From Shore to Sequelae: Delayed Hypersensitivity Reaction and Secondary Infection Following Stingray Envenomation –– A Case Report

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Onyango This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9460508/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Introduction: Stingray envenomation is a relatively common occurrence among water sports enthusiasts, including swimmers, scuba divers, and surfers, as well as fishermen. However, there is a lack of medical literature on the pathophysiology of immediate and delayed hypersensitivity reactions, and more importantly, on the range of infectious bacterial and mycobacterial infections that can result from these envenomation injuries. This paper aims to provide a general overview of the mechanisms, diagnostic challenges, and management of late hypersensitivity reactions and infections that can occur following stingray stings. Case Report: A 63-year-old man with well-controlled hyperlipidemia presented to the Mayo Clinic with a one-week-old injury from accidentally stepping on a stingray barb while walking on a beach in Ventura, California. Immediate pain was relieved with immersion in warm water. He did not take any over-the-counter or prescription medications, and over the following days, he returned to his usual activities of cycling, running, and swimming with minimal discomfort. There was no initial redness or swelling at the puncture site, but he reported intermittent sharp, localized pain with movement leading up to his hospital visit. A biopsy was performed due to concern for a developing necrotic infection, and he was diagnosed with a hypersensitivity reaction. He was initially treated with IV antibiotics, and steroids were added based on biopsy results. After completing his treatment course, his hypersensitivity reaction fully resolved over several weeks. Conclusion: This case underscores the importance of considering both immediate and delayed hypersensitivity reactions that can result from stingray envenomation. These reactions can be managed with conservative measures, such as warming the affected area in a water bath to denature heat-labile venom, as well as with conventional therapies, including topical or systemic antihistamines and steroids. It also highlights the need for early empiric antibiotic coverage and outlines the infectious agents implicated in early- and late-onset infections following stingray envenomation, including Pseudomonas aeruginosa, Vibrio vulnificus , and Mycobacterium fortuitum . Additionally, it emphasizes the need for tetanus vaccine updates, radiography, and a multidisciplinary approach to treating stingray injuries. Stingray Envenomation Vibrio vulnificus Marine Injury Case Report Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Stingray envenomation is a distinct clinical condition marked by both mechanical injury and venom-induced toxicity. Although most cases are acute and resolve spontaneously, this case highlights an often-overlooked aspect of stingray injuries—specifically, the development of delayed hypersensitivity reactions and possible infectious complications. The patient described in this report initially presented with typical symptoms, including severe pain immediately after envenomation that responded well to warm water immersion, a well-established first-line treatment because it denatures heat-sensitive venom proteins. [FIGURE 1 ] Prospective observational data show significant pain relief with this method and low complication rates when managed properly. Notably, his early clinical course was benign, with minimal local inflammation and a rapid return to baseline activity, consistent with previous reports of uncomplicated stingray injuries. However, our case differs from the typical pattern in that symptoms appeared relatively late, about a week after injury, [FIGURE 2 ] and included intermittent sharp pain and evolving local tissue changes. The absence of early erythema or swelling, followed by delayed progression, poses a diagnostic challenge that has been increasingly recognized in the recent literature. Delayed symptoms may raise concerns about a retained foreign body, developing infection, or immune-mediated reactions, all of which must be carefully distinguished. In this case, biopsy results indicated a hypersensitivity reaction rather than a necrotizing infection. This distinction is clinically important because delayed hypersensitivity to venom components is poorly understood yet can mimic infectious processes both clinically and histologically. The initial decision to start empiric intravenous antibiotics was appropriate given the known risk of marine-associated infections. However, adding corticosteroids after the biopsy confirmed the diagnosis was crucial for treating the immune-mediated process and led to complete resolution. The risk of infection after a stingray injury remains an important consideration. Marine environments expose wounds to various pathogens, including Vibrio vulnificus , Pseudomonas aeruginosa , and atypical organisms such as Mycobacterium fortuitum . Case reports show that infections can develop days after the initial injury, sometimes despite initially mild symptoms. Although this patient did not ultimately show signs of infection, the clinical similarities between infection and hypersensitivity underscore the need for early empiric antibiotic treatment in certain cases, especially when presentation is delayed or clinical signs are unclear. [FIGURE 3 ] Another important aspect of stingray injuries is the risk of retained barbed fragments, which can cause ongoing inflammation, delayed healing, or secondary infection. Recent case reports indicate that embedded spines may lead to prolonged symptoms and may require surgical removal if not detected early. Although this was not identified as a factor in this case, the patient’s intermittent sharp pain before presentation demonstrates how such symptoms can prompt further investigation, including imaging or surgical exploration when indicated. This case also underscores the importance of a multidisciplinary management approach, including clinical evaluation, imaging as needed, histopathologic assessment, and personalized pharmacologic treatment. In addition to immediate management strategies such as hot water immersion, clinicians should remain vigilant for delayed complications that may require interventions such as corticosteroids or prolonged antimicrobial therapy. Preventive measures, including tetanus vaccination, should be part of comprehensive care. Overall, this case contributes to the limited but growing body of literature on delayed hypersensitivity reactions following stingray envenomation. It underscores the need for heightened clinical awareness of unusual presentations and reinforces the importance of distinguishing between infectious and immune-mediated processes. Recognizing these delayed reactions is crucial to prevent misdiagnosis and to guide appropriate, targeted treatment. [FIGURE 4 ] Patient Information A 63-year-old man with well-controlled hyperlipidemia presented for evaluation of a stingray injury sustained one week earlier while walking on a beach in Ventura, California. The patient reported accidentally stepping on a stingray, which resulted in a puncture wound to the lower extremity. Timeline of Current Episode Immediately after the injury, he experienced intense pain that was relieved by warm water immersion, providing quick symptom relief. He did not take any over-the-counter or prescription medications. In the days that followed, he resumed his usual activities, including cycling, running, and swimming, with minimal discomfort. Notably, the patient did not exhibit early signs of redness, swelling, or infection. However, in the days before presentation, he reported intermittent, sharp, localized pain, which raised concern for a retained foreign body or a developing infection. The patient was an otherwise healthy male with no prior medical conditions except for well-controlled hyperlipidemia. He had no history of surgery. He had no infectious or allergic history and no relevant family history. He worked as a traveling medical salesperson, visiting different parts of the country, with a specific focus on the Southwest. Clinical Presentation Upon presentation, he was afebrile, with a pulse in the 60s, blood pressure in the 120s systolic and 80s diastolic, and a respiratory rate and peripheral oxygen saturation within normal limits. Examination revealed mild erythema over the right medial malleolar region, ballotable, nonpitting edema, and minimal tenderness to palpation; a punctate area with a dark scab was also noted. Laboratory testing showed no leukocytosis or peripheral eosinophilia. His initial C-reactive protein was less than 0.3 mg/dL, but it rose to 38 mg/dL over subsequent days, peaking and correlating with worsening appearance and tenderness at the envenomation site. Diagnostic Assessment Given the delayed presentation and concern for necrotizing infection, a punch biopsy was performed. Histopathologic evaluation showed epidermal hyperplasia with spongiosis and papillary dermal edema. A moderately dense, predominantly perivascular inflammatory infiltrate extended from the superficial to the deep dermis and was composed mainly of lymphocytes, with scattered neutrophils and abundant eosinophils. The punch biopsy reached the deep dermis and was transected. Special stains, including acid-fast bacilli (AFB), modified acid-fast (FITE), Gomori Methenamine Silver (GMS), and periodic acid–Schiff with diastase (PAS-D), were negative for microorganisms. Diagnosis These findings are most consistent with a hypersensitivity reaction to stingray envenomation rather than an infectious process. Other alternative diagnoses included cellulitis, necrotizing fasciitis, erysipelas, and ecthyma gangrenosum. Therapeutic Intervention The patient was initially managed empirically with oral antibiotics after consultation with Infectious Diseases. He was treated with Doxycycline 100 mg once daily, Levofloxacin 750 mg once daily, and Linezolid 600 mg twice daily. After biopsy confirmation, systemic corticosteroids were initiated with a single intravenous dose of 125 mg, resulting in gradual symptom resolution. He was treated with a prednisone taper of 60 mg once daily for 3 days, followed by 40 mg for 3 days and then 20 mg for 3 days. His antibiotics were eventually stopped after 5 days, as they had not improved his symptoms. Follow Up and Outcomes The patient reported that he had completed the prescribed course and fully recovered over several weeks. Regrettably, due to immobility from difficulty walking after the injury, the patient was assessed in clinic, and a Doppler ultrasound was ordered. This revealed that he had developed a deep venous thrombus three weeks after discharge, and he was placed on a direct oral anticoagulant for several months. Discussion Stingray injuries involve a combination of penetrating trauma and envenomation, with potential for both infectious and noninfectious complications. [ 1 ] This case highlights an uncommon but clinically significant presentation: a delayed hypersensitivity reaction that mimics a soft-tissue infection. [ 1 , 2 ] The patient’s initially benign course, followed by delayed symptom onset, raised concern for infection, a well-documented complication of marine injuries. Common pathogens include Vibrio vulnificus , Pseudomonas aeruginosa , and Aeromonas species, which can cause severe soft tissue infections and, in some cases, necrotizing fasciitis. [ 3 , 4 , 5 ] Water-associated skin and soft tissue infections may involve a diverse range of pathogens beyond the more commonly recognized marine organisms. Among these, Edwardsiella tarda , Erysipelothrix rhusiopathiae , Clostridium tetani , and fungal pathogens such as Aspergillus and Rhizopus species are less common but clinically important causes of infection following aquatic exposure. [ 3 , 4 , 5 , 6 , 7 , 8 , 9 ] Given these risks, the initial use of broad-spectrum empiric antibiotics, including levofloxacin, doxycycline, and linezolid, was appropriate to cover marine Gram-negative organisms and resistant Gram-positive pathogens. However, this case underscores the importance of reassessing therapy as diagnostic data become available [ 7 , 8 , 9 ]. Histopathologic findings showing a lymphocyte-predominant infiltrate with numerous eosinophils, in the absence of detectable microorganisms, strongly suggest a hypersensitivity reaction rather than an infection. The presence of eosinophils, especially, indicates an immune response to venom components. After ruling out an infectious cause, we de-escalated his antibiotic regimen and initiated corticosteroid therapy, resulting in rapid clinical improvement. The patient’s positive response to a structured prednisone taper further supports the diagnosis of a delayed hypersensitivity reaction. This case also highlights the diagnostic overlap between infection and immune-mediated reactions in marine injuries. Delayed infections, including those caused by non-tuberculous mycobacteria such as Mycobacterium fortuitum [ 8 , 9 ], can develop weeks after injury and require prolonged antimicrobial treatment. Differentiating these conditions is essential because management strategies vary significantly. Additionally, the possibility of retained foreign material should always be considered in patients with ongoing or delayed symptoms, as retained barbs can lead to infection and chronic inflammation [ 9 , 10 , 11 ]. Overall, this case underscores the importance of a multidisciplinary, evidence-based approach that integrates clinical findings, microbiology, and histopathology to guide appropriate management. Skin and soft tissue infections (SSTIs) following stingray envenomation are complex, involving mechanical injury, venom-induced tissue damage, and the introduction of marine pathogens. Stingray injuries usually occur when the animal’s serrated barbs pierce the skin, injecting venom and marine microorganisms into deep tissues. While the immediate toxic effects are well understood, infectious complications are increasingly recognized as a significant cause of illness. Stingray injuries are common in tropical and subtropical coastal areas, especially among swimmers, surfers, and fishermen. Most injuries involve the lower limbs and result from accidental contact in shallow water. The risk of infection depends on environmental exposure and host factors. Marine environments, particularly warm coastal waters, harbor high levels of harmful organisms, including Vibrio species. [ 4 ] Patients with chronic liver disease, diabetes, or immunosuppression are at higher risk of severe infection, particularly from Vibrio vulnificus , which has a high mortality rate. Additionally, the puncture nature of stingray wounds, often with retained foreign material, creates a favorable environment for bacterial growth and impairs wound healing. [ 4 , 5 ] The microbiology of stingray-related infections is diverse and often involves multiple microbial species. A recent case series and literature review identified a wide range of pathogens and found no standard antibiotic treatment, underscoring the complexity of these infections. The most clinically significant organisms include Vibrio vulnificus , Vibrio alginolyticus , Pseudomonas aeruginosa , and Aeromonas species. [ 12 , 13 ] Vibrio vulnificus is highly virulent and can cause rapidly progressive soft tissue infections, sepsis, and necrotizing fasciitis. Infections may result from minor injuries and can worsen within hours, especially in high-risk individuals. Recent case reports also highlight Vibrio alginolyticus as an important pathogen in stingray-related infections, capable of causing serious wound infections and vascular problems. Aeromonas species, more commonly associated with freshwater exposure, have also been implicated in marine injuries and can cause necrotizing infections with high mortality if left untreated. [ 10 , 11 , 12 , 13 , 14 , 15 ] Delayed or chronic infections after stingray injuries may involve non-tuberculous mycobacteria, particularly Mycobacterium fortuitum . These infections often emerge weeks later and may present as persistent nodules or non-healing ulcers. [ 11 ] Edwardsiella tarda is a Gram-negative bacillus commonly found in freshwater and brackish water. It has been linked to traumatic wound infections following aquatic injuries and can cause cellulitis, abscesses, or, in severe cases, systemic infection. These infections are more common in immunocompromised individuals and typically require targeted antimicrobial therapy. [ 10 ] Erysipelothrix rhusiopathiae is a Gram-positive bacterium found in both marine and freshwater settings and is frequently associated with occupational exposure among fishermen and marine workers. The skin infection, erysipeloid, presents as a localized violaceous lesion with well-defined borders. Although often self-limited, systemic complications such as endocarditis have been reported in rare cases. [ 9 ] Clostridium tetani , an anaerobic, spore-forming bacterium found in soil and aquatic environments, remains a significant concern in water-exposed puncture wounds. The organism can grow in necrotic tissue and produce tetanospasmin, leading to tetanus, a potentially life-threatening neurological condition. This underscores the importance of tetanus prophylaxis for most water-exposed wounds. Fungal pathogens, including Aspergillus and Rhizopus species, are uncommon but serious causes of soft-tissue infections after water exposure, especially in immunocompromised individuals or after traumatic implantation. These organisms can cause invasive infections characterized by tissue necrosis and angioinvasion, often mimicking bacterial necrotizing infections. Early detection and prompt treatment, including surgical debridement and antifungal therapy, are critical for favorable outcomes. Overall, these less common pathogens underscore the need for a broad differential diagnosis in water-related soft-tissue infections, particularly in atypical or non-resolving cases. Case reports also show that unusual mechanisms, such as secondary contamination or improper wound care, can introduce atypical organisms, including oral flora, further complicating the infectious profile. [ 16 , 17 ] The pathogenesis of infection after a stingray injury involves a combination of direct bacterial inoculation, venom-induced tissue damage, and the host's immune response. The serrated barb can embed bacteria deep within soft tissues, while venom components cause local necrosis, vasoconstriction, and reduced immune function, facilitating bacterial multiplication. Retained foreign bodies, such as fragments of the stingray spine, can serve as sites of ongoing infection, which may cause chronic inflammation and slow healing. [ 18 , 19 , 20 ] Clinical signs of infection after a stingray injury range from localized cellulitis to life-threatening necrotizing fasciitis. Early infections typically present with localized erythema, swelling, pain, and/or purulent discharge. In contrast, infections caused by aggressive organisms such as Vibrio vulnificus may present with hemorrhagic bullae, severe pain disproportionate to the examination findings, and rapid progression to systemic toxicity. Delayed infections may appear weeks after exposure, especially with atypical organisms, and can mimic inflammatory or hypersensitivity conditions. [ 4 , 8 , 14 ] Diagnosis requires a high index of suspicion, particularly in patients with a history of marine exposure. Key elements include a detailed exposure history, a physical examination for signs of deep or necrotizing infection, imaging to detect retained foreign bodies, and microbiologic cultures to guide treatment. Early detection of necrotizing infection is crucial, as delays are associated with increased morbidity and mortality. Management of stingray-related infections is multimodal and includes wound care, antimicrobial therapy, and surgical intervention when necessary. Initial treatment includes thorough wound irrigation and debridement, hot-water immersion to denature venom, and tetanus prophylaxis. [ 18 , 19 , 20 , 21 , 22 ] Empiric antibiotic therapy should target marine Gram-negative organisms, particularly Vibrio species. Current evidence supports the use of doxycycline, fluoroquinolones, or trimethoprim-sulfamethoxazole. Severe infections, including necrotizing fasciitis, require prompt surgical debridement and intensive supportive care. Chronic infections may require prolonged antimicrobial therapy and specialist consultation. Recent research highlights antimicrobial resistance among marine pathogens as an increasing concern, complicating empiric treatment strategies. Additionally, climate change and rising sea temperatures are expanding the geographic range of Vibrio species, resulting in more marine-related infections. [ 21 , 22 , 23 , 24 ] This case report presents a rare and instructive case of delayed hypersensitivity following stingray envenomation, highlighting the important diagnostic challenge of distinguishing immune-mediated reactions from soft-tissue infections. It also situates the case within a broad and relevant literature review covering marine pathogens, retained foreign bodies, empiric antimicrobial strategies, and evolving environmental factors, including the expanding range of Vibrio species. However, the paper has limitations inherent to a single-patient case report, including limited generalizability and an inability to establish causation or estimate the incidence of delayed hypersensitivity reactions after stingray injury. Despite these limitations, the report provides meaningful clinical insight into an area with a relatively sparse literature. Conclusion Stingray envenomation can cause both infectious and delayed hypersensitivity complications, which may present with similar clinical signs. This case underscores the importance of distinguishing between these conditions to ensure appropriate treatment. While empiric antibiotics are often necessary in delayed presentations, histopathologic evaluation is essential when the diagnosis remains unclear. Early identification of hypersensitivity reactions and treatment with corticosteroids can lead to excellent outcomes. Soft tissue infections after stingray injuries involve a complex interplay of environmental exposure, host susceptibility, and microbiologic factors. Clinicians should remain vigilant for both early and delayed infections, especially in patients with atypical symptoms. Prompt diagnosis, appropriate antimicrobial treatment, and timely surgical intervention are crucial for better outcomes. Ongoing research and case reporting are needed to refine management strategies in this evolving area. Patient Perspective: This episode was eye-opening for me as a patient because it showed how an injury that began with a simple sting and initially appeared to be healing evolved into a suspected delayed infection that did not improve with antibiotics. After the biopsy, it was reclassified as a delayed hypersensitivity reaction, which then responded to steroids. It also highlighted the need for coordination of care among infectious diseases, dermatology, and hospital medicine. Declarations Informed Consent: Written informed consent for publication was obtained from the patient, and a copy of the written consent is available for review by the Editor-in-Chief of the Journal of Case Reports upon request. Ethics Approval and Consent to Participate: Informed consent was obtained from the patient and the family throughout the research and writing process of this paper; all patient data was de-identified, and reasonable measures were taken to ensure that patient information was decoded and anonymized. Consent for Publication: Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the consent is available for review by the Editor-in-Chief of this journal. Competing interests: The author declares no competing interests. Author’s Information: Nelson O. Onyango, M.D Mayo Clinic, Department of Medicine, Division of Hospital Internal Medicine, 5881 E. Mayo Blvd. Phoenix, AZ 85054 United States of America Phone: 480-301-8484 Email: [email protected] Funding: Not applicable as the author did not receive any funding for this project. Author Contribution N.O. attended to the patient, devised a treatment plan, including the initiation of antibiotics, a biopsy, and steroids; N.O. analyzed the laboratory data, wrote and reviewed the manuscript. Acknowledgement The author wishes to acknowledge the patient, GB, whose generosity of consent, time, and images has advanced learning; without him, this project would not be possible. Availability of Supporting Data: The data supporting the findings of this study are available on request from the corresponding author, [NO]. The data are not publicly available due to restrictions on private information that could compromise the patient's privacy. References Evans RJ, Davies RS. Stingray injury. Journal of Accident and Emergency Medicine. 1996;13(3):224–225. Clark RF, Girard RH, Rao D, Ly BT, Davis DP. Stingray envenomation. Journal of Emergency Medicine. 2007;33(1):33–37. Diaz JH. Stingray injuries in travelers. Journal of Travel Medicine. 2008;15(2):102–109. Baker-Austin C, Oliver JD, Alam M, et al. Vibrio spp. infections. Nature Reviews Microbiology. 2018;16(4):223–233. Horseman MA, Surani S. Vibrio vulnificus infection: diagnosis and treatment. Journal of Infection and Public Health. 2011;4(1):1–6. Mora-Zamacona P, Águila-Ramírez RN, Muñoz-Ochoa M, et al. Stingray envenomation with retained spine: a case report. Cureus. 2023;15:e38885. Haddad V Jr, Neto DG, de Paula Neto JB. Freshwater stingrays: epidemiologic and clinical aspects. Clinical Infectious Diseases. 2004;38(1):e1-e6. Stevens DL, Bryant AE. Necrotizing soft-tissue infections. New England Journal of Medicine. 2017;377(23):2253–2265. Brooke CJ, Riley TV. Erysipelothrix rhusiopathiae : bacteriology and clinical manifestations. Clinical Microbiology Reviews. 1999;12(3):354–359. Janda JM, Abbott SL. Infections associated with Edwardsiella tarda . Clinical Infectious Diseases. 1993;17(4):742–748. Johnson MG, Stout JE. Twenty-eight cases of Mycobacterium fortuitum infection. Clinical Infectious Diseases. 2015;60(10):e60-e66. Cevik J, Hunter-Smith DJ, Rozen WM. Stingray envenomation and associated infections: a review. Travel Medicine and Infectious Disease. 2022; 47:102312. Hønge BL, Patsche CB, Jensen MM, et al. Iatrogenic infection following stingray injury: a case report. American Journal of Tropical Medicine and Hygiene. 2018;98(3):929–932. Carroll A, Chowdhury M, Zheng C. Vibrio alginolyticus infection following stingray injury: a case report. American Journal of Tropical Medicine and Hygiene. 2024 Ng BW, Ong KC, Ahmad-Azraf A, et al. Aeromonas necrotizing soft tissue infection: a case report. Medical Journal of Malaysia. 2019;74(5) Auerbach PS. Wilderness Medicine . 6th ed. Elsevier; 2012. Skiada A, Lass-Floerl C, Klimko N, et al. Challenges in the diagnosis and treatment of mucormycosis. Lancet Infectious Diseases . 2018;18(12): e396-e404. Fenner PJ. Marine envenomation: an update. Emergency Medicine Australasia. 2002;14(4):423–429. Burnett JW, Calton GJ, Morgan RJ. Venomous marine animals. Clinical Dermatology. 1987;5(3):103–118. Halstead BW. Poisonous and Venomous Marine Animals . United States Government Printing Office; 1988. Isbister GK, Kiernan MC. Neurotoxic marine envenomation. Lancet Neurology. 2005;4(4):219–228. de Oliveira JS, Haddad V Jr. Stingray injuries: a review. Revista da Sociedade Brasileira de Medicina Tropical. 2013;46(4):435–439. Baker-Austin C, Trinanes J. Climate change and Vibrio infections. Science of the Total Environment. 2019; 653:131–140. Yen LM, Thwaites CL. Tetanus. Lancet. 2019;393(10181):1657–1668. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9460508","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":636718092,"identity":"efa469f5-a7d7-464a-9d5a-6199302f9f04","order_by":0,"name":"Nelson O. Onyango","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABDklEQVRIiWNgGAWjYBACfhjD4ABzA5CygXLZcGuRbIAyLA4wgphphLUYHIAybCBaDhOh5XaP4eeCXzYMNscbmz983HE+mn9G8gGGD2WHcWu5c8ZYemZfGoPZmYNtkjPP3M6dcSMtgXHGOTxabuQYSPP2HGYwu5HYxszbdju3ASgCZODVYvwbpMX4/sPmz7xt53Lng7T8xa/FTJrnx2EGwxuMDdK8bQdyN4C0MOLRIjkjrcyatyGNx/BMItAvbcm5G888SzjYcy4dpxZ+ieTNt3n+2MgZHD98+MPHNrvceceTDz74UWaNUwsDA4cBA2MbAw9CQCCB4QAe9UDA/oCB4Q+KxQQ0jIJRMApGwYgDABpKY6fcZAwAAAAAAElFTkSuQmCC","orcid":"","institution":"Mayo Clinic","correspondingAuthor":true,"prefix":"","firstName":"Nelson","middleName":"O.","lastName":"Onyango","suffix":""}],"badges":[],"createdAt":"2026-04-19 08:38:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9460508/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9460508/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":109119352,"identity":"0c6041bc-fe99-4080-af28-1a7aa1c0200c","added_by":"auto","created_at":"2026-05-12 16:57:17","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":606435,"visible":true,"origin":"","legend":"\u003cp\u003eDay of injury\u003c/p\u003e","description":"","filename":"image1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-9460508/v1/852a92155b914b962377bf80.jpeg"},{"id":109119353,"identity":"fa8691e5-ee27-4537-aa36-a4238400128d","added_by":"auto","created_at":"2026-05-12 16:57:18","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":683504,"visible":true,"origin":"","legend":"\u003cp\u003eDay of presentation to the hospital, 7 days post injury\u003c/p\u003e","description":"","filename":"image2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-9460508/v1/47d8bc6e68b8f325e65ab425.jpeg"},{"id":109119354,"identity":"8255c165-c0aa-474b-b255-dcdba8bfd93b","added_by":"auto","created_at":"2026-05-12 16:57:18","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":442357,"visible":true,"origin":"","legend":"\u003cp\u003eDay after presentation to the hospital, post biopsy, 8 days post injury\u003c/p\u003e","description":"","filename":"image3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-9460508/v1/24ec59f98dd95e1113f0f2f3.jpeg"},{"id":109119355,"identity":"57c0ca89-1b84-4319-b6a1-c4ed8a76d164","added_by":"auto","created_at":"2026-05-12 16:57:18","extension":"jpeg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":541427,"visible":true,"origin":"","legend":"\u003cp\u003e2 weeks post-discharge, about 22 days post injury\u003c/p\u003e","description":"","filename":"image4.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-9460508/v1/b6ca7675f02555b8bcc06ad5.jpeg"},{"id":109204767,"identity":"3c68eef2-4db1-4d2f-ade3-4797bbaa0ccb","added_by":"auto","created_at":"2026-05-13 15:02:04","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2458185,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9460508/v1/71dbd079-8471-4f01-a3e8-21fde552d22d.pdf"},{"id":109119351,"identity":"d747e478-c0c9-4d6a-98b1-a4e146e829fe","added_by":"auto","created_at":"2026-05-12 16:57:17","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":2001003,"visible":true,"origin":"","legend":"","description":"","filename":"CAREchecklistEnglish2013.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9460508/v1/4d42fdaea23c0fb48ceca1fa.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"From Shore to Sequelae: Delayed Hypersensitivity Reaction and Secondary Infection Following Stingray Envenomation –– A Case Report","fulltext":[{"header":"Introduction","content":"\u003cp\u003eStingray envenomation is a distinct clinical condition marked by both mechanical injury and venom-induced toxicity. Although most cases are acute and resolve spontaneously, this case highlights an often-overlooked aspect of stingray injuries\u0026mdash;specifically, the development of delayed hypersensitivity reactions and possible infectious complications. The patient described in this report initially presented with typical symptoms, including severe pain immediately after envenomation that responded well to warm water immersion, a well-established first-line treatment because it denatures heat-sensitive venom proteins. [FIGURE \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e] Prospective observational data show significant pain relief with this method and low complication rates when managed properly. Notably, his early clinical course was benign, with minimal local inflammation and a rapid return to baseline activity, consistent with previous reports of uncomplicated stingray injuries. However, our case differs from the typical pattern in that symptoms appeared relatively late, about a week after injury, [FIGURE \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e] and included intermittent sharp pain and evolving local tissue changes. The absence of early erythema or swelling, followed by delayed progression, poses a diagnostic challenge that has been increasingly recognized in the recent literature. Delayed symptoms may raise concerns about a retained foreign body, developing infection, or immune-mediated reactions, all of which must be carefully distinguished. In this case, biopsy results indicated a hypersensitivity reaction rather than a necrotizing infection. This distinction is clinically important because delayed hypersensitivity to venom components is poorly understood yet can mimic infectious processes both clinically and histologically. The initial decision to start empiric intravenous antibiotics was appropriate given the known risk of marine-associated infections. However, adding corticosteroids after the biopsy confirmed the diagnosis was crucial for treating the immune-mediated process and led to complete resolution.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe risk of infection after a stingray injury remains an important consideration. Marine environments expose wounds to various pathogens, including \u003cem\u003eVibrio vulnificus\u003c/em\u003e, \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e, and atypical organisms such as \u003cem\u003eMycobacterium fortuitum\u003c/em\u003e. Case reports show that infections can develop days after the initial injury, sometimes despite initially mild symptoms. Although this patient did not ultimately show signs of infection, the clinical similarities between infection and hypersensitivity underscore the need for early empiric antibiotic treatment in certain cases, especially when presentation is delayed or clinical signs are unclear. [FIGURE \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e] Another important aspect of stingray injuries is the risk of retained barbed fragments, which can cause ongoing inflammation, delayed healing, or secondary infection. Recent case reports indicate that embedded spines may lead to prolonged symptoms and may require surgical removal if not detected early. Although this was not identified as a factor in this case, the patient\u0026rsquo;s intermittent sharp pain before presentation demonstrates how such symptoms can prompt further investigation, including imaging or surgical exploration when indicated. This case also underscores the importance of a multidisciplinary management approach, including clinical evaluation, imaging as needed, histopathologic assessment, and personalized pharmacologic treatment. In addition to immediate management strategies such as hot water immersion, clinicians should remain vigilant for delayed complications that may require interventions such as corticosteroids or prolonged antimicrobial therapy. Preventive measures, including tetanus vaccination, should be part of comprehensive care. Overall, this case contributes to the limited but growing body of literature on delayed hypersensitivity reactions following stingray envenomation. It underscores the need for heightened clinical awareness of unusual presentations and reinforces the importance of distinguishing between infectious and immune-mediated processes. Recognizing these delayed reactions is crucial to prevent misdiagnosis and to guide appropriate, targeted treatment. [FIGURE \u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e]\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Patient Information","content":"\u003cp\u003eA 63-year-old man with well-controlled hyperlipidemia presented for evaluation of a stingray injury sustained one week earlier while walking on a beach in Ventura, California. The patient reported accidentally stepping on a stingray, which resulted in a puncture wound to the lower extremity.\u003c/p\u003e "},{"header":"Timeline of Current Episode","content":"\u003cp\u003eImmediately after the injury, he experienced intense pain that was relieved by warm water immersion, providing quick symptom relief. He did not take any over-the-counter or prescription medications. In the days that followed, he resumed his usual activities, including cycling, running, and swimming, with minimal discomfort.\u003c/p\u003e\u003cp\u003eNotably, the patient did not exhibit early signs of redness, swelling, or infection. However, in the days before presentation, he reported intermittent, sharp, localized pain, which raised concern for a retained foreign body or a developing infection.\u003c/p\u003e\u003cp\u003eThe patient was an otherwise healthy male with no prior medical conditions except for well-controlled hyperlipidemia. He had no history of surgery. He had no infectious or allergic history and no relevant family history. He worked as a traveling medical salesperson, visiting different parts of the country, with a specific focus on the Southwest.\u003c/p\u003e"},{"header":"Clinical Presentation","content":"\u003cp\u003eUpon presentation, he was afebrile, with a pulse in the 60s, blood pressure in the 120s systolic and 80s diastolic, and a respiratory rate and peripheral oxygen saturation within normal limits. Examination revealed mild erythema over the right medial malleolar region, ballotable, nonpitting edema, and minimal tenderness to palpation; a punctate area with a dark scab was also noted. Laboratory testing showed no leukocytosis or peripheral eosinophilia. His initial C-reactive protein was less than 0.3 mg/dL, but it rose to 38 mg/dL over subsequent days, peaking and correlating with worsening appearance and tenderness at the envenomation site.\u003c/p\u003e"},{"header":"Diagnostic Assessment","content":"\u003cp\u003eGiven the delayed presentation and concern for necrotizing infection, a punch biopsy was performed. Histopathologic evaluation showed epidermal hyperplasia with spongiosis and papillary dermal edema. A moderately dense, predominantly perivascular inflammatory infiltrate extended from the superficial to the deep dermis and was composed mainly of lymphocytes, with scattered neutrophils and abundant eosinophils. The punch biopsy reached the deep dermis and was transected. Special stains, including acid-fast bacilli (AFB), modified acid-fast (FITE), Gomori Methenamine Silver (GMS), and periodic acid\u0026ndash;Schiff with diastase (PAS-D), were negative for microorganisms.\u003c/p\u003e"},{"header":"Diagnosis","content":"\u003cp\u003eThese findings are most consistent with a hypersensitivity reaction to stingray envenomation rather than an infectious process. Other alternative diagnoses included cellulitis, necrotizing fasciitis, erysipelas, and ecthyma gangrenosum.\u003c/p\u003e"},{"header":"Therapeutic Intervention","content":"\u003cp\u003eThe patient was initially managed empirically with oral antibiotics after consultation with Infectious Diseases. He was treated with Doxycycline 100 mg once daily, Levofloxacin 750 mg once daily, and Linezolid 600 mg twice daily. After biopsy confirmation, systemic corticosteroids were initiated with a single intravenous dose of 125 mg, resulting in gradual symptom resolution. He was treated with a prednisone taper of 60 mg once daily for 3 days, followed by 40 mg for 3 days and then 20 mg for 3 days. His antibiotics were eventually stopped after 5 days, as they had not improved his symptoms.\u003c/p\u003e "},{"header":"Follow Up and Outcomes","content":"\u003cp\u003eThe patient reported that he had completed the prescribed course and fully recovered over several weeks. Regrettably, due to immobility from difficulty walking after the injury, the patient was assessed in clinic, and a Doppler ultrasound was ordered. This revealed that he had developed a deep venous thrombus three weeks after discharge, and he was placed on a direct oral anticoagulant for several months.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eStingray injuries involve a combination of penetrating trauma and envenomation, with potential for both infectious and noninfectious complications. [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] This case highlights an uncommon but clinically significant presentation: a delayed hypersensitivity reaction that mimics a soft-tissue infection. [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThe patient\u0026rsquo;s initially benign course, followed by delayed symptom onset, raised concern for infection, a well-documented complication of marine injuries. Common pathogens include \u003cem\u003eVibrio vulnificus\u003c/em\u003e, \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e, and \u003cem\u003eAeromonas\u003c/em\u003e species, which can cause severe soft tissue infections and, in some cases, necrotizing fasciitis. [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] Water-associated skin and soft tissue infections may involve a diverse range of pathogens beyond the more commonly recognized marine organisms. Among these, \u003cem\u003eEdwardsiella tarda\u003c/em\u003e, \u003cem\u003eErysipelothrix rhusiopathiae\u003c/em\u003e, \u003cem\u003eClostridium tetani\u003c/em\u003e, and fungal pathogens such as \u003cem\u003eAspergillus\u003c/em\u003e and \u003cem\u003eRhizopus\u003c/em\u003e species are less common but clinically important causes of infection following aquatic exposure. [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eGiven these risks, the initial use of broad-spectrum empiric antibiotics, including levofloxacin, doxycycline, and linezolid, was appropriate to cover marine Gram-negative organisms and resistant Gram-positive pathogens. However, this case underscores the importance of reassessing therapy as diagnostic data become available [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHistopathologic findings showing a lymphocyte-predominant infiltrate with numerous eosinophils, in the absence of detectable microorganisms, strongly suggest a hypersensitivity reaction rather than an infection. The presence of eosinophils, especially, indicates an immune response to venom components.\u003c/p\u003e \u003cp\u003eAfter ruling out an infectious cause, we de-escalated his antibiotic regimen and initiated corticosteroid therapy, resulting in rapid clinical improvement. The patient\u0026rsquo;s positive response to a structured prednisone taper further supports the diagnosis of a delayed hypersensitivity reaction. This case also highlights the diagnostic overlap between infection and immune-mediated reactions in marine injuries. Delayed infections, including those caused by non-tuberculous mycobacteria such as \u003cem\u003eMycobacterium fortuitum\u003c/em\u003e [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], can develop weeks after injury and require prolonged antimicrobial treatment. Differentiating these conditions is essential because management strategies vary significantly. Additionally, the possibility of retained foreign material should always be considered in patients with ongoing or delayed symptoms, as retained barbs can lead to infection and chronic inflammation [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOverall, this case underscores the importance of a multidisciplinary, evidence-based approach that integrates clinical findings, microbiology, and histopathology to guide appropriate management. Skin and soft tissue infections (SSTIs) following stingray envenomation are complex, involving mechanical injury, venom-induced tissue damage, and the introduction of marine pathogens. Stingray injuries usually occur when the animal\u0026rsquo;s serrated barbs pierce the skin, injecting venom and marine microorganisms into deep tissues. While the immediate toxic effects are well understood, infectious complications are increasingly recognized as a significant cause of illness.\u003c/p\u003e \u003cp\u003eStingray injuries are common in tropical and subtropical coastal areas, especially among swimmers, surfers, and fishermen. Most injuries involve the lower limbs and result from accidental contact in shallow water. The risk of infection depends on environmental exposure and host factors. Marine environments, particularly warm coastal waters, harbor high levels of harmful organisms, including \u003cem\u003eVibrio\u003c/em\u003e species. [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] Patients with chronic liver disease, diabetes, or immunosuppression are at higher risk of severe infection, particularly from \u003cem\u003eVibrio vulnificus\u003c/em\u003e, which has a high mortality rate. Additionally, the puncture nature of stingray wounds, often with retained foreign material, creates a favorable environment for bacterial growth and impairs wound healing. [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThe microbiology of stingray-related infections is diverse and often involves multiple microbial species. A recent case series and literature review identified a wide range of pathogens and found no standard antibiotic treatment, underscoring the complexity of these infections. The most clinically significant organisms include \u003cem\u003eVibrio vulnificus\u003c/em\u003e, \u003cem\u003eVibrio alginolyticus\u003c/em\u003e, \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e, and \u003cem\u003eAeromonas\u003c/em\u003e species. [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] \u003cem\u003eVibrio vulnificus\u003c/em\u003e is highly virulent and can cause rapidly progressive soft tissue infections, sepsis, and necrotizing fasciitis. Infections may result from minor injuries and can worsen within hours, especially in high-risk individuals. Recent case reports also highlight \u003cem\u003eVibrio alginolyticus\u003c/em\u003e as an important pathogen in stingray-related infections, capable of causing serious wound infections and vascular problems. \u003cem\u003eAeromonas\u003c/em\u003e species, more commonly associated with freshwater exposure, have also been implicated in marine injuries and can cause necrotizing infections with high mortality if left untreated. [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] Delayed or chronic infections after stingray injuries may involve non-tuberculous mycobacteria, particularly \u003cem\u003eMycobacterium fortuitum\u003c/em\u003e. These infections often emerge weeks later and may present as persistent nodules or non-healing ulcers. [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/p\u003e \u003cp\u003e \u003cem\u003eEdwardsiella tarda\u003c/em\u003e is a Gram-negative bacillus commonly found in freshwater and brackish water. It has been linked to traumatic wound infections following aquatic injuries and can cause cellulitis, abscesses, or, in severe cases, systemic infection. These infections are more common in immunocompromised individuals and typically require targeted antimicrobial therapy. [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] \u003cem\u003eErysipelothrix rhusiopathiae\u003c/em\u003e is a Gram-positive bacterium found in both marine and freshwater settings and is frequently associated with occupational exposure among fishermen and marine workers. The skin infection, erysipeloid, presents as a localized violaceous lesion with well-defined borders. Although often self-limited, systemic complications such as endocarditis have been reported in rare cases. [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] \u003cem\u003eClostridium tetani\u003c/em\u003e, an anaerobic, spore-forming bacterium found in soil and aquatic environments, remains a significant concern in water-exposed puncture wounds. The organism can grow in necrotic tissue and produce tetanospasmin, leading to tetanus, a potentially life-threatening neurological condition. This underscores the importance of tetanus prophylaxis for most water-exposed wounds.\u003c/p\u003e \u003cp\u003eFungal pathogens, including \u003cem\u003eAspergillus\u003c/em\u003e and \u003cem\u003eRhizopus\u003c/em\u003e species, are uncommon but serious causes of soft-tissue infections after water exposure, especially in immunocompromised individuals or after traumatic implantation. These organisms can cause invasive infections characterized by tissue necrosis and angioinvasion, often mimicking bacterial necrotizing infections. Early detection and prompt treatment, including surgical debridement and antifungal therapy, are critical for favorable outcomes. Overall, these less common pathogens underscore the need for a broad differential diagnosis in water-related soft-tissue infections, particularly in atypical or non-resolving cases. Case reports also show that unusual mechanisms, such as secondary contamination or improper wound care, can introduce atypical organisms, including oral flora, further complicating the infectious profile. [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThe pathogenesis of infection after a stingray injury involves a combination of direct bacterial inoculation, venom-induced tissue damage, and the host's immune response. The serrated barb can embed bacteria deep within soft tissues, while venom components cause local necrosis, vasoconstriction, and reduced immune function, facilitating bacterial multiplication. Retained foreign bodies, such as fragments of the stingray spine, can serve as sites of ongoing infection, which may cause chronic inflammation and slow healing. [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eClinical signs of infection after a stingray injury range from localized cellulitis to life-threatening necrotizing fasciitis. Early infections typically present with localized erythema, swelling, pain, and/or purulent discharge. In contrast, infections caused by aggressive organisms such as \u003cem\u003eVibrio vulnificus\u003c/em\u003e may present with hemorrhagic bullae, severe pain disproportionate to the examination findings, and rapid progression to systemic toxicity. Delayed infections may appear weeks after exposure, especially with atypical organisms, and can mimic inflammatory or hypersensitivity conditions. [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eDiagnosis requires a high index of suspicion, particularly in patients with a history of marine exposure. Key elements include a detailed exposure history, a physical examination for signs of deep or necrotizing infection, imaging to detect retained foreign bodies, and microbiologic cultures to guide treatment. Early detection of necrotizing infection is crucial, as delays are associated with increased morbidity and mortality. Management of stingray-related infections is multimodal and includes wound care, antimicrobial therapy, and surgical intervention when necessary. Initial treatment includes thorough wound irrigation and debridement, hot-water immersion to denature venom, and tetanus prophylaxis. [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eEmpiric antibiotic therapy should target marine Gram-negative organisms, particularly \u003cem\u003eVibrio\u003c/em\u003e species. Current evidence supports the use of doxycycline, fluoroquinolones, or trimethoprim-sulfamethoxazole. Severe infections, including necrotizing fasciitis, require prompt surgical debridement and intensive supportive care. Chronic infections may require prolonged antimicrobial therapy and specialist consultation. Recent research highlights antimicrobial resistance among marine pathogens as an increasing concern, complicating empiric treatment strategies. Additionally, climate change and rising sea temperatures are expanding the geographic range of \u003cem\u003eVibrio\u003c/em\u003e species, resulting in more marine-related infections. [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThis case report presents a rare and instructive case of delayed hypersensitivity following stingray envenomation, highlighting the important diagnostic challenge of distinguishing immune-mediated reactions from soft-tissue infections. It also situates the case within a broad and relevant literature review covering marine pathogens, retained foreign bodies, empiric antimicrobial strategies, and evolving environmental factors, including the expanding range of Vibrio species. However, the paper has limitations inherent to a single-patient case report, including limited generalizability and an inability to establish causation or estimate the incidence of delayed hypersensitivity reactions after stingray injury. Despite these limitations, the report provides meaningful clinical insight into an area with a relatively sparse literature.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eStingray envenomation can cause both infectious and delayed hypersensitivity complications, which may present with similar clinical signs. This case underscores the importance of distinguishing between these conditions to ensure appropriate treatment. While empiric antibiotics are often necessary in delayed presentations, histopathologic evaluation is essential when the diagnosis remains unclear. Early identification of hypersensitivity reactions and treatment with corticosteroids can lead to excellent outcomes. Soft tissue infections after stingray injuries involve a complex interplay of environmental exposure, host susceptibility, and microbiologic factors. Clinicians should remain vigilant for both early and delayed infections, especially in patients with atypical symptoms. Prompt diagnosis, appropriate antimicrobial treatment, and timely surgical intervention are crucial for better outcomes. Ongoing research and case reporting are needed to refine management strategies in this evolving area.\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003ePatient Perspective:\u003c/h2\u003e \u003cp\u003eThis episode was eye-opening for me as a patient because it showed how an injury that began with a simple sting and initially appeared to be healing evolved into a suspected delayed infection that did not improve with antibiotics. After the biopsy, it was reclassified as a delayed hypersensitivity reaction, which then responded to steroids. It also highlighted the need for coordination of care among infectious diseases, dermatology, and hospital medicine.\u003c/p\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003ch2\u003eInformed Consent:\u003c/h2\u003e\n\u003cp\u003eWritten informed consent for publication was obtained from the patient, and a copy of the written consent is available for review by the Editor-in-Chief of the Journal of Case Reports upon request.\u003c/p\u003e\n\u003cdiv class=\"Heading\"\u003e\u003cstrong\u003eEthics Approval and Consent to Participate:\u003c/strong\u003e\u003c/div\u003e\n\u003cp\u003eInformed consent was obtained from the patient and the family throughout the research and writing process of this paper; all patient data was de-identified, and reasonable measures were taken to ensure that patient information was decoded and anonymized.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for Publication:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the consent is available for review by the Editor-in-Chief of this journal.\u003c/p\u003e\n\u003ch2\u003eCompeting interests:\u003c/h2\u003e\n\u003cp\u003eThe author declares no competing interests.\u003c/p\u003e\n\u003ch2\u003eAuthor\u0026rsquo;s Information:\u003c/h2\u003e\n\u003cp\u003eNelson O. Onyango, M.D\u003c/p\u003e\n\u003cp\u003eMayo Clinic,\u003c/p\u003e\n\u003cp\u003eDepartment of Medicine,\u003c/p\u003e\n\u003cp\u003eDivision of Hospital Internal Medicine,\u003c/p\u003e\n\u003cp\u003e5881 E. Mayo Blvd.\u003c/p\u003e\n\u003cp\u003ePhoenix, AZ 85054\u003c/p\u003e\n\u003cp\u003eUnited States of America\u003c/p\u003e\n\u003cp\u003ePhone: 480-301-8484\u003c/p\u003e\n\u003cp\u003eEmail: [email protected]\u003c/p\u003e\n\u003ch2\u003eFunding:\u003c/h2\u003e\n\u003cp\u003eNot applicable as the author did not receive any funding for this project.\u003c/p\u003e\n\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\n\u003cp\u003eN.O. attended to the patient, devised a treatment plan, including the initiation of antibiotics, a biopsy, and steroids; N.O. analyzed the laboratory data, wrote and reviewed the manuscript.\u003c/p\u003e\n\u003ch2\u003eAcknowledgement\u003c/h2\u003e\n\u003cp\u003eThe author wishes to acknowledge the patient, GB, whose generosity of consent, time, and images has advanced learning; without him, this project would not be possible.\u003c/p\u003e\n\u003ch2\u003eAvailability of Supporting Data:\u003c/h2\u003e\n\u003cp\u003eThe data supporting the findings of this study are available on request from the corresponding author, [NO]. The data are not publicly available due to restrictions on private information that could compromise the patient's privacy.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eEvans RJ, Davies RS. Stingray injury. \u003cem\u003eJournal of Accident and Emergency Medicine.\u003c/em\u003e 1996;13(3):224\u0026ndash;225.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eClark RF, Girard RH, Rao D, Ly BT, Davis DP. Stingray envenomation. \u003cem\u003eJournal of Emergency Medicine.\u003c/em\u003e 2007;33(1):33\u0026ndash;37.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDiaz JH. Stingray injuries in travelers. \u003cem\u003eJournal of Travel Medicine.\u003c/em\u003e 2008;15(2):102\u0026ndash;109.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBaker-Austin C, Oliver JD, Alam M, et al. \u003cem\u003eVibrio\u003c/em\u003e spp. infections. \u003cem\u003eNature Reviews Microbiology.\u003c/em\u003e 2018;16(4):223\u0026ndash;233.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHorseman MA, Surani S. \u003cem\u003eVibrio vulnificus\u003c/em\u003e infection: diagnosis and treatment. \u003cem\u003eJournal of Infection and Public Health.\u003c/em\u003e 2011;4(1):1\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMora-Zamacona P, \u0026Aacute;guila-Ram\u0026iacute;rez RN, Mu\u0026ntilde;oz-Ochoa M, et al. Stingray envenomation with retained spine: a case report. \u003cem\u003eCureus.\u003c/em\u003e 2023;15:e38885.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHaddad V Jr, Neto DG, de Paula Neto JB. Freshwater stingrays: epidemiologic and clinical aspects. \u003cem\u003eClinical Infectious Diseases.\u003c/em\u003e 2004;38(1):e1-e6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStevens DL, Bryant AE. Necrotizing soft-tissue infections. \u003cem\u003eNew England Journal of Medicine.\u003c/em\u003e 2017;377(23):2253\u0026ndash;2265.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrooke CJ, Riley TV. \u003cem\u003eErysipelothrix rhusiopathiae\u003c/em\u003e: bacteriology and clinical manifestations. \u003cem\u003eClinical Microbiology Reviews.\u003c/em\u003e 1999;12(3):354\u0026ndash;359.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJanda JM, Abbott SL. Infections associated with \u003cem\u003eEdwardsiella tarda\u003c/em\u003e. \u003cem\u003eClinical Infectious Diseases.\u003c/em\u003e 1993;17(4):742\u0026ndash;748.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJohnson MG, Stout JE. Twenty-eight cases of \u003cem\u003eMycobacterium fortuitum\u003c/em\u003e infection. \u003cem\u003eClinical Infectious Diseases.\u003c/em\u003e 2015;60(10):e60-e66.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCevik J, Hunter-Smith DJ, Rozen WM. Stingray envenomation and associated infections: a review. \u003cem\u003eTravel Medicine and Infectious Disease.\u003c/em\u003e 2022; 47:102312.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eH\u0026oslash;nge BL, Patsche CB, Jensen MM, et al. Iatrogenic infection following stingray injury: a case report. \u003cem\u003eAmerican Journal of Tropical Medicine and Hygiene.\u003c/em\u003e 2018;98(3):929\u0026ndash;932.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCarroll A, Chowdhury M, Zheng C. \u003cem\u003eVibrio alginolyticus\u003c/em\u003e infection following stingray injury: a case report. \u003cem\u003eAmerican Journal of Tropical Medicine and Hygiene.\u003c/em\u003e 2024\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNg BW, Ong KC, Ahmad-Azraf A, et al. \u003cem\u003eAeromonas\u003c/em\u003e necrotizing soft tissue infection: a case report. \u003cem\u003eMedical Journal of Malaysia.\u003c/em\u003e 2019;74(5)\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAuerbach PS. \u003cem\u003eWilderness Medicine\u003c/em\u003e. 6th ed. Elsevier; 2012.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSkiada A, Lass-Floerl C, Klimko N, et al. Challenges in the diagnosis and treatment of mucormycosis. \u003cem\u003eLancet Infectious Diseases\u003c/em\u003e. 2018;18(12): e396-e404.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFenner PJ. Marine envenomation: an update. \u003cem\u003eEmergency Medicine Australasia.\u003c/em\u003e 2002;14(4):423\u0026ndash;429.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBurnett JW, Calton GJ, Morgan RJ. Venomous marine animals. \u003cem\u003eClinical Dermatology.\u003c/em\u003e 1987;5(3):103\u0026ndash;118.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHalstead BW. \u003cem\u003ePoisonous and Venomous Marine Animals\u003c/em\u003e. United States Government Printing Office; 1988.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIsbister GK, Kiernan MC. Neurotoxic marine envenomation. \u003cem\u003eLancet Neurology.\u003c/em\u003e 2005;4(4):219\u0026ndash;228.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ede Oliveira JS, Haddad V Jr. Stingray injuries: a review. \u003cem\u003eRevista da Sociedade Brasileira de Medicina Tropical.\u003c/em\u003e 2013;46(4):435\u0026ndash;439.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBaker-Austin C, Trinanes J. Climate change and \u003cem\u003eVibrio\u003c/em\u003e infections. \u003cem\u003eScience of the Total Environment.\u003c/em\u003e 2019; 653:131\u0026ndash;140.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYen LM, Thwaites CL. Tetanus. \u003cem\u003eLancet.\u003c/em\u003e 2019;393(10181):1657\u0026ndash;1668.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Stingray, Envenomation, Vibrio vulnificus, Marine Injury, Case Report","lastPublishedDoi":"10.21203/rs.3.rs-9460508/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9460508/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eIntroduction:\u003c/b\u003e\u003c/p\u003e \u003cp\u003eStingray envenomation is a relatively common occurrence among water sports enthusiasts, including swimmers, scuba divers, and surfers, as well as fishermen. However, there is a lack of medical literature on the pathophysiology of immediate and delayed hypersensitivity reactions, and more importantly, on the range of infectious bacterial and mycobacterial infections that can result from these envenomation injuries. This paper aims to provide a general overview of the mechanisms, diagnostic challenges, and management of late hypersensitivity reactions and infections that can occur following stingray stings.\u003c/p\u003e\u003cp\u003e\u003cb\u003eCase Report:\u003c/b\u003e\u003c/p\u003e \u003cp\u003eA 63-year-old man with well-controlled hyperlipidemia presented to the Mayo Clinic with a one-week-old injury from accidentally stepping on a stingray barb while walking on a beach in Ventura, California. Immediate pain was relieved with immersion in warm water. He did not take any over-the-counter or prescription medications, and over the following days, he returned to his usual activities of cycling, running, and swimming with minimal discomfort. There was no initial redness or swelling at the puncture site, but he reported intermittent sharp, localized pain with movement leading up to his hospital visit. A biopsy was performed due to concern for a developing necrotic infection, and he was diagnosed with a hypersensitivity reaction. He was initially treated with IV antibiotics, and steroids were added based on biopsy results. After completing his treatment course, his hypersensitivity reaction fully resolved over several weeks.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusion:\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThis case underscores the importance of considering both immediate and delayed hypersensitivity reactions that can result from stingray envenomation. These reactions can be managed with conservative measures, such as warming the affected area in a water bath to denature heat-labile venom, as well as with conventional therapies, including topical or systemic antihistamines and steroids. It also highlights the need for early empiric antibiotic coverage and outlines the infectious agents implicated in early- and late-onset infections following stingray envenomation, including \u003cem\u003ePseudomonas aeruginosa, Vibrio vulnificus\u003c/em\u003e, and \u003cem\u003eMycobacterium fortuitum\u003c/em\u003e. Additionally, it emphasizes the need for tetanus vaccine updates, radiography, and a multidisciplinary approach to treating stingray injuries.\u003c/p\u003e","manuscriptTitle":"From Shore to Sequelae: Delayed Hypersensitivity Reaction and Secondary Infection Following Stingray Envenomation –– A Case Report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-12 16:57:07","doi":"10.21203/rs.3.rs-9460508/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"4d95e911-cb58-41f6-a28c-2b614eeea9cd","owner":[],"postedDate":"May 12th, 2026","published":true,"recentEditorialEvents":[{"type":"editorInvitedReview","content":"","date":"2026-05-18T18:59:15+00:00","index":37,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-15T06:28:53+00:00","index":36,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-08T08:36:42+00:00","index":34,"fulltext":""},{"type":"reviewerAgreed","content":"109870907431013408165936256677806505935","date":"2026-05-08T07:10:00+00:00","index":33,"fulltext":""},{"type":"reviewerAgreed","content":"252592516258613099585473411903345530279","date":"2026-05-07T03:55:20+00:00","index":32,"fulltext":""},{"type":"reviewerAgreed","content":"246578432623562055195301641130029265837","date":"2026-05-06T18:50:20+00:00","index":31,"fulltext":""},{"type":"reviewersInvited","content":"13","date":"2026-05-04T14:46:33+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-29T19:12:55+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-05-12T16:57:07+00:00","versionOfRecord":[],"versionCreatedAt":"2026-05-12 16:57:07","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9460508","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9460508","identity":"rs-9460508","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}