1Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark, 2Department of Dermatology and Regional Unit for Asthma, Allergy and Hypersensitivity, Oslo University Hospital-Rikshospitalet, Oslo, Norway, 3Dermatology and Venereology Unit, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden, 4Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark, 5Department of Dermatology, University Hospital of North Norway, Tromsø, Norway, 6Allergy Centre, Tampere University Hospital, Tampere, Finland, 7Langeland Tor, Hudlegene Tor Langeland and Gro Mørk, Oslo, Norway, 8Särnhult Tore, Hallandskustens Hudmottagning, Kungsbacka, Sweden, 9Department of Dermatology, Bispebjerg Hospital, Copenhagen, Denmark, 10Department of Dermatovenereology, Haukeland University Hospital, Bergen, Norway, 11Department of Dermatology and Venereology, Aarhus University Hospital, Aarhus, Denmark, 12Department of Dermatology, Lund University, Skåne University Hospital, Malmö, Sweden, and 13Department of Skin and Allergic Diseases, Helsinki University Central Hospital, Helsinki, Finland
Similarities and differences in the everyday clinical management of moderate-to-severe atopic dermatitis in Nordic countries are unknown. Using a modified Delphi approach, 15 dermatologists from Denmark, Finland, Norway and Sweden completed face-to-face and online questionnaires and participated in summary discussions to map expert opinion on the clinical management of moderate-to-severe atopic dermatitis in these Nordic countries. Through discussions, 6 adult patient profiles, reflecting common disease presentations of atopic dermatitis, were identified. Using these case profiles, diagnostic work-up, treatment goals, patient education and treatment approaches were discussed. Patient education was identified as essential for effective management. A treatment sequence of moderate-to-potent topical glucocorticosteroids and emollients, followed by systemic treatment, was recommended, allowing 3 months to ascertain systemic treatment response before switching, if necessary. Consensus was not reached on systemic treatment choice, reflecting differences in clinical practice and reimbursement between countries. Practical, case-based clinical recommendations were developed for optimal patient care.
Key words: atopic dermatitis; guidelines; management; Nordic; treatment; work-up.
Accepted Nov 6, 2019; E-published Nov 8, 2019
Acta Derm Venereol 2020; 100: XX–XX.
Corr: Jacob P. Thyssen, Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, Kildegaardsvej 28, DK-2900 Hellerup, Denmark. E-mail; jacob.pontoppidan.thyssen@regionh.dk
Atopic dermatitis is a disease associated with various skin complaints. There is currently no consensus on the diagnosis and treatment of atopic dermatitis in the Nordic region. We therefore gathered 15 Nordic dermatologists to discuss patient education, diagnosis and treatment of atopic dermatitis. Patient education was identified as essential for effective management of atopic dermatitis, and treatment with moderate-to-potent topical glucocorticosteroids and emollients, followed by systemic treatment, was recommended. This article provides insights into the challenges associated with effective management of atopic dermatitis across the Nordic region and provides recommendations for optimal patient care.
Atopic dermatitis (AD) is a chronic, pruritic, relapsing skin disease associated with inflammation, skin barrier dysfunction and altered skin microbiota. AD can be associated with elevated serum IgE and cytokine levels, driven by type 2 inflammation, and can occur alongside type I allergy manifestations, such as allergic asthma and rhinitis. The incidence of AD has increased 2–3-fold in the past 3 decades, but appears to have reached a plateau in developed countries (1, 2); AD affects up to 25% of the paediatric population and up to 5% of adults worldwide (2–5), either as a persistent disease from childhood or as recurring or adult-onset AD (6, 7). AD is a heterogeneous disease with a broad spectrum of clinical presentations and differential severity. In addition to these phenotypes, AD also exhibits different endotypes according to different inflammatory mediators, IgE levels and filaggrin gene mutation status, which can vary across different ethnicities and age groups (8, 9). Multiple other factors influence the clinical picture, such as age, sex, environment, occupation and lifestyle. The differential diagnosis is wide-ranging; examples of overlapping or competing conditions that need to be considered include contact dermatitis, skin infections, neurodermatitis, immunodeficiency disorders, drug eruptions and cutaneous T-cell lymphoma (10).
The primary treatment for AD is based on repairing and improving skin barrier function by avoiding exacerbating factors, using emollients and treating active lesions with anti-inflammatory medication (11, 12). Emollients, along with topical anti-inflammatory treatments, including topical glucocorticosteroids (TCS) and topical calcineurin inhibitors (TCI), are used for managing exacerbations and actively maintaining long-term symptom control (11, 13, 14). Topical treatments can provide symptom control in many patients with AD, but adults with moderate-to-severe AD may require phototherapy or systemic therapy.
Systemic treatments approved for the treatment of moderate-to-severe adult AD include cyclosporine-A, prednisolone (approved for AD in Norway) and the biologic dupilumab (15). Patients with moderate-to-severe AD are also treated using unlicensed systemic therapies, e.g. prednisolone, azathioprine, mycophenolate mofetil and methotrexate (11).
The population affected by AD is heterogeneous, and the factors determining AD management, such as age, comorbidity, pregnancy, course of disease and previous management, extend beyond objective severity. The diverse phenotypes observed in patients with AD should influence how AD is clinically managed (7). Clinical identification of factors that can impact outcomes might provide a means for more effective treatments.
There is limited insight into the similarities and differences in everyday clinical management of moderate-to-severe AD in adults in Nordic countries. Local preferences for AD management differ, which may have a bearing on the treatment selection. Treatment and diagnostic practice vary significantly across and within Nordic countries because both clinical guidance and economic factors are taken into consideration during clinical decision-making. Experts from Denmark, Finland, Norway and Sweden were invited to discuss and come to a possible consensus on the principles of managing AD, considering local differences between countries and sharing experiences.
In this consensus process, 15 dermatologists from Denmark, Finland, Norway and Sweden used a modified Delphi technique to provide patient-focused expert opinion for the work-up and treatment of adults with moderate-to-severe AD for use in a clinical setting. This expert panel, invited by the study sponsor, was independent and was not appointed by a National Dermatological Society or Regulatory Authority from any of the respective countries.
Development of case profiles
Six patient cases based on common profiles of adult patients with moderate-to-severe AD presenting in Nordic dermatology clinics were identified and described; these cases reflected key patient features of relevance to dermatologists. The Steering Committee used an iterative process, involving 2–3 rounds of drafts and review, to develop case statements ready to vote on during the consensus meeting. For each case, they developed a set of statements and questions on diagnostic work-up and treatment recommendations that were specific to that profile:
1. Presentation, signs and symptoms, patient history and family history
2. Differential diagnosis
3. Work-up: clinical and laboratory investigations from a standard checklist of:
4. Assessment of disease severity (e.g. Eczema Area and Severity Index [EASI] (16), Patient Oriented Eczema Measure [POEM] (17), SCORing Atopic Dermatitis [SCORAD] (18) and impact on HRQoL by means of Dermatology Life Quality Index [DLQI] (19))
5. Goals of treatment
6. Treatment (topical or systemic)
7. Evolution of the case (clinical presentation, patient history and family history)
8. Specific considerations for each case
Modified Delphi process
The Delphi process is a recognized method used to gain consensus between specialists in a particular field where expert opinion is important in shaping judgements. This approach provides experts with an opportunity to alter their response based on their peers’ opinions, thus increasing the likelihood of convergence of opinion. The process consisted of questionnaires during the meeting and via online surveys, plus a final validation stage via email.
Expert panel
Recommendations were developed for diagnostic work-up, treatment goals and treatment choice by an expert panel using a modified Delphi process. The expert panel of 15 dermatologists from Denmark, Finland, Norway and Sweden had a particular interest in and knowledge about AD and were selected on the basis of their clinical role and experience of managing patients with AD. The relative geographical contributions from each country were balanced, with 4 advisors each from Denmark, Norway and Sweden and 3 from Finland. Overall, 14 of the experts were involved in the final manuscript validation and the Steering Committee, comprised of one expert from each country, (JT, TB, LVK and AR), developed the 6 hypothetical patient profiles.
Expert consensus panel and follow-up online surveys
During the meeting, the Steering Committee presented each of the 6 patient profiles to the remainder of the expert panel and posed questions as per the modified Delphi method (20); based on advice from the Steering Committee, the questions were case specific. The possible answers were either scored on a 5-point Likert scale or answered using multiple choice responses (for systemic treatment options); in each instance, the experts could select only one answer. During the meeting, responses were captured using audience response voting systems provided by a third party, Crystal Interactive, Godalming, UK (a global meeting and events solution company); this methodology provided anonymous answers and allowed voting to be evaluated by country. Initially, experts voted on whether they agreed that the case profile represented a “typical” AD patient group before moving on to address diagnostic work-up, treatment goals and treatment choice. All responses were reviewed and discussed regardless of the level of consensus. If a consensus was not reached, experts had a detailed facilitated discussion to identify the reasons for the lack of agreement. Dr Thyssen acted as chair and an independent Delphi facilitator moderated the meeting. Statements were revised by the Delphi facilitator after feedback from experts and re-voting was undertaken when possible. The chair also invited discussion from the experts on what drives their decisions when selecting treatment; this was largely captured in an open discussion.
For each case, statements on diagnostic work-up, patient education, treatment goals and treatment choice were developed, refined and voted on (either in the face-to-face meeting or post-meeting via the online survey).
Owing to time constraints and the extent of discussion required, voting was only completed on all statements for cases 1 and 2, and treatment goals and treatment choice statements were only completed for case 4 during the face-to-face meeting. The priority of the cases discussed in the face-to-face meeting was driven by the expert panel. After the initial meeting, the outcomes (from the aforementioned case studies) were validated, and voting for the statements from the remaining cases (cases 3, 5 and 6 and the diagnostic statements for case 4) was conducted and validated via an online survey. The facilitator shared the results by email and independently collected feedback from each participant. A consensus threshold of 75% was specified a priori, which is in keeping with recent consensus initiatives in this field (21).
Case profile validation
The 6 typical patient presentations developed to illustrate the spectra of adult moderate-to-severe AD observed in the clinic are presented in Table I and illustrated in Fig. 1.
Table I. Case presentations: details and statements for expert voting
Fig. 1. Clinical characteristics of atopic dermatitis (AD) for 6 typical case presentations. (A) Case 1. Moderate-to-severe head and neck dermatitis. (B) Case 2. Moderate-to-severe AD with type I allergies. (C) Case 3. Moderate-to-severe AD with hand eczema. (D) Case 4. Moderate-to-severe AD with recurrent infections (E) Case 5. Moderate-to-severe lichenified AD with severe itch. (F) Case 6. Moderate-to-severe, late-onset AD.
For each case, the advisors reached consensus (100% agreed) that the patient presentation was typical of patients with moderate-to-severe AD commonly managed in Nordic countries. The advisors also reached consensus (100% agreed) that the cases reflected the spectra of the most typical presentations of adults with moderate-to-severe AD seen in Nordic clinics (Table I). Case 6 prompted the most discussion, given the complex nature and lack of clear definition for late-onset AD (compared with pre-existing AD that has been diagnosed late) and the possibility of alternative diagnoses, such as cutaneous T-cell lymphoma or contact dermatitis.
The importance of accurately detailing patient history was emphasized by the experts, particularly when taking on a new referral (Table I). Patients’ EASI scores and family histories were important features, as were relevant comorbidities (Table I). Different features were important for each case; for example, the region of the body affected, the age of the patient, with onset either in infancy or later in life, and details of skin lesions in patients with infected eczema. Incomplete medical notes could lead to erroneous conclusions; for example, patients may overestimate the severity of their allergies when self-reporting, or a perceived treatment failure could have been caused by poor patient compliance or an ineffectively implemented treatment plan. In these cases, previous treatments could potentially be re-attempted.
The results of the final consensus agreements are presented in Tables II−V and Figs S1−S6.
The discussion and considerations behind these agreements are captured in the discussion section to provide a broader context.
Table II. Diagnostic work-up statements for expert voting
Table III. Targeted patient education statements for expert voting
Table IV. Treatment goal and approach statements for expert voting
The consensus discussion approach used to map expert opinions was chosen owing to the lack of coherent agreement guidance on the clinical management of AD in adults in Denmark, Finland, Norway and Sweden. Expert insight used a patient-specific approach to review the typical practice of contemporary diagnostic work-up and AD treatment approaches in Nordic countries.
Diagnostic work-up (Table II)
AD scoring tools. Experts were in full agreement (100%) on the assessment of disease severity; they agreed that a robust clinical assessment was necessary using symptoms and skin examination to ascertain the impact on the patient. Consensus was also reached on the importance of using accepted scoring tools for assessing different aspects of AD (79% agreed); including, but not limited to, EASI, POEM and SCORAD for disease severity; the numerical rating scale or visual analogue scale for symptoms; and the DLQI for HRQoL assessment. Although the composite use of subjective and objective scoring systems is recommended in the European guidelines on AD assessment (11), experts did not feel that it was always practical to use the scoring tools during routine consultations and instead relied on their clinical experience for assessing many aspects of the disease. They also believed that the use of scoring systems should not exclude a simultaneous holistic view. Furthermore, they felt that the importance of regular, long-term measurements should be emphasized to physicians: disease activity can vary greatly between visits, hence it is essential to have a detailed timeline of disease activity including severity score and the duration of symptom-free periods. Measurements/assessments should be carried out for 3–6 months, and for assessment of long-term control, for one year (or longer).
Additional tests for AD work-up. Experts reached a consensus (93%) that testing for filaggrin gene mutations was not necessary for patient education on disease aetiology, prognosis and consequences, such as inheritance. Only in case 1 (moderate-to-severe head and neck dermatitis) was it agreed (93%) that patch testing should be performed to identify possible contact allergies to ingredients in cosmetics, emollients and other topical treatments. Patch tests were considered too onerous for routine testing in patients with AD, but the experts agreed that they should be performed at the physician’s discretion, for example for patients who have not had previous patch tests and/or where a clinical suspicion of complicating allergic contact dermatitis could not be ruled out, or in cases of treatment failure; typically with generalization of eczema or spread outside the traditional areas. Patch tests may also be considered for patients with chronic AD, or as with case 3 (moderate-to-severe AD with hand eczema) where the aetiology of hand eczema could be mixed.
Similarly, skin prick tests or measurements of specific IgE were not considered necessary as part of routine testing in moderate-to-severe adult AD; however, if there is suspicion of a type I respiratory, gastrointestinal or ocular allergy (e.g. in case 2 (moderate-to-severe AD with type I allergies)), skin prick tests or specific IgE testing should be initiated by the dermatologist. In patients with a relevant history, similar to case 3 (moderate-to-severe AD and hand eczema), physicians may perform a skin prick test with foods to confirm overlying contact urticarial and suspected protein contact dermatitis.
The panel’s recommendations for the use of standard allergen work-up varied between cases, reflecting the difference in the predominant underlying disease process. For example, testing for food allergens in case 2 (moderate-to-severe AD with type I allergies) was mandated in instances where this could be a contributing aggravating factor of AD (100% agreed). In case 3 (moderate-to-severe AD with hand eczema), experts reached a consensus that neither aero nor food allergens need to be tested in instances where they are unlikely to be an underlying trigger (80% and 87%, respectively), but there was a full consensus (100% agreed) for performing exposure analyses and environmental inspection for contact allergens in patients with hand eczema.
Evaluation before systemic treatment. The pre-treatment evaluations used before systemic treatment were found to be heterogeneous across these Nordic countries: chest X-rays may be performed before commencing methotrexate, thiopurine methyltransferase genotype and phenotype testing may be performed before azathioprine use, and it is recommended, but not mandatory, that both creatinine filtration rate and blood pressure measurement should be performed before cyclosporine use.
Infection control and differential diagnosis. Staphylococcus aureus colonization is frequent in lesional skin of patients with AD and can be an important factor in aggravating skin lesions (22). If a patient presents with widespread infected AD with oozing dermatitis, the clinician would usually immediately commence appropriate oral antibiotic treatment (e.g. dicloxacillin/flucloxacillin/cephalexin) and collect material for culture. Treatment could be adjusted if the organism is found to be resistant. Identification of infection was considered very important in case 4 (moderate-to-severe AD with recurrent infections; 80–100% agreed), particularly if the patient is starting antibiotics and systemic treatment simultaneously.
Consensus was reached on considering a differential diagnosis for case 6 (moderate-to-severe, late-onset AD) where there was a risk of misdiagnosing cutaneous T-cell lymphoma (93–100% agreed); suspected lymphoma should be investigated with repeated skin biopsies, as well as blood and bone marrow tests, and potential overlying or competing allergic contact dermatitis should be excluded with patch testing.
Allergic comorbidities and referrals. Patient referral to other specialists, such as ophthalmologists or pulmonologists, was not considered to be part of routine patient management. Instead, this should be based on the presentation of specific clinical symptoms, such as ocular or pulmonary manifestations. The experts agreed that patient history should include relevant allergic comorbidities, such as conjunctivitis, asthma and rhinoconjunctivitis; dermatologists should recognize exacerbation of symptoms that are likely to be caused by allergens, such as underlying grass pollen or another (type I) aero-allergen that can aggravate AD symptoms if the individual is exposed (23).
Experts agreed that, if appropriate, dermatologists should refer patients with moderate-to-severe AD with hand eczema (93% agreed) or moderate-to-severe, late-onset AD (100% agreed) to other specialists, such as an allergist or occupational health specialist, if local conditions lead to challenges in managing and diagnosing these patients. Experts agreed (86%) that physicians should evaluate allergic comorbidities in patients with moderate-to-severe AD with type I allergies because allergic comorbidities may have worsened their AD over a long period of time.
Targeted patient education statements and treatment goals and approaches (Tables III−IV)
Patient education, treatment approaches and goals. Patient education has proven to be effective in increasing treatment adherence and HRQoL in AD (24). Consensus was reached (93% agreed) on the importance of targeted patient education and patient support in any management plan. Table III shows a comprehensive list of education points, which may vary depending on the patient. Daily use of emollients was considered an important step in managing all cases of AD.
The experts strongly agreed that the selection of treatment should be dictated by past treatment experience, contraindications, comorbidities and patient preference (100% agreed; Table IV), and that if treatment response to topical therapy with or without phototherapy is suboptimal or not tolerated or initial treatments are contraindicated, systemic therapy should be initiated and optimized in patients with moderate-to-severe AD.
The ultimate goal of AD treatment is for patients to live a fulfilled life that is relatively unrestricted by AD. This goal is patient-specific and should address the symptoms that patients perceive to be the worst, such as cosmetic concerns, itchy or painful skin and poor-quality sleep. Table IV shows the treatment goal and approach statements. Consensus was reached (100% agreed) on the goals of treatment: to stabilize dermatitis at the lowest level and reduce the symptoms of greatest concern to the patient (for cases 1, 2 and 4−6), including reducing itch, improving sleep and HRQoL for patients with moderate-to-severe lichenified AD with severe itch and/or moderate-to-severe, late-onset AD; and to prevent infections in patients with moderate-to-severe AD with recurrent infections. Consensus on 2 treatment goals for patients with moderate-to-severe AD with hand eczema was also agreed (93%): “to maintain barrier function to control symptoms such as itch or pain and stabilize AD” and “to control hand dermatitis and re-establish function to enable the return to the workplace/labour market”.
Initial treatment of AD. The treatment approach statements are shown in Table IV. TCS are well-recognized as the first-line anti-inflammatory treatment for managing AD in children and adults (11). The consensus upheld the recommendations of the European guidelines to use TCS for treating the initial phase of AD exacerbation in the majority of these case profiles (80−100% agreed) (11); however, in case 2 (moderate-to-severe AD with type I allergies), consensus was not reached. In relevant cases, consensus was reached on tapering topical treatment from once-daily to a twice-weekly application (87−100% agreed). It was stressed that the TCS potency should always be adjusted to the anatomical region that was treated. Consensus was also reached (80% agreed) on the short-term use of oral antibiotics (dicloxacillin/flucloxacillin/cephalexin) to control moderate-to-severe AD with recurrent infections. There was no consensus for the use of 2% ketoconazole shampoo in patients with moderate-to-severe head and neck dermatitis or the use of phototherapy, with the exception of moderate-to-severe, late-onset AD, where phototherapy would be considered (87% agreed).
In agreement with the European guidelines, experts recommended exercising caution with the use of TCS on the face (11). TCS may be responsible for the “red face” described in case 2, and therefore should be restricted to a maximum use of 2 weeks. It was noted that TCI may be the preferred initial topical treatment alternative to TCS (rather than the second-line treatment) and may be preferable to TCS for long-term maintenance; however, TCI and phototherapy should not be combined (25). Consensus was not reached on how long a patient should be treated with TCS before assessing response; however, the panel generally thought that 3 weeks was not sufficient and that 4−6 weeks would be more appropriate.
Phototherapy and balneotherapy. The need for phototherapy was not universally agreed between the experts and their views may have been influenced by variation in treatment culture in these Nordic countries, as well as individual clinical experience and practicality for the patient (e.g. travel distance to the treatment centre). During discussions, experts agreed that balneotherapy (baths including potassium permanganate and bleach baths) would be an appropriate treatment for patients with moderate-to-severe AD with recurrent infections (case 4), but it was emphasized that the evidence level is poor (26, 27).
Systemic therapy (Table V). Systemic therapies commonly used for the treatment of moderate-to-severe AD include methotrexate, cyclosporine, azathioprine, mycophenolate mofetil, oral prednisolone and dupilumab (11).
In Denmark, to be considered eligible for dupilumab treatment, adult patients with AD must have tried and failed (or not tolerated/been ineligible for) 2 conventional systemic immunosuppressant treatments (e.g. methotrexate and azathioprine) and also have an EASI score >16, and DLQI >10 or POEM score >16.
In Finland, dupilumab is reimbursed in patients with severe AD, and in whom conventional systemic treatment has insufficient efficacy, is contraindicated, or is not suitable.
Although dupilumab has been approved in Norway, governmental reimbursement has not yet been granted, and it can only be prescribed in individual patients at university hospitals. Furthermore, in Norway, dupilumab is reimbursed on a regional level so the department initiating the treatment covers the costs, and consequently, few patients in Norway currently receive dupilumab treatment.
In Sweden, dupilumab is reimbursed for patients with severe AD, who, because of the insufficient efficacy of conventional systemic treatment or other medical reasons, lack additional treatment options.
The length of time a patient should try a given systemic therapy before escalating the dose or switching treatment if there is limited efficacy varies. Experts recommended that systemic treatment should be optimized and that patients should be maintained for 3 months on the maximum dose for the full treatment effect to develop and to ascertain adherence to treatment before considering switching (100% agreed); this view was consistent across all cases.
No consensus was reached for first-, second- or third-line systemic treatment in any of the cases (Table V). Countries in the Nordic region have different cultures and traditions of treatment practice, as well as reimbursement schemes, which may explain the lack of agreement on treatment (Figs S1−S6). The experts did not identify a role for oral prednisolone as a single agent for the management of moderate-to-severe AD, although some clinicians may occasionally use it as part of a bridging regimen in selected patients. Mycophenolate mofetil (including with prednisolone bridging) is rarely used in any line of therapy.
For case 1 (moderate-to-severe head and neck dermatitis), a high EASI score was considered important for clinical decision-making regarding systematic treatment; however, experts highlighted that a high EASI score may not be necessary to justify switching from one systemic treatment to another in patients with moderate AD who continue to experience symptoms.
For case 2 (moderate-to-severe AD with type I allergies), identifying a systemic AD treatment that could also treat the patient’s allergic comorbidities would be a driver in selecting a systemic treatment.
For case 3 (moderate-to-severe AD with hand eczema), treatment decisions would be driven by clinical practice and drug efficacy and safety, in addition to country-specific reimbursement. The patient was a 20-year-old woman; thus age and childbearing potential were also important drivers. Alitretinoin, mycophenolate mofetil and methotrexate are teratogenic and are therefore contraindicated in pregnancy; systemic corticosteroid and cyclosporine treatment can be used during pregnancy; there are conflicting data for azathioprine use in pregnancy; and data are not yet available for dupilumab use in pregnancy (11).
Systemic treatment decisions for case 5 (moderate-to-severe lichenified AD with severe itch) would be driven by clinical practice, drug efficacy, country-specific reimbursement and safety; however, they would also be influenced by previous treatment history, and this patient’s previously unsuccessful systemic treatments would influence the subsequent treatment choice.
Decisions on systemic treatment for case 6 (moderate-to-severe, late-onset AD) would be driven by a variety of factors, including safety, clinical practice, drug efficacy and country-specific reimbursement. With late-onset AD, patient age is also an important factor; nephrotoxicity from cyclosporine use is more common in elderly patients (11), and there is a risk of worsening of an underlying and unrecognized cutaneous T-cell lymphoma (28). The cost of medication may be a further consideration; for example, in some countries, methotrexate may be an attractive option as it is an affordable treatment.
Systemic treatment by Nordic country (Figs S1−S6). Across the patient example cases, the experts most frequently recommended first-line methotrexate, cyclosporine and azathioprine. In Denmark, methotrexate is the preferred first-line treatment for AD, whereas in Norway, cyclosporine tends to be preferred; the picture was less clear in Finland and Sweden.
The second-line treatments most frequently selected for AD were azathioprine in Denmark and dupilumab in Sweden, whereas second-line treatment selection tended to be more varied in Norway and Finland.
Local differences in treatment culture may also be associated with marketing authorization and reimbursement in AD. For each patient, the relative benefits and limitations for any systemic treatment should be weighed carefully, taking into account the patient’s preferences. As highlighted in this discussion, there are different preferences in these Nordic countries, yet they are all in accordance with international guidelines for the treatment of AD. The experts commented that, if a biologic such as dupilumab was chosen for the second-line treatment of AD, there may not be an attractive third-line option; however, if a combination of a systemic immunosuppressive plus a biologic was available, this could be a feasible alternative to dupilumab as a single agent.
Study limitations
This modified Delphi consensus approach had a number of limitations. Firstly, the profiling of cases was based on the Steering Committee’s descriptions of clinical presentation and their experience of diagnosing AD rather than any evidence base that defines specific patient “phenotypes”. Secondly, this study was limited in its ability to produce Nordic-wide recommendations on the use of systemic treatment because of the small sample size of clinical experts and varying local clinical practice and reimbursement rules within and between these Nordic countries.
Conclusion
The results of this first meeting among Nordic AD experts show that many different clinical approaches within the bounds of international guidelines, each with individual merits, are currently utilized. Marked heterogeneity in the approaches to diagnostic work-up and systemic treatment choices in moderate-to-severe AD exists across the Nordic countries, and this is likely to be influenced by local treatment culture and reimbursement guidelines.
The authors would like to acknowledge the support of K. McKillen in facilitating the Delphi meeting and A. Koning and M. Reynolds of OPEN Health Medical Communications (London, UK) in preparing the manuscript. The meeting was sponsored by Sanofi Genzyme. The views and opinions reported in the manuscript are those of the authors.
Conflicts of interest disclosures: JPT received personal fees for attendance at the meeting related to this article from Sanofi Genzyme; received personal fees for consultancy from Eli-Lilly and Sanofi-Genzyme; and received personal fees for speaking from Leo Pharma and Sanofi Genzyme. TB’s institute received research support from Sanofi Genzyme. MB received personal fees for attendance at the meeting related to this article from Sanofi Genzyme; and her institute received research support from Sanofi Genzyme. MD received personal fees from Almirall, Eli Lilly, Galapagos, Leo Pharma, Meda Pharma, Pierre Fabre, Pfizer, Regeneron, and Sanofi Genzyme; and received research support for participating as a Primary Investigator from AbbVie, Eli Lilly, Leo Pharma, and Regeneron. ØG has no conflicts of interest. LK received personal fees from Novartis, Orion, and Sanofi Genzyme. TL received personal fees for consultancy from Eli Lilly, Novartis, and Sanofi Aventis. TS has no conflicts of interest. SFT received grant fees and personal fees for advisory board participation and teaching from AbbVie, Novartis, Sanofi Genzyme, and UCB; received personal fees for advisory board participation and teaching from Eli Lilly and Leo Pharma; received personal fees for advisory board participation from Celgene, Janssen, and Roche; and received personal fees for teaching from GlaxoSmithKline and Pierre Fabre. TT received personal fees for participation at expert meetings from Sanofi Genzyme. C-FW received non-financial support for attendance at the meeting related to this article from Sanofi Genzyme; and C-FW’s institute received grant support from Sanofi Genzyme. CV received grant support from Sanofi Genzyme. LvK received financial compensation for attendance at the meeting related to this article; received research support from Sanofi Genzyme; and received personal fees for advisory board participation from Sanofi Genzyme. AR received personal fees for attendance at the meeting related to this article from Sanofi Genzyme.
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