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Case report Open Access
An Acute Generalized Exanthematous Pustulosis Induced by Intravenous Iopromide: A Case Report
Mariem Mohamed1*, Mouna Korbi1, Majed Hassine2, Saber Zerriaa1, Hayet Akkari1, Leila Njim3, Hichem Belhadjali1, Jameleddine Zili1
1Dermatology Department, Fattouma Bourguiba University Hospital, Faculty of Medicine of Monastir, Monastir, Tunisia
2Cardiology Department, Bourguiba University Hospital, Faculty of Medicine of Monastir, Monastir, Tunisia
3Pathology Department, Bourguiba University Hospital, Faculty of Medicine of Monastir, Monastir, Tunisia
*Corresponding author: M Mohamed, Dermatology Department, Fattouma Bourguiba University Hospital, Faculty of Medicine of Monastir, Monastir, Tunisia, @
Received: July 28, 2016; Accepted: October 14, 2016; Published:October 18, 2016
Citation: Mohamed M, Korbi M, Hassine M, Zerriaa S, Akkari H, et al. (2016) An Acute Generalized Exanthematous Pustulosis Induced by Intravenous Iopromide: A Case Report. Int J Pharmacovigil 1(2): 4.
Abstract
Acute Generalized Exanthematous Pustulosis (AGEP) is a relatively rare exfoliative dermatosis consisting of a generalized eruption of sterile, nonfollicular pustules arising on widespread erythematous and edematous skin. It is generally attributed to drugs, particularly β-lactam antibiotics, sulfonamide and macrolides. To date, only thirteen cases of contrast media induced AGEP (involving iohexol, iopamidol, iodixanol, and ioversol) have been reported. We describe a patient with AGEP induced by iopromide. He was aged of 49 years. He developed pustular eruption on the back and folds three days after coronarography using radio contrast dye: Iopromide. The culture from pustules was sterile. Laboratory examination revealed an elevated white blood cell count of 22,500/ L with an increased neutrophils count (19,700/ L). A skin biopsy showed the features of an AGEP. The cutaneous eruption resolved with topical corticosteroid within five days. We found only 1 previous reports of iopromideinduced AGEP.

Key-words: Drug eruptions; Acute Generalized Exanthematous Pustulosis(AGEP); Contrast Medias; Iopromide
Introduction
Acute Generalized Exanthematous Pustulosis (AGEP) is an uncommon disease. It is characterized by an erythematous pustular eruption and is usually caused by systemic medication especially β-lactam antibiotics, sulfonamide and macrolides [1]. We report a case of AGEP induced by iopromide. Iopromideinduced AGEP has been reported previously in only one case through the English literature.
Case report
A 49-year-old man was admitted to cardiology department for an acute coronary syndrome. The patient had a history of coronary heart disease for which an angioplasty was made a year ago. He reported that he was developed a cutaneous rash few days later with spontaneous resolution. He had also a psoriasis vulgaris which was in remission for years. Three days after receiving intravenous iopromide (Ultravist®) for coronary angiography, the patient had developed a pruritic rash predominant in the folds. On physical examination, we noted multiple erythematous patches surmounted by numerous non follicular pustules scattered diffusely over his back and folds (Figure 1). There was no mucosa involvement. Nikolsky sign was absent. The patient had neither fever nor adenopathy. The culture from pustules was sterile. Laboratory examination revealed an elevated white blood cell count of 22,500/ L with an increased neutrophils count (19,700/ L) and eosinophilia (700/ L). C reactive protein was also elevated (62 mg/ L). Other laboratory values were unremarkable. A biopsy specimen was done. The histological findings showed spongiform subcorneal pustules and focal necrosis of keratinocytes. The papillary dermis was the seat of a marked oedema and a perivascular infiltrates with neutrophils and exocytosis of some eosinophils and lymphocytes (Figure 2). These findings were compatible with AGEP. The patient was treated with topical betamethasone leading to desquamation within 5 days with symptom resolution. Patch tests with iopromide (Ultravist), as well as with alternative contrast medias were planned, but the patient died before doing them due to a heart attack.
Discussion
The diagnosis of AGEP was definite in our patient with a score of 10 referring to the criteria of the Euro SCAR-study [2]. In fact, AGEP was first described in 1980 by Beylot, et al. [3]. AGEP has been described after the administration of several drugs, including amoxicillin, macrolides, paracetamol and nifedipine [4]. Our patient developed AGEP following iopromide which contains iodide. It is a non ionic monomeric contrast medium [5]. Iodinated contrast media cause both immediate and non immediate hypersensitivity reactions [5]. Non immediate cutaneous hypersensitivity reactions associated with the administration of iodinated contrast media have been described with different clinical presentation [5]. These were bullous exanthema, flexural exanthema, purpura/maculopapular eruption combined
Figure 1: Erythematous patchs surmounted by numerous non follicular pustules in (a): neckline, (b) (c) and (d): trunk, (e): axillary fold, (f): buttocks and (g): leg.
with eosinophilia, psoriasis-like exanthema and AGEP [5]. Nevertheless, only thirteen cases of contrast media induced AGEP have been described [6, 7]. Cases reported incriminate iopamidol, ioversol, iohexol and iodixanol [1,5-14]. Patch tests have confirmed the diagnosis in 3 publications [8,9,11]. All cases of contrast media AGEP, including our, are summarized in table 1. Moreover, AGEP induced by iopromide has been previously
Figure 2: (a): Neutrophilic spongiosis, papillary dermal edema and a perivascular infiltrate containing eosinophilis (HE: Original x40). Insert: eosinophilis (HE: Original x400). (b): Foci of neutrophilic spongiosis with subcorneal pustules (HE: Original x200).
described in only one case [8]. It was about a 52-year-old woman who developed AGEP three hours after coronary angiography using iopromide (Ultravist®). The rapid onset delay of the AGEP in this woman was explained by advance sensitization as well as our patient [8]. In fact, the pathophysiological mechanism of AGEP is not yet clear. Some authors incriminate a type IV allergic reaction [7]. So, after drug administration, it may take 1–3 weeks before skin lesions appear [6]. However, in previously sensitized patients, the skin symptoms may occur within 24–48 hours [6]. On the other hand, the main differential diagnosis in our case was pustular psoriasis. Indeed, the predominance of the eruption in the folds, the rapid resolution of the eruption, the presence of eosinophils in the inflammatory infiltrate and the absence of histological features of conventional psoriasis suggest that our patient had an AGEP.
Table 1: Characteristic of radio contrast media acute generalized Exanthematous pustulosis.

Author

Year of

publication

Age of the patient

(Year)

Sex

Medical

history

Time to onset (Hours)

Histopathology

EuroSCAR

Iodinated

Contrast

Media

Patch

tests

Atasoy M, et al. [1]

2003

52

F

Abdominal

pain

72

Subcorneal blisters including

neutrophils and eosinophils, mildspongiosis,

and a sparse infiltrate of neutrophils and eosinophils in the papillary dermis

 

11

Iohexol

Not done

Belgodere X, et al. [6]

2004

40

M

Subarachnoid hemorrhage

Testicular tumor

20

Subcornealblisters including

neutrophis and a sparse infiltrate of neutrophils

in the papillarydermis

 

10

Iopamidol

Not done

Peterson A, et al. [13]

2006

 

 

 

 

 

 

 

 

 

 

 

2006

Case 1 : 44

 

 

 

 

 

 

 

 

 

 

Case2 : 30

F

 

 

 

 

 

 

 

 

 

 

 

F

Gastric bypass surgery

 

Hodgkin disease

 

 

 

 

 

 

 

 

Chest pressures Paresthesias

 

3 Episodes :

60 ;  14 ;

6

 

 

 

 

 

 

 

 

 

48

Subcorneal pustules, rare single apoptotic keratinocytes, and  perivascular and interstitial lymphocytes with scattered eosinophils

and neutrophils.

 

 

Not done

9

 

 

 

 

 

 

 

 

 

 

 

6

Iodixanol

 

 

 

 

 

 

 

 

 

 

 

Iodixanol

Not done

 

 

 

 

 

 

 

 

 

 

 

Not done

Hammerbeck AA, et al. [7]

2009

84

M

Bladder cancer

Hypertension

Parkinson disease

Diabetes mellitus

Hyperlipidemia

Coronary artery disease

Benign prostatic hypertrophy

Right-sided hydronephrosis

Chronic renal insufficiency

 

2 Episodes:

24, 24

Subcorneal pustules, epidermal edema and superficial neutrophilic infiltrate with eosinophils

8 For the two épisodes

Ioversol for the 2 épisodes

Not done

Paquet P, et al. [12]

2009

80

M

B-cell chronic lymphocytic leukemia

Few hours

Subcorneal pustules and perivascular and

interstitial lymphocytes with scattered eosinophils and neutrophils in the papillary dermis

 

11

Iobitridol

Not done

Kim SJ, et al. [10]

2010

27

M

Chronic renal failure due to IgA nephropathy

2 Kidney transplant operations

*Chronic allograft nephropathy

Hemodialysis 3 times a week through a left arterio-venous fistula.

 

6

Not done

8

Ioversol

Not done

Poliak N, et al. [11]

2010

4

M

Tetralogy of Fallot

3 Episodes:48H, 42H, 6H30min

Subcorneal intraepidermal pustules, spongiosis, rare

Apoptotic keratinocytes, papillary dermis edema, inflammatory infiltrates,

and few eosinophils,

11

Ioversol

Ioversol +

Iohexol +

Iothalamate -

Grandvuillemin A, et  al. [9]

2014

Case1 : 45

 

 

 

 

 

 

Case 2 : 26

 

 

 

 

 

 

Case3 ; 79

 

 

 

 

 

 

Case4 : 24

 

F

 

 

 

 

 

 

F

 

 

 

 

 

 

F

 

 

 

 

 

 

M

allergic rhinitis,

Migraine ,cerebral arterial

embolization

 

 

 

Asthma, migraine

 

 

 

 

 

Osteoarthritis, primary

amyloidosis,  tramadol-induced urticaria

 

 

Aneurysm rupture

72

 

 

 

 

 

 

24

 

 

 

 

 

 

48

 

 

 

 

 

 

24

Subcorneal pustulosis with

neutrophils infiltration

 

 

 

Idem

 

 

 

 

 

 

Idem

 

 

 

 

 

 

Idem

Not evaluated

 

 

 

 

 

Idem

 

 

 

 

 

 

Idem

 

 

 

 

 

 

Idem

Iodixanol

 

 

 

 

 

 

Iomeprol

 

 

 

 

 

 

Iobitridol

 

 

 

 

 

 

Iodixanol

Iodixanol+

ioxaglate-iomeprol-

Iopamidol-iohexol- iobitridol-

 

Iodixanol-

ioxaglate-iomeprol+

Iopamidol-iohexol- iobitridol-

 

Iodixanol-

ioxaglate-iomeprol-

Iopamidol-iohexol- iobitridol+/ -

 

Iodixanol+

ioxaglate-iomeprol-

Iopamidol-iohexol- iobitridol-

Bavbek S, et al. [8]

2014

52

F

Non-ST elevation

Myocardial infarction

3-4

Epidermal acanthosis with multifocal pustule formation in

the upper part of the epidermis, with inflammation and mild edema in the papillary dermis

 

10

Iopromide

Iodixanol+

iomeprol+

diatrizoate–iopamidol+

iopromide +

Our case

2015

49

M

Coronary heart disease

Psoriasis

72

Spongiform subcorneal pustules and focal necrosis of keratinocytes. An oedema and a perivascular infiltrates with neutrophils and exocytosis of some eosinophils and lymphocytes in the papillary dermis

 

10

Iopromide

Not done

F: female; M: Male; results of patch tests were assessed by the International Contact Dermatitis Research Group (ICDRG) scoring system: (-) negative reaction; (+/-) doubtful reaction; (+) positive reaction
Finally, we report the second case of AGEP induced by iopromide. Our aim is to remain both radiologists and dermatologist aware of this side effect of contrast media.
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