Maximizing safety of ultrasound-guided intralymphatic allergen administration in the superficial inguinal lymph node

Abstract

Traditionally, subcutaneous immunotherapy has been the gold standard method of inducing immune response to tolerance and desensitization of allergen extract for the treatment of allergic rhinoconjunctivitis. Since the first clinical trial of intralymphatic immunotherapy (ILIT) was published nearly two decades ago,¹ ILIT has emerged as an alternative choice due to its ability to deliver antigen locally while minimizing risk of systemic adverse reactions and inducing a rapid onset of effect. Several studies have shown the safety and efficacy of the ILIT therapy for seasonal and perennial allergy symptoms by targeting a variety of superficial lymph node regions, including inguinal, cervical and tonsillar.^1-5 Recently, Flory et al. presented practical recommendations on ultrasound-guided injections based on a review of videos of 173 ILIT injections performed at their institution.⁶ In addition to considerations of sonographic and injection technique, we wish to highlight to importance of a careful understanding of lymphatic anatomy and selection of the targeting lymph node prior to incorporating this procedure into clinical practice.

The lymphatic system is divided into lymphosomes, which consist of superficial lymph-collecting vessels and their corresponding lymph nodes.⁷ As each lymphosome is responsible for the regional maintenance of fluid balance, any inadvertent injuries to regional lymph nodes can lead to lymphedema, a chronic debilitating condition that leads to negative functional, esthetical, and physical impact in patient's lives.⁸ Therefore, knowledge of the normal anatomy of the lymphatic system and the potential cause of lymphedema by its damage is crucial for those who are practicing ILIT.

Typically, critical structures including the inguinal/femoral arteries and veins are identified and the region lateral to the vessels are scanned to identify a suitable lymph node in the inguinal ILIT. In the inguinal region, there are three subgroups of the superficial lymph nodes: the abdominal, lateral thigh, and medial thigh groups (Figure 1).⁹ It is critical to prevent injuries to the medial thigh group as the majority of lymph vessels originating from the feet drain to two or three dominant lymph nodes of this group, which is bordered by the inguinal ligament, the medial border of the sartorius, and the lateral border of the adductor longus. As this procedure gains popularity in clinical use, it is important to acknowledge that these superficial nodes have important functionality. Currently, microsurgeons harvest superficial inguinal lymph nodes to autograft them for the treatment of lymphedema while carefully preserving the deep lymph nodes for the lower extremity via reverse groin lymph node mapping and preoperative SPECT CT. Microsurgeons utilize high-frequency ultrasound to identify the precise location of superficial lymph nodes to prevent the injury of deep lymph nodes, reducing the risk to ~1.5%.¹⁰ While there are limited studies on the frequency of the ultrasound probe used in ILIT, the majority of the portable ultrasound probe has a low frequency (1-10 Mhz), compared to 48–70 Mhz used in ultrasound mapping for lymphedema, which provides significantly less anatomic details (Figure 2).

To conclude, ILIT represents a promising advancement in the administration of aeroallegen immunotherapy for rhinoconjunctivitis by offering localized delivery, minimizing risk of anaphylaxis and significantly reducing treatment period compared to traditional immunotherapy. While the small clinical trials to date support the safety and efficacy of this treatment, popularizing clinical use amongst allergists, there is a lack of dedicated anatomic studies and further studies should be completed to address anatomic considerations of the lymph node regions. High frequency ultrasound use should be considered to optimize visualization of lymph nodes to minimize risk of iatrogenic lymphedema which has been observed in other specialties.

M.J.-C.: Idea formulation, background search, data collection, manuscript preparation, final editing, and revisions. V.N.: Background search, data collection, manuscript preparation, final editing, and revisions. H.S.: Background search, manuscript preparation, final editing, and revisions. C.T.K.: Idea formulation, data collection, background search, manuscript preparation, final editing, and revisions. M.T.K.: Idea formulation, background search, data collection, manuscript preparation, final editing, and revisions.

All authors have no conflicts of interest to declare.