Mesenchymal stem cell therapy in eosinophilic granulomatosis with polyangiitis-related lower limb gangrene: a case report

Abstract

Background Eosinophilic granulomatosis with polyangiitis (EGPA), a rare but life-threatening systemic vasculitis, is distinguished by marked eosinophilia and presents with diverse symptoms, including asthma, cutaneous purpura, ecchymosis, skin necrosis, cardiac lesions, peripheral neuropathy, and necrotizing vasculitis. The etiology of EGPA involves a complex interaction among humoral, adaptive, innate, and allergic immune responses. Standard treatment employs prolonged high-dose glucocorticoid therapy, which is critical for survival; however, some patients’ symptoms cannot be relieved. Case report This case report details the medical management of an 11-year-old patient with EGPA, who was at risk of bilateral lower limb amputation due to differential arterial occlusion and severe, necrotizing vasculitis-induced gangrene in both feet. Treatment modalities administered included systemic infusion of Umbilical Cord Mesenchymal Stem Cells (UC-MSCs), targeted gastrocnemius muscle injections, and application of a Placenta-Derived Mesenchymal Stem Cells (PD-MSCs) hydrogel. Results After receiving a four-month regimen of allogeneic mesenchymal stem cell therapy via intravenous and local administration, the patient showed normalized eosinophil counts, reestablished blood flow in the dorsal arteries, and marked improvement in foot ulcerations. Conclusion Mesenchymal stem cell therapy is a promising option for severe EGPA cases refractory to glucocorticoids.

1. Introduction

Eosinophilic granulomatosis with polyangiitis (EGPA) is a disseminated necrotizing vasculitis accompanied by extravascular granulomas, occurring in patients with asthma and tissue eosinophilia [1, 2]. The incidence of EGPA is 0.5 to 4.2 cases per million per year, with a global prevalence of 10 to 14 cases per million residents [3, 4]. Epidemiological studies indicate that EGPA is less common in Asia, although Japan and South Korea have recently reported some large case series [5, 6]. The disease has a comparable incidence in both males and females, with the average age at diagnosis around 50 years [7], and cases in children are highly sporadic [8].

Genetic and environmental factors influence the etiology of EGPA. The precise mechanisms by which these factors determine susceptibility and clinical manifestations of EGPA are not fully understood [9, 10]. EGPA is predominantly mediated by Th2 lymphocytes, leading to elevated levels of interleukins (IL)-4, IL-13, and IL-5, which facilitate the mobilization of eosinophils from the bone marrow into the bloodstream and result in their infiltration into various organs [11, 12]. The release of eosinophil cationic protein and eosinophil-derived neurotoxin contributes significantly to tissue damage [13]. EGPA is characterized by a triphasic progression: a prodromal phase marked by asthma and allergic rhinitis, an eosinophilic phase with tissue eosinophilia, and a vasculitic phase with multiorgan involvement. Clinical presentations are diverse, including but not limited to respiratory, gastrointestinal, musculoskeletal, renal, cutaneous, and neurological symptoms [14–16]. While these phases may overlap, certain patients can experience severe complications such as thrombosis [17]. The standard treatment for severe prognosis involves a combination of glucocorticoids and immunosuppressants, whereas milder cases might be managed with glucocorticoids alone [18, 19].

Recent literature has increasingly documented the efficacy of mesenchymal stem cells (MSCs) in repairing ischemic ulcerations, predominantly those associated with thromboangiitis obliterans and diabetic foot ulcers [20–22]. Arango-Rodríguez et al. [23] demonstrated that treating patients with chronic limb-threatening ischemia using allogenic Wharton jelly-derived MSCs significantly improved limb salvage rates compared to autologous bone marrow mononuclear cells.