Chronic Venous Disease in Patients With Hidradenitis Suppurativa and Lymphedema: An Overlooked Problem

Hidradenitis suppurativa (HS) is a chronic, immune-mediated inflammatory disease associated with systemic comorbidities, including cardiovascular and metabolic disorders [1]. Despite this, CVD (chronic venous disease) has not been a major focus of research. CVD, encompassing both deep and superficial forms, is characterized by morphological and functional abnormalities of the venous system, primarily affecting the lower extremities. Symptoms include leg heaviness or achiness, with signs such as oedema, telangiectasia, and varicose veins [2, 3]. In a retrospective multicenter study on secondary lymphedema in HS [4], we explored the association and potential risk factors for its development. Based on the hypothesis that CVD and lymphedema share a common etiopathogenesis, and supported by our clinical observations, we hypothesized that patients with HS may also have an increased predisposition to CVD. The diagnosis of CVD was based on clinical examination by dermatologists experienced in HS, following the CEAP (Clinical, Etiologic, Anatomic, Pathophysiologic) classification [2]. Therefore, we assessed the demographic and clinical characteristics within a multicenter cohort of 50 patients with HS and secondary lymphedema. In this cohort (Table 1), we observed that 10 out of 50 (20%) patients with HS and secondary lymphedema also showed signs of CVD, such as pronounced superficial varicose veins in the lower legs, thighs, groins (shown in Figure 1a) and buttocks (shown in Figure 1b). These patients were mainly males (60%), with a mean age of 57.6 years old and a mean body mass index of 30.6 kg/m². All of them exhibit severe HS in the lower body, with inflammatory (80%) and follicular phenotype (20%). Consequently, general compression measures were recommended. Additionally, 2 of the 10 patients with both lymphedema and CVD were referred to a vascular surgeon due to significant varicose veins in the upper regions of their lower extremities. Following thorough evaluation and ultrasonographic assessment, both patients underwent radiofrequency ablation of the internal saphenous vein, resulting in marked improvement in symptoms including reduced leg heaviness and a decrease in visible varicosities. Understanding the pathophysiology of lymphedema and CVD is essential. In lymphedema, lymphatic injury triggers inflammation and adipogenesis, causing swelling and edema, followed by fibrosis⁴. In CVD, venous hypertension and valve dysfunction lead to endothelial damage, capillary leakage, and chronic inflammation [2]. In patients with lymphedema and HS, CVD development may be influenced by shared risk factors such as female sex, overweight/obesity, tobacco use, and a sedentary lifestyle [2]. Additionally, systemic inflammation in HS is linked to elevated pro-inflammatory markers such as tumor necrosis factor, C-reactive protein, interleukin (IL)-1ß, IL-6, IL-17, IL-32, and IL-36 [1], many related to venous injury, which could independently increase early CVD risk in predisposed patients. Untreated CVD can lead to severe complications, including venous ulcers, cellulitis, lipodermatosclerosis, stasis dermatitis, thrombophlebitis, hemorrhage, lymphedema, atrophie blanche, deep vein thrombosis, and venous thromboembolism/pulmonary embolism (VTE/PE). The impact of HS on VTE/PE risk has been subject to debate in previous studies [5-7], but Garate et al. [8] demonstrated that HS patients have an increased risk hazard ratio of VTE and PE. This study has several methodological limitations, notably a small sample size and the assessment of CVD proportion restricted to HS patients with lymphedema. Moreover, the population consists of patients with HS affected by lymphedema, which may involve predisposing factors leading to potential selection bias. Additionally, the cross-sectional nature of the study prevents the establishment of a causal relationship between CVD and lymphedema. Nevertheless, despite these limitations, this is the first study to highlight this potential issue. In conclusion, it is important to stay aware of the potential increased risk of CVD in patients with HS. Further studies, with close collaboration from vascular surgeons, are necessary to confirm these hypotheses. P.G.S., A.M.L., R.S.A.O., and E.V. authors contributed substantially to the conception and design, data acquisition and interpretation, critical revision, final approval of the manuscript, and agree to be accountable for all aspects of the work. The authors received no specific funding for this work. All patients in this manuscript have given written informed consent for participation in the study and the use of their de-identified, anonymized, aggregated data and their case details (including photographs) for publication. Ethical Approval: This study protocol was reviewed and approved by [Ethics Committee of Parc Taulí Hospital Universitari], approval number [2023/6078]. P. Garbayo-Salmons declares honoraria for participating in advisory boards from Novartis; has received speaker's honoraria and/or travel support for attending meetings sponsored by Abbie, Amgen, Lilly, LEO Pharma, Novartis, and UCB. A. Molina-Leyva declares consultancy/speaker's honoraria and/or travel grants and/or participated in clinical trials sponsored by AbbVie, Almirall, Boehringer Ingelheim, Celgene, Janssen Cilag, LEO Pharma, Lilly, Novartis, Pfizer, Sandoz, Sanofi and UCB. R. S. Aguayo-Ortiz has received speaker's honoraria from Novartis, Roche and Janssen and support for attending meetings from Lilly, Novartis, UCB, Almirall and Abbvie. E. Vilarrasa has received consultancy/speaker's honoraria and/or travel support for attending meetings and/or participated in clinical trials sponsored by Abbvie, Almirall, Amgen, Biofrontera, Boehringer Ingelheim, Bristol-Meyers Squibb, Celgene, Galderma, Gebro, Isdin, Johnson&Johnson, LEO Pharma, Lilly, Merck Serono, MSD, Novartis, Pfizer, Roche, Sandoz, Sanofi, and UCB. The data that support the findings of this study are available from the corresponding author upon reasonable request.