Atopic dermatitis (AD) is a chronic inflammatory disease characterized by the appearance of eczematous lesions, with an estimated global prevalence of 2.6% of the world population according to published series.1 It is characterized by marked heterogeneity, with a broad clinical spectrum that includes morphology, disease severity, age at onset, and associated comorbidities,2,3 with pruritus being a constant finding.4 In addition, the disease follows a recurrent and unpredictable course that may change over time.4

In recent years, the development of new targeted therapies has resulted in a qualitative leap in the control of moderate-to-severe forms of the disease. Treatment expectations are based on clinical trials focused on moderate-to-severe disease forms.5,6 Although studies addressing AD globally exist, the literature remains scarce regarding the detailed description of involvement in specific areas and its therapeutic implications, with most studies focusing on severity classification and associated comorbidities.4,7–10

However, there are locations considered “special locations” (SLs), such as the face and eyelids, genitals, and hands, in which visibility or functional impact may exert a differential influence on the course of the disease or on the perception of treatment efficacy.4,11,12

The aim of the present study was to describe the clinical and epidemiologic characteristics of patients with AD according to involvement of special locations (SLs). Secondarily, it sought to explore their possible clinical, therapeutic, and prognostic implications.

Data from the Spanish Atopic Dermatitis Registry (BIOBADATOP)13 were used for this study. BIOBADATOP is a prospective, multicenter observational cohort including pediatric and adult patients with AD who initiated systemic treatment. The characteristics of data collection within the registry have been previously described.9,13

During the study period, data from March 2020 through May 2024 were considered, with participation from 14 hospital centers distributed throughout Spain. The registry collects clinical characteristics of AD, SLs, demographic data, comorbidities, disease severity and quality-of-life characteristics, previous and current treatments, and follow-up outcomes.9,13

The face, hands, and/or genitals were considered special areas, and patients were categorized based on the number of affected SLs (none, 1, or >2). Baseline and follow-up data at 6 and 12 months were extracted.

We conducted a descriptive analysis according to the number of affected SLs, and data were stratified according to adult (≥18 years) or pediatric (<18 years) populations. Demographic and clinical data were described using conventional statistics (means and standard deviations [SD], absolute and relative frequencies). Subsequently, differences across groups were compared using the chi-square test, Student's t test, or Mann–Whitney test, as appropriate. The course of severity parameters at 6 and 12 months of follow-up was presented according to the number of affected special locations. A P value <.05 was considered statistically significant.

The BIOBADATOP registry received approval from the Clinical Research Ethics Committee of Aragón (PA18/051). This approval process adhered to the principles of the Declaration of Helsinki and fully complied with current legislation regarding ethics and clinical research. All patients provided written informed consent to be included in the study.

Patients with >2 SLs presented greater baseline severity measured by EASI, more atopic comorbidities, and a higher number of previous systemic treatments vs those with 1 SL, and both cohorts compared with the population without SLs. However, no significant differences were found in quality-of-life indices (DLQI) or pruritus. Similarly, no differences were found in the therapeutic response of the cohorts according to SL involvement.

The involvement of visible or functional anatomical areas has been associated with greater severity of dermatosis, as well as a greater impact on quality of life.13,14 The results of the present study are consistent with greater extension and objective severity. In the present registry, no differences were found in most patient-reported outcome measures (PROMs), except for the POEM measure in the adult population. Of note, these scales show differential sensitivity according to lesion location.15 DLQI, which emphasizes functionality, tends to be more affected by hand involvement. In contrast, POEM, which collects patient-reported symptoms including pruritus, correlates well with overall disease severity, but is not specifically designed to capture the psychosocial impact of visible areas such as the face.3,15,16 Therefore, the results may have been influenced by low sensitivity of the indices used to detect the impact of pruritus or pain in these SLs, for example on nocturnal rest and sexual life, which are often underrepresented in such scales.15,17

Of note, therapeutic response was generally consistent regardless of SL involvement. The identification of SLs has been a common aspect in trials and post hoc studies during the clinical development of different innovative molecules, generally demonstrating that clinical efficacy is homogeneous across all affected areas, including those considered special.18–22 Thus, the identification of an SL could justify the need for systemic or targeted treatment, although it is not identified as a criterion for preferentially choosing one option over another, nor does it represent a factor conditioning therapeutic response.23–25

Among the strengths of the present study, the collection of data through a prospective, multicenter, monitored registry with a considerable number of patients should be emphasized. Among the variables, which include an extensive clinical and epidemiological profile, prospective identification of SLs and collection of safety data were also available.

However, the use of a multicenter real-world registry represents a limitation on the collection of complementary variables, such as additional parameters to objectively and subjectively evaluate the impact of SLs, as well as other data on locations of interest such as the neck. Furthermore, SL involvement was represented by the number of SLs without specifying the affected area, elements that should be considered when interpreting the results. Finally, patients received treatment according to clinical indication rather than randomization, and treatment may have been influenced by other factors, including external criteria such as reimbursement limitations. A cohort of patients with SL involvement in whom systemic treatment was not initiated was also unavailable.

In other dermatological entities, there is greater evidence regarding the impact of lesion location on quality of life, as well as its influence on therapeutic decision-making.11 In psoriasis, involvement of certain locations represents an indication for systemic treatment independent of disease extension11,26 and, in our setting, also a reimbursement criterion in many regions. The reason is the psychological, social, and even occupational impact when, for example, the scalp, genitals, hands, or nails are affected.27

In conclusion, SL involvement may represent a factor in therapeutic decision-making in AD and in the assessment of response during follow-up. The development and implementation of specific indices evaluating the impact of SLs may allow more accurate assessment of severity and more appropriate monitoring.

This study is part of the publications of the BIOBADATOP registry, a project promoted by the Fundación Piel Sana of the AEDV, which in turn receives financial support from pharmaceutical companies (such as Sanofi, AbbVie, Pfizer, and Almirall). The study was conducted independently regarding planning and execution. The collaborating pharmaceutical companies had no involvement in the design, collection, management, analysis, or interpretation of data, nor in the preparation, review, or approval of the manuscript. The decision to submit the manuscript for publication was also made independently, without intervention from the collaborating pharmaceutical companies.

M. Munera-Campos has received fees for consulting services, presentations, and related activities from AbbVie, Leo-Pharma, Janssen, Sanofi, and Galderma. Furthermore, she has participated as principal or secondary investigator in clinical trials sponsored by Lilly, Leo-Pharma, Novartis, Janssen, Sanofi, Pfizer, AbbVie, Almirall, UCB, and Galderma.

R. Ruiz-Villaverde has received fees as scientific advisor or participant in clinical studies from AbbVie, Almirall, Leo, Sanofi, Novartis, Pfizer, Galderma, Incyte, and Janssen.

J.F. Silvestre-Salvador has collaborated as speaker, advisor, and/or investigator for AbbVie, Almirall, Amgen, AstraZeneca, Bristol Myers Squibb, Eli Lilly, Galderma, Incyte, Leo-Pharma, Novartis, Pfizer, Regeneron, and Sanofi Genzyme.

M. Espasandín-Arias has received fees or support for educational activities, acted as consultant, or participated in clinical trials for AbbVie, Sanofi, Pfizer, and Leo-Pharma.

A. González-Quesada has participated as consultant, speaker, and in clinical trials for AbbVie, Pfizer, Novartis, Sanofi, Boehringer, Bristol-Meyer, Leo-Pharma, and Janssen.

Y. Gilaberte-Calzada has participated as advisor for Isdin, Roche Posay, and Galderma; as speaker for Almirall, Sanofi, Avene, Rilastil, Lilly, Uriage, Novartis, and Cantabria Labs; and in research projects for Almirall, Sanofi, Pfizer, AbbVie, and Leo-Pharma.

P. de la Cueva Dobao has acted as advisor and/or investigator and/or speaker for AbbVie, Almirall, BMS, Boehringer, Celgene, Janssen, Leo-Pharma, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB.

P. Chicharro has participated in consultancies, scientific meetings, and clinical trials organized by Janssen Pharmaceuticals, Almirall, Sanofi Genzyme, Lilly, AbbVie, Novartis, Leo-Pharma, and Pfizer-Wyeth.

J.J. Pereyra-Rodríguez has received research grants from Novartis, AbbVie, and Sanofi, and lecture fees and other financial support from AbbVie, Almirall, Galderma, Janssen, Gebro-Pharma, Leo-Pharma, Novartis, Lilly, Novartis, Pfizer, Sanofi, and UCB.

E. Herrera-Acosta has worked as consultant and/or speaker for Leo-Pharma, Novartis, Janssen, Lilly, Celgene, and AbbVie.

T. Montero-Vilchez has collaborated in scientific meetings and clinical trials for AbbVie, Almirall, Incyte, Leo-Pharma, Lilly, Novartis, Sanofi, Pfizer-Wyeth, and UCB Pharma, as well as the Instituto de Salud Carlos III.

M. Elosua-González has participated as investigator and/or speaker for AbbVie, Lilly, Galderma, Leo-Pharma, Pfizer, UCB Pharma, and Sanofi Genzyme.

M. Bertolín-Colilla has received fees for lectures and/or advisory activities from Sanofi, AbbVie, Pfizer, Leo-Pharma, and Almirall.

E. Prat-Colilles has received fees as consultant/speaker and/or participated in clinical trials sponsored by Boehringer Ingelheim, ISDIN, La Roche Posay, Leo-Pharma, Lilly, Sanofi, and UCB.

I. Betlloch-Mas has participated as advisor in projects for Sanofi and AbbVie.

A. Batalla has received fees/collaborated in educational activities, consultancy, or participation in clinical trials for AbbVie, Celgene, Faes Farma, Isdin, Janssen, Leo-Pharma, LETI Pharma, Lilly, Mylan, Novartis, Pfizer, Pierre Fabre, and Sanofi.

M. Rodríguez Serna has participated in advisory activities for Sanofi, Pfizer, Leo, Novartis, AbbVie, and Almirall.

S. Arias-Santiago has participated as principal investigator/subinvestigator and/or received fees as speaker and/or expert committee member for AbbVie, Lilly, Almirall, and Leo-Pharma.

G. Roustan has received fees for lectures and/or advisory activities from Sanofi, AbbVie, Leo-Pharma, Lilly, and Novartis.

L. Curto-Barredo has received fees for lectures and/or advisory activities from Sanofi, AbbVie, Leo-Pharma, Almirall, Lilly, Novartis, and Uriach.

J.C. Ruiz-Carrascosa has participated as speaker and/or principal investigator/subinvestigator in clinical trials sponsored by AbbVie, Celgene, Leo-Pharma, Novartis, Janssen, Lilly, Amgen, Almirall, UCB, Pfizer, and MSD.

C. Couselo-Rodríguez has participated as subinvestigator or speaker in projects sponsored by AbbVie, Sanofi, Leo-Pharma, Lilly, UCB, Novartis, Pierre Fabre, and Janssen.

A.M. Rosell-Díaz has received fees for lectures and/or advisory activities from Sanofi, AbbVie, Leo-Pharma, Pfizer, and Almirall.

A.M. Giménez Arnau is or was recently a speaker and/or advisor and/or has received research funding from Almirall, Amgen, AstraZeneca, Avene, Blue-Print, Celltrion, Celldex, Escient Pharmaceuticals, Genentech, GSK, Harmonic Bio, Incyte, Instituto Carlos III-FEDER, Jaspers, Leo-Pharma, Menarini, Mitsubishi Tanabe Pharma, Noucor, Novartis, OVOIMMUNE, Sanofi–Regeneron, Septerna, Servier, Thermo Fisher Scientific, and Uriach Pharma.

S. Martínez-Fernández has carried out educational activities and attended courses and conferences sponsored by AbbVie, Janssen, Leo-Pharma, Lilly, Novartis, La Roche-Posay, Pierre Fabre, AstraZeneca, and Sanofi. She has also participated as subinvestigator in clinical trials sponsored by AbbVie, Pfizer, Sanofi, and Novartis.

J.M. Carrascosa has participated as principal investigator/subinvestigator and/or received fees as speaker and/or member of expert committees or steering committees for AbbVie, Novartis, Janssen, Pfizer, Sanofi, Incyte, Galderma, Lilly, Sandoz, Amgen, Almirall, BMS, Boehringer Ingelheim, Biogen, and UCB.

The remaining authors declared no conflicts of interest whatsoever.