Psoriasis is described as a chronic autoimmune inflammatory skin disease characterized by keratinocyte hyperproliferation and systemic inflammation. This has led to growing interest in molecular markers that can more accurately reflect disease activity in the skin and systemic inflammatory burden. Conventional laboratory markers of inflammation—C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)—are not always informative across all clinical scenarios, and identifying more specific signals of disease activity and treatment response is highly relevant.

In 2026, a review published in Clinica Chimica Acta examined the role of lipidomics in psoriasis and the links between alterations in lipid profiles and inflammation, barrier dysfunction, and comorbidities, including cardiometabolic risks [1]. Lipidomics is particularly valuable because it enables a shift from general inflammatory indicators to more tissue-specific changes in the skin and blood. Below is an overview of how these changes are detected and what can be measured.

What lipidomics reveals

Lipidomics is considered one of the most informative branches of metabolomics in inflammatory skin diseases. In practical terms, it combines analytical approaches that allow simultaneous:

• detection of a broad range of lipids;
• quantification of predefined lipid species;
• integration of both strategies.

These analyses rely on separating complex mixtures, followed by lipid detection based on their mass spectra. This approach enables identification of lipid classes and structures, as well as quantitative tracking of selected molecules (for example, long-chain fatty acids in serum) and their changes during therapy with interleukin-17 inhibitors. Bioinformatics tools and lipid structure databases, including LIPID MAPS (Lipid Metabolites and Pathways Strategy), are used for data processing and interpretation. At the same time, the diversity and structural complexity of lipids complicate the standardization of methods and cross-study comparability.

Specific lipid biomarkers

In the context of inflammation and potential biomarkers, several lipid classes and mediators have been highlighted. Mass spectrometry–based studies in patients with psoriasis have identified pro-inflammatory lysophospholipids, such as lysophosphatidylcholine and lysophosphatidic acid, as candidates for markers of disease activity and treatment response [2].

Another important group includes lipid mediators derived from fatty acids. These include eicosanoids and related pathways: leukotrienes, prostanoids (including prostaglandin E2 and the thromboxane pathway), as well as derivatives such as hydroxyeicosatetraenoic acids and hydroxyoctadecadienoic acids, which are associated with increased inflammatory responses and leukocyte migration into the skin.

Receptor and enzymatic components of these pathways are discussed as potential therapeutic targets (including evidence from experimental models). However, much of this data is still based on mechanistic and preclinical findings, and clinical validation with standardized endpoints remains essential.

Changes in barrier lipids

Ceramides

The clinical relevance of lipid alterations in psoriasis is closely linked to the skin barrier. Ceramides, as key sphingolipids of the stratum corneum, form an organized lipid matrix together with cholesterol and free fatty acids, influencing permeability, transepidermal water loss, and susceptibility to irritants. Beyond their structural role, ceramides regulate the cell cycle, differentiation, and apoptosis, and are therefore potentially linked to the keratinocyte hyperproliferation characteristic of psoriasis.

Observational data describe several key patterns in ceramide profiles:

• significant differences in total ceramide levels in psoriatic lesions compared with non-lesional skin and healthy controls;
• altered ratios between ceramide subclasses, with reduced ratios of specific subclass pairs in lesions;
• a lower proportion of ceramides containing long-chain fatty acids in lesions, associated with the influence of interferon-gamma on ceramide synthesis;
• additional shifts, including higher levels of ceramide and ceramide-1-phosphate and lower levels of monoglycosylceramide in lesional versus non-lesional skin, as well as changes in long-chain acylceramides and their intermediates.

From a clinical perspective, lipid imbalance in the stratum corneum sustains barrier dysfunction. It is associated with pronounced dryness, increased irritability, elevated transepidermal water loss, pruritus, and reduced tolerance to external triggers, even during anti-inflammatory therapy.

In such cases, baseline barrier-supportive topical care becomes particularly important. In a randomized controlled trial of interleukin-23 inhibition (guselkumab), normalization of barrier function in lesions was accompanied by restoration of ceramide profiles toward those of healthy controls, with ceramide dynamics correlating with transepidermal water loss and lesion severity [4].

Fatty acids

Psoriasis is associated with a shift in lipid profiles toward higher levels of saturated and omega-6 polyunsaturated fatty acids, and lower levels of monounsaturated and omega-3 polyunsaturated fatty acids, compared with healthy individuals. Treatment with interleukin-17A inhibitors has been shown to modify these long-chain fatty acid profiles in serum, suggesting their potential use as monitoring tools [3].

Lipidomic analysis in clinical practice

Understanding molecular alterations in psoriasis opens new opportunities for a personalized approach in dermatology. Lipidomic data already support the use of lipid profiles as objective tools for refining diagnosis and assessing treatment efficacy.

Diagnosis and patient stratification

Lipidomic profiles, particularly ceramides and fatty acids, are considered sources of candidate biomarkers that may complement clinical assessment and nonspecific inflammatory markers. Some metabolites and models demonstrate high diagnostic performance, although validation in independent cohorts remains necessary.

Prognosis and therapy monitoring

Certain lipid markers correlate with changes in disease severity and barrier function. Examples include changes in ceramide profiles during anti-inflammatory therapy and in fatty acid profiles during treatment with interleukin-17A inhibitors [3, 4].

Therapy targeting lipid balance restoration

Two complementary approaches are highlighted. The first is systemic anti-inflammatory treatment (including biologics), which influences lipid metabolism and barrier properties. The second is topical barrier support (emollients, including those containing linoleic acid and ceramides), which reduces transepidermal water loss and subjective symptoms and may improve disease control between flares.

In a multicenter randomized controlled trial, adding a moisturizer containing linoleic acid and ceramides to topical mometasone was associated with lower relapse rates and sustained improvement in clinical parameters during maintenance use [5].

Conclusion

Lipidomics is rapidly evolving, but its main limitation remains standardization: differences in analytical platforms, sample preparation protocols, and reference standards complicate direct comparison between studies. Therefore, even promising candidate markers (such as lysophosphatidylcholine/lysophosphatidic acid and ceramide profile parameters) require validation in independent cohorts with standardized endpoints linked to clinical outcomes [2, 4].

In the lipidomic context, psoriasis appears not only as an inflammatory condition but also as a complex disorder of barrier function and lipid homeostasis, in which ceramides, fatty acids, and lipid mediators act both as structural components and as signaling regulators. Lipidomics provides tools to measure these alterations, identify markers of disease activity and treatment response, and highlight therapeutic targets—from eicosanoid pathways to barrier restoration strategies. At present, this remains largely a translational field, with the most promising directions including standardized lipid panels for monitoring and combined treatment approaches integrating systemic anti-inflammatory therapy with targeted barrier support [3–5].

References

1. Boboryko D., Bratborska A.W., Skorka P,. Pawlik A. The role of lipidomics in psoriasis. Clin Chim Acta 2026; 578: 120515. doi:10.1016/j.cca.2025.120515
2. Zeng C., Wen B., Hou G. et al. Lipidomics profiling reveals the role of glycerophospholipid metabolism in psoriasis. Gigascience 2017; 6(10): gix087.
3. Guo X., Zhou J., Yu H. et al. Serum lipidomic study of long-chain fatty acids in psoriasis patients before and after anti-IL-17A monoclonal antibody treatment by quantitative GC-MS analysis with in situ extraction. Lipids Health Dis 2024; 23(1): 6.
4. Rousel J., Mergen C., Bergmans M.E. et al. Guselkumab treatment normalizes the stratum corneum ceramide profile and alleviates barrier dysfunction in psoriasis: results of a randomized controlled trial. J Lipid Res 2024; 65(8): 100591.
5. Li X., Yang Q., Zheng J. et al. Efficacy and safety of a topical moisturizer containing linoleic acid and ceramide for mild-to-moderate psoriasis vulgaris: a multicenter randomized controlled trial. Dermatol Ther 2020; 33(6): e14263.