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E-IJD CASE REPORT
Year : 2015  |  Volume : 60  |  Issue : 4  |  Page : 422
Acute generalized exanthematous pustulosis due to insect bites?


1 Department of Dermatology, STD and Leprosy, Government Medical College, University of Kashmir, Srinagar, Jammu and Kashmir, India
2 Department of Pathology, Government Medical College, University of Kashmir, Srinagar, Jammu and Kashmir, India

Date of Web Publication10-Jul-2015

Correspondence Address:
Dr. Yasmeen J Bhat
Department of Dermatology, STD and Leprosy, Government Medical College, Srinagar, Jammu and Kashmir
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-5154.160529

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   Abstract 

Acute generalized exanthematous pustulosis is a rare severe cutaneous adverse reaction pattern that is mostly caused by the intake of drugs and rarely associated with viral infections, food allergens or toxins. Here we present the report of three patients who got admitted in our hospital for generalized pustulosis and fever after insect bites. The diagnosis of acute generalized exanthematous pustulosis was made by EuroSCAR scoring. The drug etiology was excluded and spider bite was implicated as the etiological agent in these cases of AGEP which are the first such reported cases in India.


Keywords: Acute generalized exanthematous pustulosis, EuroSCAR, spider bites, sterile pustules


How to cite this article:
Bhat YJ, Hassan I, Sajad P, Yaseen A, Wani R. Acute generalized exanthematous pustulosis due to insect bites?. Indian J Dermatol 2015;60:422

How to cite this URL:
Bhat YJ, Hassan I, Sajad P, Yaseen A, Wani R. Acute generalized exanthematous pustulosis due to insect bites?. Indian J Dermatol [serial online] 2015 [cited 2021 Mar 4];60:422. Available from: https://www.e-ijd.org/text.asp?2015/60/4/422/160529

What was known?
Acute generalized exanthematous pustulosis (AGEP) is a rare severe cutaneous reaction pattern caused mostly by drugs and rarely associated with viral infections, food allergens or toxins.



   Introduction Top


Acute generalized exanthematous pustulosis (AGEP) or toxic pustuloderma is a rare severe cutaneous adverse reaction pattern that is mostly caused by the intake of drugs (in >90% cases). Rarely it can be associated with viral infections, food allergens and toxins. [1],[2] It can occur in both sexes and all age groups. The eruption in AGEP is characterized by erythematous and edematous nonfollicular papules and pustules which starts in flexures or on face and then generalizes to other parts of the body. There is usually associated history of itching and burning sensation.


   Case Report Top


Here we present the case report of three patients (two females and one male) who presented in the summer months with acute generalized pustulosis and erythema with fever and had the history of insect bite prior to the onset of rash. The clinical features have been tabulated [Table 1]. One of these patients was admitted for spider bite and developed generalized pustular rash during hospital stay which was initially attributed to the antibiotic amoxycillin-potassium clavulanate but the pustular crops continued to appear despite the drug being stopped. The other two were admitted for the generalized pustulosis who gave the prior history of insect bite. All the routine hematological and biochemical investigations of the patients were done. Gram staining and biopsy of the pustules was carried out in all the three patients. The insect bites were presumed to be spider bites as the patients gave history of spiders present in their houses (circumstantial evidence) and the cutaneous examination at bite site was consistent with it but due to lack of facilities the toxin identification was not possible. Symptoms of loxoscelism were not seen in these patients. The outcome was favorable in all cases with symptomatic treatment. The diagnosis of AGEP was made after validation score of the EuroSCAR study group [Table 2].
Table 1: Clinical data of the three patients

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Table 2: AGEP validation score of the EuroSCAR group

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   Discusssion Top


AGEP or toxic pustuloderma is a rare severe cutaneous adverse reaction pattern that is mostly caused by the intake of drugs (in >90% cases). Rarely it can be associated with viral infections, food allergens and toxins. [1],[2] Hypersensitivity to mercury has been reported as a precipitating factor. AGEP is usually due to penicillins or macrolides, especially ampicillin/amoxicillin with or without clavulanic acid, quinolones, hydroxychloroquine, sulfonamides, terbinafine, diltiazem and carbamazepine. It can occur in both sexes and all age groups. The eruption in AGEP is characterized by erythematous and edematous nonfollicular papules and pustules which start in flexures or on face and then generalize to other parts of the body. There is usually associated history of itching and burning sensation. The main differential diagnosis is pustular psoriasis. [3],[4],[5] Mucus membrane involvement may be seen in approximately 25% of the cases. The eruption resolves spontaneously in few days in majority of the cases. The eruption in AGEP is usually associated with fever, leukocytosis and eosinophilia. [6] Internal organ involvement is rarely seen. EuroSCAR study criteria are used for the validation of AGEP. These criteria were fulfilled by our patients.

On histopathology two patterns may be seen: (1) A toxic pustuloderma with spongiform intraepidermal pustulosis, papillary edema and a mixed upper dermal perivascular inflammatory infiltrate; or (2) a leukocytoclastic vasculitis with neutrophil collections both below and within the epidermis. [7]

In our case series three patients (2 females and 1 male) were admitted in the summer months following spider bite (which was diagnosed presumptively on the basis of clinical features and exclusions of other insect bites). One patient had taken the antibiotic amoxicillin-clavulinic acid before admission which was stopped but the eruption continued and increased in severity. There was no history suggestive of viral infection or an allergic cause. Polymorphonuclear leukocytosis (in all three) and eosinophilia (in 1 patient) was noted on routine blood testing. Histopathology was consistent with the diagnosis of AGEP in all three cases and excluded the possibility of pustular psoriasis which is the closest differential diagnosis. Spider bite was implicated as the most likely causative factor leading to AGEP as the drug etiology was excluded in all the three cases- circumstantial evidence only. The necrotic cutaneous form was seen in all the three cases and systemic symptoms were mild [Figure 1] [Figure 2] [Figure 3]. The other form known as viscerocutaneous loxoscelism was not seen.Histopathology was suggestive of AGEP in all the cases [Figure 4]. RICE therapy (Rest, application of ice compresses and elevation) was employed to reduce inflammation and pain.
Figure 1: (a) Spider bite on neck presenting with necrosis, ulceration, erythema surrounded by pustules. (b) Diffuse erythema and pustules on the body

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Figure 2: (a) Spider bite on lower back with erythema, edema and necrosis. (b) Diffuse erythema and pustules mainly in skin folds

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Figure 3: (a) Spider bite on right shoulder with erythema, necrosis and ulceration. (b) Post pustular desquamation

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Figure 4: (a) Photomicrograph showing subcorneal bulla filled by acute inflammatory cell infiltrate with edema of superficial dermis and dermal inflammation (H and E 40). (b) Photomicrograph showing subcorneal pustule formation with edema of papillary dermis and mild dermal inflammatory cell infiltrate (H and E 100)

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The occurrence of AGEP following spider bite has been rarely reported in the literature (only six case reports to the best of our knowledge). This is probably the first such reported case from India. Davidovici et al. in a study from Israel reported AGEP following spider bite in three cases in 2006. The eruption (AGEP) in their case series had occurred 24 to 48 hours after a spider bite. [8] Ben Said et al. reported AGEP following spider bite in three cases from Tunisia in 2010. They diagnosed it on the basis of characteristic skin lesions, chronology of event and exclusion of other common causes of AGEP. [9] Ermertcan et al. reported AGEP with lymphangitis triggered by a spider bite in a female patient from Turkey in 2010. Because there was no history of drug use in their case, they attributed her AGEP lesions to the spider bite. [10] Makris et al. reported (AGEP) triggered by a spider bite in 2009; [11] Pippirs et al. reported AGEP following a Loxosceles spider bite in Great Britain in 2009; [12] and Lane et al. reported AGEP and Coombs-positive hemolytic anemia in a child following Loxosceles reclusa envenomation in 2011. [13]

The exact mechanism leading to AGEP following spider bites is not known. It is believed that the spider venom contains spingomyelinase which can stimulate the release of cytokines and chemokines especially IL-8 and GM-CSF and it is these inflammatory mediators which have been found to trigger AGEP. [14],[15],[16]



 
   References Top

1.
Webster GF. Pustular drug reactions. Clin Dermatol 1993;11:541-3.  Back to cited text no. 1
    
2.
Spencer JM, Silvers DN, Grossman ME. Pustular eruption after drug exposure: Is it pustular psoriasis or a pustular drug eruption? Br J Dermatol 1994;130:514-9.  Back to cited text no. 2
    
3.
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. 3
    
4.
Menders SM, Heymann WR. Acute generalized exanthemic pustulosis. Cutis 1994;54:194-6.  Back to cited text no. 4
    
5.
Saissi EH, Beau-Salinas F, Jonville-Béra AP, Lorette G, Autret-Leca E; Centres Régionaux de Pharmacovigilance. Drugs associated with acute generalized exanthematic pustulosis. Ann Dermatol Venereol 2003;130:612-8.  Back to cited text no. 5
    
6.
Sidoroff A, Dunant A, Viboud C, Halvey S, 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. 6
    
7.
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. 7
    
8.
Burrows NP, Russell Jones RR. Pustular drug eruptions: A histopathological spectrum. Histopathology 1993;22:569-73.  Back to cited text no. 8
    
9.
Davidovici BB, Pavel D, Cagnano E, Rozenman D, Halevy S; EuroSCAR; RegiSCAR study group. 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. 9
    
10.
Ben Said Z, Saidi W, Boussofara L, Ghariani N, Belajouza C, Sriha B, et al. Acute generalized exanthematous pustulosis following a spider bite: Three cases from Tunisia. Ann Dermatol Venereol 2010;137:813-8.  Back to cited text no. 10
    
11.
Makris M, Spanoudaki N, Giannoula F, Chliva C, Antoniadou A, Kalogeromitros D. Acute generalized exanthematous pustulosis (AGEP) triggered by a spider bite. Allergol Int 2009;58:301-3.  Back to cited text no. 11
    
12.
Pippirs U, Mehlhorn H, Antal AS, Schulte KW, Homey B. Acute generalized exanthematous pustulosis following a Loxosceles spider bite in Great Britain. Br J Dermatol 2009;161:208-9.  Back to cited text no. 12
    
13.
Lane L, McCoppin HH, Dyer J. Acute generalized exanthematous pustulosis and Coombs-positive hemolytic anemia in a child following Loxosceles reclusa envenomation. Pediatr Dermatol 2011;28:685-8.  Back to cited text no. 13
    
14.
Ermertcan AT, Demirer O, Inanir I, Bilaç C, Temiz P. Acute generalized exanthematous pustulosis with lymphangitis triggered by a spider bite. Cutan Ocul Toxicol 2010;29:67-9.  Back to cited text no. 14
    
15.
Hogan CJ, Barbaro KC, Winkel K. Loxoscelism: Old obstacles, new directions. Ann Emerg Med 2004;44:608-24.  Back to cited text no. 15
    
16.
Britschgi M, Steiner UC, Schmid S, Depta JP, Senti G, Bircher A, et al. T cell involvement in drug-induced acute generalized exanthematous pustulosis. J Clin Invest 2001;107:1433-41.  Back to cited text no. 16
    

What is new?
Our cases and the few others published in the literature indicate that spider bites may be added to the list of the possible causes of AGEP.


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2]



 

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