\receivedDD MMMM YYYY \acceptedDD MMMM YYYYAllergic Contact Dermatitis Induced by Pure Titanium Implants: A Case ReportAiliang Huang1, Xiaomei Luo1+, Huiqiu Luo1, Huahui Jian1*1 Department of Dermatology, Baise People’s Hospital, Affiliated Southwest Hospital of Youjiang Medical University for Nationalities, Guangxi, China*Corresponding author+These authors contributed equally to this workCorrespondence: Department of Dermatology, Baise People’s Hospital, Affiliated Southwest Hospital of Youjiang Medical University for Nationalities, Guangxi, 53000, ChinaEmail: janehuah@163.comWord count: 639; Total number of figures and tables:1Key Clinical MessageDupilumab has not been previously reported for treating allergic contact dermatitis induced by pure titanium implants. Betamethasone and antihistamines only provided temporary relief. Given the side effects of long-term glucocorticoid use, the treatment plan was adjusted to Dupilumab. Dupilumab resolved symptoms within a week, with no recurrence after three biweekly treatments.KEYCORDS: allergic contact, dermatitis, dupilumab, titanium, case report1 INTRODUCTIONTitanium (Ti) and its alloys are extensively utilized in orthopedic implantation, including joint replacements, due to their superior biocompatibility and favorable strength-to-density ratio(1). To our knowledge, dupilumab has not been previously reported for the treatment of allergic contact dermatitis induced by pure titanium implants.2 CASE HISTORY / EXAMINATIONA 35-year-old male with a history of pure Ti implant surgery for a fracture presented with delayed hypersensitivity. Two weeks postoperatively, the surgical site had healed, and sutures were removed. However, 1.5 months later, erythemas, papule, erosions, exudate, and pruritus developed at the incision site on the right lower leg. Despite a two-week course of oral cefuroxime axetil and topical antibiotics, the rash persisted. No history of similar illnesses, drug or food allergies, and similar family history was reported.On physical examination, vital signs were within normal limits. Diffuse dusky erythema with multiple superficial erosions and erythematous papules, serous exudate, and honey-colored crusts on the skin surface above the implant in the right lower leg;The lesions were localized to the site of the pure titanium implant used in the surgical treatment of the fracture ((Figure 1 a-c).3 DIFFERENTIAL DIAGNOSIS, INVESTIGATIONS, TREATMENTThe differential diagnoses of this clinical presentation include cutaneous infection and disinfectant allergy. The outpatient physician initially suspected a cutaneous infection and prescribed oral antibiotics along with topical antibiotic therapy. However, the skin condition on the patient’s right lower leg did not improve. Subsequent evaluations, including complete blood count, high-sensitivity C-reactive protein, and bacterial culture and identification of skin exudates, revealed no abnormalities, thus failing to support the diagnosis of cutaneous infection. The possibility of disinfectant allergy was also excluded, as the patient’s surgical sutures had been removed, and the use of disinfectants had been discontinued for more than two weeks prior to the onset of the rash.The final diagnosis was allergic contact dermatitis attributed to a pure titanium implant. This conclusion was based on the patient’s development of a rash (erythema, papules, and erosions) 1.5 months after the implantation of a pure titanium device, the rash was localized to the area above the implant, with well-defined margins, and other potential causes such as skin infection and other allergens were ruled out. Given the diagnosis of allergic contact dermatitis, initial treatment with betamethasone and antihistamines provided temporary relief. However, symptoms recurred within five days of discontinuing the medications. Subsequently, the treatment was switched to dupilumab. Within two days of dupilumab treatment, exudation ceased and erythema decreased. By one week post-treatment, the majority of the rash had resolved, and pruritus was significantly alleviated. Dupilumab was continued at biweekly intervals, and after three treatments, the rash and pruritus completely resolved without recurrence (Figure 1 d-f).4 DISCUSSIONNo definitive diagnostic tests for Ti hypersensitivity exist, the diagnosis in this case was largely informed by the 10-point criteria for suspecting metal hypersensitivity from orthopedic implants, which were established in 2011 and include: (i) chronic dermatitis beginning weeks to months after metallic implantation; (ii) an eruption overlying the metal implant; (iii) a morphology consistent with dermatitis (erythema, induration, papules, and vesicles)(1); additionally, the patient exhibited a positive response to corticosteroid-based antiallergic therapy, whereas antimicrobial monotherapy proved ineffective, which is consistent with an allergic diagnosis. But the chronic use of corticosteroids carries potential side effects, such as heightened susceptibility to infections and compromised healing of skin wounds and fractures. Abrocitinib, as indicated in the prescribing information, is associated with an increased risk of thrombosis, given the patient’s history of lower limb fracture surgery, is also at an elevated risk for thrombotic events. Dupilumab was chosen as the treatment of choice. Dupilumab does not impact bone growth and has the added benefit of potentially reducing the frequency of skin infections and the necessity for antibiotic therapy(2, 3). Dupilumab may emerge as a promising alternative for the treatment of treatment-resistant contact dermatitis triggered by implants.AUTHOR CONTRIBUTIONSAiliang Huang: conceptualization, investigation, methodology, resources, writing-original draft, writing-review and editing. Xiaomei Luo: conceptualization, investigation, methodology, resources, writing-original draft. Huiqiu Luo: conceptualization, investigation, methodology, resources. Huahui Jian: conceptualization, methodology, resources, writing-original draft, writing-review and editing.ACKNOWLEDGMENTSThe authors have nothing to report.FUNDING INFORMATIONNo funding source for this work.CONFLICT OF INTEREST STATEMENTThe authors report no conflicts of interest.DATA AVAILABILITY STATEMENTAll necessary data are available in the article itself.ETHICS STATEMENTNo ethical approval is necessary.CONSENTWritten informed consent was obtained from the patient to publish this case report and accompanying images.ORCID:Ailiang Huang: https://orcid.org/0009-0000-4767-6380Huahui Jian: https://orcid.org/0009-0009-4109-9725Xiaomei Luo: https://orcid.org/0009-0005-5378-7059Huiqiu Luo: https://orcid.org/0009-0009-4656-5190References: 1 Fage S W, Muris J, Jakobsen S S, Thyssen J P. Titanium: a review on exposure, release, penetration, allergy, epidemiology, and clinical reactivity. CONTACT DERMATITIS 2016:74 : 323-45.2 Yang N, Ye Y, Shao J, Wu H, Xu Q, Zhu J, Liu J, Li Z. Efficacy of Dupilumab in Children 6 Months to 11 Years Old With Atopic Dermatitis: A Retrospective Real-World Study in China.DERMATITIS 2024: 35 : S39-S46.3 Tsai S Y, Phipatanakul W, Hawryluk E B, Oyoshi M K, Schneider L C, Ma K S. Comparative safety of oral Janus kinase inhibitors versus dupilumab in patients with atopic dermatitis: A population-based cohort study. J Allergy Clin Immunol 2024: 154 : 1195-1203.e3.