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Open research questions in Dermatology and Skin Diseases

984 gap statements mined from Dermatology and Skin Diseases papers in our 7.9M-paper local library, which holds 4,212 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.

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What the literature leaves open

  • Several limitations of the present study should be consid‑ ered when interpreting the findings. These findings provide a scientific basis for further investigation of PTFAb as a natural product‑based material for AD‑related research.

    Ameliorative effects of Paulownia tomentosa flower absolute on atopic dermatitis‑related responses in mast cells and keratinocytes and its chemical composition · 2026 · DOI

  • Given the small sample size, retrospective design, and limitations related to control‑group selec‑ tion, larger prospective multicenter studies incorporating clinical predictors and patient‑ reported outcomes are warranted to validate these findings and establish optimized treat‑ ment algorithms for refractory hemodialysis‑associated pruritus.

    Efficacy and Safety of Switching from Nalfurafine to Difelikefalin in Hemodialysis Patients with Refractory Pruritus · 2026 · DOI

  • Despite rapid advances, several critical gaps still exist. One major unresolved area involves how microbial signals influence sensory neuroimmune circuits.

    Sensory Neuroimmunology: Bidirectional Neuro-Immune Circuits Governing Pain, Itch, Inflammation, and Host Defense at Barrier Surfaces · 2026 · DOI

  • While microbiota alterations are consistently associated with AD and psoriasis, causality in human studies remains insufficiently established, and microbi‐ ota‐targeted interventions require further clinical confirmation.

    Gut Dysbiosis and the Molecular Landscape of the Gut–Skin Axis: Comparative Insights and Therapeutic Implications for Atopic Dermatitis and Psoriasis · 2026 · DOI

  • Acceptability is negatively affected by the one-week recall period of three PROMs, as patients found this insufficient in capturing fluctuating disease.

    Acceptability and feasibility of patient-reported outcome measures for atopic eczema: an evaluation of PROMs from the HOME core outcome set · 2026 · DOI

  • Based on the critical appraisal of current evidence, we propose the following priorities for future research, which can be grouped into four core therapeutic classes of gut microbiome modulation illustrated in Fig. 4: microbiota modulation, substrate provision, metabolite-based therapies and combinatorial synbiotic approaches.

    Gut microbiome‑based interventions for treatment of atopic dermatitis—a mini review · 2026 · DOI

  • One possible limitation of this study is that the participants recruited were not strictly healthy individuals, presenting with conditions such as macromastia or keloid. This may underscore a potential role of skin fungi dysbiosis in the pathogenesis of these diseases; however, this is beyond the scope of the current study.

    Exploring the Skin Mycobiome: A Comparison of Skin Swabs and Tissue Specimens · 2026 · DOI

  • First, the mechanism underlying skin PA increases in AD-like lesions, as well as the biological significance of alterations in skin ML-CFAs other than PA in AD, remains to be explored. Several limitations of this study cannot be ignored.

    Palmitic acid aggravates atopic dermatitis by regulating SGK1/NEDD4L-involved cutaneous neuroimmune inflammation through driving TRPV1 and MRGPRB2 S-palmitoylation · 2026 · DOI

  • Future research should explore the molecular mechanisms by which Tmem45b interacts with IL-31 receptor pathways and evaluate whether its functional relevance is primarily restricted to acute pruritogen-evoked itch or specific inflammatory contexts.

    Transmembrane protein 45b in peripheral sensory neurons selectively mediates IL-31-dependent chemical itch · 2026 · DOI

  • Future investigations are warranted to elucidate the precise role of NMDAR in the development of pruritus following intrathecal morphine administration.

    Xiaofeng Granules alleviate intrathecal morphine-induced pruritus via inhibiting the NR2B/PKC/CAMK II signaling pathway · 2026 · DOI

  • The most important limitations of this study are analytical. Intra- and inter-assay precision could not be determined from our own data, and in-house verification of dilution linearity and recovery, which is recommended for commercial kits, was not available to us; the adipolin–MaR1 correlation discussed above suggests that part of the measured signal may be non-specific.

    Circulating Pro-Resolving Mediators Maresin-1 and Maresin-2 and Adipolin/CTRP12 in Adults with Atopic Dermatitis: A Case–Control Study · 2026 · DOI

  • Future research should prioritize adequately powered head- to-head randomized trials comparing currently approved and emerging targeted therapies for PN.

    Comparative efficacy and safety of targeted systemic therapies for prurigo nodularis: a systematic review and network meta-analysis · 2026 · DOI

  • Although a causal role could not be established, this case expands the recognized clinicopathologic spectrum of canine psoriasiform-lichenoid reaction patterns and highlights the uncertainty regarding the underlying etiology, including a possible but unproven contribution of bacterial involvement.

    Psoriasiform-Lichenoid-like Dermatosis in a Bichon Frise Dog Without Prior Systemic Cyclosporine Exposure · 2026 · DOI

  • Although current guidelines do not mention/support H1-AH monotherapy for AD-associated pruritus/inflammation, our results indicate that this relationship/treatment possibility needs to be further explored.

    Salivary Melatonin Levels in Comparison with Disease Features and Antihistamine Use: Prospective Follow-Up of Atopic Dermatitis Patients · 2026 · DOI

  • A short single low-humidity stay (SSLHS) induces rapid changes in stratum corneum (SC) function, but their significance and inter-individual variability remain unclear.

    Rapid Skin Responses to a Low Humidity Environment and the Benefits of a Fine Fiber Film · 2026 · DOI

  • Abrocitinib, an oral selective Janus kinase 1 inhibitor, is approved for the treatment of moderate-tosevere atopic dermatitis (AD) in adults, but realworld evidence remains limited.

    Efficacy and Safety of Abrocitinib for Moderate-to-severe Atopic Dermatitis in Adults: A 52-week Real-world Multicentre StudyIL-AD (Italian Landscape Atopic Dermatitis) · 2026 · DOI

  • While previous studies have explored the expressions of pro-inflammatory markers in AD skin using biopsies and tape-stripping techniques, non-invasive sampling from the skin surface in pediatricpaediatric AD patients has not been examined.

    Noninvasive Skin Surface Sampling Identifies Elevated IL-1β and IL-6 in Paediatric Atopic Dermatitis Patients · 2026 · DOI

  • Atopic dermatitis (AD) has been linked to psychiatric disorders, but the cumulative contribution of psychiatric multimorbidity to incident AD remains unclear.

    Plasma Metabolomic and Proteomic Profiling of the Mechanisms Underlying the Cumulative Impact of Co-occurring Psychiatric Disorders on Atopic Dermatitis · 2026 · DOI

  • These trials have validated AHR as a therapeutic target for inflammatory skin disease and provide a rationale for further investigation into its use in other inflammatory skin conditions. For example, a dysregulation in tryptophan metabolism and a reduction in AHR activation, shown as reduced expression of CYP1A1, AHRR, and CYP1A2, has been detected in the skin of patients with hidradenitis suppurativa (HS).

    The Aryl Hydrocarbon Receptor (AHR): Peacekeeper of the Skin · 2025 · DOI

  • The main limitation of this study is the small sample size of subjects enrolled and the conspicuous number of patients that were lost at follow-up. Several studies have analyzed the role of probiotics in the prevention of AD, producing conflicting data. Further studies on a larger scale must be performed to provide more robust results to prove this theory.

    Effect of Supplementation with a Specific Probiotic (Bifidobacterium bifidum PRL2010) in Pregnancy for the Prevention of Atopic Dermatitis in Children: Preliminary Results of a Randomized Trial · 2025 · DOI

  • While the reduction in IL-4 supports mast cell inhibition by BCL-2, the mechanistic link to the modulation of T-cell responses observed in vivo remains unclear. Further investigation is required to clarify the in vivo mechanisms underlying mast cell regulation and subsequent T-cell modulation by BCL-2.

    BCL-2 Multi-Strain Probiotics for Immunomodulation In Vitro and In Vivo Alleviation of Atopic Dermatitis · 2025 · DOI

  • Future research should focus on elucidating the molecular pathways through which microbiome modulators influence immune responses, skin barrier function, and microbial composition. Understanding these mechanisms will facilitate the development of more targeted and effective treatments.

    Microbiome and Postbiotics in Skin Health · 2025 · DOI

  • In cholestatic liver disease, pruritogens or pro-pruritogenic substances presumed to be produced in the liver are transported through the systemic circulation to the skin. Lysophosphatidic acid (LPA), bile acids, steroids and bilirubin have all been implicated as the cause of the itch that initiates itch signaling pathways in the skin.

    Scratching the Surface: Lipidomic Profiling of the Stratum Corneum in the Search for Pruritogens in Cholestatic Liver Diseases · 2026 · DOI

  • To our knowledge, the high expression of TSLPR and IL-7Rα proteins in the dermis of moderate to severe AD biopsies, compared to non-lesional and mild AD skin, has not been described.

    Dynamic Thymic Stromal Lymphopoietin and Its Receptor Complex Expression on Skin Langerhans Cells in Response to MC903‐induced Skin Inflammation · 2026 · DOI

  • In conclusion, this review highlights the intricate interplay between metabolic disorders, skin microbiota, and dermatologic health, emphasizing the systemic drivers of inflammatory skin conditions such as psoriasis, atopic dermatitis, and acne.

    Skin Microbiota: Mediator of Interactions Between Metabolic Disorders and Cutaneous Health and Disease · 2025 · DOI

Most-cited papers in Dermatology and Skin Diseases

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Open questions raised by papers listed on this page include: (1) The mechanism underlying skin PA increases in AD-like lesions, as well as the biological significance of alterations in skin ML-CFAs other than PA in AD, remains to be explored (“Palmitic acid aggravates atopic dermatitis by regulating SGK1/NEDD4L-involved…”, 2026); (2) Future investigations are warranted to elucidate the precise role of NMDAR in the development of pruritus following intrathecal morphine administration (“Xiaofeng Granules alleviate intrathecal morphine-induced pruritus via…”, 2026); (3) Future research should prioritize adequately powered head- to-head randomized trials comparing currently approved and emerging targeted therapies for PN (“Comparative efficacy and safety of targeted systemic therapies for prurigo…”, 2026); (4) A short single low-humidity stay (SSLHS) induces rapid changes in stratum corneum (SC) function, but their significance and inter-individual variability remain unclear (“Rapid Skin Responses to a Low Humidity Environment and the Benefits of a Fine…”, 2026); (5) Abrocitinib, an oral selective Janus kinase 1 inhibitor, is approved for the treatment of moderate-tosevere atopic dermatitis (AD) in adults, but realworld evidence remains limited (“Efficacy and Safety of Abrocitinib for Moderate-to-severe Atopic Dermatitis in…”, 2026). 984 gap statements have been mined from Dermatology and Skin Diseases papers in our 7.9M-paper local library, which holds 4,212 papers on the topic; the gaps come from whichever of those papers state one. They are mostly the research gaps the authors state and the papers' abstracts, plus future-work, limitations and challenges passages. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one, so you can read the original claim in context.

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