A case report of fixed drug eruption caused by several drugs because of cross‐reactivity and co‐sensitization

Sobrino‐García, Miriam; Gómez-Cardeñosa, Aida; Moreno-Rodilla, Esther; Muñoz-Bellido, Francisco J.; Lázaro‐Sastre, Milagros; Dávila, Ignacio

doi:10.1111/cod.13115

Cited by 8 publications

(8 citation statements)

References 7 publications

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“…There is a possibility of cross‐reactivity among imidazole derivatives due to their chemical structure similarities and has been shown in some case reports of FDEs. These were reported between different pairs of 5‐nitroimidazoles such as metronidazole and tinidazole, 23,25 metronidazole and albendazole, 27 metronidazole and esemoprazole, 30 metronidazole and ketoconazole, 29 fluconazole and tinidazole, 28 ornidazole and secnidazole, 6 and ornidazole and fluconazole 26 . In patch tests of a patient with contact dermatitis due to thioconazole, bifonazole, and metronidazole, positivity was detected revealing a cross‐reactivity between these three drugs 43 .…”

Section: Discussionmentioning

confidence: 97%

“…Examples of these case reports are FDEs due to metronidazole and tinidazole, 23‐25 and ornidazole and secnidazole 6 . Reported cross‐reactivity is more common between drugs with high molecular mimicry, but interestingly, it can also be seen among derivatives containing different imidazole rings 6,26‐30 . Consequently, it can be speculated that cross‐reactivity may occur among different agents with an imidazole ring and additional factors apart from the molecular structure are likely to play a role.…”

Section: Introductionmentioning

confidence: 99%

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Diagnostic workup including CD203c‐based basophil activation test in immediate hypersensitivity due to metronidazole and ornidazole and evaluation of cross‐reactivity in between

Beyaz

Akdeniz

Yilmaz

et al. 2020

Allergy

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Background Little is known about the diagnostic approaches for immediate hypersensitivity reactions (IHRs) due to 5‐nitroimidazole antibiotics. The aim was to evaluate the usefulness of in vivo tests and basophil activation test (BAT) for the diagnosis of IHRs due to metronidazole and ornidazole and to determine possible cross‐reactivity in between. Methods Forty‐nine patients with a clear history of IHRs due to these drugs and 20 healthy subjects who were known to tolerate these drugs were included. Skin tests (STs) and single‐blind placebo‐controlled drug provocation tests (SBPCDPTs) were performed with both drugs whereas BAT was applied only with the culprit drug. Results The most and least common reaction types were urticaria/angioedema (34.7%) and anaphylaxis (14.3%), respectively. SBPCDPTs were positive in 15 out of 47 patients, and only 7 had positive STs. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of STs for metronidazole/ornidazole were 33.3%/16.6%, 94.2%/97.3%, 60%/50%, and 84.6%/88.1%, respectively. BAT was positive in 12 out of 15 patients and negative in 10 control subjects, giving a sensitivity rate of 71.4% (CI, 29.0%‐96.3%) for metronidazole and 83.3% (CI, 35.8%‐99.5%) for ornidazole. The optimal concentration of both drugs for BAT was determined as 5 mg/mL. No cross‐reactivity among two drugs was observed according to in vivo tests. Conclusions Our study showed that SBPCDPT and BAT are both useful diagnostic tools for IHRs due to 5‐nitroimidazole antibiotics and can be used as supplementary to each other. No cross‐reactivity between metronidazole and ornidazole in IHRs exists.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Diagnostic workup including CD203c‐based basophil activation test in immediate hypersensitivity due to metronidazole and ornidazole and evaluation of cross‐reactivity in between

Beyaz

Akdeniz

Yilmaz

et al. 2020

Allergy

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“…This otherwise relatively common drug‐induced skin eruption is usually caused by nonsteroidal anti‐inflammatory drugs and antibiotics . FDE has been reported in three patients with omeprazole use, and only one case of a diffuse nonpigmented FDE was described with esomeprazole and confirmed with a patch test as well as an oral provocation test . Other reported esomeprazole‐related dermatologic side effects include immediate hypersensitivity reactions, maculopapular eruption, drug rash with eosinophilia and systemic symptoms syndrome, Stevens‐Johnson syndrome, and toxic epidermal necrolysis …”

Section: Discussionmentioning

confidence: 99%

Esomeprazole fixed drug eruption

2020

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K E Y W O R D S : case report, cutaneous adverse drug reaction, esomeprazole, fixed drug eruption, proton-pump inhibitors Fixed drug eruption (FDE) is a unique type of cutaneous adverse drug reaction characterized by one or multiple erythematous and edematous plaques that recur in the same locations within 48 hours after reexposure to the offending drug and resolve leaving residual postinflammatory hyperpigmentation. 1 A bullous form can also occur. 2To date, only seven cases due to proton-pump inhibitors (PPIs) have been reported. CASE REPORTA 65-year-old man presented for a diffuse pruritic and painful rash of the lower limbs, abdomen, and scalp that had gradually developed over the past 2 months. He had a medical history of hypertension, diabetes, and coronary artery disease. His medications included moxonidine, sitagliptin, metformin, and aspirin. The patient also reported occasional self-medication with rabeprazole, which he had recently replaced with esomeprazole. Physical examination revealed well-demarcated erythematous plaques with secondary blistering and crusting, mainly affecting the trunk, upper, and lower extremities (Figures S1 and 1). Mucous membranes were not involved. A skin biopsy performed from one of the lesions on the back revealed a normal basket-weave epidermis and a lichenoid infiltrate in the dermis with scattered lymphocytes and eosinophils. FDE was diagnosed based on clinical examination and supportive histopathology. The patient was advised to stop esomeprazole and was prescribed topical betamethasone. His symptoms improved quickly, and the skin lesion resolved with residual postinflammatory hyperpigmented patches.Three months later he accidentally took esomeprazole again and the same symptoms recurred 48 hours later at the sites of the old lesions. This re-exposure confirmed that esomeprazole was actually the culprit medication, and it was subsequently discontinued for good. 334 SALLOUM ET AL. DISCUSSION Despite the good overall safety profile of PPI, PPI-associated cutaneous adverse effects are common and can range from localized dermatosis to severe, life-threatening eruptions. 3 However, PPI-induced FDE is rare. This otherwise relatively common drug-induced skin eruption is usually caused by nonsteroidal anti-inflammatory drugs and antibiotics. 2 FDE has been reported in three patients with omeprazole use, 4-6 and only one case of a diffuse nonpigmented FDE was described with esomeprazole and confirmed with a patch test as well as an oral provocation test. 7 Other reported esomeprazole-related dermatologic side effects include immediate hypersensitivity reactions, 8 maculopapular eruption, 9 drug rash with eosinophilia and systemic symptoms syndrome, 10 Stevens-Johnson syndrome, and toxic epidermal necrolysis. 11 All PPIs currently on the market are composed of a benzimidazole ring and a pyridine ring. While omeprazole, esomeprazole, and pantoprazole have changes in their benzimidazole rings, lansoprazole and rabeprazole have changes in their pyridine ring. 12 This could explain w...

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“…Fixed drug eruption (FDE) is a distinctive type of cutaneous drug reaction that is characterized by one or multiple erythematous and edematous plaques that recur in the same locations upon re‐exposure to the offending drug. PPI‐induced FDE is rare, and only 5 cases were reported so far: 3 cases associated with omeprazole 21‐23 and 2 cases of diffuse FDE reported with esomeprazole, 24,25 both confirmed with an oral provocation test.…”

Section: Ppi‐induced Fixed Drug Eruptionmentioning

confidence: 99%

Dermatologic adverse reactions to proton‐pump inhibitors: A synthetized review

Salloum

Nasr

Maalouf

2020

J of Cosmetic Dermatology

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Background Proton‐pump inhibitors (PPIs) are one of the most prescribed drugs. Their dermatological adverse reactions are multiple and vary in severity. Aims This review discusses all reported cutaneous side effects of PPIs in order to help physicians understand them and provide appropriate management. Methods A thorough search of PubMed, Embase, and FDAAQ8 drugs websites was conducted. 56 articles including case reports, case series, and review articles of PPI‐induced cutaneous adverse reactions were selected. Data were recorded regarding patient age, gender, history, clinical manifestations, diagnostic tests, management, and clinical outcomes. Results PPI‐induced adverse skin reactions are mostly immunological and include both immediate and delayed‐type hypersensitivity reactions. These reactions are sometimes life‐threatening. All PPIs can induce immediate IgE‐mediated reactions. Most of previously published cases of delayed‐type hypersensitivity reactions have involved esomeprazole, omeprazole, and lansoprazole. Skin tests are helpful in confirming PPI‐induced hypersensitivity reactions and diagnosing potential cross‐reactivities. PPIs should also be added to our list of usual suspects when considering possible culprits for a new presentation of drug‐induced subacute lupus erythematosus. PPI‐related occupational contact dermatitis has also been numerously reported. Conclusion PPIs should be considered in our list of culprits when considering a patient with a cutaneous drug reaction, taking into account that these drugs can cause severe immunological manifestations.

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A case report of fixed drug eruption caused by several drugs because of cross‐reactivity and co‐sensitization

Cited by 8 publications

References 7 publications

Diagnostic workup including CD203c‐based basophil activation test in immediate hypersensitivity due to metronidazole and ornidazole and evaluation of cross‐reactivity in between

Diagnostic workup including CD203c‐based basophil activation test in immediate hypersensitivity due to metronidazole and ornidazole and evaluation of cross‐reactivity in between

Esomeprazole fixed drug eruption

Dermatologic adverse reactions to proton‐pump inhibitors: A synthetized review

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