Carsten Sand

Significant decrease in the incidence of genital warts in young Danish women after implementation of a national human papillomavirus vaccination program.

Background Approximately 90% of genital warts (GWs) are caused by human papillomavirus (HPV) types 6 and 11. Denmark has provided the quadrivalent HPV vaccine to all 12-year-old girls since 2009 and catch-up vaccination to girls up to 15 years since 2008, with up to 80% to 85% vaccine coverage. We determined the incidence of GWs in Denmark since 1996, focusing on the period after licensing of HPV vaccination (October 2006). Methods From the Danish National Patient Register, we identified all hospitalizations and outpatient consultations for GWs between January 1995 and July 2011. Poisson regression was used to estimate average annual percentage changes. Results The overall incidence of GWs in women increased significantly until 2007, followed by an average yearly decline of 3.1% (95% confidence interval [CI], −5.5 to −0.7). In men, the incidence increased by 6.2% per year from 2004 (95% CI, 4.6–7.8). Stratifying on age, a significant decline was seen only for young women, particularly those aged 16 to 17 years, in whom GWs were virtually eliminated (average annual percentage change, −45.3%; 95% CI, −55.8 to −33.3). The incidences of genital Chlamydia, syphilis, and gonorrhea were stable or increased during the study period. Conclusions The incidence of GWs decreased substantially among women with high HPV vaccine coverage, pointing to the effect of the national HPV vaccination program.

A multicentre, randomized, double‐blind, controlled study of long‐term treatment with 0·1% tacrolimus ointment in adults with moderate to severe atopic dermatitis

Background  Atopic dermatis (AD) is a chronic disease that often requires long‐term treatment. Topical corticosteroids are the usual therapy for patients with AD, but prolonged usage can result in skin atrophy and other side‐effects.

Omalizumab for chronic urticaria: a case series and overview of the literature.

Omalizumab is a recombinant humanized monoclonal antibody that blocks the high-affinity Fc receptor of IgE. Omalizumab has been approved for the treatment of moderate to severe asthma; however, there is currently more and more data showing promising results in the management also of chronic urticaria. We present a case series of 19 patients with chronic urticaria treated in a university department with omalizumab and give an overview of the existing literature comprising an additional 59 cases as well as a total of 139 patients enrolled in two randomized controlled trials comparing omalizumab with placebo. The collective evidence points to omalizumab as a safe and effective treatment option for patients with chronic urticaria who do not sufficiently respond to standard therapy as recommended by existing guidelines.

Dose-Related Differences in Effectiveness of Human Papillomavirus Vaccination Against Genital Warts: A Nationwide Study of 550 000 Young Girls

BACKGROUND Reducing the number of doses in the human papillomavirus (HPV) vaccination regimen from 3 to 2 could increase coverage rates. In this cohort study, we assessed the risk of genital warts (GWs) according to timing and number of doses of quadrivalent HPV vaccine. METHODS From population-based registries, we identified all girls in Denmark born during 1985-1999, for whom information on HPV vaccinations was retrieved. The cohort was followed for GW occurrence during 2006-2012. Incidence rate ratios (IRRs) were calculated by Poisson regression to determine differences in GW rates by number of vaccine doses. RESULTS Of the 550,690 girls in the cohort, 361 734 had been vaccinated. Of these, 25.9% had been vaccinated twice and 58.8% 3 times. The risk of GWs decreased significantly with each additional dose of vaccine. For girls who received 2 doses, extension of the interval between doses reduced the incidence of GWs. In comparison with a 2-month interval, the incidence of GWs was reduced by 45% (95% confidence interval [CI], 20%-62%), 55% (95% CI, 35%-69%), and 63% (95% CI, 44%-75%), with an interval of 4, 5, and 6 months, respectively. The IRR of 2 vs 3 doses was close to 1, with an interval of about 6 months between the first 2 doses. CONCLUSIONS With the original vaccine schedule, completion of 3 doses seems to be required to obtain full protection against GWs. A 2-dose regimen may be as effective if the dosing interval is extended to around 6 months, although the long-term effectiveness of this regimen is unknown.

Effectiveness and safety of omalizumab in chronic spontaneous or inducible urticaria: evaluation of 154 patients.

DEAR EDITOR, Out-of-trial data on long-term safety and predictors of effectiveness of omalizumab (anti-IgE) in chronic urticaria are lacking. We evaluated the outcome of treatment with omalizumab in a large cohort of patients with chronic spontaneous or chronic inducible urticaria (CSU and CINDU, respectively). Data were retrieved via retrospective review of patient records from a tertiary dermatological referral centre (Department of Dermatology, Bispebjerg Hospital, Copenhagen, Denmark). Complete ascertainment of patient records was possible as the department keeps track of all administered biological therapy. A consultant dermatologist (S.F.T.) verified the urticaria diagnosis and assessed response to treatment. Two authors (M.N.G. and S.F.T.) extracted the data and, in cases of disagreement, consensus was obtained by discussion with all the authors. According to Danish law, scientific ethics approval is not needed for retrospective chart reviews. Approval for the study was obtained from the National Board of Health (to examine patient records) and from the Data Protection Agency (to save patient data on file). All patients diagnosed with CSU or CINDU who had received at least one injection of omalizumab from 30 June 2010 to 31 December 2014 were included in the study. Response to omalizumab treatment was graded according to the degree of relief of symptoms reported by the patient and according to the physician’s assessment. It was possible to score the clinical response to treatment with omalizumab for each patient as a ‘complete or almost complete response’, ‘partial response’ and ‘no/limited response’ after 3–6 months of treatment. This grading is in accordance with the modified physician global assessment used in other dermatological diseases, where a complete or almost complete response corresponds to ≥ 90% reduction of symptoms; partial response is reduction in symptoms of between 30% and 89%; and no response or a limited response is a reduction in symptoms of < 30%. In total, 154 patients were identified; 110 (71 4%) women and 44 (28 6%) men (Table 1). The majority of the patients were diagnosed with CSU (89 0%). Of these, 30 7% had concomitant angioedema, 34 3% had a positive histamine release (HR) test and 22 6% had significant comorbidities, the most common being asthma, diabetes, hypertension and hypothyroidism. The 17 patients with CINDU had delayed-pressure urticaria (n = 5), cold urticaria (n = 5), cholinergic urticaria (n = 4), symptomatic dermographism (n = 2) and solar urticaria (n = 1). The average age at disease onset was significantly

Long-term treatment with 0.1% tacrolimus ointment in adults with atopic dermatitis: results of a two-year, multicentre, non-comparative study.

Atopic dermatitis often requires long-term treatment. This European, multicentre, non-comparative, 24-month, follow-up study investigated the efficacy and safety of 0.1% tacrolimus ointment applied to adults with atopic dermatitis. Patients (n=672) applied a thin layer of 0.1% tacrolimus ointment twice daily for 3 weeks to all affected body areas. After 3 weeks, ointment was applied once daily. Clinical improvement became apparent after 2 weeks of treatment and 65.5% of patients had a rating of clearance, excellent or marked improvement by month 3. Skin burning (31.7%) was the most common causally-related adverse event, followed by pruritus (11.3%) folliculitis (6.4%), alcohol intolerance (5.7%), herpes simplex (5.7%), skin infection (4.6%), skin erythema (3.3%) and hyperaesthesia (2.4%). The most commonly reported infections were flu syndrome (12.9%), skin infection (9.8%), folliculitis (7.4%) and herpes simplex (7.0%). Long-term treatment up to 24 months with 0.1% tacrolimus ointment is safe and efficacious in adults with atopic dermatitis.

Omalizumab for atopic dermatitis: case series and a systematic review of the literature

Omalizumab is a recombinant humanized monoclonal antibody targeting the high‐affinity Fc receptor of IgE, registered for the treatment of chronic spontaneous urticaria and severe allergic asthma. We present a case series of nine patients with atopic dermatitis (AD) treated off‐label with omalizumab and a systematic review of the existing literature. Patients were selected consecutively from a tertiary dermatological referral center during a 5‐year period. All patients were treated with omalizumab at a starting dose of 300 mg subcutaneously every 4 weeks. Systematic literature searches were performed in PubMed, Web of Science, EMBASE, and ClinicalTrials.gov to identify any study (case reports, case series, and controlled trials) evaluating the effect of treatment with omalizumab in AD. Based on physicians’ assessment, 50% of our patients had a good or excellent response to treatment with omalizumab; a further 12.5% had a moderate response, while 37.5% experienced no response or deterioration of symptoms during treatment. Treatment was generally well tolerated. Twenty‐six studies with a median of four patients each (range 1–21), comprising 174 patients, were included in the systematic review. Summed over all studies, a total of 129 patients (74.1%) experienced a beneficial effect of treatment ranging from little to complete response. Omalizumab appears to be a safe and well tolerated, however expensive, treatment with some clinical benefit in patients with severe recalcitrant AD. Recommendation for use in clinical practice awaits evidence from larger randomized controlled trials.

Considerable Variability in the Efficacy of 8% Capsaicin Topical Patches in the Treatment of Chronic Pruritus in 3 Patients with Notalgia Paresthetica

Notalgia paresthetica (NP) is a focal neuropathic itch condition manifesting in intense chronic or recurrent episodic itch in a hyperpigmented, macular, uni- or bilateral skin area located below and/or medially to the scapulae. Achieving satisfactory relieve in NP patients is challenging. In this case-series three female NP patients were treated with 8% capsaicin patches following a spatial quantification of their alloknetic area with a von Frey filament. The use of a von Frey filament in order to delimit the precise area of itch sensitization and thus patch application, proved clinically feasible. Although 8% topical capsaicin relieved itch in all three patients, the duration of the effectiveness varied greatly from only 3 days to >2 months. The treatment was well tolerated in the patients and there appear to be no significant hindrances to applying this treatment with NP as an indication, although it may only exhibit satisfactory effectiveness in certain patients. Placebo-controlled double-blinded trials are needed to confirm the effectiveness of the treatment and assess predictive parameters of the treatment outcome.

Prevalence of Human Papillomavirus in Anal and Oral Sites Among Patients with Genital Warts

Genital warts are caused by human papillomavirus (HPV). HPV is a leading cause of anogenital malignancies and a role of HPV in the aetiology of oro-pharyngeal cancers has been demonstrated. The frequency of oral HPV infection in patients with genital warts and the association between concomitant genital, anal and oral infection is unclear. A total of 201 men and women with genital wart-like lesions were recruited. Swab samples were obtained from the genital warts and the anal canal and an oral rinse was collected. Anal HPV was found in 46.2% and oral HPV in 10.4% of the participants. Concordance between anal and genital wart HPV types was 78.1%, while concordance between oral and genital wart types was 60.9%. A lower concordance of 21.7% was observed between anal and oral HPV types. Significantly more women than men had multiple HPV types and anal HPV. In conclusion, extra genital HPV is common in patients with genital warts. A gender inequality seems to exist.

Combination of antitumour necrosis factor-α and anti-interleukin-12/23 antibodies in refractory psoriasis and psoriatic arthritis: a long-term case-series observational study.

DEAR EDITOR, Despite the availability of highly efficacious biologics, psoriasis still remains an area of medical need. In particular, manifestations of the disease in different organs (skin, joints) may respond differently to the same treatment, providing rationale for combination treatments. However, experience with concomitant biological treatment is very limited due to safety concerns and high cost. In this report we describe our experience of 16 2 patient years of treatment with ustekinumab combined with an antitumour necrosis factor-a agent for recalcitrant psoriasis with psoriatic arthritis (PsA) (Table 1). Patient 1 is a 67-year-old man who developed psoriasis and PsA (peripheral arthritis and spondyloarthropathy) at the ages of 24 and 55 years, respectively. He could not complete the treatment with methotrexate due to nausea and hepatotoxicity. Combination of ciclosporin A (400 mg daily) and methotrexate 5 mg weekly was unsuccessful, and therefore treatment with infliximab (5 mg kg 1 every 8th week) was initiated. After six infusions his Psoriasis Area and Severity Index (PASI) decreased from 18 2 to 10 1, but there was no effect on his arthritis [pain visual analogue scale (VAS) 7 2/10]. Infliximab was changed to etanercept and subsequently to adalimumab, which were efficacious on his arthritis, but not the skin (PASI fluctuating between 10 and 16). Attempts to combine adalimumab with acitretin and methotrexate did not improve the efficacy, and ustekinumab 90 mg (every 12th week) combined with etanercept 50 mg weekly was started. He achieved a satisfactory clinical response (PASI < 1 8, pain VAS < 5, no swollen joints) but developed flares of herpes zoster after injections of ustekinumab, which were controlled only partially with prophylactic valaciclovir (500 mg). The dose of etanercept was eventually reduced to 25 mg weekly, which reduced the flares of zoster and still provided adequate control of PsA and psoriasis (VAS < 4 5, PASI < 1 8). Patient 2 is a 39-year-old man with psoriasis and PsA since the age of 21 years and a history of Gilbert–Meulengracht syndrome and hepatitis B. Methotrexate was tried but discontinued due to lack of efficacy, severe nausea and concerns of hepatic comorbidities. He was treated with adalimumab, which was discontinued because of alopecia, and subsequently with etanercept (50 mg weekly titrated to 100 mg weekly) for 3 years with satisfactory effect on PsA, but with only a moderate efficacy on the skin. Because of high psoriasis activity (PASI 11 2, Dermatology Life Quality Index 21), ustekinumab (90 mg every 12th week) was added and this resulted in excellent disease control (PASI reduction to 1 6, pain VAS < 1). Etanercept was reduced to 25 mg weekly without compromising the clinical efficacy. However, the patient developed a retrotonsillar abscess while treated with combination therapy. It was successfully treated by incision and intravenous antibiotics and no other adverse events were noted. Patient 3 is a 49-year-old woman with psoriasis and PsA since age 19 years. Comorbidities included obesity, type II diabetes,