Sinecatechins ointment as a potential novel treatment for usual type vulval intraepithelial neoplasia: a single-centre double-blind randomised control study.

OBJECTIVE: To compare the safety and efficacy of 10% sinecatechins (Veregen® ) ointment against placebo in the treatment of usual type vulvar intraepithelial neoplasia (uVIN). DESIGN: A Phase II double-blind randomised control trial. SETTING: A tertiary gynaecological oncology referral centre. POPULATION: All women diagnosed with primary and recurrent uVIN. METHODS: Eligible patients were randomised 1:1 to receive either sinecatechins or placebo ointment (applied three times daily for 16 weeks) and were followed up at 2, 4, 8, 16, 32 and 52 weeks. MAIN OUTCOME MEASURES: The primary outcome measure, recorded at 16 and 32 weeks, was histological response (HR). Secondary outcome measures included clinical (CR) response, toxicity, quality of life and pain scores. RESULTS: There was no observed difference in HR between the two arms. However, of the 26 patients who were randomised, all 13 patients who received sinecatechins showed either complete (n = 5) or partial (n = 8) CR, when best CR was evaluated. In placebo group, three patients had complete CR, two had partial CR, six had stable disease and two were lost to follow up. Patients in the sinecatechins group showed a statistically significant improvement in best observed CR as compared with the placebo group (P = 0.002). There was no difference in toxicity reported in either group. CONCLUSION: Although we did not observe a difference in HR between the two treatment arms, we found that 10% sinecatechins application is safe and shows promise in inducing clinical resolution of uVIN lesions and symptom improvement, thus warranting further investigation in a larger multicentre study. TWEETABLE ABSTRACT: A randomised control study indicating that sinecatechins ointment may be a novel treatment for uVIN.

Vulval acne: a case series describing clinical features and management.

Intermittent inflammation of the vulval pilosebaceous units is common and usually self-limiting, but some patients experience recurrent and more troublesome symptoms. There is a scarcity of information on this problem. We describe the clinical and histological features in these patients and the response to treatment. A retrospective, observational study of 16 patients with this phenomenon of recurrent, protracted folliculocentric inflammation of the vulval pilosebaceous unit was performed. Details on the clinical features, histology and response to treatment were collected. Mean age at presentation was 32 years (range 21-45). All patients reported recurrent painful papules and pustules on the labia majora and labia minora. Nine patients reported a cyclical pattern to the development of lesions, with premenstrual exacerbation being most common. Histological examination of these lesions showed a folliculocentric microabscess formation surrounded by an acute and chronic inflammatory cell infiltrate, with a focal foreign-body granulomatous reaction. All our patients responded well to tetracycline, antiandrogenic or retinoid therapy. We propose the term 'vulval acne' for this condition and propose a stepwise approach to its management. We hope to highlight this as a common but underreported entity.

Secukinumab for treatment of psoriasis: does secukinumab precipitate or promote the presentation of cutaneous T-cell lymphoma?

Secukinumab is an interleukin (IL)-17 monoclonal antibody inhibiting T-helper (Th)1-mediated immune response. It has proven high efficacy for moderate to severe psoriasis but data on its long-term toxicities are limited. We describe two patients who received secukinumab for clinically presumed psoriasis, but were subsequently diagnosed with mycosis fungoides (MF) following skin biopsies triggered by skin deterioration while on secukinumab. Previous studies suggested decreased numbers of regulatory T cells (Tregs) with increasing stage of MF, which may lead to the shift in the Treg/Th17 balance towards the Th17 pathway. Theoretically, the use of IL-17 monoclonal antibodies to inhibit Th17 pathway may lead to further immunosuppression and disease progression in cutaneous T-cell lymphoma (CTCL) by shifting the balance towards Tregs, although this hypothesis has not been proven. With uncertainty over the role of IL-17 and Treg/Th17 as well as diagnostic challenges in CTCL, we recommend that patients should have a confirmatory skin biopsy prior to the commencement of biologic therapy.

Treatment outcomes of patients with Atopic Dermatitis (AD) treated with dupilumab through the Early Access to Medicines Scheme (EAMS) in the UK.

BACKGROUND: Dupilumab, a monoclonal antibody against interleukin (IL)-4 receptor alpha that inhibits IL-4/IL-13 signalling is indicated in dermatology for the treatment of moderate-to-severe atopic dermatitis (AD) in adult and adolescent patients 12 years and older and severe AD in children 6-11 years, who are candidates for systemic therapy. Dupilumab received Early Access to Medicines Scheme (EAMS) approval for adults in March 2017. OBJECTIVES: The purpose of this study was to assess the efficacy outcomes of treatment with dupilumab in EAMS. METHODS: A retrospective analysis of adult patients enrolled in the dupilumab EAMS in the UK. Scores were assessed at baseline and follow up, including the Eczema Area and Severity Index (EASI), Investigator's Global Assessment Score (IGA) and Dermatology Life Quality Index (DLQI). RESULTS: Data were available for 57 adult patients treated with dupilumab for at least 12 weeks; 73.6% of patients had received prior treatment with 3 or 4 immunosuppressants. Baseline scores for the EASI and DLQI were 27.93 (standard deviation, SD 13.09) and 18.26 (SD 6.18) respectively. AD severity scores showed statistically significant improvement at week 16±4 weeks (p <0.001 for all). The mean change in EASI was 14.13 points with 66.7% and 36.7% achieving a 50% (EASI-50) and 75% (EASI-75) improvement in EASI, respectively at 16+/- 4 weeks. IGA scores improved by at least two categories for 75% patients. DLQI scores decreased by a mean of 9.0 points, with 80% patients demonstrating a MCID 4-point improvement. For 85% patients, clinicians rated the treatment response as being either 'better' (19%) or 'much better' (65%). CONCLUSIONS: Dupilumab is associated with a significant and clinically relevant improvements in AD as measured by patient- and physician-reported outcome measures. Importantly, the clinical efficacy, despite the refractory disease of this EAMS cohort, is comparable to that previously reported in clinical trials.

Venous lakes of the vermillion lip treated by infrared coagulation.

We reviewed the treatment of 20 venous lakes by infrared coagulation in 18 patients. Seventeen cleared after one treatment; in three patients a further treatment was required, and one patient needed a total of three sessions to clear the venous lake. At 1-6 months follow-up there was complete clearance with no discernible mark in all but four patients who had minimal scarring, including the patient who had three treatments.

Topical pimecrolimus in the treatment of genital lichen planus: a prospective case series.

BACKGROUND: A potent topical steroid is the conventional therapy for genital lichen planus (GLP). Side-effects or steroid resistance can be encountered and second-line therapy such as topical tacrolimus may be required. In our experience tacrolimus may be poorly tolerated in genital skin because of a burning sensation. In addition, there is impairment of Langerhans cell function, raising concerns about its long-term use. These adverse effects may not be as marked with pimecrolimus. To our knowledge, pimecrolimus has not been used in the treatment of GLP. OBJECTIVES: To assess the efficacy and tolerability of topical pimecrolimus in the treatment of GLP. METHODS: Eleven women with GLP were recruited: 10 had erosive vulval disease and one had classical lichen planus of perianal skin. Ten patients had poor disease control, and despite using topical steroids appropriately, two of these also had steroid-related side-effects in adjacent unaffected skin. The eleventh patient had adequate disease control but marked steroid atrophy. Topical pimecrolimus 1% cream (Elidel cream; Novartis, Camberley, U.K.) was applied twice daily to affected areas. Patients were followed up between 4 and 6 weeks later. They remain under regular review and at the time of writing mean follow-up is 5.2 months (range 2-10). RESULTS: Nine patients (82%) tolerated pimecrolimus, including three patients previously intolerant of tacrolimus. These nine patients showed a clinical response at 4-6 weeks: two showed a complete response with no residual disease activity visible and seven had a partial response. With longer follow-up, six (55%) of the women had a complete response and three (27%) were considered to have a partial response. Eight patients noted symptomatic improvement and one felt that her symptoms were the same as with steroid use. Two patients (18%) with erosive lichen planus were unable to tolerate pimecrolimus due to local irritation. CONCLUSIONS: We have found that topical pimecrolimus 1% cream is an effective treatment for GLP. Local irritation can limit its use, but it may be better tolerated than topical tacrolimus: three of our complete responders had previously been intolerant of tacrolimus. Topical pimecrolimus may be a valuable second-line treatment for patients with steroid-related side-effects or steroid-resistant GLP.

Pyoderma gangrenosum associated with hidradenitis suppurativa.

Pyoderma gangrenosum (PG) is associated with a number of systemic diseases. PG in association with hidradenitis suppurativa (HS) has been rarely reported. We describe six patients (three men, three women; aged 35--51 years), who developed PG on a background of HS. The onset of PG occurred only after HS had been present for at least two decades. No relationship in disease activity between the two conditions was observed. Three patients described previous severe adolescent acne vulgaris, one had concurrent systemic lupus erythematosus and another had chronic iron-deficiency anaemia. The course of PG was severe and refractory in four patients, who required treatment including high-dose oral corticosteroids, ciclosporin, intravenous immunoglobulin and intravenous cyclophosphamide.

Why are scars pale? An immunohistochemical study indicating preservation of melanocyte number and function in surgical scars.

The cosmetic effect of many mature scars is largely due to their paler appearance than the surrounding skin. The aim of the study was to identify whether melanocytes are present and functioning within pale scars. Cryosections from scar and normal tissue were stained with murine monoclonal antibodies mel-5, c-kit and NKI/beteb to detect melanocytes and precursor melanocytes. The mean number of mel-5 immunopositive melanocytes within scar tissue was similar to that seen in normal skin (26, SEM 3.5, versus 28.9, SEM 4.1, per 200 basal cells). Where paired samples were available, there was no statistically significant difference between scar tissue and adjacent skin (95% CI = -7.8 to +4.6, p=0.53). Masson-Fontana stain for melanin was positive in both scar tissue and adjacent normal skin, with no evidence for differences in melanin transfer to keratinocytes. Our results suggest that neither differences in melanocyte number nor melanogenic activity explain the appearance of scars. It would seem likely that a combination of both vascular and optical factors relating to dermal or epidermal characteristics are more important.

Preoperative monitoring of warfarin in cutaneous surgery.

BACKGROUND: We report a patient who developed postoperative bleeding as a result of inadvertent excessive warfarin intake. We subsequently introduced a policy of checking the international normalization ratio (INR) 24 h before cutaneous surgery for all patients on warfarin. OBJECTIVES: To review the perioperative INR and outcome of all patients on warfarin who had cutaneous surgery from January 1999 to June 2002 at the Department of Dermatology, Sunderland Royal Hospital. METHODS: A retrospective review was undertaken from patients' medical records. RESULTS: Sixty-eight patients (1.84% of total) underwent 85 skin procedures comprising 33 excisions, 16 punch biopsies, 15 curettages, 13 diagnostic biopsies, five shave biopsies, two Mohs micrographic surgical excisions and one delayed reconstruction. Repairs included 50 direct closures, five secondary intention healing, seven local flaps, two full-thickness skin grafts and 20 by electrocautery. Forty-five surgical procedures were undertaken with the INR checked on the day of surgery, 37 procedures within 24 h, and three within 2 days. The preoperative INR ranged from 1.1 to 3.4, median 2.5. There was no excess intraoperative or postoperative bleeding or haematoma for all patients. CONCLUSIONS: Our experience supports the continued and safe use of warfarin for a wide variety of cutaneous surgical procedures with a preoperative INR of < 3.5. We recommend a routine INR before the procedure, preferably within 24 h.