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Research Case Report: Commercial Cannabinoid Oil-Induced Stevens-Johnson Syndrome

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Case Report: Commercial Cannabinoid Oil-InducedStevens-Johnson SyndromeHan Y. Yin,1,2Nicholas Hadjokas,1Kanish Mirchia,3Robert Swan,1and Samuel Alpert11Department of Ophthalmology and Visual Sciences, SUNY Upstate Medical University, Syracuse, NY, USA2Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA3Department of Pathology, SUNY Upstate Medical University, Syracuse, NY, USACorrespondence should be addressed to Han Y. Yin; hhyin003@gmail.comReceived 30 August 2019; Accepted 10 February 2020; Published 20 February 2020AcademicEditor:Takaaki HayashiCopyright © 2020 Han Y. Yin et al.

This is an open access article distributed under the Creative Commons Attribution License,which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Purpose. To report an unusual presentation of commercial cannabidiol (CBD) oil-induced Stevens-Johnson Syndrome/toxicepidermal necrolysis (SJS-TEN).Methods. A 56-year-old woman presented with acute onset of a diffuse, blistering,maculopapular rash with over 30% total body surface area (BSA) involvement two days after taking CBD oil sublingually forchronic pain. Biopsy confirmed SJS-TEN. Ophthalmology was consulted and mild eye involvement was found. She was startedon topical cyclosporine, prednisone, moxifloxacin, and erythromycin ointment to prevent progression, which was successful.She was otherwise treated with supportive therapy in the intensive care burn unit and ultimately passed away from septic shock.Conclusion. In this case, we described an unusual drug-induced SJS from a commercial, non-FDA-regulated cannabis product.The use of a commercial CBD product should be cautioned due to potential for series of drug reactions to the cannabis productand the risk for reaction to other unregulated other pharmacological components.

1. BackgroundStevens-Johnson syndrome (SJS) and toxic epidermal necro-lysis (TEN) are devastating mucocutaneous hypersensitivityreactions characterized by progressive severe exfoliative rashaffecting mainly the skin and mucous membranes. Often,these are preceded by diffuse mucocutaneous tendernessand erythematous macules and blisters [1]. These two syn-dromes exist on a spectrum, with SJS involving less than10% body surface area (BSA) and TEN involving greater than30% BSA.SJS-TEN have been reported in various age groups butoccurs more frequently in females, HIV-infected patients,and the elderly. Common causes include medications includ-ing antibiotics and antiepileptics and infections such asmycoplasma; however, 50% of cases remain idiopathic [2].The increased incidence in the elderly population is likelydue to increased medication usage with age [3]. Drug hyper-sensitivity has been associated with genetic factors. In certainethnic groups, medications like carbamazepine and allopuri-nol have a strong correlation with human leukocyte antigen-(HLA-) B∗1502 and HLA-B∗5801, respectively [4]. Unfortu-nately, the RegiSCAR study demonstrated that HLA-B∗1502is not a confirmatory marker for any of the high-risk drugsknown to cause SJS-TEN in Europeans; so, these HLAmarkers cannot be used to confirm the diagnosis [2, 4].Mortality rates for SJS-TEN range from 10 to 50%. Thus,prompt identification and discontinuation of the causativeagent is vital. There have been reported cases of SJS fromcomplementary and alternative products [5], but few fromcannabis products. Cannabidiol (CBD) is one of the activeingredients of cannabis that stimulates cannabinoid recep-tors without causing psychotropic effects. It is currently beinginvestigated for use in childhood epilepsy syndromes, anxi-ety, and chronic pain. Herein, we present an unusual caseof drug-induced SJS from commercial CBD oil.HindawiCase Reports in Ophthalmological MedicineVolume 2020, Article ID 6760272, 5 pageshttps://doi.org/10.1155/2020/6760272

2. Case ReportA 56-year-old female with a past medical history of herniateddisc with chronic pain, hypertension, and coronary arterydisease presented to her local emergency room for diffusevesicular rash and skin ulceration management. She deniesprior history of dermatological rashes, or recent sick con-tacts, fever, or malaise prior to the onset of her symptoms.One week prior, she had tried a new liposomal CBD extractspray (Natural Native, Norman, Oklahoma, 73072) sublin-gually. Two days following the use of the new CBD product,she noticed a mild rash on her extremities, which was treatedby her primary care physician with diphenhydramine andoral prednisone without improvement. Her symptoms pro-gressed and she developed diffuse erythematous and vesicu-lar rashes involving her entire body over the next 48 hours.She was transferred to a university hospital for a higher levelof care. Her chronic outpatient medications for the past 5years included famotidine, lisinopril-hydrochlorothiazide,and meloxicam. She had previously used other CBD productswithout any adverse effect.On exam, she had diffuse erythematous macules andcentral necrosis with vesicles on her face. She had beenexperiencing crusting of the eyelashes and itching of themedial canthi, but she denied changes in vision and foreignbody sensation. Her best corrected visual acuity was 20/20with pinhole in both eyes, intraocular pressures were 16 inthe right eye, 17 in the left eye, pupils were equal and brisklyreactive without APD, and extraocular muscles were full.Her ophthalmic exam showed a maculopapular rash onthe upper and lower eyelids without conjunctival injection,fibrin formation, or corneal epithelial defect in either eye(Figures 1(a)–1(d)). She had extensive oral mucosal ulcera-tion (Figure 2(a)) and generalized erythematous maculesand blisters with multiple ruptured bullae on her trunk andback (Figures 2(a) and 2(b)). In addition, she had extensiveerythematous macules and central necrosis on all fourextremities (Figures 3(a)–3(d)) along with urethral and labialinvolvement, totaling 30 percent BSA.The patient was admitted to the burn intensive careservice for presumed SJS-TEN and started on a wound careregimen and intravenousfluid. Her outpatient oral predni-sone was discontinued in addition to all CBD products. Shewas started on topic cyclosporine drops OU.BID, prednisolone OU QID for 1 week, and moxifloxacinOU QID for 1 week to prevent progression of ophthalmicinvolvement. Punch biopsy was obtained and was consistentwith SJS (Figure 4). The patient expired about 1 month afterinitial presentation from septic shock.

3. DiscussionThis case addresses some interesting considerations in themanagement and etiologies of SJS-TEN. Management usu-ally consists of hospital admission, ideally with isolation ina burn unit to minimize potential hospital-acquired infec-tions and provide supportive therapy including IV hydrationfor adequate nutrition. For drug-induced SJS-TENS, theoffending agent is stopped immediately.Medications for management of SJS-TEN at the acutestage are controversial. Some believe that T-cell-mediatedimmunologic responses are the cause of SJS-TEN and haveconsequentially administered high-dose glucocorticoids,cyclophosphamide, or cyclosporine as a means of arrestingthe progression of skin lesions [6]. These drugs, however,are of unproven benefit in the acute stage and may have sys-temic adverse effect when used at the chronic stage [7].(a)(b)(c)(d)Figure1: (a, b) External photo and (c, d) withfluorescein, without conjunctival injection, signs of pseudomembrane, or gross epithelialdefect OU.2Case Reports in Ophthalmological Medicine

The use of systemic glucocorticoids is controversial.Many physicians no longer prescribe glucocorticoids, dueto limited evidence to support their use. Others treat empir-ically under the assumption that such a short-term high doseof steroids can curb disease progression [6]. There is concernthat systemic high-dose glucocorticoids may heighten theexisting risk of inciting infections. Despite the associated riskwith systemic steroids, some suggested that high dose ofsteroids (methylprednisolone 500 or 1000 mg/day for 3 to 4days) within four days of disease onset has beneficial thera-peutic effect in preventing ocular complications [8]. In addi-tion, topical steroid also shows great promise for preventingcorneal epithelial stem cell loss in the limbal region and cic-atricial changes. Systemic therapeutic measures such asTNF-alpha inhibitor, thalidomide, and cyclophosphamidehave been associated with increased mortality [9]. In ourcase, systemic steroids were not continued in the inpatientsetting, due to passing the therapeutic window of 3 to 4 dayssince onset of her symptoms. However, topical steroids wereprescribed to prevent further eye involvement.The exact etiology of our patient’s rash is unclear, but thetemporal association of initiation of a new CBD oil and theonset of the rash is suggestive of association. There is an asso-ciation between SJS and meloxicam which our patient hadbeen taking. However, her chronic use of this medication(over 5 years) suggests that it is an unlikely trigger. Reportsof systemic cannabis/cannabidiol hypersensitivity reactionare extremely rare. However, reports of marijuana associatedwith skin reactions such as allergic reactions, acute urticaria,and cannabis arteritis—a necrotic process presenting withulceration of the lower extremities in the setting of chronicuse [10]. There has been one case report of acute generalized(a)(b)(c)Figure2: (a) External photo of diffuse oral ulceration and erythematous macules with vesicles on the trunk (b) and bullae and denudation onthe back (c).3Case Reports in Ophthalmological Medicine


exanthematous pustulosis (AGEP) in the setting of CBD usewhich is a type IV hypersensitivity similar to SJS-TEN [11].In our case, the patient has previously utilized other commer-cial CBD products without side effects or associated allergicreactions. This suggests involvement of other ingredientsin this non-FDA-regulated product as the causative agent.(a)(b)(c)(d)Figure3: External photo of diffuse ruptured vesicle and ulceration right and left upper extremities (a, b) and erythematous macules withcentral necrosis on the right and left lower extremities (c, d).(a)(b)Figure4: Biopsy of the skin from the patient. Biopsy examination under 20x magnification (a): green—subepidermal blister, red—detachedand necrotic epidermis and under 100x magnification (b): black arrows detailing chronic inflammation.4Case Reports in Ophthalmological Medicine


The complete chemical analysis from the patient’s com-mercial CBD oil was not performed. In addition, our casealso had minimal ocular involvement compared to othermucocutaneous surfaces.We presented a case of a patient with CBD oil-inducedSJS-TEN. Progression of ophthalmic involvement wasprevented with cessation of the CBD oil product andinitiation of an aggressive lubrication and topical anti-inflammatory regimen. It is unclear if marijuana-deri-ved/CBD products can induce SJS-TEN. However, ourcase suggests an association. Further research and commu-nity surveillance is required to determine the risks of SJS-TEN from CBD products, especially given the severity andeven potential fatality of this disease. Given the increasedavailability and use of commercial CBD products, cliniciansshould be aware of the possible association of CBD andSJS-TEN.

Conflicts of InterestThe authors declare that they have no conflicts of interest.

References[1] M. Mockenhaupt,“The current understanding of Stevens-Johnson syndrome and toxic epidermal necrolysis,”ExpertReview of Clinical Immunology, vol. 7, pp. 803–813, 2011.[2] A. O. J. Fakoya, P. Omenyi, P. Anthony et al.,“Stevens -Johnsonsyndrome and toxic epidermal necrolysis; extensive review ofreports of drug-induced etiologies, and possible therapeuticmodalities,”Open Access Macedonian Journal of MedicalSciences, vol. 6, no. 4, pp. 730–738, 2018.[3] R. Schwartz, P. McDonough, and B. Lee,“Toxic epidermalnecrolysis,”Journal of the American Academy of Dermatology,vol. 69, no. 2, pp. 187.e1–187.e16, 2013.[4] W. H. Chung, S. I. Hung, H. S. Hong et al.,“A marker forStevens-Johnson syndrome,”Nature, vol. 428, no. 6982,p. 486, 2004.[5] M. T. Ventura, M. Viola, G. F. Calogiuri, F. Gaeta, O. Pesole,and A. Romano,“Hypersensitivity reactions to complemen-tary and alternative medicine products,”Current Pharmaceu-tical Design, vol. 12, no. 26, pp. 3393–3399, 2006.[6] S. C. G. Tseng,“Acute management of Stevens-Johnsonsyndrome and toxic epidermal necrolysis to minimize ocularsequelae,”American Journal of Ophthalmology, vol. 147,no. 6, pp. 949–951, 2009.[7] P. O. Fritsch and R. Ruiz-Moldanoda,“Stevens-Johnsonsyndrome - toxic epidermal necrolysis,”inFitzpatrick’sDermatology in General Medicine, I. M. Freedberg, A. Z. Eisen,K. Wolff, K. Frank Austen, L. A. Goldsmith, S. I. Katz, and T.B. Fitzpatrick, Eds., vol. 5, pp. 644–654, McGraw-Hill, 1999.[8] Y. Araki, C. Sotozono, T. Inatomi et al.,“Successful treatmentof Stevens-Johnson Syndrome with steroid pulse therapy atdisease onset,”American Journal of Ophthalmology, vol. 147,no. 6, pp. 1004–1011.e1, 2009.[9] S. Kohanim, S. Palioura, H. N. Saeed et al.,“Stevens-JohnsonSyndrome/Toxic Epidermal Necrolysis - a comprehensivereview and guide to therapy. I. Systemic disease,”The OcularSurface, vol. 14, no. 1, pp. 2–19, 2016.[10] G. Dhadwal and M. G. Kirchhof,“Therisksand benefits ofcannabis in the dermatology clinic,”Journal of CutaneousMedicine and Surgery, vol. 22, no. 2, pp. 194–199, 2018.[11] C. Pettit, S. Massick, and M. Bechtel,“Cannabidiol-inducedacute generalized exanthematous pustulosis,”Dermatitis,vol. 29, no. 6, pp. 345-346, 2018.5Case Reports in Ophthalmological Medicine

Download available with photos: Case Report: Commercial Cannabinoid Oil-InducedStevens-Johnson
 
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Baron23

Well-Known Member
The complete chemical analysis from the patient’s com-mercial CBD oil was not performed.
And the $64K question is why the fuck NOT!

I'm not clapping back at you, my friend. But it seems that this article is of limited value as although it describes her disease and treatment in detail, there is no infomation on WTF she really put in her body (or did I miss that part, above).

For all we know, it was full of rat poison or worse.
 

momofthegoons

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Staff member
And the $64K question is why the fuck NOT!
I would agree. However I don't know that the article is of no value.... I'll explain why in a sec...

She had previously used other CBD productswithout any adverse effect.
The exact etiology of our patient’s rash is unclear, but thetemporal association of initiation of a new CBD oil and theonset of the rash is suggestive of association.
the patient has previously utilized other commer-cial CBD products without side effects or associated allergicreactions. This suggests involvement of other ingredientsin this non-FDA-regulated product as the causative agent.
Clearly she had used CBD products in the past with no issue. What this article/report speaks to, imo, is the whole problem with CBD. It's a total gamble that you're going to get a viable product in today's market. I just posted an article in the CBD thread that found 'CBD products' that contained little or no CBD at all. In this market, it's anything goes. Who knows what you are getting in your CBD creams, capsules, etc. Buyer beware.
 

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