Successful treatment of Kimura disease in earlobes with dupilumab

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Kimura Disease (KD) is a chronic inflammatory disorder of unknown aetiology. It usually affects Asian young men of age 20 to 30 years and presents as slowly enlarging, painless soft tissue tumours of the head and neck, in the retroauricular area. It is often accompanied by regional lymphadenopathy, infiltration of eosinophils and mast cells in subcutaneous tissue, elevated serum immunoglobulin E (IgE) level, and raised circulating eosinophil level. It is pathologically characterised by marked florid germinal centre hyperplasia, proliferating blood vessels, and eosinophilic infiltration. Conventional therapeutic strategies for KD include surgery, oral steroids, immunosuppressive drugs, and radiation therapy, which have limitations due to high recurrence rates and side effects. Currently, there are no established standardised treatment guidelines for KD.

Dupilumab is a human monoclonal antibody that targets and binds to interleukin 4 (IL-4) and IL-13 receptors and subsequently blocks the inflammatory process induced by type 2 helper T (Th2) cells. Dupilumab has shown robust clinical efficacy across multiple diseases with underlying type 2 signatures, such as atopic dermatitis (AD), prurigo nodularis, and bullous pemphigoid. We report a case of a patient with bilateral earlobe KD treated with dupilumab and analyse the pathological changes before and after treatment.

A 36-year-old woman presented with gradually increasing, painless red nodules on both earlobes since 2 years. Physical examination revealed non-tender, smooth, red nodules without lymph node involvement. The nodule on the left earlobe measured 1.5 cm x 1.8 cm, while the nodule on the right earlobe measured 2 cm x 2.3 cm [Figures 1a and b]. Biopsy showed multiple lymphoid follicles with dense lymphocytic infiltration (CD3⁺, CD20⁺, CD5⁺, PAX-5⁺) and some eosinophils and plasma cells [Figures 2a and 2b]. Laboratory findings showed elevated serum IgE (572.24 IU/mL). Flow cytometry revealed elevated cytokine production: 25.55% of Th1 cells expressed IFN-γ, 65.53% expressed IL-2, and 3.16% of Th2 cells expressed IL-4. Eosinophil counts were normal. The patient also had itchy erythematous papules on the trunk and limbs since 2 years. She had been treated with topical corticosteroids and oral antihistamines for 6 months but showed insignificant improvement. She was diagnosed with KD and moderate AD.

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Figure 1a-b:

Single, smooth-surfaced, red nodule on both earlobes before treatment.

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Figure 2a-b:

The pathological photo before treatment shows numerous lymphoid follicles of varying sizes in the dermis with extensive infiltration of eosinophils and plasma cells. (Haematoxylin & eosin, 40x and 400x).

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Dupilumab was administered to the patient at an initial dose of 600 mg, followed by 300 mg every 2 weeks for 4 months. By the second week, the nodules began shrinking, and by 4 months, both the AD rash and earlobe nodules significantly improved [Figures 3a and 3b], with IgE levels decreasing to 157 IU/mL. Excision of the remaining nodule on the right side was performed to get a better result. The postoperative biopsy showed dermal vessel proliferation, accompanied by reduced lymphoid follicles and eosinophils [Figures 4a and 4b]. We have since followed up with the patient for 6 months. There has been no recurrence of the earlobe masses or AD in the patient so far.

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Figure 3a-b:

The nodules significantly shrank after 4 months of dupilumab treatment.

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Figure 4a-b:

Lymphocyte and eosinophil infiltration were markedly reduced after 4 months of dupilumab treatment. (Haematoxylin & eosin, 40x and 400x).

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The pathogenesis of KD is still unknown. Allergic reactions, infections, and autoimmune responses, involving an aberrant immune reaction, have been proposed to be associated with KD. The characteristics of KD include elevated serum IgE levels and increased peripheral blood eosinophils, which are typical manifestations of a Th2 cell immune response. Studies have shown that peripheral blood mononuclear cells in KD patients exhibit increased CD4(+) T-cells and Th2 cytokines, including IL-3, IL-4, IL-5, IL-13, and granulocyte-macrophage colony-stimulating factor.¹ Additionally, type 2 immune cells, such as CD4⁺ GATA3⁺ T-cells, IL-4⁺ IgE⁺ c-kit⁺ mast cells, and IL-13⁺ T follicular (Tfh) cells, prominently infiltrate affected lesions.² Notably, approximately 40% of KD patients have a history of diffuse pruritus or atopic diathesis, and 58% are diagnosed with AD or lichen simplex chronicus.³

Given that type 2 inflammation may contribute to KD pathogenesis, dupilumab could represent a promising treatment option. Indeed, recent research has demonstrated dupilumab’s effectiveness in KD patients.⁴ However, the precise immunological mechanism by which dupilumab acts in KD remains unclear.

In this case, earlobe lesions reduced significantly with a remarkable decrease in the eosinophilic infiltration in affected tissues after dupilumab treatment. We speculate that IL-4 and IL-13 blockade prevented eosinophil infiltration into the skin. Previous studies indicate that dupilumab suppresses Th2 cell activity and reduces IL-9 expression, alleviating KD symptoms.⁵ These findings highlight the role of type 2 inflammation in KD pathogenesis and the potential involvement of IL-9 downregulation in symptom improvement.

In summary, we present a typical KD patient treated with dupilumab, showing significant efficacy accompanied by a reduction in tissue eosinophils. Further research with larger sample sizes and long-term follow-up is necessary to confirm these findings and explore the underlying mechanisms.