Beyond swelling: could lymphedema be a Whole-Body biological disorder?

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

General inclusion criteria for all participants: * Adults aged 18 to 45 years. * Ability to understand the study information and provide written informed consent. * Willingness and ability to attend one study visit and undergo the planned clinical assessment, blood sampling, and skin swab collection. Additional inclusion criteria for participants with primary lymphedema: * Clinically and, where appropriate, imaging-confirmed primary lymphedema of an upper or lower extremity. * Lymphedema classified as Stage I or II according to the applicable clinical classification. Participants with Stage III disease may be included if disease progression is associated with recurrent cellulitis or erysipelas and this is documented separately. * Current treatment or follow-up at the Department of Dermatovenereology, University Medical Centre Ljubljana. Additional inclusion criteria for participants with secondary lymphedema: * Clearly established acquired cause of lymphedema. * Comparable anatomical location and, where feasible, disease stage to the primary lymphedema group. * Completion of active oncological treatment, where secondary lymphedema is cancer-related. Healthy control participants: * No clinical signs or previous history of lymphedema. * Comparable age and sex distribution to the lymphedema groups. Exclusion Criteria * Other major causes of limb swelling, including heart failure, nephrotic syndrome, clinically significant thyroid disease, or medications likely to cause edema when the effect cannot be adequately accounted for. * Acute systemic infection or cellulitis/erysipelas within 4 weeks before study enrollment. * Pregnancy or breastfeeding. * Active oncological treatment. * Active smoking. * Active inflammatory skin disease that could substantially affect the skin microbiome or systemic inflammatory biomarkers. * Clinically manifest cardiovascular disease or previous cardiovascular event. * Treatment with medications that are expected to substantially affect the selected immunological or metabolic outcomes when their effects cannot be adequately accounted for in the analysis. * Inability to provide valid informed consent. Gender eligibility: \- Eligibility is not restricted by gender identity. Biological sex will be recorded where relevant for clinical and laboratory analyses, including sex-specific calculation of selected metabolic indices. Withdrawal: Participants may withdraw from the study at any time without providing a reason and without any effect on their subsequent medical care.