SKIN Disease Profiling by an Exploratory, pRospective, Biomarker Study in dermatoloGY Practice (SKINERGY)

NCT07021495 | Recruiting DMC

• 3 other identifiers: SKINERGYNWA.1389.20.182NGID
• Study Type: observational
• Target: 840
• Locations: 1 country
• Sites: 8

Brief Summary

The goal of this observational study is to comprehensively profile six immune-mediated inflammatory diseases, including atopic dermatitis (AD), plaque psoriasis (PSO), hidradenitis suppurativa (HS), cutaneous T-cell lymphoma subtype mycosis fungoides (MF), chronic spontaneous urticaria (CSU), and cutaneous lupus erythematosus (CLE) in daily practice. Data will be compared with data from healthy volunteers. This study is part of the larger NGID (Next Generation ImmunoDermatology) initiative, of which the main objective is to develop infrastructure that enables personalised patient care. The main questions the SKINERGY study aims to answer are:

• Which biomarkers can discriminate between responders and non-responders to treatment in patients with AD, CLE, CSU, HS, MF, and PSO?
• How do disease-related biomarkers in patients with AD, CLE, CSU, HS, MF, and PSO differ from those in healthy volunteers?
• Which (multi-omics) biomarkers are associated with disease subtypes and predict response or non-response to (targeted) therapies in daily clinical practice?
• How do biomarker profiles compare across different cohorts of patients with immune-mediated inflammatory skin diseases (AD, CLE, CSU, HS, MF, PSO)
• How do biomarker levels change over time in response to treatment in these patient populations?
• Which skin tissue biomarkers are associated with disease progression or treatment response?
• How do the genomic profiles of patients differ across diseases or correlate with treatment outcomes?
• Can additional imaging biomarkers enhance the characterization of disease profiles or treatment monitoring over time? Researchers will compare both differences beween patients within a disease group in different treatment arms, as well as patients within the same treatment arm. Additionally, biomarker profiles of patients with different diseases will be evaluated. These comparisons will be made to see if shared or distinct biomarker patterns exist across diseases and treatments, which could inform patient stratification, optimize therapeutic decision-making, and identify potential targets for future interventions. Participants will start medication according to national guidelines for the treatment of their inflammatory skin disease (AD: Cyclosporin A, anti-IL4/13, or anti-JAK; PSO: anti-TNF, anti-IL23, ani-IL17, anti-TYK2; HS: anti-TNF, anti-IL17; MF: CHLORM, TSC, PUVA-UV-B; CSU: anti-IgE, Cyclosporin A, anti-BTK\*; CLE: TSC, HCQ, MTX) \*once approved and reimbursed in the Netherlands Participants will:
• Take the prescribed medication for their skin disease (in line with standard care in the Netherlands).
• Visit the clinic for a study visit combined with their standard care appointment 3 times (baseline, month 3, and month 6. An additional 4th visit at month 12 is optional).
• Fill in an online set of questionnaires from home, 3 times during the study period (an additional 4th time is optional).
• Patients with CSU fill in the UAS7 (and if applicable the AAS7) daily for the study period.

Conditions

Chronic Spontaneous Urticaria (CSU); Hidradenitis Suppurativa (HS); Psoriasis (PsO); Atopic Dermatitis (AD); CTCL/ Mycosis Fungoides

Keywords

Urticaria; Hives; Mast cells; Autoimmune; Autoallergic; Wheals; Angioedema; Abscess; Nodules; Sweat glands; Acne inversa; Eczema; Itchy, dry skin; Mycosis Fungoides; Skin patches; Tumors; T-cells; Lupus; Skin rash; Photosensitivity; Plaques; Scaling; Erythema; Induration; Inflammatory skin diseases; Immune-mediated; Deep phenotyping; Multi-omics; Transcriptomics; Lipidomics; Metabolomics; Proteomics; Genomics; Microbiomics; Imaging mass cytometry (CyTOF); Real-world practice; Standard care; NextGenerationImmunoDermatology; NGID; Biomarkers

Outcome Measures

Primary Outcomes (17)

• Lipidomics of the stratum corneum and OLINK

  Tape stripping will be performed on (non-)lesional skin and healthy skin for extraction of lipids for analysis and analysis will be performed using OLINK.

  Baseline - month 12

• Cutaneous microbiome

  The microbiome is collected by swabbing. The abundance of bacteria is thereafter determined using next-generation sequencing.

  Baseline - month 12

• Serum biomarkers

  Blood serum will be collected and processed for subsequent biomarker extraction and analysis. The specific biomarkers to be assessed will be determined at a later stage, based on the results of preliminary pilot studies.

  Baseline - month 12

• Plasma biomarkers

  Blood plasma will be collected and processed for the extraction and analysis of biomarkers. The specific biomarkers to be assessed will be determined at a later stage, based on the results of preliminary pilot studies.

  Baseline - month 12

• Eczema Area and Severity Index (EASI)

  The Eczema Area and Severity Index (EASI) is a validated clinician-reported outcome measure used to assess the severity and extent of atopic dermatitis. The total EASI score ranges from 0 to 72, with higher scores indicating more severe disease. A score of 0 reflects no disease activity, whereas a score of 72 represents the most severe possible presentation. The EASI score will be assessed exclusively in patients diagnosed with atopic dermatitis.

  Baseline - month 12

• objective Severity Scoring of Atopic Dermatitis (oSCORAD)

  The objective SCORAD (oSCORAD) is a validated clinician-reported outcome measure used to evaluate the severity of atopic dermatitis, focusing on objective clinical signs. The total oSCORAD score ranges from 0 to 83, with higher scores indicating more severe disease. A score of 0 reflects the absence of clinical symptoms, while a score of 83 represents the most severe disease presentation. The oSCORAD score will be assessed exclusively in patients diagnosed with atopic dermatitis.

  Baseline - month 12

• Validated Investigator Global Assessment scale for Atopic Dermatitis (vIGA-AD)

  The Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) is a clinician-reported outcome measure used to assess the overall severity of atopic dermatitis based on clinical signs. The vIGA-AD score ranges from 0 to 4, with higher scores indicating more severe disease. A score of 0 corresponds to "clear" skin, while a score of 4 represents "severe" disease. The vIGA-AD score will be assessed exclusively in patients diagnosed with atopic dermatitis.

  Baseline - month 12

• Cutaneous LE Disease Area and Severity Index Activity (CLASI-A)

  The Cutaneous Lupus Erythematosus Disease Area and Severity Index - Activity Score (CLASI-A) is a validated clinician-reported outcome measure used to assess the degree of inflammatory disease activity in patients with cutaneous lupus erythematosus. The CLASI-A score ranges from 0 to 70, with higher scores indicating more active and severe skin involvement. A score of 0 reflects no disease activity, while a score of 70 indicates the most severe activity. The CLASI-A score will be assessed exclusively in patients diagnosed with cutaneous lupus erythematosus.

  Baseline - month 12

• Total Sum Score

  The Total Sum Score is a clinician-reported composite outcome measure used to quantify overall disease activity in patients with cutaneous lupus erythematosus and psoriasis. It is calculated by summing the individual scores of predefined clinical signs across affected body regions. The score range depends on the number and weighting of assessed parameters, with higher scores indicating more severe disease activity. A score of 0 reflects no observable disease, whereas the maximum score represents the most severe manifestation based on the scoring algorithm. The Total Sum Score will be assessed only in patients diagnosed with cutaneous lupus erythematosus and plaque psoriasis.

  Baseline - month 12

• The Cutaneous Lupus Activity-Investigator Global Assessment (CLA-IGA)

  The Cutaneous Lupus Activity-Investigator Global Assessment (CLA-IGA) is a validated clinician-reported outcome measure used to assess overall disease activity in patients with cutaneous lupus erythematosus. The scale ranges from 0 to 5, where 0 indicates no disease activity and 5 reflects very severe disease. Higher scores correspond to greater clinical severity. The CLA-IGA will be assessed only in patients with cutaneous lupus erythematosus.

  Baseline - month 12

• International Hidradenitis Suppurativa Severity Score System (IHS4)

  The International Hidradenitis Suppurativa Severity Score System (IHS4) is a validated clinician-reported outcome measure used to assess the severity of hidradenitis suppurativa. The total IHS4 score is calculated based on the number of nodules, abscesses, and draining tunnels, with no fixed maximum but typically ranging from 0 upwards. Higher scores indicate more severe disease activity, while a score of 0 reflects no active disease. The IHS4 score will be assessed only in patients with hidradenitis suppurativa.

  Baseline - month 12

• Modified Severity-Weighted Assessment Tool (mSWAT)

  The Modified Severity-Weighted Assessment Tool (mSWAT) is a clinician-reported outcome measure used to assess the severity and extent of Cutaneous T-Cell Lymphoma, specifically Mycosis Fungoides. The total mSWAT score ranges from 0 to 360, with higher scores indicating more severe disease involvement. A score of 0 reflects no active disease. The mSWAT score will be assessed only in patients with Cutaneous T-Cell Lymphoma subtype Mycosis Fungoides.

  Baseline - month 12

• Cutaneous Lymphoma Activity and Severity Index (CAILS)

  The Cutaneous Lymphoma Activity and Severity Index (CAILS) is a clinician-reported outcome measure used to evaluate disease activity and severity in patients with Cutaneous T-Cell Lymphoma, including Mycosis Fungoides. The total CAILS score ranges from 0 to 70, with higher scores indicating greater disease severity. A score of 0 corresponds to no active disease. The CAILS score will be assessed only in patients with Cutaneous T-Cell Lymphoma subtype Mycosis Fungoides.

  Baseline - month 12

• Psoriasis Area and Severity Index (PASI)

  The Psoriasis Area and Severity Index (PASI) is a validated clinician-reported outcome measure used to assess the severity and extent of plaque psoriasis. The total PASI score ranges from 0 to 72, with higher scores indicating more severe disease. A score of 0 represents no psoriasis involvement. The PASI score will be assessed only in patients with psoriasis.

  Baseline - month 12

• Physician Global Assessment (PGA)

  The Physician Global Assessment (PGA) for Psoriasis is a validated clinician-reported outcome measure used to assess the overall severity of psoriasis, including all clinical forms. The PGA score typically ranges from 0 to 6, depending on the specific scale used, with higher scores indicating more severe disease. A score of 0 represents clear skin with no signs of psoriasis. The PGA score will be assessed only in patients with psoriasis.

  Baseline - month 12

• Body Surface Area (BSA)

  The Body Surface Area (BSA) is a clinician-reported measure used to estimate the percentage of the body affected by psoriasis. The score ranges from 0% to 100%, where 0% indicates no skin involvement and 100% represents the entire body surface affected. Higher BSA values correspond to more extensive disease. The BSA will be assessed only in patients with psoriasis.

  Baseline - month 12

• Psoriasis Area and Severity Index - High Discrimination (PASI-HD)

  The Psoriasis Area and Severity Index - High Discrimination (PASI-HD) is a clinician-reported outcome measure designed to provide enhanced sensitivity and precision in assessing the severity and extent of psoriasis. The score ranges from 0 to 72, where 0 indicates no disease activity and 72 represents the most severe possible presentation. Higher scores correspond to more severe disease. The PASI-HD will be assessed only in patients with psoriasis.

  Baseline - month 12

Secondary Outcomes (34)

• User experience and subjective burden questionnaire

  Baseline, month 6

• Patient reported outcomes

  Baseline - month 12

• Skin barrier function by Electrical Impedance Spectroscopy (EIS)

  Baseline - month 12

• Line-Field Confocal Optical Coherence Tomography (LC-OCT)

  Baseline - month 12

• Laser Speckle Contrast Imaging (LSCI)

  Baseline - month 12

Study Arms (18)

AD - CsA

Adult patients with moderate-to-severe AD who start treatment with cyclosporine A. Cyclosporine A (CsA) is a lipophilic, cyclic undecapeptide produced by fungi, acting as a potent immunosuppressant by inhibiting T-cell receptor activation. It's prescribed twice daily at 3-5 mg/kg/day, starting with 3 mg/kg/day and increasing based on clinical response. CsA inhibits cytokine production, especially interleukin-2 (IL-2). In the Netherlands, CsA is the only oral immunosuppressant for moderate-to-severe atopic dermatitis (AD). CsA has shown superiority over placebo in numerous trials, and is the treatment of choice for severe AD. Common adverse reactions include renal dysfunction, tremor, hirsutism, hypertension, diarrhea, nausea, and vomiting. Contraindications include hypersensitivity and certain drug combinations. Regular monitoring is necessary due to potential risks like acute infections, hepatotoxicity, and renal toxicity.

AD - Anti-IL4/13

Adult patients with AD who start treatment with anti-IL4/13 (dupilumab, tralokinumab, lebrikizumab). Dupilumab is a human monoclonal antibody that targets the IL-4 receptor alpha chain, inhibiting IL-4 and IL-13. In the Netherlands, it's the first biologic registered for moderate-to-severe atopic dermatitis (AD). Administered subcutaneously every other week at 300mg, following a loading dose of 600mg at baseline, it follows standard treatment guidelines with regular monitoring. Dupilumab's efficacy has been shown in clinical trials, with long-term benefits in AD. Common adverse reactions include injection site reactions, conjunctivitis, arthralgia, oral herpes, and eosinophilia. Tralokinumab, another monoclonal antibody, neutralizes IL-13 to reduce AD symptoms. Administered similarly to dupilumab, its efficacy has also been demonstrated in trials, showing superiority over placebo. Common ADRs include upper respiratory infections, injection site reactions, and conjunctivitis.

AD - JAK1 inhibitor

Adult patients with AD who start treatment with JAK1 inhibitors (upadacitinib/abrocitinib). Upadacitinib and abrocitinib are selective JAK1 inhibitors that reduce immune system activity by blocking Janus Kinases, enzymes involved in inflammatory responses, which drive atopic dermatitis (AD) symptoms like eczematous skin lesions and pruritus. Upadacitinib is dosed at 15mg or 30mg once daily, with clinical trials showing significant improvements in IGA-AD, EASI 75, and pruritus compared to placebo. Common ADRs include upper respiratory infections, acne, and herpes simplex. Abrocitinib is dosed at 100mg or 200mg once daily, with 200mg recommended for severe AD. It has also shown significant efficacy in clinical trials. ADRs for abrocitinib include nausea, headache, and acne.

PSO - Anti-TNF

Adult patients with moderate-to-severe PSO who start treatment with anti-TNF (e.g. adalimumab, certolizumab, biosimilars). Adalimumab is a monoclonal antibody used to treat moderate-to-severe rheumatoid arthritis, plaque psoriasis, and hidradenitis suppurativa. It inhibits TNF, reducing inflammation. Common adverse events include infections, injection site reactions, headache, and musculoskeletal pain. For plaque psoriasis, the recommended dose is 80 mg at week 0, followed by 40 mg biweekly. Certolizumab, another TNF inhibitor, treats plaque psoriasis with an initial dose of 400 mg at weeks 0, 2, and 4, followed by 200 mg biweekly (or 400 mg if efficacy is insufficient).

PSO - anti-IL23

Adult patients with moderate-to-severe PSO who start treatment with anti-IL 23 (e.g. guselkumab, risankizumab, tildrakizumab). Guselkumab (Tremfya) is an anti-IL-23 monoclonal antibody approved for moderate-to-severe plaque psoriasis in patients eligible for systemic treatment. It blocks IL-23 interaction with its receptor, reducing pro-inflammatory cytokines. The recommended dose is 100 mg at weeks 0 and 4, followed by 100 mg every 8 weeks. Common adverse reactions include respiratory tract infections and diarrhea. Risankizumab (Skyrizi) also targets IL-23, with a dosing regimen of 150 mg at weeks 0 and 4, followed by 150 mg every 12 weeks. Common AEs include respiratory infections, injection site reactions, tinea, headache, itching, fatigue, and rash. Tildrakizumab (Ilumetri) targets the IL-23 p19 subunit. It is dosed at 100 mg at weeks 0 and 4, followed by 100 mg every 12 weeks. Common AEs include respiratory infections, injection site pain, nausea, diarrhea, and headache.

PSO - anti-IL17

Adult patients with moderate-to-severe PSO who start treatment with anti IL-17 (e.g. secukinumab, ixekizumab, brodalumab, bimekizumab). Secukinumab is an IL-17A inhibitor for psoriasis and hidradenitis suppurativa. It blocks IL-17 interaction with its receptor. The dose is 300 mg at weeks 0, 1, 2, 3, and 4, followed by 300 mg monthly. Common AEs include respiratory infections, nasopharyngitis, oral herpes, diarrhea, headache, and fatigue. Ixekizumab, another IL-17A inhibitor, is dosed at 160 mg in week 0, followed by 80 mg every 2 weeks for 10 weeks, then 80 mg every 4 weeks. AEs include injection site reactions and respiratory infections. Brodalumab binds IL-17RA, with a dose of 210 mg at weeks 0, 1, and 2, followed by biweekly doses. Common AEs include infections, tinea, headache, and fatigue. Bimekizumab inhibits IL-17A, IL-17F, and IL-17A/F, dosed at 320 mg at weeks 0, 4, 8, 12, and 16, followed by 320 mg every 8 weeks. Common AEs include infections, candidiasis, and fatigue.

PSO - anti-TYK2

Adult patients with moderate-to-severe PSO who start treatment with TYK2 inhibitor (e.g. deucravacitinib). Deucravacitinib is a selective TYK2 inhibitor used for moderate-to-severe plaque psoriasis. It selectively binds the allosteric pocket of TYK2, leading to high selectivity in inhibition. Inhibiting TYK2 interferes with cytokine signaling involved in plaque psoriasis. The recommended dose is 6 mg daily. The most common adverse reactions occurring in ≥1% of patients are (viral) upper respiratory infections, nasopharyngitis, pharyngitis, sinusitis, herpes simplex, oral ulceration, acneiform rash, folliculitis, and increased creatine kinase levels.

HS - anti-TNF

Adult patients with moderate-to-severe HS who start treatment with anti-TNF (e.g. adalimumab, certolizumab, biosimilars). Adalimumab is a monoclonal antibody used to treat moderate-to-severe rheumatoid arthritis, plaque psoriasis, and hidradenitis suppurativa. It inhibits TNF, reducing inflammation. Common adverse events include infections, injection site reactions, headache, and musculoskeletal pain. For hidradenitis suppurativa, the dose starts with 160 mg at week 0, then 80 mg at week 2, followed by 40 mg weekly or 80 mg biweekly.

HS - anti-IL17

Adult patients with moderate-to-severe HS who start treatment with anti-IL 17, i.e. secukinumab, bimekizumab\* (\*once approved and reimbursed in the Netherlands). Secukinumab is an IL-17A inhibitor for psoriasis and hidradenitis suppurativa. It blocks IL-17 interaction with its receptor. The dose is 300 mg at weeks 0, 1, 2, 3, and 4, followed by 300 mg monthly. Common AEs include respiratory infections, nasopharyngitis, oral herpes, diarrhea, headache, and fatigue. Ixekizumab, another IL-17A inhibitor, is dosed at 160 mg in week 0, followed by 80 mg every 2 weeks for 10 weeks, then 80 mg every 4 weeks. AEs include injection site reactions and respiratory infections. Brodalumab binds IL-17RA, with a dose of 210 mg at weeks 0, 1, and 2, followed by biweekly doses. Common AEs include infections, tinea, headache, and fatigue. Bimekizumab inhibits IL-17A, IL-17F, and IL-17A/F, dosed at 320 mg at weeks 0, 4, 8, 12, and 16, followed by 320 mg every 8 weeks. Common AEs include infections, cand

MF - Topical chlormethine

Adult patients with stage 1 or 2 cutaneous T-cell lymphoma subtype mycosis fungoides who start treatment with topical chlormethine. Chlormethine (CL) gel 0.016% (Ledaga®) is an FDA-approved orphan drug (since August 23, 2013) for stage IA and IB mycosis fungoides in patients previously treated with skin-directed therapy. It forms DNA interstrand crosslinks, blocking replication and transcription, leading to cell death in rapidly dividing cells. CL gel showed no systemic absorption up to 6 hours post-application and after 1 month (Lessin et al., 2013). In a follow-up study with CL gel 0.04%, no detectable drug or degradation product was found in blood up to 6 months (Kim et al., 2014). In a randomized trial (n=128, median 52 weeks), 61.7% had skin-related side effects, mainly dermatitis (54.7%), pruritus (20.3%), infections (11.7%), ulceration/blistering (6.3%), and hyperpigmentation (5.5%). Hypersensitivity occurred in 2.3%. No systemic side effects or overdoses were reported.

MF - Topical corticosteroids

Adult patients with stage 1 or 2 cutaneous T-cell lymphoma subtype mycosis fungoides who start treatment with topical corticosteroids. Topical corticosteroids are anti-inflammatory medications that are used in the treatment of various inflammatory skin diseases, such as cutaneous T-cell lymphoma subtype mycosis fungoides. Corticosteroids inhibit the release of inflammation factors and therefore, the inflammatory response is reduced. Topical corticosteroids are divided in four subclasses, based on their potency. Topical corticosteroids are generally described as highly effective in the treatment of certain skin diseases. The recommended dose of topical corticosteroids depends on the subclass and specific therapy, however, generally 2 applications per day are recommended over a limited time period. AE's as skin thinning, and increased risk of infections are often reported.

MF - PUVA/UB-B

Adult patients with stage 1 or 2 cutaneous T-cell lymphoma subtype mycosis fungoides who start treatment with PUVA/UV-B. Psoralen UV-A (PUVA) is used to treat cutaneous T-cell lymphoma subtype mycosis fungoides. It combines UVA light with psoralen, a drug that makes the skin more sensitive to light. Typically, 2-3 treatments per week are required for effectiveness. Common side effects include nausea (due to psoralen) and skin redness (from UVA). Long-term use may lead to premature skin aging. UV-B light therapy, including narrowband UVB, is also used for (folliculotropic) mycosis fungoides. It uses short-wave UVB light that penetrates the outer skin layers. While generally safer than older phototherapies, long-term treatment may increase the risk of skin cancer.

CSU - anti-IgE

Adult patients with moderate to severe CSU who start (add-on) treatment with anti-IgE. Omalizumab is a highly effective treatment for chronic spontaneous urticaria. It is a recombinant humanized IgG1 monoclonal antibody targeting immunoglobulin E (IgE). Experimental models in cynomolgus monkeys and mice have been used to study its pharmacokinetics. The mouse model focused on antigen-independent behavior in the absence of IgE binding. After subcutaneous administration, bioavailability was 90% in mice and 64-104% in monkeys. Peak concentrations occurred around day 5, with a half-life of approximately 7 days. Clearance of omalizumab:IgE complexes was significantly slower than that of free IgE, leading to up to 20-fold increases in total IgE levels. In use since 2004, omalizumab has a well-established safety profile in asthma, CSU, and CRSwNP, both in trials and post-marketing. The most common AEs in CSU include nasopharyngitis, headache, sinusitis, and injection site reactions.

CSU - CsA

Adult patients with moderate to severe CSU who start (add-on) treatment with cyclosporin A. Cyclosporine A (CsA) is a lipophilic, cyclic undecapeptide produced by fungi, acting as a potent immunosuppressant by inhibiting T-cell receptor activation. It's prescribed twice daily at 3-5 mg/kg/day, starting with 3 mg/kg/day and increasing based on clinical response. CsA inhibits cytokine production, especially interleukin-2 (IL-2). In the Netherlands, CsA is the only oral immunosuppressant for moderate-to-severe atopic dermatitis (AD). CsA has shown superiority over placebo in numerous trials, and is the treatment of choice for severe AD. Common adverse reactions include renal dysfunction, tremor, hirsutism, hypertension, diarrhea, nausea, and vomiting. Contraindications include hypersensitivity and certain drug combinations. Regular monitoring is necessary due to potential risks like acute infections, hepatotoxicity, and renal toxicity.

CSU - anti-BTK

Adult patients with moderate to severe CSU who start (add-on) treatment with anti-BTK\*. Bruton's tyrosine kinase (BTK) inhibitors block BTK, a key enzyme in B-cell receptor signaling that controls B-cell activation and survival. By inhibiting BTK, these drugs disrupt B-cell function and pathological immune responses. They are mainly approved for B-cell cancers like chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). Common BTK inhibitors include ibrutinib, acalabrutinib, and zanubrutinib, which are orally administered and generally well tolerated. BTK also plays a crucial role in mast cell and basophil activation via the FcεRI receptor, central to chronic spontaneous urticaria (CSU). Inhibiting BTK blocks mast cell degranulation and histamine release, reducing symptoms in CSU patients, especially those unresponsive to antihistamines or omalizumab. This makes BTK inhibitors promising oral therapies for CSU. \*once approved and reimbursed in the Netherlands

CLE - Topical corticosteroids

Adult patients with mild to severe chronic lupus erythematosus (CLE) who start treatment with topical corticosteroids. Topical corticosteroids are anti-inflammatory medications that are used in the treatment of various inflammatory skin diseases, such as cutaneous T-cell lymphoma subtype mycosis fungoides. Corticosteroids inhibit the release of inflammation factors and therefore, the inflammatory response is reduced. Topical corticosteroids are divided in four subclasses, based on their potency. Topical corticosteroids are generally described as highly effective in the treatment of certain skin diseases. The recommended dose of topical corticosteroids depends on the subclass and specific therapy, however, generally 2 applications per day are recommended over a limited time period. AE's as skin thinning, and increased risk of infections are often reported.

CLE - Hydroxychloroquine

Adult patients with mild to severe chronic lupus erythematosus (CLE) who start treatment with HCQ. HCQ is an antimalarial used to treat rheumatoid arthritis, systemic lupus erythematosus, and cutaneous lupus. It accumulates in lysosomes, raising pH, and inhibits TLR3, TLR7, and TLR9, reducing plasmacytoid dendritic cell activation and lowering IFNα and TNF production. HCQ also suppresses T and B cell activation, reducing Th1, Th2, and Th17 responses, while sparing cytotoxic T cells. Orally, HCQ has 74% bioavailability, a Tmax of 2-4.5 hours, and a plasma half-life around 32 days. It concentrates in blood cells and tissues like lungs, kidneys, and eyes. Metabolized in the liver, it is cleared by the kidneys. Common side effects are nausea, abdominal pain, and diarrhea, often reduced by taking HCQ with food. Risks include hypoglycemia, retinopathy, cardiac toxicity, and blood count changes, requiring regular monitoring.

CLE - Methotrexate

Adult patients with mild to severe chronic lupus erythematosus (CLE) who start treatment with methotrexate. Methotrexate (MTX), introduced in 1947 for cancer, has been used since the 1980s at low doses to treat rheumatoid arthritis (RA). It is given once weekly, orally or by injection (s.c., i.m., i.v.). MTX's anti-inflammatory effects involve inhibition of nucleotide synthesis, NF-κB signaling, JAK-STAT pathway modulation, nitric oxide production, adenosine release, and regulation of certain RNAs. Orally, MTX has \~70% bioavailability with peak levels in 1-2 hours; subcutaneous administration offers higher and faster plasma levels. About 50% binds serum proteins and accumulates in liver, kidneys, and spleen as polyglutamates. The half-life varies from 3 to 17 hours. Common side effects include nausea, fatigue, mouth sores, liver enzyme elevation, and leukopenia. Early detection allows reversibility; patients are closely monitored. Folic acid is recommended to reduce adverse events.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with six different inflammatory skin diseases (AD, PSO, CLE, HS, CSU, and MF) will be enrolled. Each indication will include multiple treatment groups, with up to 40 patients per group. In total, approximately 120 patients per disease will be studied, except for PSO (4 treatment groups, N=160) and HS (2 treatment groups, N=80), covering a range of disease severities. Patients will be recruited from the local hospital where they receive standard care and will also attend study visits at this location. Healthy volunteers will be recruited through the Centre for Human Drug Research.

You may qualify if:

• Patients:
• Able to understand and provide a written informed consent prior to any study procedures
• Male or non-pregnant female, ≥18 years of age
• Patient is willing to refrain from extensively washing (including bathing, swimming) the target lesional skin 12 hours before every study visit day.
• Patient is willing and able to comply with the study protocol
• Female participants are willing to not get pregnant between M0 until M12, from study entry to the last study visit
• The patient is willing to start the prescribed treatment.
• For patients with AD:
• To be eligible to participate in this study, a subject must meet all of the following criteria:
• \. Diagnosis and history of chronic, moderate-to-severe AD (by the Eichenfield revised criteria of Hanifin and Rajka for at least 3 years before baseline visit.
• \. Documented recent history (last 6 months) of eligibility for (local or systemic) treatment with immunosuppressants, biologics or JAK-inhibitors.
• \. When applicable, documented recent history (last 6 months) of inadequate response to treatment with topical therapy, immunosuppressants, biologics or JAK-inhibitors.
• \. EASI≥7 (moderate-to-severe disease) 11. At least one suitable target lesion at the discretion of the investigator 12. Intention to start treatment with cyclosporine A, dupilumab, tralokinumab, lebrikizumab or a JAK1-inhibitor (abrocitinib or upadacitinib)
• For patients with CLE:
• Participants must have a diagnosis of CLE, including SCLE, CDLE or LET that fulfil the following:

You may not qualify if:

• Patients:
• Have any other relevant skin infection/disease in the treatment area other than the investigated skin disease.
• Subjects who have received treatment with any non-marketed drug substance (that is, an agent which has not yet been made available for clinical use following registration) within 4 weeks prior to the baseline visit.
• week for topical treatment, e.g. corticosteroids, retinoids, vitamin D analogs, calcineurin inhibitors
• weeks for phototherapy, e.g. UVB, PUVA, PDT
• weeks for non-biologic systemic treatment, e.g. retinoids, methotrexate, cyclosporine, JAK inhibitors
• weeks for radiotherapy or surgery in the treatment area
• weeks for biologics
• months for any systemic chemotherapeutical treatment
• \. Diagnosed with SLE
• \. Treatment with omalizumab within 8 weeks prior to Day 1 6. Urticarial or angioedema symptoms such as urticarial vasculitis, erythema multiforme, cutaneous mastocytosis (urticaria pigmentosa) and hereditary, acquired angioedema or drug-induced (e.g., due to C1 esterase inhibitor deficiency, ACE-inhibitor induced).
• \. Ongoing uncontrolled active skin infection, other than secondary impetiginized CTCL lesions as judged by the investigator
• \. Having primarily erythrodermic, pustular or guttate psoriasis; 6. Having drug-induced psoriasis;
• Healthy volunteers:
• History of immunological abnormality (e.g. immune suppression, severe allergy, or anaphylaxis) that may interfere with study objectives as per judgement of the investigator.

Sponsors & Collaborators

• Leiden University Medical Center: lead
• Erasmus Medical Center: collaborator
• Radboud University Medical Center: collaborator
• Amsterdam University Medical Center: collaborator
• UMC Utrecht: collaborator
• Maastricht University Medical Center: collaborator
• University Medical Center Groningen: collaborator
• Centre for Human Drug Research, Netherlands: collaborator

Study Sites (8)

Radboud University Medical Center

Nijmegen, Gelderland, 6525GA, Netherlands

NOT YET RECRUITING

Maastricht University Medical Center+

Maastricht, Limburg, 6229HX, Netherlands

NOT YET RECRUITING

Amsterdam University Medical Center

Amsterdam, North Holland, 1105AZ, Netherlands

NOT YET RECRUITING

University Medical Center Groningen

Groningen, Provincie Groningen, 9713GZ, Netherlands

NOT YET RECRUITING

Leiden University Medical Center

Leiden, South Holland, 2333 ZA, Netherlands

NOT YET RECRUITING

Centre for Human Drug Research

Leiden, South Holland, 2333CL, Netherlands

NOT YET RECRUITING

Erasmus Medical Center

Rotterdam, South Holland, 3015GD, Netherlands

NOT YET RECRUITING

University Medical Center Utrecht

Utrecht, Utrecht, 3584 CX, Netherlands

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

* Blood samples (including blood sample for genomics analysis, optionally) * Skin punch biopsies (optional) * Tape strips of skin surface * Swab of skin surface

MeSH Terms

Conditions

Chronic Urticaria; Hidradenitis Suppurativa; Psoriasis; Dermatitis, Atopic; Mycosis Fungoides; Urticaria; Angioedema; Abscess; Eczema; Pruritus; Neoplasms; Exanthema; Photosensitivity Disorders; Plaque, Amyloid; Erythema

Condition Hierarchy (Ancestors)

Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Diseases, Bacterial; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Skin Diseases, Infectious; Suppuration; Hidradenitis; Sweat Gland Diseases; Skin Diseases, Papulosquamous; Skin Diseases, Genetic; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Dermatitis; Skin Diseases, Eczematous; Lymphoma, T-Cell, Cutaneous; Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Vascular Diseases; Cardiovascular Diseases; Inflammation; Skin Manifestations; Signs and Symptoms; Pathological Conditions, Anatomical

Central Study Contacts

Robert Rissmann, Professor

CONTACT

+31 71 526 9111; r.rissmann@lumc.nl

Martijn van Doorn, MD, PhD

CONTACT

+31 10 704 0704; m.b.a.vandoorn@erasmusmc.nl

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. dr. Robert Rissmann

Study Record Dates

• First Submitted: May 20, 2025
• First Posted: June 15, 2025
• Study Start: July 29, 2025
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2029
• Last Updated: August 19, 2025

Record last verified: 2025-08

Locations

NL (8)