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Year : 2022  |  Volume : 67  |  Issue : 6  |  Page : 774-776
Azole antifungal–induced erythema annulare centrifugum in a case of extensive Tinea: A rare case report

1 From the Department of Dermatology, AIIMS Raebareli, Raebareli, Uttar Pradesh, India
2 Department of Pharmacology, AIIMS Raebareli, Raebareli, Uttar Pradesh, India
3 Department of Pathology and Lab Medicine, AIIMS Raebareli, Raebareli, Uttar Pradesh, India

Date of Web Publication23-Feb-2023

Correspondence Address:
K Geetha
From the Department of Dermatology, AIIMS Raebareli, Raebareli, Uttar Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijd.ijd_128_22

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How to cite this article:
Geetha K, Upadhyaya A, Puja, Kumari N, Gupta S. Azole antifungal–induced erythema annulare centrifugum in a case of extensive Tinea: A rare case report. Indian J Dermatol 2022;67:774-6

How to cite this URL:
Geetha K, Upadhyaya A, Puja, Kumari N, Gupta S. Azole antifungal–induced erythema annulare centrifugum in a case of extensive Tinea: A rare case report. Indian J Dermatol [serial online] 2022 [cited 2023 Mar 29];67:774-6. Available from:


Erythema annulare centrifugum (EAC), a chronic inflammatory skin condition with uncertain aetiology, is considered a hypersensitivity reaction induced by many factors. EAC appears as erythematous papules or plaques that expand by peripheral extension and central clearing, leading to an annular or polycyclic pattern.[1] EAC is a self-limiting condition with a wide range of symptoms that can persist anywhere from a few weeks to three decades. Various agents, however, have indeed been implicated, notably arthropod bites, hypersensitive reaction to medications (penicillin, salicylates, hydrochlorothiazide), infections (bacterial, mycobacterial, viral, fungal, filarial), food allergies (blue cheese Penicillium), cancer (lymphoma, multiple myeloma, breast cancer), autoimmune, and endocrine disorders (Hashimoto thyroiditis, Sjogren syndrome).[2] The presence of erythematous macular lesions or urticarial papules that enlarge peripherally to form an annular, arcuate, or polycyclic appearance is usually used to clinically diagnose EAC. Characteristic alterations in the form of epidermal parakeratosis and spongiosis with superficial perivascular infiltrates can be seen on histological investigation.[3] Drug-induced erythema annulare centrifugum is usually diagnosed by examining the presenting symptoms, reviewing the patient's drug history, and, if necessary, performing a skin biopsy. Discontinuing the use of these medications may slow or inhibit the progression of drug-induced EAC, or perhaps cure it. With proper treatment, the prognosis is favourable in the majority of those patients.

A 52-year-old female patient presented to our outpatient department (OPD) with extensive tinea for 1 month and was started on topical and oral azole antifungals. After 2 weeks, she came with a 5-day history of nonpruritic, spreading annular reddish eruptions. Skin examination revealed multiple annular, non-scaly, erythematous, indurated plaques over the abdomen and face along with few erosions on the chest [Figure 1] and [Figure 2]. Laboratory examinations, including complete blood count and biochemistry profile, were normal. KOH mount from the erythematous lesions was negative. Skin biopsy specimens were taken from the erythematous lesions on the arm and abdomen. Histopathological examination revealed parakeratosis, hyperkeratosis, and mild spongiosis. Focal collection of neutrophilis with nuclear debris in the stratum corneum was seen. Dermis showed moderate perivascular lymphomononuclear cell infiltrate with absence of granuloma or necrosis [Figure 3]. After a short course of oral prednisolone 20 mg for 5 days, the EAC reaction subsided. She developed recurrence of symptoms once steroids were stopped, and topical luliconazole with oral terbinafine was being given for tinea probably because of re-challenge by the topical azole. The recurrence subsided once topical azole was stopped. Then the patient was started on oral terbinafine and antihistamine without any topical medication and her tinea lesions started to improve after 3 weeks. She received clinical and mycological cure after 8 weeks of terbinafine.
Figure 1: Annular, non-scaly, erythematous, indurated plaques before and after resolution over the chest

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Figure 2: Annular, non-scaly, erythematous, indurated plaques before and after resolution over the abdomen

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Figure 3: Histology showing parakeratosis, hyperkeratosis, focal collection of neutrophilis with nuclear debris in the stratum corneum

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EAC is a reactive figurate erythema disorder which clinically manifests as enlarging papules commonly over the abdomen, trunk, and arms, which subsequently clear in the centre; sometimes fine trailing scale is noticeable. Drug-induced EAC has previously been reported with amitryptalline, sorafenib,[4] aceclofenac, etizolam, pegylated interferon-α-2a plus ribavirin combination therapy, finasteride, rituximab and sipuleucel-T infusion.[5] Though it is usually a delayed hypersensitivity reaction, the exact mechanism of drug-induced EAC is unclear. Probable hypotheses include IFN-γ release by lymphocytes, cytokine storm resulting from activation of cytotoxic T cells, and cross-reactivity of autologous immune cells to keratinocyte surface antigens.[6] The azole antifungals include two broad classes: imidazoles and triazoles. Though cross-reactivity within members of antifungal triazoles and imidazoles has been observed in literature, no consistent pattern of cross-reactivity has been described, and it remains poorly understood.[7]

In our case, the patient developed the EAC for the first time with topical luliconazole and oral itraconazole and improved after stopping the azoles, both oral and topical (positive dechallenge test). After that, similar lesion recurred with the use of oral terfinafine and topical luliconazole (positive rechallenge test). As per the World Health Organization-Uppasala Monitoring Center (WHO-UMC), the Causality Assessment for the adverse drug reaction is certain as it has plausible time relationship with drug intake and the causality is confirmed by the rechallange test.[8] To the best of our knowledge, this case of cutaneous adverse drug reaction due the suspected drug is the first case report of EAC with topical luliconazole and oral itraconazole with WHO-UMC causality category - certain.

Temporal correlation between intake of the drug and appearance of the rash, negative KOH mount, and corroborative histopathological features pointed towards the diagnosis. The probability of development of EAC to antifungal drugs in tinea cases should be kept in mind as the clinical picture is overlapping and the patient would not respond to the antifungal therapy. The present case highlights the same and warrants a high clinical suspicion in such cases. Management of EAC usually aims at identifying and treating the underlying cause, topical and/or oral steroids, and anti- histamines. Anecdotal reports of resolution of EAC with oral metronidazole, fluconazole, topical vitamin D analogues, calcineurin inhibitors, biologicals like etanercept, interferon-α, and NBUVB have been noted.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Kim DH, Lee JH, Lee JHY, Park YM. Erythema annulare centrifugum: Analysis of associated diseases and clinical outcomes according to histopathologic classification. Ann Dermatol 2016;28:257-9.  Back to cited text no. 1
Al Hawsawi K, Alzanbagi H, Almatrafi S, Refae S, Al-Shahrani F, Alsulimani H, et al. Erythema annulare centrifugum (deep type): A rare case report. Dermatol Open J 2017;2:4-6.  Back to cited text no. 2
Munirah Bulqini R, Tabri F, Djawad K. Erythema annulare centrifugum: A rare case report. Acta Dermatovenerol Alp Pannonica Adriat 2021;30:109-11.  Back to cited text no. 3
Yao CA. Sorafenib-induced erythema annulare centrifugum with spontaneous resolution after skin biopsy. Australas J Dermatol 2018;59:e150-1.  Back to cited text no. 4
Tadros J, Rahnama-Moghadam S. Erythema annulare centrifugum-type eruption in a patient undergoing cancer vaccine immunotherapy. Dermatol Online J 2018;24:13030.  Back to cited text no. 5
Ena L, Mazzarello V, Ferrari M, Ena P. Recurrent erythema annulare centrifugum due to influenza type A. Case Rep Dermatol 2021;13:134-40.  Back to cited text no. 6
Mithari HS, Gole PV, Kharkar VD, Mahajan SA. Generalized bullous fixed drug eruption to fluconazole; with cross-reactivity to tinidazole. Indian J Dermatol 2019;64:335-7.  Back to cited text no. 7
[PUBMED]  [Full text]  
Zaki SA. Adverse drug reaction and causality assessment scales. Lung India 2011;28:152-3.  Back to cited text no. 8
[PUBMED]  [Full text]  


  [Figure 1], [Figure 2], [Figure 3]


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