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CORRESPONDENCE
Year : 2022  |  Volume : 67  |  Issue : 3  |  Page : 298-299
Acute localized exanthematous pustulosis (ALEP) due to itraconazole


1 Department of Dermatology, Venerology and Leprology, Vardhaman Mahavir Medical College and Safdarjung Hospital, New Delhi, India
2 National Institute of Pathology, Indian Council of Medical Research(ICMR), India

Date of Web Publication22-Sep-2022

Correspondence Address:
Sushruta Kathuria
Department of Dermatology, Venerology and Leprology, Vardhaman Mahavir Medical College and Safdarjung Hospital, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijd.IJD_577_20

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How to cite this article:
Singh R, Kathuria S, Sharma S. Acute localized exanthematous pustulosis (ALEP) due to itraconazole. Indian J Dermatol 2022;67:298-9

How to cite this URL:
Singh R, Kathuria S, Sharma S. Acute localized exanthematous pustulosis (ALEP) due to itraconazole. Indian J Dermatol [serial online] 2022 [cited 2022 Sep 30];67:298-9. Available from: https://www.e-ijd.org/text.asp?2022/67/3/298/356743




Sir,

An 18-year-old male presented with multiple, small pus-filled lesions over the neck and ears for 3 days associated with a mild burning sensation. Preceding the onset, he had taken oral itraconazole 100 mg twice daily 10 days back for tinea corporis. There was no history of any systemic complaints. The general and systemic examination was normal. On cutaneous examination, multiple, discrete, grouped, non-follicular, pin-head-sized pustules were present over an erythematous base over the forehead, eyes, neck, and around the ears [Figure 1]. The palms, soles, and mucosa were within normal limits. The Gram stain and 10% potassium hydroxide mount were negative for organisms. Histopathological examination showed hyperkeratosis, acanthosis, and spongiosis of the epidermis with neutrophilic pustule present in the stratum corneum. No organisms were seen. There was also mild perivascular infiltrate of lymphocytes, histiocytes, neutrophils, and occasional eosinophils [Figure 2]. On stopping all antifungals, a complete resolution of the pustules was seen in 14 days [Figure 3]. The patient was advised to get a hemogram and patch test done, but he refused. After 2 weeks, the patient was started on terbinafine with which he improved.
Figure 1: Multiple, discrete, grouped, non-follicular, pin-head-sized pustules present over an erythematous base over the forehead (a), eyes (a), neck (b), and around the ears (c).

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Figure 2: (a) Photomicrograph shows hyperkeratosis, acanthosis, and spongiosis of epidermis. A neutrophilic pustule is present within the stratum corneum. Papillary and upper dermis shows perivascular and interstitial inflammatory cell infiltrate (H&E, 100X). (b) Photomicrograph showing dermal infiltrate rich in lymphocytes and eosinophils (H&E, 400X).

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Figure 3: Resolution of pustules with scaling over the forehead (a), eyes (a), and around the ears (b).

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The differential diagnoses considered were an extension of tinea corporis, ALEP, bacterial folliculitis, and localized pustular contact dermatitis. But, the evolution of the lesions, temporal correlation with the intake of itraconazole, histopathology, resolution of lesions on stopping of the drug, and a EuroSCAR score of 8 [Table 1] were all definitive for acute generalized exanthematous pustulosis (AGEP). However, as the lesions were localized to the head and neck, a diagnosis of ALEP was made.
Table 1: Diagnostic score for acute generalized exanthematous pustulosis from EuroSCAR study[1]

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AGEP is an uncommon type of severe cutaneous adverse drug reaction presenting with non-follicular sterile pustules on the erythematous background. ALEP is its localized variant where similar clinical features are present over one part of the body. Besides drugs, AGEP has been uncommonly reported with viral and bacterial infections.[2] ALEP was first described by Prange et al.[3] in a patient with a presentation similar to AGEP but localized to the face. Previously, ALEP has been seen with various antibiotics such as amoxicillin-clavulanic acid, levofloxacin; Non steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen, flurbiprofen, diclofenac, docetaxel, and sorafenib. To the best of our knowledge, ALEP to itraconazole has not been reported. Most cases of drug-induced ALEP are females above 17 years of age.[4] In children, non-drug-related etiologies causing ALEP such as viruses, plants, and air-borne allergens have been suggested.[5] ALEP most commonly presents on the face and neck as seen in our case. Fever, neutrophilia, and systemic symptoms may or may not be present in the ALEP.[4]

The pathogenesis of AGEP is largely unknown. Drug-specific activation of CD4 + and CD8 + T-cells leads to the release of pro-inflammatory cytokines and apoptosis causing vesicle formation, as demonstrated by the patch test and the lymphocyte transformation test to the drug.[2] In ALEP, these tests have been found positive, indicating a similar pathomechanism as AGEP, but due to weaker activation of pro-inflammatory cytokines, a localized involvement is seen.[4] Genetic predisposition due to mutations in the Interleukin-6 (IL-36) receptor antagonist (IL36RN) gene has also been implicated.[4]

The treatment includes the immediate withdrawal of the drug. Sometimes, topical or oral corticosteroids and anti-histamines may be required to alleviate the symptoms.

To conclude, we present a case of ALEP to itraconazole confirmed by histopathology.

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.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Sidoroff A, Dunant A, Viboud C, Halevy S, Bouwes Bavinck JN, Naldi L, et al. Risk factors for Acute generalized exanthematous pustulosis (AGEP)-results of a multinational case-control study (EuroSCAR). Br J Dermatol 2007;157:989-96.  Back to cited text no. 1
    
2.
Feldmeyer L, Heidemeyer K, Yawalkar N. Acute generalized exanthematous pustulosis: Pathogenesis, genetic background, clinical variants and therapy. Int J Mol Sci 2016;17:1214.  Back to cited text no. 2
    
3.
Prange B, Marini A, Kalke A, Hodzic-Avdagic N, Ruzicka T, Hengge UR. Acute localized exanthematous pustulosis (ALEP). J Dtsch Dermatol Ges 2005;3:210-2.  Back to cited text no. 3
    
4.
Villani A, Baldo A, De Fata Salvatores G, Desiato V, Ayala F, Donadio C. Acute localized exanthematous pustulosis (ALEP): Review of literature with report of case caused by Amoxicillin-Clavulanic acid. Dermatol Ther (Heidelb) 2017;7:563-70.  Back to cited text no. 4
    
5.
Mohamed M, Soua Y, Njim L, Hammemi S, Youssef M, Akkari H, et al. [Acute localized exanthematous pustulosis on the face: 6 cases in Tunisia]. Ann Dermatol Venereol 2014;141:756-64.  Back to cited text no. 5
    


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