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POWERED BY • Sclerodermoid Reaction due to Injection of Fish Oil

By Jesse I. Payton, BS, Adam Blechman, MD, Mary Eid, MD and Barrett J. Zlotoff,MD There are numerous reports of adverse reactions from off-label substances that are used for soft tissue augmenta- tion—paraffin, ivory balls, glass balls, vegetable oils, mineral oil, lanolin, beeswax, shellac, silk fabric, epoxy resin, rubber, ox cartilage, sponges, goat’s milk, Teflon, soybean, peanut oil, and glazier’s putty are among the materials that have been injected for augmentation purposes. Associated side effects of these agents include hypersensitivity reactions, panniculitis and granulomatous inflammation.1,2 Even FDA-approved soft tissue filler materials such as collagen and , which are used for facial augmentation, have been associated with allergic reactions, infection, tissue necrosis, and granulomatous reactions.2 The benefits of fish oil have been well-reported in mainstream media and peer-reviewed articles. Several articles Figure 1. Image shows erythematous indurated plaques with a display its efficacy in reducing triglycerides and low-density lipo- peau d’orange appearance. Patient had a similar lesion on the protein in diabetics, decreasing acute liver injury as a compo- right thigh and buttock. nent of total parenteral nutrition (TPN), prolonging remission in patients with Crohn’s disease, and modulating inflammatory tender and indurated plaques with a peau d’orange quality cytokines.3-7 It is therefore not surprising that misconceptions but no purulent discharge (Figure 1). Her labs were significant have arisen around its potential uses. A Google search reveals for a white blood cell count of 14.9 with neutrophilic pre- bodybuilding and medical advice forums routinely discuss the dominance and her urinalysis was positive for ketones, protein, utility of subcutaneous and intramuscular injection of com- bilirubin, and blood. CT imaging showed inflammatory changes mercial fish oil for cosmetic purposes. Other anecdotal sources at the injection sites and possible cellulitis. The patient was advocate its topical use for breast and buttock enhancement. admitted and treated with intravenous (IV) Cefazolin and IV Vancomycin. Dermatology was consulted and a skin biopsy was CASE obtained for histologic examination and bacterial, fungal, and A 33-year-old African American female with a history of insu- mycobacterial tissue cultures. Tissue cultures and blood cul- lin-dependent diabetes presented to the emergency room with tures were negative. Her skin biopsy showed a sclerotic pain in her bilateral buttocks and hips. She reported using her with thick collagen bundles and a perivascular and periadnexal insulin syringes to inject 100 units of material from Spring Valley lymphohistiocytic infiltrate along with fat necrosis, consistent Fish Oil softgel capsules into these areas daily for the previous with trauma from her injection history (Figure 2). No organ- month. Associated symptoms included fever and chills, but she isms were observed with a Gomori Methenamine-Silver Nitrate denied drainage from the sites. The patient was febrile with a Stain, Fite, and gram stain. The patient was discharged with a temperature of 38.3ºC and tachycardic with a pulse of 127. Her PICC line to finish a 10-day course of intravenous Vancomycin. physical exam was notable for bilateral 10x8cm erythematous, At outpatient follow-up two weeks and two months later, she

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nism for the reaction to fish oil in the current patient given the similarity of the reactions and absence of infection. However, skin testing was not performed. It is also possible the patient reacted to a chemical other than the fish oil within the soft gel capsules. The manufacturer lists fish oil, gelatin, glycerin, water, mixed natural tocopherols, and sunflower oil as ingredients. Glycerin has been associated with a dose-dependent, transient erythematous reaction when injected subcutaneously.9 Lastly, the intradermal and subcutaneous placement of fish oil could have resulted in the accumulation of intrinsic lipophilic chemi- cals such as vitamin K and subsequently, an inflammatory reac- tion. Importantly, there is no reason to believe that the patient’s diabetes contributed to the sclerodermatous reaction, in that no such association has been published with regard to Texier’s disease. There is a condition called scleredema diabeticorum, Figure 2. Histology shows sclerotic dermis with thick collagen but the histopathology is different from the patients slides bundles and a pervascular and periadnexal lymphohistiocytic which look more like /. infiltrate. The biopsy also showed fat necrosis, which is not cap- tured on this image. CONCLUSION Despite their health benefits, cutaneous injection of commer- complained of superficial skin desquamation, but remained cial fish oil products can result in severe inflammatory reactions. afebrile and her lesions were noted to be less red, painful and This case highlights a sclerodermoid reaction as the result of indurated at each visit. She was advised to apply pure petrola- intradermal and subcutaneous injection of fish oil. This reaction tum jelly and continue observation. was similar to Texier’s Disease, which occurs after cutaneous This case demonstrates the dangers of off-label soft tissue injection of vitamin K. Patients may present with constitutional augmentation techniques. One similar case is described in symptoms either from systemic effects of the cutaneous inflam- the literature, in which a 37-year-old veterinarian developed matory reaction or from secondary skin infection. n bilateral mastitis after serial injections of commercial fish oil for breast augmentation. Her hospital course was complicated by Jesse I. Payton, BS is a medical student at the Staph chromogenes infection of the bilateral breasts. Biopsies University of Virginia. Adam Blechman, MD is a showed fat necrosis and granulomatous inflammation. The dermatology fellow at NYU Langone. Mary Eid, MD patient did not respond to prolonged antibiotic treatment and (not picutred) is a dermatopathology fellow at the recurrent debridement and she ultimately underwent bilateral University of Virginia. Barrett J. Zlotoff, mastectomy.9 MD is a dermatologist and Associate The patient in our current case did meet Systemic Professor at the University of Virginia. Inflammatory Response Syndrome (SIRS) criteria upon pre- Disclosure: None of the authors have sentation and was treated with IV antibiotics, but no causative any conflicts of interest, financial or organisms to support an infectious diagnosis were isolated on otherwise. blood and tissue cultures. 1. Turk E, Karagulle E, Koksal H, et al. Bilateral Breast Necrosis Due to Local Injection of Fish Oil. The Breast Journal. 2013;19(2):196-198. These clinical findings are similar to those seen with Texier’s doi:10.1111/tbj.12082. Disease, a reaction to subcutaneous vitamin K1 injection.8 2. Fernández-Aceñero MJCBA, Zamora E, Borbujo J. Granulomatous Against Hyaluronic Acid. Dermatologic Surgery. 2003;29(12):1225-1226. doi:10.1097/00042728-200312000-00018. Texier’s Disease can present with an acute eczematoid reac- 3. Calkins K, Lowe A, Shew SB, et al. Short-term intravenous fish oil and pediatric intestinal failure associated liver disease: 3-year follow- tion days to weeks after injection or a sclerodermoid reaction up on liver function and nutrition. Journal of Pediatric Surgery. 2013;48(1):228-232. doi:10.1016/j.jpedsurg.2012.10.044. 9 4. Cooper A, Gibbons L, Horan M, Little R, Rothwell N. Effect of dietary fish oil supplementation on fever and cytokine production in weeks to years later. Histology is also similar in Texier’s, which human volunteers. Clinical Nutrition. 1993;12(6):321-328. doi:10.1016/0261-5614(93)90027-2. can show dermal sclerosis with lymphocytes and plasma cells. 5. Kalish BT, Le HD, Fitzgerald JM, et al. Intravenous fish oil lipid emulsion promotes a shift toward anti-inflammatory proresolving lipid mediators. AJP: Gastrointestinal and Liver Physiology. 2013;305(11). doi:10.1152/ajpgi.00106.2013. However, Texier’s Disease might also exhibit eosinophils and 6. Mallah HS, Brown MR, Rossi TM, Block RC. Parenteral Fish Oil-Associated Burr Cell Anemia. The Journal of Pediatrics. 2010;156(2). mast cells in the acute phase and granulomatous foreign body doi:10.1016/j.jpeds.2009.07.062. 7. Montori VM, Farmer A, Wollan PC, Dinneen SF. Fish oil supplementation in type 2 diabetes: a quantitative systematic review. Diabetes reactions. Such findings were not observed in our patient. The Care. 2000;23(9):1407-1415. doi:10.2337/diacare.23.9.1407. etiology of Texier’s Disease is thought to be a delayed type 8. Pang BK, Munro V, Kossard S. Pseudoscleroderma secondary to phytomenadione (vitamin K1) injections: Texiers disease. Australasian Journal of Dermatology. 1996;37(1):44-47. doi:10.1111/j.1440-0960.1996.tb00994.x. hypersensitivity reaction to vitamin K1 and has been associated 9. Metre TEV, Rosenberg GL, Vaswani SK, Ziegler SR, Adkinson N. Pain and dermal reaction caused by injected glycerin in immuno- with positive intradermal skin testing.8 This is a possible mecha- therapy solutions. Journal of Allergy and Clinical Immunology. 1996;97(5):1033-1039. doi:10.1016/s0091-6749(96)70254-3

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