Clinical spectrum and long-term outcomes of mpox: a cohort study spanning from acute infection to six-month follow-up.

BACKGROUND: Cases of mpox have been reported worldwide since May 2022. Limited knowledge exists regarding the long-term course of this disease. To assess sequelae in terms of scarring and quality of life (QoL) in mpox patients 4-6 months after initial infection. METHODS: Prospective observational study on clinical characteristics and symptoms of patients with polymerase chain reaction (PCR)-confirmed mpox, including both outpatients and inpatients. Follow-up visits were conducted at 4-6 months, assessing the Patient and Observer Scar Assessment Scale (POSAS), the Dermatology Life Quality Index (DLQI) and sexual impairment, using a numeric rating scale (NRS) from 0 to 10. RESULTS: Forty-three patients, age range 19-64 years, 41 men (all identifying as MSM) and 2 women, were included. Upon diagnosis, skin or mucosal lesions were present in 93.0% of cases, with 73.3% reporting pain (median intensity: 8, Q1-Q3: 6-10). Anal involvement resulted in a significantly higher frequency of pain than genital lesions (RR: 3.60, 95%-CI: 1.48-8.74). Inpatient treatment due to pain, superinfection, abscess or other indications was required in 20 patients (46.5%). After 4-6 months, most patients did not have significant limitations, scars or pain. However, compared to patients without such complications, patients with superinfection or abscess during the acute phase had significantly more extensive scar formation (median PSAS: 24.0 vs. 11.0, p = 0.039) and experienced a significantly greater impairment of their QoL (median DLQI: 2.0 vs. 0.0, p = 0.036) and sexuality (median NRS: 5.0 vs. 0.0, p = 0.017). CONCLUSION: We observed a wide range of clinical mpox manifestations, with some patients experiencing significant pain and requiring hospitalization. After 4-6 months, most patients recovered without significant sequelae, but those with abscesses or superinfections during the initial infection experienced a significant reduction in QoL and sexuality. Adequate treatment, including antiseptic and antibiotic therapy during the acute phase, may help prevent such complications, and hence, improve long-term outcomes.

Position statement of the German STI Society on the prophylactic use of doxycycline to prevent STIs (Doxy-PEP, Doxy-PrEP).

Over the past two decades, there has been a rise in the incidence of syphilis, particularly among men who have sex with men (MSM). This has sparked interest in studying the prophylactic use of doxycycline to prevent syphilis and other sexually transmitted infections (STIs), commonly referred to as Doxycycline Pre- or Post-Exposure Prophylaxis (Doxy-PrEP, Doxy-PEP). At the same time, demand from potential users for this preventive measure is increasing. Several randomized controlled trials have demonstrated that the prophylactic use of doxycycline in MSM and trans women using HIV pre-exposure prophylaxis (HIV-PrEP) or living with an HIV infection effectively reduces the risk of syphilis and chlamydia infections. At present, however, unresolved questions remain, particularly regarding implications of a broad implementation of prophylactic doxycycline to prevent STIs on tetracycline and other antimicrobial resistance in bacterial STIs, non-STI-related bacterial pathogens, and the microbiome. In response to the increasing demand and the challenge of balancing effectiveness, safety, and the risk of promoting antibiotic resistance, the German STI Society (DSTIG) has issued a position statement, providing specific recommendations regarding potential indications, criteria, and occasions for the use of doxycycline in STI prevention. These recommendations are based on current evidence and expert opinion.

S3 Guideline Atopic dermatitis: Part 1 - General aspects, topical and non-drug therapies, special patient groups.

This S3 guideline was created based on the European S3 guideline, with special consideration of the medical conditions in the German-speaking region and incorporating additions from the previous German-language version. The interdisciplinary guideline commission consisted of representatives from the German Dermatological Society, the Professional Association of German Dermatologists, the Austrian Society of Dermatology and Venereology, the Swiss Society of Dermatology and Venereology, the German Society for Allergology and Clinical Immunology, the German Society for Pediatric and Adolescent Medicine, the Professional Association of Pediatricians and Adolescent Medicine, the Society for Pediatric Allergology and Environmental Medicine, the German Society for Pediatric Rehabilitation and Prevention, the German Society for Psychosomatic Medicine and Medical Psychotherapy, the German Network for Health Services Research, the German Eczema Association and the German Allergy and Asthma Association. This first part of the guideline focuses on the definition and diagnostic aspects of atopic dermatitis (AD), addressing topical therapy as well as non-pharmacological treatment approaches such as UV therapy, psychoeducational therapy, dietary interventions for AD, allergen immunotherapy for AD, and complementary medicine. This part of the guideline also covers specific aspects of AD in children and adolescents, during pregnancy and lactation, and in the context of family planning. Additionally, it addresses occupational aspects of AD and highlights the perspective of the patients. The second part of the guideline, published separately, addresses the systemic therapy of AD.

S3 guideline Atopic dermatitis: Part 2 - Systemic treatment.

The present S3 guideline was created based on the European English-language S3 guideline, with special consideration given to the medical conditions in the German-speaking region, and with additions from the previous German-language version, in accordance with the criteria of the AWMF. This second part of the guideline addresses the systemic therapy of atopic dermatitis (AD). It covers topics such as the indication for systemic therapy in children, adolescents, and adult patients with AD. Furthermore, it addresses all medications approved for AD, such as the biologics dupilumab and tralokinumab, the Janus kinase inhibitors abrocitinib, baricitinib, and upadacitinib, as well as conventional immunosuppressive therapies with systemic glucocorticosteroids and ciclosporin. Additionally, it discusses systemic off-label therapies. The first part of the guideline, published separately, includes the definition and diagnostic aspects of AD, describes topical therapy, non-drug therapy approaches, and addresses aspects related to special patient groups.

[Herpes zoster-prevention, diagnosis, and treatment]. / Herpes zoster ­ Prävention, Diagnostik und Behandlung.

BACKGROUND: Herpes zoster (HZ) is a common skin disease resulting from a regionally limited reactivation of a latent infection with the varicella zoster virus (VZV). Despite its usually self-limiting course, HZ is associated with a considerable individual and public health burden of disease, particularly due to its high rate of postherpetic neuralgia (PHN). OBJECTIVES: To improve knowledge of the current recommendations for the prevention, diagnosis and treatment. MATERIALS AND METHODS: Narrative review and summary of current guideline recommendations. RESULTS: In Germany, the recombinant VZV subunit zoster vaccine is recommended for all adults of 60+ years and for immunocompromised persons of 50+ years. The diagnosis of HZ is clinical; in case of uncertainty, laboratory investigations can help confirm the diagnosis. For patients with HZ ophthalmicus, HZ oticus or neurological complications, an interdisciplinary approach is advantageous. Antiviral treatment should be started as early as possible; various factors, including the duration and location of the disease, the patient's age and signs of a complicated course, serve to determine the indication to initiate an antiviral medication. The choice of the appropriate treatment depends, among other factors, on the intravenous availability, comorbidities and intake preferences. Early and sufficient analgesic treatment according to the WHO pain ladder and, if required, with anticonvulsant adjuvants is necessary to treat acute pain and to reduce the risk for PHN. CONCLUSION: Implementation of the current recommendations for the prevention, diagnosis and treatment of HZ and PHN is important to reduce the high burden of disease and improve quality of life of the patients.

Perioperative management of antithrombotic drugs in skin surgery - A survey of dermatologists in Germany.

BACKGROUND: We identified substantial heterogeneity in the perioperative management of antithrombotic drugs in skin surgery in Germany in 2012 and 2017 in two cross-sectional surveys. The first national guideline on this subject was published in 2014 and updated in 2021. We sought to identify whether the management of these drugs had changed. METHODS: We sent a paper-based survey to 1115 dermatologists throughout Germany asking them about their perioperative management of antithrombotic drugs in skin surgery, as well as their familiarity with the guideline. RESULTS: We received responses from 65 hospital- and 202 office-based dermatologists. Most dermatologists reported continuing antithrombotic drugs in their patients when performing minor surgeries. A notable proportion of dermatologists reported discontinuing phenprocoumon treatment perioperatively and bridging patients with heparin when performing more invasive surgeries. Continuation was less common during combination therapies. CONCLUSIONS: The proportion of physicians in Germany who reported managing antithrombotic drugs during skin surgery in ways that are in concordance with the national guideline has increased since 2012. However, continuing antithrombotic drugs during large excisions and sentinel lymph node biopsies, abstaining from bridging patients on phenprocoumon with heparin, and continuing antithrombotic combination therapies perioperatively need to be further encouraged, especially among office-based dermatologists.

Perioperatives Management von Antithrombotika in der Dermatochirurgie - Eine Umfrage unter Dermatologen in Deutschland.

Hintergrund und Zielsetzung: Wir haben in zwei Querschnittsumfragen in den Jahren 2012 und 2017 eine erhebliche Heterogenität im perioperativen Management von Antithrombotika unter Dermatologen in Deutschland festgestellt. Die erste deutsche Leitlinie zu diesem Thema wurde 2014 veröffentlicht und im Jahr 2021 aktualisiert. Wir wollten herausfinden, wie sich der Umgang mit Antithrombotika verändert hat. Methodik: Wir haben eine papierbasierte Umfrage an 1115 Dermatologen in ganz Deutschland versandt und sie zu ihrem perioperativen Management von Antithrombotika bei Operationen an der Haut sowie zu ihrer Vertrautheit mit der Leitlinie befragt. Ergebnisse: Wir erhielten Antworten von 65 stationär tätigen und 202 niedergelassenen Dermatologen. Die meisten Dermatologen gaben an, Antithrombotika bei kleineren Operationen fortzuführen. Ein nennenswerter Anteil der Dermatologen gab an, bei invasiveren Operationen die Behandlung mit Phenprocoumon perioperativ zu pausieren und mit Heparin zu überbrücken. Bei Kombinationstherapien war das Fortführen der Behandlung weniger verbreitet. Schlussfolgerungen: Der Anteil der Dermatologen in Deutschland, die angaben, Antithrombotika bei Operationen an der Haut leitlinienkonform zu managen, ist seit 2012 gestiegen. Das Fortführen von Antithrombotika bei großen Exzisionen und Wächterlymphknotenexstirpationen, der Verzicht auf die Überbrückung von Phenprocoumon mit Heparin und das perioperative Fortführen antithrombotischer Kombinationstherapien müssen jedoch weiterhin propagiert werden, insbesondere unter niedergelassenen Dermatologen.

S2k guideline: Rosacea.

This updated and upgraded S2k guideline deals with the diagnosis and treatment of rosacea, which is a common, chronic inflammatory skin disease mostly affecting the face. Initially, rosacea is characterized by recurrent erythema, telangiectasia and flushing. Later, the inflammatory component predominates, with persistent erythema with follicular papules, papulopustules and pustules. The development of phyma, which usually occurs on the acral localizations, is the most severe manifestation. For the treatment of rosacea, the interdisciplinary guideline committee, with representatives of the German Dermatological Society (DDG), the Professional Association of German Dermatologists (BVDD), the German Opthalmological Society (DOG), the Society for Dermopharmacy (GD), the Swiss Society for Dermatology and Venereology (SGDV) and the German Rosacea Aid e. V., recommends the avoidance of trigger factors and topical applications of metronidazole, azelaic acid or ivermectin. For symptomatic treatment of persistent centrofacial erythema, the topical vasoconstrictors brimonidine or oxymetazoline can also be used. Systemic therapy is recommended for therapy-resistant and severe forms of rosacea papulopustulosa. The drug of choice is low-dose doxycycline. Alternatively, low-dose isotretinoin can be recommended. Ocular rosacea should be treated with lid margin hygiene. For topical treatment, ciclosporin eye drops, azithromycin, ivermectin or metronidazole are suggested.

German S1 guidelines for the diagnosis and treatment of perianal dermatitis (anal eczema).

Perianal dermatitis (anal eczema, perianal eczema) is one of the most common proctological conditions. It may occur as a sequela or a presenting symptom of various proctological, dermatological, allergic or pathogen-induced disorders. The three main types of anal eczema are irritant-toxic, atopic and allergic contact dermatitis. Adequate and successful treatment requires a comprehensive diagnostic workup to determine disease etiology and includes treatment/elimination of causative factors as well as nonpharmacological interventions (avoidance of aggravating factors). In addition, adjuvant topical anti-inflammatory and/or specific symptomatic treatment may be required. The present guidelines contain recommendations for the diagnostic and therapeutic management of perianal dermatitis. Target users of these guidelines are clinicians in the fields of dermatology and proctology, as well as all other specialties involved in the management of patients with perianal dermatitis, both in hospital and office-based settings.

Time until onset of action when treating psoriatic arthritis: meta-analysis and novel approach of generating confidence intervals.

Psoriatic arthritis (PsA) is associated with progressive joint destruction and reduced quality of life. The time until a drug treatment starts to show an effect (TOA) is important for preventing joint destruction. The objective was to assess the time until onset of action of drugs when treating PsA. A systematic review of PsA drug trials was performed. Outcomes were: time until 25% of patients (TOA) reached (1) ≥ 20%, (2) ≥ 50% improvement in modified American College of Rheumatology response criteria (ACR), (3) ≥ 75% reduction in Psoriasis Area and Severity Index (PASI75). 95% confidence intervals were calculated extracting data from graphs using a novel method. Meta-analysis was conducted. Two head-to-head trials show no difference between ixekizumab and adalimumab or adalimumab and tofacitinib for TOA-ACR outcomes. For PASI75, ixekizumab had a faster onset than adalimumab. Infliximab plus MTX was faster than MTX alone. Pooled results from 32 study arms for TOA-ACR20 (week [95% CI]) are: < 2 weeks: infliximab (1.18 [0.72-1.65]), ixekizumab (1.04 [0.80-1.28]), tofacitinib (10 mg 1.56 [1.14-1.98]); ≤ 4 weeks: adalimumab (1.95 [1.35-2.55]), secukinumab (75 mg 1.89 [0.16-3.62], 150 mg 2.13 [1.34-2.91], 300 mg 2.26 [1.75-2.76]), tofacitinib (5 mg 2.20 [1.41-2.99]); 4 + weeks: apremilast, ustekinumab. For TOA-ACR50, all pooled point estimates are > 4 weeks. For TOA-PASI75, the range is between 2.24 [1.65-2.84] for ixekizumab and 6.03 [3.76-8.29] for adalimumab. Indirect, mixed comparison suggest a faster onset of infliximab, ixekizumab and tofacitinib compared to apremilast, methotrexate and ustekinumab for ACR20, not ACR50. For PASI75, ixekizumab is faster than adalimumab.

Chronic inducible urticaria: A systematic review of treatment options.

BACKGROUND: Chronic inducible urticaria (CindU) is a condition characterized by the appearance of recurrent wheals, angioedema, or both as a response to specific and reproducible triggers. OBJECTIVE: We sought to systematically assess evidence on the efficacy and safety of treatment options for CindU. Results were used to inform the 2017 update of "The EAACI/GA2LEN/EDF/WAO guideline for the definition, classification, diagnosis and management of urticaria." METHODS: Randomized controlled trials and controlled intervention studies were searched systematically in various databases. Included studies were evaluated with the Cochrane Risk of Bias tool. Where possible, results from single studies were meta-analyzed, applying the Mantel-Haenszel approach by using a random-effects model (Der Simonian-Laird). RESULTS: We identified 30 studies that included patients with cold urticaria, symptomatic dermographism, delayed-pressure urticaria, or cholinergic urticaria. No studies on other forms of CindU were eligible. Risk of bias was often rated as unclear or high. Overall, second-generation antihistamines were more effective than placebo, and available data indicate that updosing might be effective. Omalizumab proved effective in patients with symptomatic dermographism, who did not respond to antihistamines. Detailed results are given for each type of CindU. CONCLUSIONS: The available evidence is limited by small samples, heterogeneous efficacy outcomes, and poor reporting quality in many of the included studies. The findings are congruent with the suggested stepwise approach to treating CindUs. However, the data do not allow for drawing specific conclusions for specific subtypes of CindU.

S2k guidelines for the treatment of psoriasis in children and adolescents - Short version part 2.

The present guidelines are aimed at residents and board-certified physicians in the fields of dermatology, pediatrics, pediatric dermatology and pediatric rheumatology as well as policymakers and insurance funds. They were developed by dermatologists and pediatric dermatologists in collaboration with pediatric rheumatologists using a formal consensus process (S2k). The guidelines highlight topics such as disease severity, quality of life, treatment goals as well as problems associated with off-label drug therapy in children. Trigger factors and diagnostic aspects are discussed. The primary focus is on the various topical, systemic and UV-based treatment options available and includes recommendations for use and treatment algorithms. Other aspects addressed herein include vaccinations in children and adolescents with psoriasis as well as various disease subtypes such as guttate psoriasis, diaper psoriasis, pustular psoriasis and psoriatic arthritis. Finally, we also provide recommendations for imaging studies and the diagnostic workup to rule out tuberculosis prior to initiating systemic treatment. Note: This article constitutes part 2 of the Sk2 guidelines for the treatment of psoriasis in children and adolescents. Part 1 was published in last month's issue. It contained introductory remarks and addressed aspects of diagnosis and topical treatment.

S2k guidelines for the treatment of psoriasis in children and adolescents - Short version part 1.

The present guidelines are aimed at residents and board-certified physicians in the fields of dermatology, pediatrics, pediatric dermatology and pediatric rheumatology as well as policymakers and insurance funds. They were developed by dermatologists and pediatric dermatologists in collaboration with pediatric rheumatologists using a formal consensus process (S2k). The guidelines highlight topics such as disease severity, quality of life, treatment goals as well as problems associated with off-label drug therapy in children. Trigger factors and diagnostic aspects are discussed. The primary focus is on the various topical, systemic and UV-based treatment options available and includes recommendations for use and treatment algorithms. Other aspects addressed herein include vaccinations in children and adolescents with psoriasis as well as various disease subtypes such as guttate psoriasis, diaper psoriasis, pustular psoriasis and psoriatic arthritis. Finally, we also provide recommendations for imaging studies and the diagnostic workup to rule out tuberculosis prior to initiating systemic treatment. Note: This article constitutes part 1 of the Sk2 guidelines for the treatment of psoriasis in children and adolescents. Part 2 will be published in the next issue. It contains chapters on UV therapy, systemic treatment, tonsillectomy and antibiotics, vaccinations, guttate psoriasis, psoriatic arthritis, complementary medicine, as well as imaging studies and diagnostic workup to rule out tuberculosis prior to systemic treatment.

Adjuvant treatment of anogenital warts with systemic interferon: a systematic review and meta-analysis.

BACKGROUND: Interferons are natural messenger proteins that are used to treat various disease entities. Due to their immunomodulating, antiviral and antiproliferative effects, the systemic administration of interferons after ablative treatment for anogenital warts (AGWs) has been advocated to increase clearance and decrease recurrence rates. However, studies investigating the efficacy of adjuvant systemic interferon have yielded inconsistent results. The objective of this systematic review and meta-analysis was to comprehensively assess and evaluate the available evidence from randomised controlled trials. METHODS: A literature search was conducted in Cochrane Central Register of Controlled Trials, Embase and MEDLINE. Available data were classified according to the interferon type and dosage. Pooled effect estimates were calculated for predefined outcomes. The Cochrane Collaboration's risk of bias tool was used to assess the included trials and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to evaluate our confidence in the effect estimates. RESULTS: Twelve trials were identified that met the inclusion criteria and assessed immunocompetent patients with external AGW. Compared with placebo, adjuvant alpha-, beta- and gamma-interferon were generally not significantly superior in terms of complete clearance over the short, intermediate or long term, nor with regard to intermediate- or long-term recurrence. However, the low-dose subgroup of adjuvant alpha-interferon was significantly superior compared with placebo regarding intermediate-term complete clearance and recurrence. Further data were available for the comparison of different dosages of alpha- and beta-interferon and for comparisons of the three interferon types. No significant differences were seen in these comparisons regarding efficacy. Data on quality of life were not available. CONCLUSIONS: The GRADE quality of the evidence ranged from 'very low' to 'high'. The significantly higher efficacy of low-dose alpha-interferon compared with placebo was based on a single trial, and our confidence in the effect estimates rated as 'low'. Overall, we found no reliable evidence favouring the systemic use of interferon after ablative treatment of AGW.

Umgang mit Antithrombotika bei Operationen an der Haut vor und nach Publikation der entsprechenden S3-Leitlinie.

HINTERGRUND: Laut einer Befragung im Jahre 2012 war der Umgang mit Antithrombotika bei dermatochirurgischen Eingriffen in Deutschland sehr heterogen. 2014 wurde erstmals eine evidenzbasierte Leitlinie zu diesem Thema veröffentlicht. METHODIK: Es wurde eine anonyme Befragung derselben Stichprobe zum Umgang mit Antithrombotika sowie zu Kenntnissen der Leitlinie durchgeführt. Die Ergebnisse wurden als relative Häufigkeiten berichtet und denen aus 2012 gegenübergestellt. ERGEBNISSE: 208 Antwortbögen wurden ausgewertet (Rücklaufquote: 36,6 %). Die große Mehrheit der Dermatologen erklärte, kleinere Eingriffe unter Fortführung der Therapie mit Phenprocoumon, niedrig dosierter Acetylsalicylsäure (≤ 100 mg) und Clopidogrel sowie mit direkten oralen Antikoagulanzien durchzuführen. Bei größeren Eingriffen war der Umgang hingegen weiterhin heterogen, insbesondere unter niedergelassenen Dermatologen. Der Anteil der Dermatologen, die Phenprocoumon, Acetylsalicylsäure und Clopidogrel leitlinienkonform verwendeten, hat sich insgesamt vergrößert. Führten 2012 beispielsweise 53,8 % der Klinikärzte bzw. 36,3 % der niedergelassenen Dermatologen eine große Exzision unter Fortführung der Therapie mit niedrig dosierter Acetylsalicylsäure durch, taten dies 2017 90,2 % bzw. 57,8 % (Phenprocoumon: 33,8 % bzw. 11,9 % auf 63,9 % bzw. 29,9 %; Clopidogrel: 36,9 % bzw. 23,2 % auf 63,9 % bzw. 30,6 %). Unter den Klinikärzten war ein hoher Anteil mit der Leitlinie vertraut und fand diese hilfreich. SCHLUSSFOLGERUNGEN: Eine Zunahme des leitlinienkonformen Verhaltens war bei allen Eingriffen zu verzeichnen. Bei größeren Eingriffen zeigte sich trotz deutlicher Verbesserung die Notwendigkeit verstärkter Anstrengungen zur Leitlinienumsetzung bzw. zur Identifizierung von Implementierungsbarrieren.

Management of antithrombotic agents in dermatologic surgery before and after publication of the corresponding German evidence-based guideline.

BACKGROUND: A survey in 2012 revealed marked heterogeneity in the management of antithrombotic agents in dermatologic surgery in Germany. An evidence-based guideline on this topic was published for the first time in 2014. METHODS: Using the same study sample, we conducted an anonymous survey on the management of antithrombotic agents and familiarity with the guideline. We reported the results as relative frequencies and compared them with those from 2012. RESULTS: We analyzed a total of 208 questionnaires (response rate: 36.6 %). A large majority of dermatologists reported performing minor procedures without discontinuing low-dose aspirin (≤ 100 mg), clopidogrel, or direct oral anticoagulants. In contrast, antithrombotic management was still heterogeneous in the context of major procedures, especially among office-based dermatologists. Overall, there was an increase in the proportion of dermatologists who managed phenprocoumon, aspirin, and clopidogrel in compliance with the guideline. For example, while 53.8 % of hospital-based dermatologists and 36.3 % of office-based dermatologists had performed large excisions on continued low-dose aspirin treatment in 2012, these figures showed an increase to 90.2 % and 57.8 %, respectively, by 2017 (phenprocoumon: from 33.8 % and 11.9 % to 63.9 % and 29.9 %, respectively; clopidogrel: from 36.9 % and 23.2 % to 63.9 % and 30.6 %, respectively). Among hospital dermatologists a large proportion was familiar with the guideline and considered it to be useful. CONCLUSIONS: Our results suggest that compliance with the German guideline on the perioperative management of antithrombotics in dermatologic surgery has increased for all procedures. Despite this positive development, greater efforts are needed to improve implementation of the guideline and address barriers to its use in everyday practice.

Self-administered interventions for anogenital warts in immunocompetent patients: a systematic review and meta-analysis.

BACKGROUND: Anogenital warts (AGWs, condylomata acuminata) are among the most common STIs and may severely impact quality of life (QoL). Available treatment options are characterised by a high proportion of non-responders and recurrences. OBJECTIVE: To systematically review and meta-analyse the available evidence from randomised controlled trials (RCTs) on topical treatments for AGWs considering short-term and long-term efficacy, effects on QoL and adverse events (AE). METHODS: A comprehensive literature search was performed in Cochrane Central Register of Controlled Trials, Embase and MEDLINE. Included studies were evaluated with the Cochrane Collaboration's risk of bias tool. The confidence in the pooled effect estimates was evaluated according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach and categorised as 'very low', 'low', 'moderate' or 'high'. RESULTS: Eighteen RCTs met the inclusion criteria. Regarding complete clearance (CC), imiquimod 3.75% and 5% cream, podophyllotoxin 0.5% solution and gel and polyphenon E 10% and 15% ointment were superior to placebo. Although more local AE and pain occurred in the actively treated groups, differences regarding dropouts due to AE were not statistically significant. For podophyllotoxin 0.15% cream, no placebo-controlled trials were available; however, in an active-controlled trial, it was inferior to podophyllotoxin 0.5% solution with respect to CC. No significant differences were detected between imiquimod 5% cream and podophyllotoxin 0.5% solution and between polyphenon E 10% and 15% ointment. No data on the influence on health-related QoL were available. CONCLUSION: Our confidence in the pooled estimates (GRADE quality of the evidence) ranged from very low to high. Apart from the given results, other aspects such as availability, costs or patient preference have to be considered when making a treatment choice. Due to the limited number of direct comparisons, conclusions on the relative efficacy of the different treatment options are restricted.