Dermatology: Practical and Conceptual Review | Dermatol Pract Concept. 2025;15(1):4629 1 Stevens-Johnson Syndrome and Erythema Multiforme Induced by Imiquimod 5% Cream Ilaria Salvi1, Ilaria Trave1, Riccardo Castelli1, Aurora Parodi1, Emanuele Cozzani1 1 Section of Dermatology, DISSAL, University of Genoa, IRCCS Ospedale-Policlinico San Martino, Genova, Italy Key words: Imiquimod, Stevens-Johnson Syndrome, Erythema multiforme, Adverse drug reaction Citation: Salvi I, Trave I, Castelli R, Parodi A, Cozzani E. Stevens-Johnson Syndrome and Erythema Multiforme Induced by Imiquimod 5% Cream. Dermatol Pract Concept. 2025;15(1):4629. DOI: https://DOI.org/10.5826/dpc.1501a4629 Accepted: August 28, 2024; Published: January 2025 Copyright: ©2024 Salvi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution- NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: None. Competing Interests: None. Authorship: All authors have contributed significantly to this publication. Corresponding Author: Ilaria Trave, Section of Dermatology, DISSAL, University of Genoa, IRCCS Ospedale-Policlinico San Martino, Via A. Pastore 10, Genova, Italy, 16132. Phone: 010 5555768. E-mail: ilaria.trave@gmail.com Introduction: Topical imiquimod is a safe and effective treatment for actinic keratoses, superficial basal cell carcinomas, and anogenital warts. The treatment is commonly associated with local inflam- matory reactions, while systemic side effects are rare and generally mild. Only few cases of erythema multiforme and Stevens-Johnson syndrome have been described in association with topical imiquimod application. Objective: We present a narrative review of the existing cases of erythema multiforme and Stevens-Johnson syndrome reported in the literature, analyzing the clinical appearance, the histology, and the treatment of the lesions. Method: Twenty-one articles were retrieved. All the sourced articles were full-text reviewed to ensure that the contents were relevant to the study, which resulted in the exclusion of 10 articles. Results: Nine case of erythema multiforme were reported, characterized by cutaneous rash, bullae, crusting, and erosive and targetoid lesions, mainly located at the extremities. Mucosal involvement and systemic symptoms were present in five and in three cases, respectively. Three cases of Stevens-Johnson syndrome were associated with topical imiquimod. In all cases, the authors reported targetoid lesions and areas of erosion affecting trunk and limbs, associated with systemic symptoms, and, in two cases, with mucosal erosions. Conclusions: We hypothesize a possible role of interferon-γ, a cytokine involved in the pathogene- sis of both herpes-associated erythema multiforme and Stevens-Johnson syndrome, which is released in response to the administration of imiquimod. ABSTRACT 2 Review | Dermatol Pract Concept. 2025;15(1):4629 Introduction Imiquimod is a toll-like receptor-7 agonist that acts as an immune response modifier by stimulating monocytes/macro- phages and dendritic cells to produce cytokines that promote cellular immunity [1]. The topical formulation of imiquimod is approved for the treatment of actinic keratoses (AKs), superficial basal cell carcinomas (BCCs), and anogenital warts [2]. Moreover, off-label use of imiquimod cream has been reported as effective in other skin cancers, such as squa- mous cell carcinoma in situ and melanoma in situ [2]. Local skin reactions after the application of imiquimod are extremely common and include erythema, scabbing, in- duration, edema, erosion, flaking, ulceration, and vesicle for- mation, accompanied by itching, burning, and pain. On the contrary, systemic side effects are uncommon and generally mild; the most frequently reported ones are flu-like symp- toms, myalgia, malaise, fatigue, fever, upper respiratory tract infections, sinusitis, and headaches [1]. Although the topical application of imiquimod is rarely associated with severe sys- temic side effects, sporadic cases of systemic drug reactions, including erythema multiforme (EM) and Stevens-Johnson syndrome (SJS), have been reported [3]. EM is an acute, self-limiting disease that is typically asso- ciated with hypersensitivity reactions to infections, in partic- ular by herpes simplex virus and mycoplasma pneumoniae, or to drugs. EM has been further subdivided into EM minor and EM major according to the extent of the mucosal in- volvement [4]. SJS and toxic epidermal necrolysis (TEN) are potentially life-threatening mucocutaneous reactions, predominantly drug induced. In EM and SJS, skin detachment affects less than 10% of the body surface area (BSA), while TEN is char- acterized by an involvement of over 30% of the skin surface. Involvement between 10% and 30% of BSA is defined as SJS/TEN overlap [5]. Historically, EM major, SJS, and TEN have been consid- ered part of the same disease spectrum; however, due to their distinct morphological characteristics, EM major and SJS are currently accepted as separate entities [5]. Objectives This narrative review aimed to summarize the current un- derstanding of severe systemic drug reactions caused by the topical application of imiquimod and to offer some insight on the potential pathogenetic mechanism of such reactions. Methods We performed a literature search using the PubMed database using the following search terms: “imiquimod”, “erythema multiforme” and “Stevens-Johnson syndrome”. Addition- ally, we reviewed references from relevant original papers to identify further eligible studies not covered by the original database search. Criteria for inclusion of the studies for the review were as follows: articles in English; case reports; use of imiquimod for in-label indications. A total of 21 articles were retrieved. All the sourced articles were full-text re- viewed to ensure that the contents were relevant to the study, which resulted in the exclusion of 10 articles. Results We found 11 studies related to EM and SJS occurring in patients treated with imiquimod 5% for BCCs or AKs, for a total of 12 case reports, published from 2010 to 2024 (Table 1). Imiquimod cream was applied 2–5 times a week for BCCs and 2–3 times a week for AKs (Table 1). Nine cases of EM associated with imiquimod 5% were described, both during treatment of BCCs [3,6-9] and of AKs [9-12]. Clinical manifestations appeared after an average of 21 days after having started treatment with imiquimod 5% and were characterized by maculopapular rash [8-10], macu- lopustular rash [3,7], maculovescicular rash [3,9,12], bullae [9,10], crusting, and erosive and atypical targetoid lesions [6,7,9,11] frequently involving extremities and associated with systemic flu-like symptoms [3,6,10]. Mucosae were also involved in 5/9 cases, with stomatitis [7,9,11], conjunc- tivitis [3,7], and erosions of the nose [7]. The scheme of ap- plication of imiquimod 5% in patients was twice a week [9], three times a week [3], or five times a week [6-8] for patients with BCCs and twice a week [9,11] or three times a week [6,10,12] for patients with AKs. Skin biopsy was performed in 6/9 cases and was characterized by keratinocyte necrosis and intraepidermal vesiculation affecting the epidermis, ac- companied by an inflammatory lymphohistiocytic infiltrate in the papillary dermis [3,6-8,10,12]. These reactions were managed with imiquimod interruption [3,6-12], systemic [3,7,9,11] or topical corticosteroids [7,8,12], opical [6] or oral antibiotics [7,11]. The lesions started to improve after between a few days and up to 15 days and were completely resolved after a maximum of 21 days. Only one patient had a past history of HSV infection, but he denied any recent flares [11]. SJS associated with imiquimod 5% cream was previ- ously described in three patients. All patients were treated with imiquimod 5% for BCCs and SJS symptoms starting 8–42 days from the beginning of the treatment. All patients presented targetoid lesions and areas of erosion affecting trunk and limbs [13-15], associated with systemic symptoms such as malaise [13,15], hypotension [13], tachycardia [14], and fever [13,14]. Mucosal lesions were present in 2/3 cases Review | Dermatol Pract Concept. 2025;15(1):4629 3 Ta b le 1 . R ev ie w o f th e L it er at ur e. A u th o rs A g e Se x C o m o rb id it y Si te o f B C C / A K Sc h em e o f A p p lic at io n o f Im iq u im o d Ti m e o f A p p ea ra n ce o f EM / SJ S A ft er A p p lic at io n o f Im iq u im o d Sk in L es io n s Si te s o f Le si o n s M u co u s In vo lv em en t Sy st em ic In vo lv em en t Tr ea tm en t Ti m e o f R es o lu ti o n E ry th em a M ul ti fo rm e G ar ci a- A rp a et a l. (2 01 0) 66 F H yp er te ns io n, de pr es si on , os te oa rt hr it is B C C c he ek , A K n os e/ up pe r lip 3 ti m es w ee kl y fo r A K , 5 t im es w ee kl y fo r B C C 35 d ay s A re as o f cr us ti ng th at le ft e ro si on s w he n lif te d, an d ro un d er yt he m at ou s pa pu le s, s om e w it h er os io n, so m e w it h ta rg et m or ph ol og y C he st , fo re ar m s, ha nd s, le gs N o Fe ve r, m al ai se Im iq ui m od di sc on ti nu ed , to pi ca l a nt ib io ti cs A f ew d ay s B al le st er et a l. (2 01 4) 70 M H yp er te ns io n A K s ca lp , no se 3 ti m es w ee kl y 21 d ay s M ac ul op ap ul ar er up ti on , b ul la e E lb ow s, kn ee s, pa lm s, s ol es N o Fl u- lik e sy nd ro m e Im iq ui m od di sc on ti nu ed 15 d ay s C ha n et a l. (2 01 7) 66 M H yp er te ns io n, hy pe rc ho le st er - ol em ia B C C o n an te ri or ch es t 5 ti m es w ee kl y 21 d ay s M ac ul ar a nd pu st ul ar e ru pt io n W id es pr ea d St om at it is a nd co nj un ct iv it is N o B et am et ha so ne va le ra te 0 .1 % oi nt m en t N K (c om pl et e re so lu ti on at 1 2 w ee ks ) C ha n et a l. (2 01 7) 79 M C hr on ic ly m ph oc yt ic le uk em ia B C C o n ri gh t up pe r ba ck N K 6 da ys A cr al a ty pi ca l ta rg et le si on s E xt re m it ie s St om at it is a nd na sa l e ro si on s N o Pr ed ni so ne , ny st at in a nd ro xi th ro m yc in N K (c om pl et e re so lu ti on at 6 w ee ks ) Y an es et a l. (2 01 7) 60 M N o A K s ca lp tw ic e w ee kl y 14 d ay s Ta rg et oi d le si on s E xt re m it ie s St om at it is N o O ra l p re dn is on e, flu oc in on id e m ou th w as h, o ra l cl in da m yc in 14 d ay s Pe na - L op ez et a l. (2 01 7) 56 F G or lin s yn dr om e B C C n os e 5 ti m es w ee kl y 28 d ay s E ry th em at ou s- ed em at ou s pa pu le s an d pl aq ue s D or su m o f th e ha nd s, fo re ar m s, ar m s, a nk le s N o N o Im iq ui m od di sc on ti nu ed , m om et as on e fu ro at e on n os e 15 d ay s T ab le 1 c on ti nu es 4 Review | Dermatol Pract Concept. 2025;15(1):4629 A u th o rs A g e Se x C o m o rb id it y Si te o f B C C / A K Sc h em e o f A p p lic at io n o f Im iq u im o d Ti m e o f A p p ea ra n ce o f EM / SJ S A ft er A p p lic at io n o f Im iq u im o d Sk in L es io n s Si te s o f Le si o n s M u co u s In vo lv em en t Sy st em ic In vo lv em en t Tr ea tm en t Ti m e o f R es o lu ti o n M ax fie ld et a l. (2 01 9) 83 M N K 2 B C C sh ou ld er , A K le ft w ri st ri gh t do rs al ha nd tw ic e w ee kl y 7 da ys M ac ul es , p at ch es , pl aq ue s, v es ic le s, bu lla e, t ar ge to id le si on s E xt re m it ie s St om at it is N o Im iq ui m od di sc on ti nu at io n, or al p re dn is on e 21 d ay s C am ac ho M ol in a et a l. (2 02 0) 84 M H yp er te ns io n, at ri al fi br ill at io n B C C te m po ra l 3 ti m es w ee kl y 28 d ay s M ac ul ar a nd pu st ul ar /v es ic ul ar er up ti on T ru nk , a rm s C on ju nc ti vi ti s M al ai se , fe ve r, dy sp ha gi a, co ug h Im iq ui m od di sc on ti nu ed , E V m et hy lp re dn is ol on e 21 d ay s T rč ko (2 02 0) 77 M N o A K s ca lp 3 ti m es w ee kl y 21 d ay s Sy m m et ri ca lly di st ri bu te d m ac ul ar a nd ve si cu la r er up ti on A rm s, n ec k N o N o Im iq ui m od di sc on ti nu ed , to pi ca l co rt ic os te ro id s 20 d ay s St ev en s- Jo hn so n sy nd ro m e L ei tn er et a l. (2 01 6) N K F N K B C C c he st N K 42 d ay s A ty pi ca l t ar ge to id le si on s, la te r er os io ns N ik ol sk i + on 2 0% B SA T ru nk , a rm s, ex tr em it ie s N o M al ai se , hy po te ns io n, fe ve r H os pi ta liz at io n, im iq ui m od di sc on ti nu ed , in te ns iv e sk in c ar e N K T ed m an et a l. (2 02 0) 65 F H yp er lip id em ia B C C le ft fo re ar m a nd hi p N K 10 d ay s B lis te ri ng e ru pt io n C en tr al ch es t, fo re ar m C on ju nc ti vi ti s, st om at it is Fe ve r, ta ch yc ar di a Im iq ui m od di sc on ti nu at io n, ho sp it al iz at io n, in te ns iv e sk in , m ou th a nd e ye c ar e 7 da ys T ra ve et a l. (2 02 4) 79 M H yp er te ns io n, be ni gn p ro st at ic hy pe rp la si a 2 B C C c he st 5 ti m es w ee kl y 8 da ys Ta rg et oi d le si on s, er os io ns T ru nk , fa ce , a rm s, ex tr em it ie s St om at it is , ge ni ta l e ro si on s M al ai se , fa ti gu e Im iq ui m od di sc on ti nu at io n, or al p re dn is on e, in te ns iv e sk in c ar e 20 d ay s A bb re vi at io ns : A K : a ct in ic k er at os is ; B C C : b as al c el l c ar ci no m a; B SA : b od y su rf ac e ar ea ; E M : e ry th em a m ul ti fo rm e; N K : n ot k no w n; S JS : S te ve ns -J oh ns on s yn dr om e. Ta b le 1 . R ev ie w o f th e L it er at ur e. ( co nt in ue d) Review | Dermatol Pract Concept. 2025;15(1):4629 5 overexpression of major histocompatibility complex on keratinocytes, which makes them more susceptible to the action of T CD8+ cytotoxic lymphocytes [24]. Since imiqui- mod induces the release of IFN-γ [25], this drug may itself be particularly likely to cause EM or SJS. The reported rarity of this occurrence could be related to the topical route of administration and minimal systemic absorption of imiqui- mod [26]. However, the above-hypothesized mechanism may represent an exception, since IFN-γ has been reported as in- volved in herpes-associated EM, while tumor necrosis factor alpha (TNF-α) is expressed in drug-induced EM lesions [27]. We hypothesize that an increased systemic absorption caused by the application of the drug could raise the risk of systemic reactions, including EM and SJS. For instance, in Italy, topical imiquimod can be prescribed for superfi- cial BCCs, which are often ulcerated lesions [28] inducing a higher systemic absorption. In addition, as 4/9 cases of EM and 3/3 cases of SJS were associated with the treatment of two or more BCCs or AKs, it can be hypothesized that the application of the drug in a wider area of skin may increase the risk of systemic absorption and drug reaction. Moreover, all authors reported an intense local inflammatory reaction preceding or contemporary to the diagnosis of EM and SJS, a factor which may favor systemic absorption through vasodi- lation and increased vascular permeability, predisposing the patients to systemic reactions. The diagnoses of EM and SJS were based on clinical features in all reports and supported by histology in eight cases. In all case reports, a detailed drug history was obtained, and possible alternative causes of SJS and EM, such as infections and new medications, were excluded. The management of EM and SJS was vastly different in various case reports, especially in EM, where topical and sys- temic antibiotics and steroids were often prescribed. Due to the severity of the clinical manifestations, it is important to be aware of the possibility of EM and SJS caused by topi- cal imiquimod and to provide suspected cases with standard treatment: culprit drug interruption accompanied by sup- portive care including skin care and symptom control, with the possible addition of immunomodulatory drugs such as corticosteroids, cyclosporine, and intravenous immunoglob- ulins in SJS [29]. Conclusions In conclusion, EM and SJS caused by topical imiquimod are a rare but reported occurrence. Nonetheless, we believe that clinicians should be mindful of such a possibility and be ready to manage it appropriately. Further studies are needed to investigate the pathogenesis of imiquimod-mediated EM and SJS, particularly pertaining to the role of IFN-γ. and affected the mouth [14,15], conjunctiva [14], and geni- tals [15]. A skin biopsy was performed in 2/3 cases [13, 14], which showed full-thickness epidermal necrosis and inflam- matory infiltrates. Two patients with SJS were hospitalized [13, 14] and one was managed at home with systemic ste- roids [15]. In all cases, imiquimod was discontinued and in- tense skin care was started [13-15]. The lesions resolved in 7–20 days [14,15]. In all case reports, a detailed drug history was obtained, and possible alternative causes of SJS and EM, such as infec- tions and new medications, were excluded. Discussion The clinical presentation and evolution of EM and SJS caused by topical imiquimod does not differ from classic forms caused by systemic drugs. EM cases were charac- terized by localized target lesions, with predominant acral localization, and SJS cases were mainly characterized by non-palpable atypical targetoid lesions that predominantly affected the trunk [5]. In both EM and SJS, limited areas of erosion and crusting were described. Both EM major and SJS are characterized by mucosal involvement, but, unlike EM, SJS is generally accompanied by systemic involvement such as fever, malaise, fatigue, and other flu-like symptoms [16]. Interestingly, in one of the reported SJS cases, mucosal in- volvement was absent. However, the systemic and cutaneous involvement were severe, so the case was still included. Systemic drugs are a well-recognized cause of EM and SJS, particularly antibacterial drugs, rifampicin, barbitu- rates, anti-inflammatory agents, thiazide diuretics, anticon- vulsants, and vaccines. On the other hand, SJS and EM have been rarely associated with topical treatments. In most cases, the culprit drug was applied on mucosal membranes, such as antibiotic eyedrops [17,18], mesalazine enema [19,20], and antibiotic intranasal cream [21]. Cases of SJS and EM follow- ing the cutaneous application of drugs other than imiquimod seemed much rarer and were mostly associated with exten- sive skin damage [22], like in a case of topical application of nitrogen mustard in a patient with mycosis fungoides [23]. Imiquimod appears to represent an exception, and, to the best of our knowledge, the pathogenetic reasons for this ex- ception have not yet been investigated. The pathogenesis of SJS and EM is complex and likely determined by a dysregulation of cell-mediated immunity resulting from a combination of genetic predisposition and exogenous triggering factors [24]. Numerous cytokines and chemokines have a role in promoting these conditions. The increase in interferon gamma (IFN-γ), a cytokine produced by T lymphocytes, is probably involved in the pathogenesis of herpes-associated EM and SJS/TEN, mainly by inducing 6 Review | Dermatol Pract Concept. 2025;15(1):4629 Jun;43(6):860-861. DOI: 10.1016/j.jcrs.2017.03.043. PMID: 28732631. 18. Shaw B, Madden M, Crespo A, Madruga M, Carlan SJ. A Rare Case of Severe Stevens-Johnson Syndrome Triggered by Top- ical Ofloxacin. Am J Case Rep. 2023 Nov 12;24:e941992. DOI: 10.12659/AJCR.941992. PMID: 37952083; PMCID: PMC10654684 19. Núñez Ortiz A, Trigo Salado C, de la Cruz Ramírez MD, Herrera Justiniano JM, Leo Carnerero E. Topical mesalazine as a cause of Stevens-Johnson syndrome. Rev Esp Enferm Dig. 2018 Nov;110(11):736-738. DOI: 10.17235/reed.2018.5429/2017. PMID: 29931986. 20. Dhavaleshwar A, Nayak V, Hande M, Pai R. Topical moxifloxacin-induced toxic epidermal necrolysis and Stevens- Johnson syndrome. J Postgrad Med. 2019 Apr-Jun;65(2):125-126. DOI: 10.4103/jpgm.JPGM_535_18. PMID: 31036782. 21. Praz SM, De Torrente A, Zender H, Schmied E, Schleppy CA, Genné D. Toxic epidermal necrolysis after topical intranasal ap- plication of Mupirocin.  Infect Control Hosp Epidemiol 2003; 24: 459–460 22. Sachs B, Fischer-Barth W, Erdmann S, Merk HF, Seebeck J. Anaphylaxis and toxic epidermal necrolysis or Stevens-Johnson syndrome after nonmucosal topical drug application: fact or fiction? Allergy. 2007 Aug;62(8):877-83. DOI: 10.1111/j.1398 -9995.2007.01398.x. PMID: 17620064 23. Newman JM,  Rindler JM,  Bergfeld WF,  Brydon JK.  Stevens– Johnson syndrome associated with a topical nitrogen mustard therapy. J Am Acad Dermatol 1997; 36: 112–114 24. Caproni M, Torchia D, Schincaglia E, Volpi W, Frezzolini A, Schena D, Marzano A, Quaglino P, De Simone C, Parodi A, Barletta E, Fabbri P. Expression of cytokines and chemokine receptors in the cutaneous lesions of erythema multiforme and Stevens-Johnson syndrome/toxic epidermal necrolysis. Br J Der- matol. 2006;155:722-8. 25. Bubna AK. Imiquimod - Its role in the treatment of cutaneous malignancies. Indian J Pharmacol. 2015 Jul-Aug;47(4):354-9. DOI: 10.4103/0253-7613.161249. PMID: 26288465; PMCID: PMC4527053. 26. Harrison LI, Skinner SL, Marbury TC, Owens ML, Kurup S, McKane S, Greene RJ. Pharmacokinetics and safety of imiqui- mod 5% cream in the treatment of actinic keratoses of the face, scalp, or hands and arms. Arch Dermatol Res. 2004;296: 6-11. 27. Kokuba H, Aurelian L, Burnett J. Herpes simplex virus associ- ated erythema multiforme (HAEM) is mechanistically distinct from drug-induced erythema multiforme: interferon-gamma is expressed in HAEM lesions and tumor necrosis factor-alpha in drug-induced erythema multiforme lesions. J Invest Dermatol. 1999 Nov;113(5):808-15. DOI: 10.1046/j.1523-1747.1999 .00754.x. PMID: 10571738. 28. Giacomel J, Zalaudek I. Dermoscopy of superficial basal cell carcinoma. Dermatol Surg. 2005;31:1710-3. 29. Frantz R, Huang S, Are A, Motaparthi K. Stevens-Johnson Syn- drome and Toxic Epidermal Necrolysis: A Review of Diagnosis and Management. Medicina (Kaunas). 2021 Aug 28;57(9):895. DOI: 10.3390/medicina57090895. PMID: 34577817 References 1. Geisse J, Caro I, Lindholm J, Golitz L, Stampone P, Owens M. Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: results from two phase III, randomized, vehicle- controlled studies. J Am Acad Dermatol. 2004 May;50(5): 722-33. DOI: 10.1016/j.jaad.2003.11.066. PMID: 15097956. 2. Nanda J, Bermudez R. Imiquimod. 2022 Jul 12. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022. 3. Camacho Molina A, Alarcón Manoja E, Corzo Gilabert JR, García Gil D. Erythema multiforme induced by topical imiqui- mod. Emergencias. 2020;32:219. 4. Lerch M, Mainetti C, Terziroli Beretta-Piccoli B, Harr T. Current Perspectives on Erythema Multiforme. Clin Rev Allergy Immu- nol. 2018;54:177-184. 5. Grünwald P, Mockenhaupt M, Panzer R, Emmert S. Ery- thema multiforme, Stevens-Johnson syndrome/toxic epidermal necrolysis - diagnosis and treatment. J Dtsch Dermatol Ges. 2020 Jun;18(6):547-553. DOI: 10.1111/ddg.14118. Epub 2020 May 29. PMID: 32469468.) 6. García-Arpa M, Rodríguez-Vázquez M, Delgado Portela M, Vera Iglesias E. Eritema multiforme por imiquimod 5% crema [Erythema multiforme due to 5% imiquimod cream]. Actas Der- mosifiliogr. 2010;101:551-2. 7. Chan MYL, Kennedy J, Oakley A. Erythema multiforme trig- gered by imiquimod 5% cream. Australas J Dermatol. 2017;58: e257-e258. 8. Peña-López S, Suárez-Magdalena O, Monteagudo B, Cabanillas M. Erythema Multiforme Caused by Treatment With Topical Imiquimod 5% in a Patient With Gorlin Syndrome. Actas Der- mosifiliogr (Engl Ed). 2018; (3):277-278. 9. Maxfield L, Gaston D, Peck A, Hansen K. Topical Imiquimod and Subsequent Erythema Multiforme. J Am Osteopath Assoc. 2019. 10. Ballester I, Guijarro J, Silvestre JF, Niveiro M. Erythema mul- tiforme induced by imiquimod 5% cream. Int J Dermatol. 2014;53:e347-8. 11. Yanes DA, Kaffenberger JA, Carr DR. Erythema multiforme as a reaction to imiquimod 5% cream. Dermatol Online J. 2017;23 12. Trčko K. Imiquimod-associated erythema multiforme. Acta Dermatovenerol Alp Pannonica Adriat. 2020;29:47-49. 13. Leitner C. Topical imiquimod—Be aware of the unexpected. JAAD. 2016;74:AB223. 14. Tedman A, Malla U, Vasanthakumar L, Buzacott K, Banney L. Stevens-Johnson syndrome due to topical imiquimod 5%. Aust J Gen Pract. 2020;49:662-664. 15. Trave, I., Salvi, I., Micalizzi, C., Castelli, R., Parodi, A., & Cozzani, E. (2024). Stevens-Johnson induced by imiquimod 5% cream: a case report.  Dermatology Reports. https://DOI .org/10.4081/dr.2024.9930 16. Newkirk RE, Fomin DA, Braden MM. Erythema Multi- forme Versus Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis: Subtle Difference in Presentation, Major Difference in Management. Mil Med. 2020 Sep 18;185(9-10):e1847-e1850. DOI: 10.1093/milmed/usaa029. PMID: 32373930 17. Das A, Banerjee A, Tripathy K. Topical moxifloxacin-induced Stevens-Johnson syndrome. J Cataract Refract Surg. 2017