Kimura disease: Successful treatment with dupilumab

Dear Editors, Kimura disease (angiolymphoid hyperplasia with eosinophilia; KD) is a rare chronic inflammatory disorder characterized by subcutaneous masses in the head and neck region, often accompanied by lymph node or salivary gland enlargement, as well as elevated peripheral blood eosinophil counts and serum immunoglobulin E (IgE) levels.1 Studies have reported atypical skin manifestations such as pruritus, urticaria, chronic eczema, and hyperpigmentation.2 Herein, we report an unusual clinical case of KD successfully treated with dupilumab, with palmoplantar involvement being one of the observed manifestations. A 74-year-old male presented with bilateral peri-auricular plaques and nodules persisting for 3 years, accompanied by generalized eczema, hyperpigmentation, and palmar and plantar hyperkeratosis with erythematous plaques over the past 2 years. These localized skin lesions were accompanied by itching, particularly on the palms and soles. The patient had previously presented to an external oncology department, where a fine-needle aspiration biopsy was performed; however, no definitive diagnosis was established. Physical examination revealed bilateral peri-auricular plaques and nodules, eczema affecting the head, trunk, and limbs, hyperpigmentation on the trunk, and palmar-plantar hyperkeratosis with firm erythematous plaques. (Figure 1a–g). Laboratory tests revealed a serum IgE level of 2,350 IU/ml and an eosinophil count of 0.59 × 10⁹/l (10.8 %). A skin biopsy of the lesion behind the right ear showed dermal collagen proliferation and fibrosis, with infiltration of lymphocytes and histiocytes in nodular or mass-like formations, forming lymphoid follicle-like structures (Figure 1h). This was surrounded by substantial eosinophilic infiltration and accompanied by vascular proliferation and dilation (Figure 1i). The patient's medical history included diabetes, hypertension, and chronic obstructive pulmonary disease, all managed with regular treatment. Kimura disease was diagnosed. Given the patient's advanced age and widespread cutaneous lesions, surgical intervention was deemed inappropriate. Moreover, corticosteroid therapy was ruled out as a primary treatment option owing to its potential to impair glycemic control in this diabetic patient. After thorough consultation with the patient, dupilumab treatment was initiated in July 2023 with a loading dose of 600 mg, followed by 300 mg every 2 weeks for 4 months. Subsequently, the frequency was reduced to 300 mg once every 4 weeks. After 12 weeks of treatment, the skin lesions had nearly resolved, with serum total IgE reduced to 819 IU/ml and eosinophil counts normalized. By 10 months, the lesions had fully resolved (Figure 2), with serum total IgE at 171 IU/ml, and eosinophil levels remaining within normal ranges. The patient continues to receive dupilumab at a dosage of 300 mg every 4 weeks and is under follow-up care. Kimura disease is a rare chronic inflammatory disorder predominantly affecting young Asian males, with an unclear etiology.2 Current evidence links its pathogenesis to T helper 2 cell (Th2)-mediated inflammation, characterized by elevated eosinophil counts, increased IgE levels, and tissue eosinophilic infiltration.3 Elevated T helper 2 (Th2) cytokines (interleukin [IL]-4, IL-5, IL-13) drive KD progression: IL-4 and IL-13 promote IgE production via B-cell differentiation and class switching, while IL-5 synergizes with IL-4 and IL-13 to facilitate eosinophil maturation, activation, and tissue infiltration, culminating in tissue remodeling and fibrosis.3, 4 Clinically, KD typically presents as subcutaneous nodules or masses, but atypical cutaneous manifestations, such as eczema, pruritus, urticaria, and hyperpigmentation, may also occur.1, 5, 6 These nonspecific lesions correlate with the Th2 inflammatory axis in KD and should be recognized as systemic manifestations reflecting its immunopathological basis.6 Our case report further highlights palmoplantar involvement, manifesting as hyperkeratosis, erythematous plaques, and pruritus. Although histopathological confirmation was lacking, the resolution of these lesions following dupilumab treatment suggests they may represent an extension of the KD spectrum. The diagnosis of KD relies on histopathological examination, which reveals characteristic features including eosinophilic infiltration, lymphoid follicle-like structures, capillary venule proliferation, and fibrosis.2, 7 These findings, particularly the presence of lymphoid follicle-like structures and eosinophilic infiltration, are considered key diagnostic hallmarks of KD. Core needle biopsy is generally discouraged because of its low diagnostic accuracy; excisional biopsy of lymphadenopathy or subcutaneous lesions is preferred.5 Major laboratory findings include markedly elevated serum IgE levels and peripheral blood eosinophilia, which serve as valuable diagnostic markers in KD.5, 7 Treatment options include surgical excision, corticosteroids, and radiation therapy, but these are often associated with high recurrence rates and lack standardization.1, 5 Recent case reports, including ours, demonstrate the efficacy of dupilumab, a monoclonal antibody targeting the IL-4 receptor α subunit (IL-4Rα).3, 8 By inhibiting IL-4 and IL-13 signaling, dupilumab suppresses Th2-mediated inflammation, reduces IgE levels, and mitigates eosinophilic infiltration, potentially inducing remission with lower relapse rates.3, 8-10 Despite promising results, dupilumab remains an off-label treatment for KD, and evidence is largely limited to case reports and small series, raising concerns about publication bias. Large-scale, multicenter studies with extended follow-up are needed to validate its long-term efficacy and safety. None.