Anakinra for palmoplantar pustulosis: results from a randomized, double-blind, multicentre, two-staged, adaptive placebo-controlled trial (APRICOT).

BACKGROUND: Palmoplantar pustulosis (PPP) is a rare, debilitating, chronic inflammatory skin disease that affects the hands and feet. Clinical, immunological and genetic findings suggest a pathogenic role for interleukin (IL)-1. OBJECTIVES: To determine whether anakinra (an IL-1 receptor antagonist) delivers therapeutic benefit in PPP. METHODS: This was a randomized (1 : 1), double-blind, two-staged, adaptive, UK multicentre, placebo-controlled trial [ISCRTN13127147 (registered 1 August 2016); EudraCT number: 2015-003600-23 (registered 1 April 2016)]. Participants had a diagnosis of PPP (> 6 months) requiring systemic therapy. Treatment was 8 weeks of anakinra or placebo via daily, self-administered subcutaneous injections. Primary outcome was the Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI) at 8 weeks. RESULTS: A total of 374 patients were screened; 64 were enrolled (31 in the anakinra arm and 33 in the placebo arm) with a mean (SD) baseline PPPASI of 17·8 (10·5) and a PPP investigator's global assessment of severe (50%) or moderate (50%). The baseline adjusted mean difference in PPPASI favoured anakinra but did not demonstrate superiority in the intention-to-treat analysis [-1·65, 95% confidence interval (CI) -4·77 to 1·47; P = 0·30]. Similarly, secondary objective measures, including fresh pustule count (2·94, 95% CI -26·44 to 32·33; favouring anakinra), total pustule count (-30·08, 95% CI -83·20 to 23·05; favouring placebo) and patient-reported outcomes, did not show superiority of anakinra. When modelling the impact of adherence, the PPPASI complier average causal effect for an individual who received ≥ 90% of the total treatment (48% in the anakinra group) was -3·80 (95% CI -10·76 to 3·16; P = 0·285). No serious adverse events occurred. CONCLUSIONS: No evidence for the superiority of anakinra was found. IL-1 blockade is not a useful intervention for the treatment of PPP.

Outcomes and pathological review of a cohort of children with melanoma.

BACKGROUND: Prepubertal malignant melanoma is rare, pathological criteria are difficult and follow-up data on patients are lacking in the literature. OBJECTIVES: To review prepubertal cases of melanoma diagnosed in the West of Scotland 1979-2002. METHODS: Twenty cases were identified in whom melanoma was diagnosed before the age of 15. Pathological review was possible for 13 of 20 cases, and current follow-up information is available for all 20. Three pathologists not responsible for the original diagnosis reviewed the slides independently, in every case without knowledge of the outcome. RESULTS: Of the 13 cases reviewed, there was concordance of diagnosis between the three pathologists in 12 cases. Eight of the 13 cases reviewed were considered to be unusual naevi rather than melanoma. One child has died of melanoma and all three pathologists agreed with the original pathological diagnosis. One patient has experienced nodal metastases but is alive and disease-free 12 years later. The remaining 18 cases have had no recurrence since primary surgery 2-21 years ago. CONCLUSIONS: There may be a tendency to overdiagnose prepubertal melanoma. Good communication between clinician and pathologist and the use of an expert pathology panel is recommended before making the diagnosis.

Randomized comparison of photodynamic therapy with topical 5-fluorouracil in Bowen's disease.

BACKGROUND: Bowen's disease (BD; intraepithelial squamous cell carcinoma) is therapeutically challenging because lesions, which may be multiple, are frequently located at sites that heal poorly. There is a small risk of progression to invasive carcinoma. Photodynamic therapy (PDT) is an effective treatment for certain non melanoma skin cancers, but comparison studies with other, better-established therapies are limited. OBJECTIVES: To compare the efficacy and tolerability of PDT and topical 5-fluorouracil (5-FU) in BD. METHODS: Forty patients from two centres were randomized to either topical PDT or 5-FU. The PDT group was treated with 20% 5-aminolaevulinic acid (ALA) applied 4 h before illumination with 100 J cm-2 narrowband red light (630 +/- 15 nm). 5-FU was applied to lesions for 4 weeks. A repeat treatment cycle was performed after 6 weeks if required. Results Twenty-nine of 33 (88%) lesions treated with PDT initially responded completely, compared with 22 of 33 (67%) after 5-FU. After 12 months, two recurrences in the PDT group and six in the 5-FU group reduced complete clinical clearance rates to 82% and 48%, respectively. PDT was significantly more effective (P = 0.006, odds ratio 4.78, 95% confidence interval 1.56-14.62). In the 5-FU group, severe eczematous reactions developed around seven lesions, ulceration in three and erosions in two. No such reactions occurred following PDT. There was no difference in overall pain experienced during each therapy. CONCLUSIONS: Topical ALA-PDT is more effective than topical 5-FU in the treatment of BD, with fewer adverse events. ALA-PDT should be considered one of the first-line therapeutic options for BD.

Topical 5-ALA photodynamic therapy for the treatment of cutaneous T-cell lymphoma.

Therapeutic options for cutaneous T cell lymphoma (CTCL) include topical steroids, topical chemotherapy and phototherapy. Patients with limited disease that is unresponsive to these therapies present a particular challenge. We report successful treatment of a patient with two plaques of CTCL using topical photodynamic therapy (PDT). 5-aminolaevulinic acid (5-ALA) was applied 6-24 h preillumination with 100 J/cm2 red light. Treatment was repeated on four occasions with clinical and histological clearance. ALA-PDT may be a useful addition to the therapeutic options for CTCL. Further studies are required to define optimal treatment protocols.

Photodynamic therapy: applications in dermatology.

Photodynamic therapy (PDT) offers the potential of an effective new treatment in several areas of medicine. Topical photodynamic therapy is practical and non-invasive and is particularly suited to dermatological indications. A variety of pre-malignant and malignant skin lesions including Bowen's disease, actinic keratoses (AKs) and basal cell carcinoma (BCC) have been treated with success. The role of PDT in inflammatory dermatoses remains to be established. The currently available literature is reviewed.

Localized papular cutaneous schistosomiasis: two cases in travellers.

Schistosomiasis is endemic in many parts of the tropics and subtropics with an estimated 200 million people, at least, infected worldwide. The symptoms and signs of vesical and gastrointestinal forms are readily recognized but ectopic forms are rare even in endemic areas and present a greater diagnostic challenge, particularly when they are encountered in nontropical climes. We now report two cases of cutaneous schistosomiasis presenting in Edinburgh with subtle, but remarkably similar, skin lesions.

Verrucas. Guidelines for management.

Most people will experience infection with human papilloma virus (HPV) at some point in their life. Diagnosis, based on clinical examination, is usually straight forward. Treatment can, however, be challenging. Indications for treatment include pain, interference with function, cosmetic embarrassment, and risk of malignancy. Clearance rates are highest in young, healthy individuals with short duration of infection. Treatment may be with destructive agents (keratolytics, cryotherapy, curettage and cautery, laser, photodynamic therapy), with antimitotic agents (podophyllin, bleomycin, retinoids), with immune stimulants (topical sensitizers, cimetidine), or with topical virucidal agents [formaldehyde (formalin), glutaral (gluteraldehyde)]. As yet, there is no single totally effective treatment for viral warts. Some patients may choose to leave their warts untreated until spontaneous resolution. In those who seek intervention, simple, well tolerated therapies should be chosen initially in preference to more complicated, potentially harmful agents. It is likely that future research will be directed to developing an antiviral agent specific for HPV which would be safe, effective and not prohibitively expensive.