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Acute generalized exanthematous pustulosis induced by : A case report

Y. Cherif, Moez Jallouli, M. Mseddi1, H. Turki1, Z. Bahloul

ABSTRACT Departments of Internal Medicine, and 1Dermatology, Hedi Chaker Acute generalized exanthematous pustulosis (AGEP) is a severe adverse cutaneous reaction University Hospital, Sfax, Tunisia characterized by an acute episode of sterile pustules over erythematous‑edematous skin. The main triggering drugs are antibiotics, mainly beta‑lactam and macrolides. Received: 27‑06‑2013 Non‑steroid anti‑inflammatory drugs may rarely be responsible. We describe a case of Revised: 30‑07‑2013 a woman with AGEP, who presented with generalized pustulosis lesions after the use Accepted: 21‑01‑2014 of piroxicam for renal colic. The diagnosis was confirmed by the clinical and histological correlations and the dermatosis resolved after withdrawal of the drug. Correspondence to: Dr. Moez Jallouli, KEY WORDS: Acute generalized exanthematous pustulosis, adverse drug reactions, E‑mail: [email protected] piroxicam, pustulosis

Introduction and dyslipidemia treated with simvastatin. She was given oral piroxicam 20 mg/day by her primary care physician for Cutaneous adverse drug reactions are estimated to be treatment of renal colic. There were no other medications prior about 30% of all adverse drug reactions and observed in to starting piroxicam. At 4 days after starting oral piroxicam, 2‑3% of hospitalized patients.[1] The cutaneous drug reaction she developed a generalized itchy eruption consisting of multiple shows various clinical features and mechanisms.[1,2] Acute papules that sometimes coalesced to larger and scaly plaques, generalized exanthematous pustulosis (AGEP) is a generalized pustular eruption that is primarily drug‑induced in probably on a background of widespread erythema with associated more than 90% of case.[3] In a few cases infections including multiple 2‑3 mm pustules [Figure 1]. The mucus membranes, cytomegalovirus[4] and parvovirus B19,[5] chlamydia and palms and soles were spared. Nikolsky’s sign was negative. The mycoplasma pneumoniae[6,7] have been suspected. A spider remaining physical examination was normal. Her white blood cell 3 3 3 3 bite was recently implicated as a possible cause of AGEP in count was 10.8 × 10 /mm , with a 6.42 × 10 /mm neutrophil three patients.[8] Although various drugs have been implicated count. The remaining laboratory tests performed were within in this condition, there are no reported cases of AGEP caused the normal range: creatinine 61.1 µmol/l, erythrocyte rate by oral in the current literature. We report here a case sedimentation at 30 mm/h, C‑reactive protein 19.48 mg/l and of AGEP induced by piroxicam. Figure 1: Multiple papules and pustules that coalesced to larger and Case Report scaly plaques 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,

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DOI: 10.4103/0253-7613.129332

232 Indian Journal of Pharmacology | April 2014 | Vol 46 | Issue 2 Cherif, et al.: Piroxicam induced exanthematous pustulosis her liver function tests were: Aspartate transaminase 38 U/ml, In this case, the clinical presentation and histology of a skin bilirubin 9 µmol/l and alkaline phosphatase 88 U/ml. A skin biopsy were consistent with AGEP. Resolution began without biopsy specimen revealed well‑developed subcorneal pustules further use of piroxicam, which advocates the diagnosis in associated with epidermal spongiosis. Scattered neutrophils retrospect. The other medications (nifedipine, captopril, as well as eosinophils were noted within the dermis (According indapamide, glibenclamide, glimepiride and simvastatin) were to the EuroSCAR score, the most of criteria have been met by continued. This association could have been strengthened by our patient who had a score of 9). Within a week of piroxicam performing patch test with piroxicam.[11] Due to the self‑limited withdrawal, the patient’s lesions gradually began clearing. and benign course of this disease, treatment is usually not The patient remained on the same therapies for her arterial necessary except for symptomatic therapy and withdrawal of the hypertension, diabetes mellitus and dyslipidemia. culprit drug.[8] Some cases have been treated with intravenous hydrocortisone, oral prednisolone or methylprednisolone or Discussion topical agents alone.[9,10] Drugs like infliximab were used in an AGEP is a rare pustular severe cutaneous adverse reaction over lop of AGEP‑toxic epidermal necrolysis.[10] In our case, the that generally presents with an acute edematous erythema and withdrawal of piroxicam was sufficient to resolve all clinical small non‑follicular sterile pustules mostly beginning in folds features in only 1 week. or face and within hours becomes diffuse. Skin symptoms are almost always accompanied by fever (≥38°C) and leukocytosis References with a high neurophil count (≥7000/μl). Other skin symptoms 1. Turk BG, Gunaydin A, Ertam I, Ozturk G. Adverse cutaneous drug reactions among such as marked edema of the face, purpura, blisters and vesicles hospitalized patients: Five year surveillance. Cutan Ocul Toxicol 2013;32:41‑5. have been described.[3] Additional systemic manifestations 2. Wedi B. Definitions and mechanisms of drug hypersensitivity. Expert Rev Clin Pharmacol 2010;3:539‑51. include mild eosinophilia, lymphadenopathy, acute renal failure 3. Sidoroff A, Halevy S, Bavinck JN, Vaillant L, Roujeau JC. Acute generalized and a mild elevation of liver .[1,3,9] exanthematous pustulosis (AGEP) – A clinical reaction pattern. J Cutan Pathol The multinational epidemiological case‑control study on 2001;28:113‑9. severe cutaneous adverse reactions (EuroSCAR‑project) has 4. Haro‑Gabaldón V, Sánchez‑Sánchez‑Vizcaino J, Ruiz‑Avila P, developed and used the well‑defined EuroSCAR group criteria to Gutiérrez‑Fernández J, Linares J, Naranjo‑Sintes R. Acute generalized [3] exanthematous pustulosis with cytomegalovirus infection. Int J Dermatol establish the diagnosis of AGEP. The accuracy of the EuroSCAR 1996;35:735‑7. [3,9] group criteria has been validated. It allots 0, 1 or 2 points for 5. Calistru AM, Lisboa C, Cunha AP, Bettencourt H, Azevedo F. Acute generalized each of 4 variables of morphology, −10, 0, 1, 2 or 3 for each of 5 exanthematous pustulosis to amoxicillin associated with parvovirus B19 variables of histological findings. In addition, it assigns −4, −2, reactivation. Cutan Ocul Toxicol 2012;31:258‑61. 0 or 1 for each of 5 items of the disease’s course. Its involved 6. Lim CS, Lim SL. Acute generalized exanthematous pustulosis associated with asymptomatic Mycoplasma pneumoniae infection. Arch Dermatol 2009;145:848‑9. items yield causality levels of definite with a scale at 8‑12 7. Manzano S, Guggisberg D, Hammann C, Laubscher B. Acute generalized points, probable (5‑7 points), possible (1‑4 points) and excluded exanthematous pustulosis: First case associated with a Chlamydia pneumoniae AGEP (0 point).[3] The range of the score is between −18 and 12. infection. Arch Pediatr 2006;13:1230‑2. In our case, the EuroSCAR score was 9 and therefore, the case 8. Davidovici BB, Pavel D, Cagnano E, Rozenman D, Halevy S, EuroSCAR, et al. was specified as definite AGEP. Acute generalized exanthematous pustulosis following a spider bite: Report of Histological findings show subcorneal and/or intraepidermal 3 cases. J Am Acad Dermatol 2006;55:525‑9. 9. Chang SL, Huang YH, Yang CH, Hu S, Hong HS. Clinical manifestations and pustules, with pronounced edema in the papillary dermis and a characteristics of patients with acute generalized exanthematous pustulosis in perivascular infiltrate of neutrophils and eosinophils.[3] Asia. Acta Derm Venereol 2008;88:363‑5. A wide spectrum of cutaneous diseases or reactions is 10. Peermohamed S, Haber RM. Acute generalized exanthematous pustulosis associated with pustular eruptions.[10] However, the chief simulating toxic epidermal necrolysis: A case report and review of the literature. differential diagnosis would include pustular psoriasis.[3,11] Arch Dermatol 2011;147:697‑701. [3] 11. Speeckaert MM, Speeckaert R, Lambert J, Brochez L. Acute generalized Most cases of AGEP have been attributed to drug reactions. exanthematous pustulosis: An overview of the clinical, immunological and [12] Roujeau et al. found that 87% of cases resulted from drug diagnostic concepts. Eur J Dermatol 2010;20:425‑33. reactions. Studies show that antibiotics were the most common 12. Roujeau JC, Bioulac‑Sage P, Bourseau C, Guillaume JC, Bernard P, Lok C, et al. drugs implicated (75%), with no attributes to non‑steroidal Acute generalized exanthematous pustulosis. Analysis of 63 cases. Arch Dermatol anti‑inflammatory drugs (NSAIDs). Furthermore, there is an 1991;127:1333‑8. [1,3,11] 13. Rastogi S, Modi M, Dhawan V. Acute localized exanthematous pustulosis (ALEP) increasing number of cases caused by anti‑fungals. A study caused by . A case report. Br J Oral Maxillofac Surg 2009;47:132‑4. [9] done by Chang et al. analyzed 16 cases of AGEP with a 14. Ziemssen T, Bauer A, Bär M. Potential side effect of high‑dose corticosteroid relatively low association with systemic drugs (62.5%), there relapse treatment: Acute generalized exanthematous pustulosis (AGEP). Mult was no case of causative NSAIDs. There have been few cases Scler 2009;15:275‑7. implicating NSAIDs,[1] including ibuprofen,[13] ,[1,11] Cite this article as: Cherif Y, Jallouli M, Mseddi M, Turki H, Bahloul Z. Acute topical bufexamac, and .[11] As generalized exanthematous pustulosis induced by piroxicam: A case report. corticosteroids are commonly used in the treatment of severe Indian J Pharmacol 2014;46:232-3. AGEP; they nevertheless, may trigger severe and rare AGEP.[14] Source of Support: Nil. Conflict of Interest: No.

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