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Indian Journal of Dermatology, Venereology and Leprology
Medknow Publications on behalf of The Indian Association of Dermatologists, Venereologists and Leprologists (IADVL)
ISSN: 0378-6323 EISSN: 0973-3922
Vol. 75, Num. 4, 2009, pp. 408-410

Indian Journal of Dermatology, Venereology and Leprology, Vol. 75, No. 4, July-August, 2009, pp. 408-410

Letter to the Editor

Nifedipine-induced acute generalized exanthematous pustulosis in a case of acute glomerulonephritis

Department of Dermatology, Venereology, and Leprology, Hi-Tech Medical College and Hospital, Pandara, Bhubaneswar
Correspondence Address:Dr. Satyabrata Tripathy, Department of Dermatology, Venereology, and Leprology, Hi-Tech Medical College and Hospital, Pandara, Bhubaneswar
drsatyabrata@rediffmail.com

Code Number: dv09158

PMID: 19584474
DOI: 10.4103/0378-6323.53150

Sir,

Acute generalized exanthematous pustulosis (AGEP) is a disease characterized by the rapid occurrence of many sterile nonfollicular pustules usually arising on an edematous erythema, often accompanied by leucocytosis and fever. [1] Drugs are attributed as the most important cause of AGEP, although, rarely, it can be due to infections or idiopathic. [2] Herein, we report a case of AGEP induced by nifedeipine in a patient of acute glomerulonephritis.

A 27-year-old male patient diagnosed as a case of acute glomerulonephritis on furosemide and enalapril for last 3 months was admitted to the medical unit of our institute with severe hypertension and was prescribed nifedipine for control of the hypertension. On the third day of treatment with nifedipine, he developed fever, which was followed by a generalized skin rash consisting of numerous discrete 2-3mm pustules over an erythematous skin affecting the upper extremity, chest, abdomen and thighs [Figure - 1]. The patient′s past medical history was negative for any similar eruptions, psoriasis or any drug allergies. On bacteriological and mycological examination of the pustules, no organisms could be isolated. Tzanck test was negative for any acantholytic cells or multinucleated giant cells. A skin biopsy showed spongiosis with dense subcorneal neutrophilic infiltrate and edematous papillary dermis with perivascular mixed mononuclear cell infiltrate. Based on the clinical features, negative microbiological study and histopathological findings, a diagnosis of AGEP was made and the suspected drug nifedipine was withdrawn and the patient prescribed oral cetrizine and paracetamol. After 2 days of stopping nifedipine, the patient became afebrile and there were no further new eruptions. At the end of 1 week, all the skin lesions were healing with desquamation.

Cutaneous drug reactions occur at a frequency of 1-8% and can be higher for certain classes of drugs.[3] AGEP is a severe cutaneous adverse reaction and has a typical clinical evolution pattern, in that the eruptions occur 24 h-3 weeks (average, 5 days) after administration of the offending drug and quickly resolve on discontinuation of the drug in a 1-2 week time period. [1],[2],[4],[5] A recent multinational case control study, Euro SCAR, has found the highest risk of AGEP due to drugs like antibiotics (macrolides- pristinomycin, aminopenicillin, quinolone, sulfonamide), anticonvulsants, hydroxychloroquine, terbinafine and diltiazem. [1] Other drugs reported to be associated are glucocortcoids, oxicam, nonsteriodal anti inflammatory drugs (NSAIDs), fluconazole, chlorpromazine, mesalazine, allopurinol, enalapril, furosemide, nystatin and hydroxyzine. [1],[2],[3],[4],[5],[6],[7],[8],[9],[10],[11],[12] The Euro SCAR study did not find any association of AGEP with psoriasis or infective causes, although earlier studies have shown a higher incidence of AGEP in psoriasis and even some have considered it as an entity no different from pustular psoriasis. [1],[6] However, the clinical evolution pattern of AGEP is different as compared with pustular psoriasis. AGEP is mediated by T-cells, which produce high levels of CXL8 (interleukin-8) and granulocyte monocyte CSF. [2] CXCL-8 is also produced by keratinocytes in the lesion of AGEP. [2] AGEP can be confused with other pustular cutaneous dermatoses like pustular psoriasis, drug hypersensitivity syndrome with pustules, subcorneal pustular dermatosis, pustular vasculitis, bacterial, viral and fungal infections and, in severe cases, from toxic epidermal necrolysis. The temporal relationship of the development of the eruption with the intake of the suspected drug and its prompt subsidence on withdrawal of the drug along with the histopathological findings and negative microbiological study helps to arrive at a diagnosis. Among the calcium channel blockers, diltiazem has a very high risk of developing the eruption. [1],[13],[14] Cross reactivity with other calcium channel blockers like nifedipine and verapamil has been demonstrated by patch testing. [13] A knowledge of the possible groups of drugs responsible for the reactions is essential for the clinicians as prompt withdrawal of the offending drug helps resolution of the eruption, which otherwise can be occasionally fatal. Some patients may require the use of systemic corticosteroids. [15] Because AGEP is a T-cell-mediated reaction, it is suppressed by steroids like any other T-cell-mediated reaction; nevertheless, it should be kept in mind that steroids can themselves be a cause of AGEP. [1],[9]

References

1.Sidoroff A, Dunant A, Viboud C, Halevy S, Bavinck Bouwess JN, Naldi L, et al. Risk factors for acute generalized exanthematous pustolsis(AGEP)-results of a multinational case-control study (EuroSCAR). Br J Dermatol 2007;157:989-96.  Back to cited text no. 1    
2.James WD, Berger TG, Melston D, editors. Contact Dermatitis and Drug Eruptions. In:Andrews' diseases of the Skin -Clinical Dermatology. 10 th ed. Philadelphia: Saunders Elsevier Health Science; 2006. p. 91-138.  Back to cited text no. 2    
3.Arroyo MP, Heller P, Pomeranz MK. Generalized pustules in a healthy woman. J Drugs Dermatol 2002;1:63-5.  Back to cited text no. 3    
4.Shear NH, Knowles SR, Sullivan JR, Shapiro L. Cutaneous reactions to drugs. In: Freedberg IM, Eisen AZ, Wolff K, Austen KF, Goldsmith LA, Katz SI, editors. Fitzpatricks' Dermatology in General Medicine. 6 th ed. New York: McGraw-Hill; 2003. p. 1330-7.  Back to cited text no. 4    
5.Breathnach SM. Drug reactions. In: Burns T, Breathnach S, Cox N, Griffiths C, editors. Rooks' Textbook of Dermatology. 7 th ed. Massachusetts: Blackwell Science; 2004. p. 73.1-180.  Back to cited text no. 5    
6.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. 6    
7.Hall AP, Tate B. Acute generalized exanthematous pustulosis associated with oral terbinafine. Australas J Dermatol. 2000;41: 42-5.  Back to cited text no. 7    
8.Fabre B, Albes B, Belhadjali H, Bajex J. Acute generalized exanthematous pustulosis due to fluconazole. Ann Dermatol Venereol 2002;129:294-7.  Back to cited text no. 8    
9.Mussot-Chia C, Flechet ML, Napolitano M, Herson S, Frances C, Chosidow O. Methylprednisolone-induced acute generalized exanthematous pustulosis. Ann Dermatol Venereol 2001;128:241-3.  Back to cited text no. 9    
10.Saissi EH, Beau-Salinas F, Jonville-Bera AP, Lorette G, Autret-Leca E; Centres Rιgionaux de Pharmacovigilance. Drugs associated with acute generalized exanthematous pustulosis. Ann Dermatol Venereol 2003;130:612-8.  Back to cited text no. 10    
11.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. 11    
12.Tsai YS, Tu ME, Wu YH, Lin YC. Hydroxyzine-induced acute generalized pustulosis. Br J Dermatol 2007;157:1296-7.  Back to cited text no. 12    
13.Knowles S, Gupta AK, Shear NH. The spectrum of cutaneous reactions with diltiazem: Three cases and a review of literature. J Am Acad Dermatol 1998;38:201-6.  Back to cited text no. 13    
14.Wakelin SH, James MP. Diltiazem-induced acute generalized exanthematous pustulosis. Clin Exp Dermatol 1995;20:341-4.  Back to cited text no. 14    
15.Shear NH, Knowles SR, Saphiro L. In: Wolf K,Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffel DJ, editors. Fitzpatrick's Dermatology in General Medicine. 7 th ed. New York: McGraw-Hill; 2008. p. 356-62.  Back to cited text no. 15    

Copyright 2009 - Indian Journal of Dermatology, Venereology and Leprology


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