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 »  Abstract
 » Introduction
 » Case Report
 » Discussion
 »  References
 »  Article Figures

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DRUG WATCH
Year : 2014  |  Volume : 46  |  Issue : 2  |  Page : 232-233
 

Acute generalized exanthematous pustulosis induced by piroxicam: A case report


1 Department of Internal Medicine, Hedi Chaker University Hospital, Sfax, Tunisia
2 Department of IDermatology, Hedi Chaker University Hospital, Sfax, Tunisia

Date of Submission27-Jun-2013
Date of Decision30-Jul-2013
Date of Acceptance21-Jan-2014
Date of Web Publication24-Mar-2014

Correspondence Address:
Moez Jallouli
Department of Internal Medicine, Hedi Chaker University Hospital, Sfax
Tunisia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0253-7613.129332

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 » Abstract 

Acute generalized exanthematous pustulosis (AGEP) is a severe adverse cutaneous reaction characterized by an acute episode of sterile pustules over erythematous-edematous skin. The main triggering drugs are antibiotics, mainly beta-lactam and macrolides. Non-steroid anti-inflammatory drugs may rarely be responsible. We describe a case of a woman with AGEP, who presented with generalized pustulosis lesions after the use of piroxicam for renal colic. The diagnosis was confirmed by the clinical and histological correlations and the dermatosis resolved after withdrawal of the drug.


Keywords: Acute generalized exanthematous pustulosis, adverse drug reactions, piroxicam, pustulosis


How to cite this article:
Cherif Y, Jallouli M, Mseddi M, Turki H, Bahloul Z. Acute generalized exanthematous pustulosis induced by piroxicam: A case report. Indian J Pharmacol 2014;46:232-3

How to cite this URL:
Cherif Y, Jallouli M, Mseddi M, Turki H, Bahloul Z. Acute generalized exanthematous pustulosis induced by piroxicam: A case report. Indian J Pharmacol [serial online] 2014 [cited 2019 Sep 17];46:232-3. Available from: http://www.ijp-online.com/text.asp?2014/46/2/232/129332



 » Introduction Top


Cutaneous adverse drug reactions are estimated to be about 30% of all adverse drug reactions and observed in 2-3% of hospitalized patients. [1] The cutaneous drug reaction shows various clinical features and mechanisms. [1],[2] Acute generalized exanthematous pustulosis (AGEP) is a generalized pustular eruption that is primarily drug-induced in probably more than 90% of case. [3] In a few cases infections including cytomegalovirus [4] and parvovirus B19, [5] chlamydia and mycoplasma pneumoniae [6],[7] have been suspected. A spider bite was recently implicated as a possible cause of AGEP in three patients. [8] Although various drugs have been implicated in this condition, there are no reported cases of AGEP caused by oral oxicams in the current literature. We report here a case of AGEP induced by piroxicam.


 » Case Report Top


This was a case report of a 61-year-old female patient who was admitted to internal medicine department for renal colic. She had no history of psoriasis or any other skin disorder. The patient had a history of longstanding arterial hypertension for 3 years treated with captopril, indapamide, nifedipine and diabetes mellitus for 3 years treated with glibenclamide, glimepiride and dyslipidemia treated with simvastatin. She was given oral piroxicam 20 mg/day by her primary care physician for treatment of renal colic. There were no other medications prior to starting piroxicam. At 4 days after starting oral piroxicam, she developed a generalized itchy eruption consisting of multiple papules that sometimes coalesced to larger and scaly plaques, on a background of widespread erythema with associated multiple 2-3 mm pustules [Figure 1]. The mucus membranes, palms and soles were spared. Nikolsky's sign was negative. The remaining physical examination was normal. Her white blood cell count was 10.8 × 10 3 /mm 3 , with a 6.42 × 10 3 /mm 3 neutrophil count. The remaining laboratory tests performed were within the normal range: creatinine 61.1 μmol/l, erythrocyte rate sedimentation at 30 mm/h, C-reactive protein 19.48 mg/l and her liver function tests were: Aspartate transaminase 38 U/ml, bilirubin 9 μmol/l and alkaline phosphatase 88 U/ml. A skin biopsy specimen revealed well-developed subcorneal pustules associated with epidermal spongiosis. Scattered neutrophils as well as eosinophils were noted within the dermis (According to the EuroSCAR score, the most of criteria have been met by our patient who had a score of 9). Within a week of piroxicam withdrawal, the patient's lesions gradually began clearing. The patient remained on the same therapies for her arterial hypertension, diabetes mellitus and dyslipidemia.
Figure 1: Multiple papules and pustules that coalesced to larger and scaly plaques

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 » Discussion Top


AGEP is a rare pustular severe cutaneous adverse reaction that generally presents with an acute edematous erythema and small non-follicular sterile pustules mostly beginning in folds or face and within hours becomes diffuse. Skin symptoms are almost always accompanied by fever (≥38°C) and leukocytosis with a high neurophil count (≥7000/μl). Other skin symptoms such as marked edema of the face, purpura, blisters and vesicles have been described. [3] Additional systemic manifestations include mild eosinophilia, lymphadenopathy, acute renal failure and a mild elevation of liver enzymes. [1],[3],[9]

The multinational epidemiological case-control study on severe cutaneous adverse reactions (EuroSCAR-project) has developed and used the well-defined EuroSCAR group criteria to establish the diagnosis of AGEP. [3] The accuracy of the EuroSCAR group criteria has been validated. [3],[9] It allots 0, 1 or 2 points for each of 4 variables of morphology, −10, 0, 1, 2 or 3 for each of 5 variables of histological findings. In addition, it assigns −4, −2, 0 or 1 for each of 5 items of the disease's course. Its involved items yield causality levels of definite with a scale at 8-12 points, probable (5-7 points), possible (1-4 points) and excluded AGEP (0 point). [3] The range of the score is between −18 and 12. In our case, the EuroSCAR score was 9 and therefore, the case was specified as definite AGEP.

Histological findings show subcorneal and/or intraepidermal pustules, with pronounced edema in the papillary dermis and a perivascular infiltrate of neutrophils and eosinophils. [3]

A wide spectrum of cutaneous diseases or reactions is associated with pustular eruptions. [10] However, the chief differential diagnosis would include pustular psoriasis. [3],[11]

Most cases of AGEP have been attributed to drug reactions. [3] Roujeau et al. [12] found that 87% of cases resulted from drug reactions. Studies show that antibiotics were the most common drugs implicated (75%), with no attributes to non-steroidal anti-inflammatory drugs (NSAIDs). Furthermore, there is an increasing number of cases caused by anti-fungals. [1],[3],[11] A study done by Chang et al. [9] analyzed 16 cases of AGEP with a relatively low association with systemic drugs (62.5%), there was no case of causative NSAIDs. There have been few cases implicating NSAIDs, [1] including ibuprofen, [13] diclofenac, [1],[11] topical bufexamac, naproxen and phenylbutazone. [11] As corticosteroids are commonly used in the treatment of severe AGEP; they nevertheless, may trigger severe and rare AGEP. [14]

In this case, the clinical presentation and histology of a skin biopsy were consistent with AGEP. Resolution began without further use of piroxicam, which advocates the diagnosis in retrospect. The other medications (nifedipine, captopril, indapamide, glibenclamide, glimepiride and simvastatin) were continued. This association could have been strengthened by performing patch test with piroxicam. [11] Due to the self-limited and benign course of this disease, treatment is usually not necessary except for symptomatic therapy and withdrawal of the culprit drug. [8] Some cases have been treated with intravenous hydrocortisone, oral prednisolone or methylprednisolone or topical agents alone. [9],[10] Drugs like infliximab were used in an over lop of AGEP-toxic epidermal necrolysis. [10] In our case, the withdrawal of piroxicam was sufficient to resolve all clinical features in only 1 week.

 
 » References Top

1.Turk BG, Gunaydin A, Ertam I, Ozturk G. Adverse cutaneous drug reactions among hospitalized patients: Five year surveillance. Cutan Ocul Toxicol 2013;32:41-5.  Back to cited text no. 1
    
2.Wedi B. Definitions and mechanisms of drug hypersensitivity. Expert Rev Clin Pharmacol 2010;3:539-51.  Back to cited text no. 2
    
3.Sidoroff A, Halevy S, Bavinck JN, Vaillant L, Roujeau JC. Acute generalized exanthematous pustulosis (AGEP) - A clinical reaction pattern. J Cutan Pathol 2001;28:113-9.  Back to cited text no. 3
    
4.Haro-Gabaldón V, Sánchez-Sánchez-Vizcaino J, Ruiz-Avila P, Gutiérrez-Fernández J, Linares J, Naranjo-Sintes R. Acute generalized exanthematous pustulosis with cytomegalovirus infection. Int J Dermatol 1996;35:735-7.  Back to cited text no. 4
    
5.Calistru AM, Lisboa C, Cunha AP, Bettencourt H, Azevedo F. Acute generalized exanthematous pustulosis to amoxicillin associated with parvovirus B19 reactivation. Cutan Ocul Toxicol 2012;31:258-61.  Back to cited text no. 5
    
6.Lim CS, Lim SL. Acute generalized exanthematous pustulosis associated with asymptomatic Mycoplasma pneumoniae infection. Arch Dermatol 2009;145:848-9.  Back to cited text no. 6
    
7.Manzano S, Guggisberg D, Hammann C, Laubscher B. Acute generalized exanthematous pustulosis: First case associated with a Chlamydia pneumoniae infection. Arch Pediatr 2006;13:1230-2.  Back to cited text no. 7
    
8.Davidovici BB, Pavel D, Cagnano E, Rozenman D, Halevy S, EuroSCAR, et al. Acute generalized exanthematous pustulosis following a spider bite: Report of 3 cases. J Am Acad Dermatol 2006;55:525-9.  Back to cited text no. 8
    
9.Chang SL, Huang YH, Yang CH, Hu S, Hong HS. Clinical manifestations and characteristics of patients with acute generalized exanthematous pustulosis in Asia. Acta Derm Venereol 2008;88:363-5.  Back to cited text no. 9
    
10.Peermohamed S, Haber RM. Acute generalized exanthematous pustulosis simulating toxic epidermal necrolysis: A case report and review of the literature. Arch Dermatol 2011;147:697-701.  Back to cited text no. 10
    
11.Speeckaert MM, Speeckaert R, Lambert J, Brochez L. Acute generalized exanthematous pustulosis: An overview of the clinical, immunological and diagnostic concepts. Eur J Dermatol 2010;20:425-33.  Back to cited text no. 11
    
12.Roujeau JC, Bioulac-Sage P, Bourseau C, Guillaume JC, Bernard P, Lok C, et al. Acute generalized exanthematous pustulosis. Analysis of 63 cases. Arch Dermatol 1991;127:1333-8.  Back to cited text no. 12
    
13.Rastogi S, Modi M, Dhawan V. Acute localized exanthematous pustulosis (ALEP) caused by Ibuprofen. A case report. Br J Oral Maxillofac Surg 2009;47:132-4.  Back to cited text no. 13
    
14.Ziemssen T, Bauer A, Bär M. Potential side effect of high-dose corticosteroid relapse treatment: Acute generalized exanthematous pustulosis (AGEP). Mult Scler 2009;15:275-7.  Back to cited text no. 14
    


    Figures

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This article has been cited by
1 Piroxicam
Reactions Weekly. 2014; 1500(1): 31
[Pubmed] | [DOI]



 

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