Use of Dupilumab to Treat Cutaneous Complications of Continuous Prostacyclin Infusion in Pulmonary Hypertension: A Case Report and Review of Literature

ABSTRACT

Adhesive reactions are common complications of continuous treprostinil infusions, limiting their recommended use as a treatment for severe pulmonary hypertension. We present the case of a 10‐year‐old male with recurrent adhesive‐related skin reactions, which compromised both subcutaneous and intravenous continuous treatment. Due to comorbid atopic dermatitis (AD), dupilumab was initiated to decrease skin reactions to adhesives. Within 48 h of initiation, skin reactions completely resolved. With sustained dupilumab treatment, he remains symptom‐free and is successfully tolerating intravenous treprostinil infusion.

1. Introduction

For pediatric patients with severe pulmonary hypertension (PH), continuous prostacyclin infusion is a cornerstone of therapy, but the method of administration presents unique challenges. Treprostinil, a prostacyclin analog, can be administered intravenously (IV) through a central venous line (CVL) or subcutaneously through a subcutaneous (SQ) catheter system, with protective overlying adhesive dressing. Local skin reactions—including irritation, pain at the insertion site, inflammation, and infection—are frequent complications of SQ therapy that often necessitate frequent site changes, perpetuating cycles of catheter‐related insertion pain. Ultimately, patients may elect to discontinue therapy and transition to IV therapy [1]. However, skin sensitivity and irritation may persist and threaten CVL integrity.

Over time, advancements in adhesive technology have led to a better understanding of biocompatibility—the ability of the adhesive materials to interact with skin tissue without causing toxicity, irritation, allergic reactions, or carcinogenic effects [2]. Common adhesive options like Nexcare Tegaderm (3M, Maplewood, Minnesota, USA) and Opsite IV3000◊ (Smith&Nephew, Watford, England, UK) vary in permeability and skin moisture retention, influencing their suitability for different patients. The standard first‐line adhesive for securing catheters to skin is typically 3M Tegaderm, which consists of a polyurethane film with an acrylic adhesive that maintains a moist environment at the site of placement through moisture‐reactive properties [3]. IV3000◊, often recommended for patients with sensitive skin since it is a low allergy adhesive, is also made of polyurethane film and acrylic adhesive. It has been shown to be more permeable and associated with a lower skin moisture retention rate compared to 3M Tegaderm, reducing the risk of infections, skin maceration and improved adhesion [4].

Predilection for cutaneous reactions may be influenced by atopic dermatitis (AD) as well, a condition driven by the complex interaction of inflammatory markers, particularly IL‐4 and IL‐13, which contribute to skin barrier dysfunction and an increased susceptibility to skin infections. Dupilumab, a monoclonal antibody targeting IL‐4 and IL‐13 signaling [5, 6], is a well‐described treatment for moderate to severe AD and has demonstrated efficacy in improving skin barrier function and reducing local inflammation in patients 6 months and older with AD. This results in less pruritis, overall improved skin appearance and patient‐ and caregiver‐reported outcomes including quality of life across communities and comorbidities, including heart, kidney, and liver disease [7, 8, 9].

2. Case Presentation

We present the case of a 10‐year‐old boy with severe World Symposium of Pulmonary Hypertension grouped as Group 3 PH due to developmental lung disease (pulmonary hypoplasia in the context of congenital diaphragmatic hernia) with Group 1 features due to its progressive nature [10]. He had comorbid asthma, AD and chronic hypoxemia requiring continuous supplemental oxygen. He was receiving combination therapy including continuous SQ treprostinil infusion.

3 M Nexcare Tegaderm was initially used to secure the catheter at the insertion site. However, he reported nearly continuous pruritis, rash, and lichenification at the catheter site (Figure 1a). Persistent itching led to frequent site dislodgement and severe skin irritation, necessitating continual dressing changes and site replacement. Over 6 years, multiple dressing options were trialed including AquaGuard Moisture Barrier, 3M Nexcare Tegaderm, BIOPATCH and Opsite IV3000◊. Emollients, bleach baths, topical clobetasol and triamcinolone were trialed without improvement. Nasal swab was negative for methicillin‐resistant Staphylococcal aureus. Skin preparation solution was changed from chlorhexidine to povidone‐iodine, which was better tolerated but did not eliminate skin reactions. Despite efforts, skin symptoms progressed, with frequent SQ catheter site dislodgements requiring increasing frequency of replacements, from monthly to weekly. Previous SQ sites healed poorly and were marked by profound hyperpigmentation and lichenification. He was trapped in a vicious cycle of pain and inflammation which had a profound negative impact on his participation in activities and quality of life.

Figure 1.

(a) Baseline photo pre‐dupilumab initiation of peripherally inserted central catheter. There is diffuse scarring, hyperpigmentation and lichenification. (b) Photo taken of the same site 2 days after dupilumab injection was given. [Color figure can be viewed at wileyonlinelibrary.com]

He was transitioned from SQ to IV treprostinil administration by CVL and Nexcare Tegaderm and Opsite IV 3000◊ dressings were trialed. However, once again, he immediately developed severe skin reactions to these dressings, compromising site integrity and necessitating frequent dressing changes. He even had CVL dislodgement due to pruritus‐associated suture loss. There was clinical concern for poor medication absorption and heightened risk for bloodstream infection.

In the setting of his known AD, we hypothesized that dupilumab would minimize his chronic hypersensitivity and allow tolerance of adhesive products. He received a loading dose of 600 mg for dosing weight of 19.6 kg, and within 48 h of administration, the skin irritation at the CVL dressing site and his flexural eczema completely resolved. He was instantly able to tolerate Opsite IV3000◊ without issue (Figure 1b).

Three years post‐initiation of dupilumab therapy, the patient remains on dupilumab injections every 3 weeks and has been able to maintain his IV infusion by CVL, with either Nexcare Tegaderm or SorbaView 2000 Window Dressing to protect the site. He remains free of adverse reactions resulting in optimized site integrity and minimized risk for infusion interruption or bloodstream infection.

3. Discussion

Skin irritation and adhesive intolerance are usual challenges for pediatric patients on continuous prostacyclin infusions, and while advancements in adhesive technology have improved outcomes, these issues continue to impact treatment adherence and patient quality of life [1]. This case study reviews the novel use of dupilumab for management of these infusion‐related challenges, improving infusion tolerance and quality of life. The patient elected to continue PH treatment with continuous IV treprostinil infusion and he remains symptom‐free. However, we speculate that if he were to switch back to SQ infusion, we would likely see similar tolerance because the reason for previous SQ failure (adhesive reaction) has been alleviated.

While the cost of a biologic therapy such as dupilumab is substantial, this cost must be considered in the context of downstream effects: less wound care needs and exploration of dressing supplies, prevention of hospitalization for CVL‐associated bloodstream infections and surgery for line replacement, and reduction in life‐threatening complications due to infusion site instability. The benefits in treatment with dupilumab are significant and in this patient, support its continued use.

This case study highlights a gap in treatment options for adhesive‐related skin reactions in continuous prostacyclin infusions. In this patient, we were able to use dupilumab to successfully manage cutaneous complications of his IV infusion because he had comorbid AD, which is an approved indication for this treatment. Unfortunately, chronic adhesive‐related skin complaints alone are not an indication for dupilumab which may preclude its use. Therefore, there is a need to not only improve upon adhesive options to secure catheter sites, but also to find preventative strategies to minimize skin irritation in patients of all skin types.

4. Conclusion

Chronic skin irritation related to the use of medical adhesives remains a significant challenge for pediatric PH patients receiving continuous prostacyclin infusion therapy. This case study highlights the benefits of dupilumab in managing skin complications related to comorbid AD, offering a promising alternative for similar patients when traditional approaches fail. Further research into reactive and preventative strategies, as well as exploring the broader applications of biologic therapies will be essential to optimize the integrity of continuous prostacyclin infusions in pediatric PH.

Author Contributions

Conceptualization: N.P.V. and E.W., Data curation: E.E., R.F., C.C, and E.W. Writing – original draft: E.W, E.E., C.C., R.F., and N.P.V. Writing – review and editing: N.P.V. and E.C.W. Guarantor: N.P.V.

Ethics Statement

N/A; consent obtained for case report and sharing of media.

Conflicts of Interest

The authors declare no conflicts of interest.

Varghese NP, Ely E, Fombin R, Champion C, Whalen E, “Use of Dupilumab to Treat Cutaneous Complications of Continuous Prostacyclin Infusion in Pulmonary Hypertension: A Case Report and Review of Literature,” Pulmonary Circulation 15 (2025): 1‐3. 10.1002/pul2.70158.