Ten percent of posts in online rosacea forum composed of 3350 members and 27 051 posts, discussing patient viewpoints and concern, selected by stratified random sampling. Three hundred and nine queries were directly categorized to patients “seeking advice” by two investigators and qualitatively analyzed. Results: Patients primarily sought advice about treatments (n = 155, 50.1%), triggers (n = 53, 17.1%), diet (n = 48, 15.5%), skin care (n = 37, 11.9%) and special presentations of the disease (n = 22, 7.1%). Questions frequently pertained to adverse effects, efficacy and target of therapy (78, 49, 30 posts, respectively). Conclusion: Proactively providing reliable resources and comprehensive explanations on treatments, triggers, diet and skin care could be helpful in reducing patients’ confusion about rosacea and enhancing rosacea patient–physician relationships.

New developments in the treatment of rosacea – role of once-daily ivermectin cream

Rosacea is a chronic dermatological disorder with a variety of clinical manifestations localized largely to the central face. The unclear etiology of rosacea fosters therapeutic difficulty; however, subtle clinical improvement with pharmacologic treatments of various drug categories suggests a multifactorial etiology of the disease. Factors that may contribute to disease pathogenesis include immune abnormality, vascular abnormality, neurogenic dysregulation, presence of cutaneous microorganisms, UV damage, and skin barrier dysfunction. The role of ivermectin in the treatment of rosacea may be as an anti-inflammatory and anti-parasitic agent targeting Demodex mites. In comparing topical ivermectin and metronidazole, ivermectin was more effective; this treatment modality boasted more improved quality of life, reduced lesion counts, and more favorable participant and physician assessment of disease severity. Patients who received ivermectin 1% cream had an acceptable safety profile. Ivermectin is efficacious in decreasing inflammatory lesion counts and erythema.

Interventions to increase adherence to acne treatment

Background Adherence to acne medication is poor and is a major reason why treatment plans are ineffective. Recognizing solutions to nonadherence is critical. Objective The purpose of this study is to describe the hurdles associated with acne nonadherence and to provide mechanisms on how to ameliorate them. Methods PubMed database was searched. Of the 419 search results, 29 articles were reviewed to identify hurdles to adherence and corresponding solutions. Results Hurdles to primary nonadherence where the medication is not even started, include lack of knowledge, confusion about usage, weak physician–patient relationship, fear of adverse reactions, and cost. Secondary nonadherence hurdles where the medication is started but is not taken as directed include lack of results, complex regimens, side effects, busy lifestyle, forgetfulness, inconvenience, and psychiatric comorbidity. Solutions to these hurdles include treatment simplification, technology, and dynamic education. Limitations Adherence is affected by numerous factors, but available literature analyzing acne adherence and interventions to improve adherence to treatment is limited. Conclusion There are several hurdles in adhering to acne treatment. Recognition of these hurdles and finding appropriate solutions may be as important to treatment outcomes as choosing the right medication to prescribe.

Emerging treatment options for psoriasis

License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php Psoriasis: Targets and Therapy 2014:4 27–35 Psoriasis: Targets and Therapy Dovepress

Method and Equipment Selection

Main methods to deliver cryogens include the cryospray and the cryoprobe techniques. A flat cryoprobe applied with pressure can result in a deeper freeze in relation to lateral spread than obtained with the spray method. A pointed cryo probe tip produces an ice ball that is deeper than its radius on the surface whereas a round probe produces a hemisphere-shaped ice ball. Open-ended cryoprobes are devices where a central opening sprays nitrogen on center of a lesion rather than near the enclosed periphery. This is best used with a pyrometer or electrical impedance needle. When selecting a cryosurgical unit find one that is well constructed and has a good safety record. The cryogen of choice is generally LN. Solid carbon dioxide can be used for treatment of benign lesions. Nitrous oxide units are available but have disadvantages and are not recommended for treatment of malignant lesions. Fluorocarbon sprays can be used for treatment of acne pustules and cysts and for peeling of the skin surface, for acne scarring as well as treating plaques of psoriasis, actinic or seborrheic keratoses.

Topical clobetasol in conjunction with topical tretinoin is effective in preventing scar formation after superficial partial-thickness burn ulcers of the skin: A retrospective study

Abstract Background: Deep erythema and inflammation after re-epithelialization of superficial wounds is a sign of scar formation. Corticosteroids may prevent scarring by suppression of inflammation and fibroblast activity. Tretinoin may increase the efficacy of corticosteroids in this setting. Objective: To evaluate the efficacy of corticosteroids plus tretinoin for prevention of scars after superficial wounds. Methods: In a retrospective study of patients with superficial partial thickness thermal skin burn, we compared the patients who received clobetasol plus tretinoin after re-epithelialization with patients who did not receive any medication. Clobetasol propionate 0.05% ointment was used twice daily with overnight occlusive dressing in conjunction with twice weekly topical tretinoin 0.05% cream. Results: Among 43 patients who had light pink or no erythema after re-epithelialization and consequently did not receive clobetasol + tretinoin, no scar was developed. Among patients who had deep erythema after re-epithelialization, rate of scar formation was significantly higher in 14 patients who did not receive clobetasol + tretinoin than in 21 patients who received clobetasol + tretinoin (64% and 19%, respectively; p = 0.01). Conclusion: Clobetasol + tretinoin can significantly decrease the incidence of scar formation in patients with inflammation after re-epithelialization of superficial wounds.