Comparison of Perceptions of Skin Condition, Product Use and Allergen Reactivity Between People with Psoriasis and Controls in the European Dermato-Epidemiology Network (EDEN) Fragrance Study.

Psoriasis, a chronic inflammatory skin disease, goes beyond visible symptoms and affects the general well-being of patients. The aim of this study is to understand how patients with psoriasis perceive their skin characteristics and reactivity to allergens. The study population includes 11,283 participants within the European Dermato-Epidemiology Network (EDEN) Fragrance study, covering several European regions. The study compared perceptions of skin dryness, sensitivity, product avoidance and reactivity to allergens between patients with psoriasis and controls, evaluating the potential influence of psoriasis severity. The results showed that subjects with psoriasis reported dry skin (71.1%) and sensitive skin (49.4%) more often than did controls (51.6% and 38.5%, respectively). Psoriasis patients were more likely to avoid specific products. Interestingly, there were no significant differences in patch-test results between the 2 groups and the severity of psoriasis did not have a consistent impact on these perceptions. In conclusion, people with psoriasis tend to perceive their skin as drier and more sensitive. Notably, the severity of psoriasis did not consistently influence these perceptions and objective reactivity to allergens did not align with subjective perception. Understanding these aspects is crucial for tailoring treatments to improve the well-being of patients with psoriasis, which warrants further research to explore subjective perceptions of skin well-being in patients with psoriasis.

Isotretinoin-associated acne fulminans: A multicentre, retrospective study of the European Academy of Dermatology and Venereology Task Force on Acne, Rosacea and Hidradenitis Suppurativa.

BACKGROUND: Acne fulminans (AF) is a rare severe acne entity. Although occasionally reported, it is unclear whether AF development is associated with oral isotretinoin treatment. OBJECTIVES: To investigate the occurrence of isotretinoin-associated AF, clinical characteristics and prognosis at follow-up. METHODS: An international, multicentre, retrospective study was performed in eight hospitals following the call of the EADV Task Force on Acne, Rosacea and Hidradenitis Suppurativa (ARHS). Characteristics of patients treated with isotretinoin before the development of AF (isotretinoin-associated acne fulminans, IAF) were compared with non-IAF (NAF). RESULTS: Forty-nine patients diagnosed with AF from 2008 to 2022 were included (mean age 16.4 years, SD 2.9, 77.6% male). Αrthralgias/arthritis occurred in 11 patients (22.9%). AF occurred without any previous acne treatment in 26.5% of the patients. Overall, 28 patients (57.1%) developed AF after oral isotretinoin intake (IAF group), while the remaining 21 patients (42.9%) developed AF without previous oral isotretinoin administration (NAF group). IAF occurred after a median duration of isotretinoin treatment of 45 days (IQR: 30, 90). Patients with IAF were more frequently male compared to patients with NAF (89.3% vs. 61.9%, respectively, p = 0.023). There were no differences in patients with IAF versus NAF in patient age, the duration of pre-existing acne, a family history of AF, the distribution of AF lesions or the presence of systemic symptoms or arthralgias. Regarding the management of AF, patients with IAF were treated more frequently with prednisolone (96.2%) compared to those with NAF (70%; p = 0.033) and less frequently with isotretinoin (32.1%) compared to NAF (85.7%; p < 0.001). At a median follow-up of 2.2 years, 76.4% of patients were free of AF and scarring was present in all patients. CONCLUSIONS: No specific clinical or demographic characteristics of IAF compared with NAF could be detected, a fact that does not support IAF as a district clinical entity.

Increasing Access to Effective Systemic Treatments in Patients with Moderate-to-Severe Psoriasis: Narrative Review.

Psoriasis is a chronic, immune-mediated inflammatory disease with a worldwide prevalence ranging between 0.51 and 11.43%. It results in a large clinical and social burden, with patients frequently suffering from reduced quality of life, psychologic distress and debilitating comorbidities. Biologic agents are used to establish and maintain disease control in patients with moderate-to-severe psoriasis and are essential to improving quality of life. However, a substantial proportion of patients have limited access to therapy due to economics, health policies and clinical considerations, which creates clinical unmet needs that disadvantage both patients and healthcare professionals. Biosimilars are a cost-effective alternative to off-patent biologic therapies, and there is mounting evidence to suggest they offer a valuable pharmacoeconomic strategy to lower healthcare costs in patients with psoriasis. Furthermore, the introduction of biosimilars can increase the number of patients able to receive biologics, allowing these patients to be treated earlier in the disease course, potentially modifying the course of their disease and reducing the risk of comorbidities. In time, the emergence of additional data, particularly those related to long-term safety, efficacy in extrapolated indications and the effects of switching, should reassure physicians and help overcome the final hurdles for a wider implementation of biosimilars. This review aims to provide an overview of current treatment approaches for patients with moderate-to-severe psoriasis in the biosimilars era and explores both the current challenges and potential opportunities to improve access to high-quality, effective treatments.

The Hairdex quality of life instrument-A translation and psychometric validation in patients with alopecia areata.

Background: The German Hairdex quality of life (QoL) instrument is specific to hair and scalp diseases, developed for self-rating and consists of 48 statements divided into five domains: Symptoms, Functioning, Emotions, Self-confidence and Stigmatisation. There was a need of a Swedish reliability tested, validated hair and scalp specific QoL instrument why the German Hairdex was chosen to be translated and reliability tested in a systematic way. Objectives: To make a translation, a reliability test of stability, and validation of the German Hairdex QoL instrument among 100 Swedish patients with a dermatological ICD-10 diagnosis of alopecia areata (AA). Methods: An eight-step method by Gudmundsson was used as a model with a forward and backward translation and with comments from an expert panel. A statistical test-retest (ICC (2,1)) analysis was made, followed by an internal consistency analysis. A comparison between the German and Swedish Hairdex-S constructs by a principal component analysis was performed. Results: The Hairdex-S was very well accepted by patients. The ICC(2,1) test-retest showed a good to excellent correlation of 0.91 (CI [0.85-0.95]). Internal consistency was α = 0.92. Like the original Hairdex, Hairdex-S showed good factorability with a Kaiser-Meyer-Olkin measure of 0.82 and with one component explaining 70% of the variance: original Hairdex instrument (69%). When tested on patients with AA, the domains Functioning and Emotions had the strongest loadings, followed by Stigmatisation and Self-confidence. Younger AA patients at self-assessment and patients who reported to be younger at the onset of AA, scored statistically significantly higher on the Hairdex-S, indicating an overall lower QoL on domains Emotions and Functioning, respectively. Conclusions: The Hairdex-S is very well accepted by AA patients, shows very good psychometric properties, and a very good agreement with the original Hairdex. The Swedish Hairdex instrument can be recommended for evaluation of patients QoL as well as for research purposes.

Relationship between Eczema and Self-reported Difficulties Keeping up with School Education: A Cross-sectional Study.

Eczema is a common chronic disease that affects both children and adults, and may have an adverse impact on school performance, as it is characteristically pruritic, and hence may lead to poor concentration and inadequate sleep. The aim of this study was to elucidate the relationship between eczema and self-reported difficulties keeping up with school education. The study was based on cross-sectional questionnaire data collected in schools among all 9th graders (15-16 years old) within a Swedish county. Logistic regression analyses were used to assess the association between having eczema and self-reported difficulties keeping up with school education. A total of 2,620 pupils participated (50.1% female). An increased odds ratio (OR) of self-reported difficulties keeping up with school education was found in adolescents with eczema compared with those without eczema after adjustment for sex and  family residence (OR 2.13, 95% confidence interval (95% CI) 1.32-3.44), and with additional adjustment for sleeping problems, attention-deficit hyperactivity disorder, allergy, rhinitis, asthma, and alcohol consumption (adjusted OR 1.78, CI 1.05-3.00). Eczema may be a relevant risk factor for difficulty keeping up with school education in adolescents. However, studies that can assess temporality, based in different settings with objective reports of both eczema and self-reported difficulties at school, are needed to confirm these findings.

Establishment and Utility of SwedAD: A Nationwide Swedish Registry for Patients with Atopic Dermatitis Receiving Systemic Pharmacotherapy.

SwedAD, a Swedish nationwide registry for patients with atopic dermatitis receiving systemic pharmacotherapy, was launched on 1 September 2019. We describe here the establishment of a user-friendly registry to the benefit of patients with atopic dermatitis. By 5 November 2022, 38 clinics had recorded 931 treatment episodes in 850 patients with an approximate national coverage rate of 40%. Characteristics at enrolment included median Eczema Area and Severity Index (EASI) 10.2 (interquartile range 4.0, 19.4), Patient-Oriented Eczema Measure (POEM) 18.0 (10.0, 24.0), Dermatology Life Quality Index (DLQI) 11.0 (5.0, 19.0) and Peak Itch Numerical Rating Scale-11 (NRS-11) 6.0 (3.0, 8.0). At 3 months, median EASI was 3.2 (1.0, 7.3) and POEM, DLQI, and NRS-11 were improved. Regional coverage varied, reflecting the distribution of dermatologists, the ratio of public to private healthcare, and difficulties in recruiting certain clinics. This study highlights the importance of a nationwide registry when managing systemic pharmacotherapy of atopic dermatitis.

Quality of life measurement in vitiligo. Position statement of the European Academy of Dermatology and Venereology Task Force on Quality of Life and Patient Oriented Outcomes with external experts.

Members of the European Academy of Dermatology and Venereology (EADV) Task Force on Quality of Life (QoL) and Patient Oriented Outcomes reviewed the instruments available for health-related (HR) QoL assessment in vitiligo and together with external vitiligo experts (including representatives of the EADV Vitiligo Task Force) have made practical recommendations concerning the assessment of QoL in vitiligo patients. The Dermatology Life Quality Index (DLQI) was the most frequently used HRQoL instrument, making comparison of results between different countries possible. Several vitiligo-specific instruments were identified. The vitiligo Impact Scale (VIS) is an extensively validated vitiligo-specific HRQoL instrument with proposed minimal important change and clinical interpretation for VIS-22 scores. VIS-22 was developed for use in India, where there are some specific cultural beliefs concerning vitiligo. The EADV Task Force on QoL and Patient Oriented Outcomes recommends use of the DLQI and the Children's Dermatology Life Quality Index (CDLQI) as dermatology-specific instruments in vitiligo. There is a strong need for a valid (including cross-cultural validation) vitiligo-specific instrument that can be either a new instrument or the improvement of existing instruments. This validation must include the proof of responsiveness.

Increased prevalence of human papillomavirus in fresh tissue from penile cancers compared to non-malignant penile samples: a case-control study.

BACKGROUND: HPV has been detected in approximately 50% of invasive penile cancers but with a large span between 24 and 89%, most likely due to different types of tumors and various methods for HPV analysis. Most studies of HPV in penile cancer have been performed using paraffin-embedded tissue, argued to be at risk for contaminated HPV analysis. Viral activity of HPV, by the use of HPV mRNA expression is well studied in cervical cancer, but seldom studied in penile cancer. The aim was to determine prevalence of HPV types in fresh tissue of penile cancers compared to non-malignant age-matched penile controls. Additional aims were to analyze the viral expression and copy numbers of HPV16-positive tumors and 10 mm adjacent to the tumor. METHODS: Fresh tissue from penile cancer cases was biopsied inside the tumor and 10 mm outside the tumor. Controls were males circumcised for non-malignant reasons, biopsied at surgery. PCR and Luminex assays were used for identification of HPV types. HPV16-positive samples were investigated for copy numbers and expression of HPV16-mRNA. RESULTS: Among tumors (n = 135) and age-matched controls (n = 105), HPV was detected in 38.5% (52/135) and 11.4% (12/105), respectively (p < 0.001), adjusted odds ratio 12.8 (95% confidence interval 4.9-33.6). High-risk HPV types were found in 35.6% (48/135) of tumors and 4.8% (5/105) of controls (p < 0.001). Among tumors and controls, HPV16 was present in 27.4% (37/135) and 1% (1/105), respectively (p < 0.001). Among HPV16-positive penile cancers, mean HPV16 viral copy/cell was 74.4 (range 0.00003-725.4) in the tumor and 1.6 (range 0.001-14.4) 10 mm adjacent from the tumor. HPV16-mRNA analysis of the tumors and 10 mm adjacent from the tumors demonstrated viral activity in 86.5% (32/37) and 21.7% (5/23), respectively. CONCLUSIONS: The prevalence of HPV was significantly higher in penile cancer (38.5%) than among age-matched non-malignant penile samples (11.4%). HPV16 predominates (27.4%) in penile tumors. HPV16 expression was more common in penile cancer than in adjacent healthy tissue, strongly suggesting an etiological role for HPV16 in the development of penile cancer.

Atopy patch testing and associations with atopic conditions and specific IgE tests: a population-based study in adolescents

Background: The clinical usefulness of the atopy patch test (APT) is unclear for investigating aeroallergen- and food-triggered atopic dermatitis (AD). Objectives: This study aimed to assess the prevalence of positive APT reactions in a population of adolescents and investigate possible associations between the APT, specific serum (s) immunoglobulin E (IgE) tests, self-reported atopic conditions and health-related quality of life. Materials & Methods: A population-based study was performed on 211 adolescents (13-14 years old). Collected data included questionnaires, an APT with food and aeroallergens and s-IgE tests. Results: Positive APT reactions were observed in 9.0% (19/211) of the adolescents. Timothy grass was the top allergen with 11 (5.2%) positive reactions, followed by cat dander (2.8%) and house dust mites (2.4%). Rhinoconjunctivitis increased the odds of any positive APT (crude odds ratio: 3.32; 95% confidence interval [CI]: 1.17­9.40), particularly when an APT was positive for aeroallergens (odds ratio: 5.02, 95% CI: 1.54-16.42). There was no association between a positive APT and AD. Four adolescents without AD and no IgE-sensitization had a positive APT. Conclusion: Based on a population of adolescents, the APT is associated with rhinoconjunctivitis but not AD. This finding should be taken into consideration in further attempts to clarify the role of the APT in the clinical setting.

Curettage and electrodessication combined with photodynamic therapy in the treatment of large squamous cell carcinomas in unfit and frail patients.

A Caucasian female patient in her 90s was referred to the department of plastic and reconstructive surgery for surgical removal of a large invasive squamous cell carcinoma on the anterior chest wall. A skin biopsy prior to the referral indicated that the tumour was moderately differentiated. The patient suffered from severe congestive heart failure with a mechanical valve prosthesis and atrial fibrillation, and was therefore treated with anticoagulants. Hence, a surgical procedure would be hazardous. Therefore, other treatment options were considered. The principal aim was to reduce the amount of tumour tissue to an appropriate size suitable for later excision with primary wound closure. After interdisciplinary discussions, curettage and electrodessication combined with photodynamic therapy was judged the best alternative treatment in this case. At the 1.5 years follow-up after the intervention there was no indication for further surgery. The patient was at that stage content with the treatment and its outcome.

Use of systemic therapies in adults with atopic dermatitis: 12-month results from the European prospective observational study in patients eligible for systemic therapy for atopic dermatitis (EUROSTAD).

BACKGROUND: The European Prospective Observational Study in Patients Eligible for Systemic Therapy for Atopic Dermatitis (EUROSTAD) is an ongoing observational study aiming to describe characteristics of patients with atopic dermatitis (AD) treated with systemic therapy over time and the management of their disease in a real-world setting. METHODS: Data from patients enrolled in EUROSTAD between March 2017 and April 2019 were analyzed for systemic therapy use and treatment change over 12 months. RESULTS: 288 patients reported taking systemic medications; 42.7% received cyclosporine, 35.3% dupilumab, 28.1% methotrexate, 25.4% oral corticosteroids, 6.8% azathioprine, 6.1% injectable corticosteroids, and 3.4% mycophenolate. The median duration of treatment was 1.1 months for oral systemic corticosteroids, 3.2 months for injectable corticosteroids, 4.8 months for cyclosporine, 7.3 months for methotrexate, and 14.9 months for dupilumab. The most frequent reasons for stopping treatment included lack of efficacy, patient decision, adverse events, and disease well controlled. CONCLUSION: The 12-month interim EUROSTAD study analysis highlights the current trends and outcomes of systemic treatments for moderate-to-severe AD. Among all systemic treatments for AD, dupilumab was the least likely to be discontinued, whereas cyclosporine and corticosteroids, whilst effective, were primarily limited to episodic flare management consistent with treatment guidelines.

Incidence of penile intraepithelial neoplasia and treatment strategies in Sweden 2000-2019.

OBJECTIVES: To analyse the incidence, treatment strategies and complications associated with penile intraepithelial neoplasia (PeIN) in Sweden over a period of 20 years. MATERIALS AND METHODS: Data on PeIN from the Swedish National Penile Cancer Register were analysed regarding treatment in relation to age, size of the PeIN lesion, localization of the PeIN lesion and complications using chi-squared tests and logistic regression. The incidence of PeIN was calculated and age-standardized according to the European Standard population. RESULTS: Between 2000 and 2019 a total of 1113 PeIN cases were reported. The age-standardized incidence of PeIN was 1.40 per 100 000 men (95% confidence interval [CI] 1.32-1.49). An increase in incidence over time was seen, with a standardized incidence rate of 2.37 (95% CI 1.56-3.70) in 2019 compared to the baseline year, 2000. Surgical or topical treatments were given in 75.0% and 14.6% of cases, respectively. The complication rate was higher in laser surgery (12.1%, 7/58) compared to local surgery (4.6%, 16/348; P = 0.03) with an age-adjusted odds ratio (OR) of 2.82 (95% CI 1.10-7.19; P = 0.03). Local surgery was more common than laser surgery in the last 5 years compared to the first 5 years of the study period: OR 5.75 (95% CI 2.94-11.27). Treatments with imiquimod and topical 5-fluorouracil (5-FU) were more common than destructive methods such as photodynamic therapy, cryotherapy, curettage and electrocautery in the last 5 years compared to the first 5 years: OR 9.48 (95% CI 2.29-39.24). CONCLUSIONS: A twofold increase in the age-standardized incidence of PeIN was seen in Sweden over 20 years. Complications were three times more common in laser surgery compared to local surgery. Changes in treatment showed an increase of treatment strategies such as local surgery and treatment with imiquimod and topical 5-FU over time.

Incidence Rate of Hand Eczema in Different Occupations: A Systematic Review and Meta-analysis.

Hand eczema is a chronic disease that results in economic and psychosocial burdens. The aim of this study was to systematically review and assess the magnitude of the association between exposure related to occupations and the incidence rate of hand eczema. A systematic search in PubMed, EMBASE, CINAHL and Cochrane databases, from inception to September 2017, of full-text observational studies reporting incident cases of hand eczema during employment, and a supplementary search in PubMed to September 2020, were conducted. Among 2,417 screened abstracts, 15 studies fulfilled the inclusion criteria. Incidence rates were reported per 100 person-years. Based on the Newcastle-Ottawa Scale, 9 studies were good quality, 2 fair quality, and 4 poor quality. Hairdressers had a high incidence of hand eczema of 21.4 (95% confidence interval [CI] 15.3-27.4), as did nurses, 16.9 (95% CI 11.2-22.7), and metal workers, 12.4 (95% CI 3.5-21.3). Hairdressers were predominantly women, and metal worker were predominantly men. Office occupations had an incidence rate of hand eczema of 4.9 (95% CI 1.2-9.6). The high risk of hand eczema for hairdressers, nurses, and metal workers, should be considered by healthcare policymakers. Even occupations with low irritant profile, such as office workers, were at risk of developing hand eczema, and more occupations should be investigated regarding the related risk of developing hand eczema.

Body dysmorphia in common skin diseases: results of an observational, cross-sectional multicentre study among dermatological outpatients in 17 European countries.

BACKGROUND: Body dysmorphic disorder (BDD) is a common psychiatric disorder associated with high costs for healthcare systems as patients may repeatedly ask for different, often not effective, interventions. BDD symptoms are more prevalent in patients with dermatological conditions than in the general population, but there are no large sample studies comparing the prevalence of BDD symptoms between patients with dermatological conditions and healthy skin controls. OBJECTIVES: To compare the prevalence of BDD symptoms between patients with different dermatological conditions and healthy skin controls and to describe sociodemographic, physical and psychological factors associated with BDD symptoms to identify patients who may have a particularly high chance of having this condition. METHODS: This observational, cross-sectional, comparative multicentre study included 8295 participants: 5487 consecutive patients with different skin diseases (56% female) recruited among dermatological outpatients at 22 clinics in 17 European countries, and 2808 healthy skin controls (66% female). BDD symptoms were assessed by the Dysmorphic Concern Questionnaire. Sociodemographic data and information on psychological factors and physical conditions were collected. Each patient was given a dermatological diagnosis according to ICD-10 by a dermatologist. The study was registered with number DRKS00012745. RESULTS: The average participation rate of invited dermatological patients was 82.4% across all centres. BDD symptoms were five times more prevalent in patients with dermatological conditions than in healthy skin controls (10.5% vs. 2.1%). Patients with hyperhidrosis, alopecia and vitiligo had a more than 11-fold increased chance (adjusted Odds Ratio (OR) > 11) of having BDD symptoms compared with healthy skin controls, and patients with atopic dermatitis, psoriasis, acne, hidradenitis suppurativa, prurigo and bullous diseases had a more than sixfold increased chance (adjusted OR > 6) of having BDD symptoms. Using a logistic regression model, BDD symptoms were significantly related to lower age, female sex, higher psychological stress and feelings of stigmatization. CONCLUSIONS: Clinical BDD symptoms are significantly associated with common dermatological diseases. As such symptoms are associated with higher levels of psychological distress and multiple unhelpful consultations, general practitioners and dermatologists should consider BDD and refer patients when identified to an appropriate service for BDD screening and management.

Prevalence of contact allergies in the population compared to a tertiary referral patch test clinic in Jena/Germany.

BACKGROUND: The contact allergy prevalences in patch-tested patients are usually higher than those in the population, owing to morbidity-driven selection. OBJECTIVES: To examine the differences between two samples, one from the population, one from the patch test clinic, in one area of Germany (Jena, Thuringia). METHODS: Between August 2008 and October 2011, a total of 519 participants of the population-based european dermato-epidemiology network (EDEN) fragrance study were patch tested in Jena using a TRUE Test baseline series extended with some pet.-based (fragrance) allergen preparations. Between 2007 and 2012 (inclusive), 1906 routine patients were patch tested for suspected allergic contact dermatitis (ACD) in the Jena University Hospital Department; of these 1694 (83.2%) with the German baseline series using pet./aq.-based, investigator-loaded allergens. RESULTS: In the population (clinical) sample, 19.6% (41.1%) were sensitized to at least one of the allergens considered. The most common baseline series allergens in the population/clinical sample were nickel (10.5%/13.2%), fragrance mix (FM) II (2.9%/6.7%), FM I (2.3%/8.3%), and cobalt (1.6%/5%). The clinical sample was slightly older (71.5% vs 55.9% age 40+) and included less males (36% vs 49.3%). CONCLUSIONS: Results are quite similar, although prevalences are usually higher in the clinical setting, with the exception of p-tert-butylphenol formaldehyde resin.

Skin exposure to scented products used in daily life and fragrance contact allergy in the European general population - The EDEN Fragrance Study.

BACKGROUND: Fragrances are widely used in scented products used in daily life with the potential to induce skin sensitization. OBJECTIVE: To evaluate exposure to scented products and to explore associations between exposure and fragrance contact allergy. METHODS: A cross-sectional study on individuals from 18 to 74 years of age, who were randomly selected from the general population in five European countries. A random sample (N = 3119) was patch tested and interviewed on exposure to scented products. RESULTS: Female participants were strongly associated with exposure to scented products relative to male participants. Participants age 40 years and older showed an inverse association with exposure to scented products. Compared to Sweden, The Netherlands followed by Germany showed the highest overall exposure to scented products. Sensitive skin was associated with exposure to scented products and with fragrance allergy. In univariable regression analysis, exposure to leave-on products and to specific scented product subgroups was significantly associated with fragrance allergy. CONCLUSION: Exposure to scented products depends primarily on sex and age. Female sex and sensitive skin are relevant indicators for developing fragrance allergy. Because aggregate exposure, especially to scented leave-on products, may enhance the prevalence of contact allergy to fragrances, further investigations into exposure amounts and frequencies is warranted.

Asymmetric contributions of seed and pollen to gene dispersal in the marsh orchid Dactylorhiza umbrosa in Asia Minor.

Orchids differ from other plants in their extremely small and partly air-filled seeds that can be transported long distances by wind. Seed dispersal in orchids is expected to contribute strongly to overall gene flow, and orchids generally express low levels of genetic differentiation between populations and low pollen to seed flow ratios. However, studies in orchids distributed in northern Europe have often found a poor geographic structuring of genetic variation. Here, we studied geographic differentiation in the marsh orchid Dactylorhiza umbrosa, which is widely distributed in upland regions from Asia Minor to Central Asia. These areas were less affected by Pleistocene ice ages than northern Europe and the orchid should have been able to survive the last ice age in local refugia. In the plastid genome, which is dispersed by seeds, populations at close distance were clearly divergent, but the differentiation still increased with geographic distance, and a significant phylogeographic structure had developed. In the nuclear genome, which is dispersed by both seeds and pollen, populations showed an even stronger correlation between genetic and geographic distance, but average levels of differentiation were lower than in the plastid genome, and no phylogeographic structure was evident. Combining plastid and nuclear data, we found that the ratio of pollen to seed dispersal (mp/ms) decreases with physical distance. Comparison with orchids that grow in parts of Europe that were glaciated during the last ice suggests that a balanced structure of genetic diversity develops only slowly in many terrestrial orchids, despite efficient seed dispersal.