Introduction

Acute generalized exanthematous pustulosis (AGEP) is an uncommon pustular eruption usually caused by administration of drugs. Typically, small, non-follicular pustules on an erythematous background appear suddenly, sometimes associated with fever and neutrophilia (1). The onset is usually abrupt, within 24 hours after drug exposure, and the eruption progresses and resolves rapidly without treatment.

A large proportion of cases are triggered by drugs, especially antibiotics. In a minority of cases, triggers such as acute viral and bacterial infections or ultravio-let radiation have been implicated. In rare cases, the etiologic agent cannot be described (2).

To the best of our knowledge, there are only 2 reports in the literature describing a total of 4 AGEP cases caused by a spider bite (3,4). In this article, we present AGEP associated with lymphangitis caused by a spider bite.

Case report

A 39-year-old woman presented to our outpatient clinic with the complaint of generalized erythema, burning, and rash on her body. She explained that 2 days before admission, a spider bite had occurred on her left forearm, after which she had experi-enced pain and erythema spreading gradually to the left upper extremity. She also had generalized pruritus. On her dermatologic examination, she had an indurated necrotic plaque on the left forearm, which had an upward-spreading linear erythema (Figures 1 and 2). Additionally, she had diffuse erythema on her body (Figure 3) and had small pustules over erythematous skin, especially located on the left popliteal fossa and gluteal region (Figure 4). Her laboratory results showed leukocytosis and neutrophilia.

A skin punch biopsy was performed for histopatho-logic examination. Histopathologic findings revealed

Cutaneous and Ocular Toxicology, 2010; 29(1): 67–69

C A S E R E P O R T

Acute generalized exanthematous pustulosis with lymphangitis triggered by a spider bite

Aylin Türel Ermertcan1, Orhan Demirer1, Işıl İnanir1, Cemal Bilaç1, and Peyker Temiz2

1Celal Bayar University Faculty of Medicine, Department of Dermatology, Manisa, Turkey, and 2Celal Bayar University Faculty of Medicine, Department of Pathology, Manisa, Turkey

AbstractAcute generalized exanthematous pustulosis (AGEP) is a rare, severe cutaneous reaction pattern that, in the majority (>90%) of cases, is related to administration of medication. It can be seen in both genders and in all ages. The cutaneous manifestations of AGEP are usually seen 1–14 days after drug administration. A 39-year-old woman presented to our outpatient clinic with the complaint of generalized erythema, burn-ing, and rash. She explained that 2 days before presentation a spider bite had occurred on her left forearm, after which she had experienced pain and erythema spreading gradually to the left upper extremity. On her dermatologic examination, she had an indurated necrotic plaque on the left forearm, which had an upward-spreading linear erythema. Additionally, she had diffuse erythema on her body and small pustules over erythematous skin, especially located on the left popliteal fossa and gluteal region. Based on the clinical and histopathologic findings, she was diagnosed as having AGEP. Because there was no drug use in her his-tory, we attributed her AGEP lesions to the spider bite. This case is interesting, because the patient also had lymphangitis. Herein, we present the fifth case reported in the literature of AGEP caused by a spider bite.

Keywords: Acute generalized exanthematous pustulosis (AGEP); spider bite; lymphangitis

Address of Correspondence: Aylin Türel Ermertcan, Celal Bayar Üniversitesi Tıp Fakültesi, Dermatoloji Anabilim Dalı, 45010 Manisa, Türkiye. Tel.: +90 532 224 33 84. E-mail: draylinturel@hotmail.com

(Received 01 October 2009; revised 23 October 2009; accepted 26 October 2009)

ISSN 1556-9527 print/ISSN 1556-9535 online © 2010 Informa UK LtdDOI: 10.3109/15569520903455916 http://www.informahealthcare.com/cot

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subcorneal and intraepidermal pustules, edema of the papillary dermis, and diffuse perivascular inflamma-tory infiltration (Figure 5). According to the clinical and histopathologic findings, the patient was diagnosed as having AGEP.

The patient had no other infection or drug use his-tory, so we attributed her AGEP lesions to the spider bite. Because she also had lymphangitis, we started systemic antibiotic therapy, topical antiseptic agents, and wet dressing with Rivanol 0.1% solution. Systemic corticosteroid was also applied for the cutaneous manifestations of AGEP. With this treatment regimen, the patient’s lesions resolved within 10 days.

Discussion

AGEP is a rare and severe cutaneous reaction pat-tern characterized by a sudden onset of small sterile

Figure 1. Spider bite on the patient’s left forearm (an indurated necrotic plaque).

Figure 2. Indurated necrotic lesion and upward-spreading linear erythema on the patient’s arm.

Figure 3. Erythema on the patient’s back.

Figure 4. Small sterile pustules over erythematous skin in the patient’s gluteal region.

Figure 5. Histopathologic specimen showing subcorneal pus-tule and subepidermal edema (Hematoxylin and Eosin X 40 (HEX40)).

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AGEP with lymphangitis triggered by spider bite 69

pustules over erythematous skin, accompanied by fever and leukocytosis (4). It is perhaps the most important differential, occurring as an acute, spontaneously heal-ing reaction to drugs, usually antibiotics (5).

The estimated incidence rate of AGEP is approxi-mately 1–5 cases per million per year (6). A drug etiology is found in the vast majority (>90%) of cases. The main causative drugs are antibiotics (3). Since antibiotics are used to treat infections, the possibility also exists that the underlying infection is the trigger, in the sense of a bactericide. Beta-hemolytic strepto-coccal infections are most often implicated, usually as bronchitis or pharyngitis. In rare cases, no cause is even suggested. When drugs are involved, the most common agents are beta-lactam antibiot-ics, macrolides, tetracyclines, other antibiotics, carbamazepine, nystatin, isoniazid, furosemide, diltiazem, and some nonsteroidal anti-inflammatory drugs (2,7).

After drug administration, it may take 1–3 weeks before skin lesions appear; however, in previously sen-sitized patients, the skin symptoms may occur within 2–3 days (6). Dozens to hundreds of small, pinhead-sized, nonfollicular sterile pustules arise, mainly in the folds. Mucous membrane involvement may occur in about 20% of cases. Pustules resolve spontaneously within a few days and are followed by a characteristic postpustular pinpoint desquamation (3).

The cutaneous manifestations of AGEP are usually associated with fever above 38°C and leukocytosis. Mild eosinophilia may be present in about one-third of the patients. Internal organ involvement is relatively rare, and the mortality rate is approximately 5% (8). In our patient, fever was not observed. According to the laboratory findings, leukocytosis and neutrophilia were present. The patient’s liver and kidney function values were found to be in the normal ranges.

The differential diagnosis of AGEP includes pus-tular psoriasis, hypersensitivity syndrome reaction with pustulation, subcorneal pustular dermatosis (Sneddon-Wilkinson disease), pustular vasculitis, and toxic epidermal necrolysis (TEN), especially in severe cases of AGEP (6). The diagnosis is confirmed with his-topathologic findings. Histologically, the lesions show subcorneal and/or intraepidermal pustules, edema of the papillary dermis, and perivascular infiltrates with neutrophils and exocytosis of some eosinophils (4).

Spider bites are common; however, most domestic spiders are not substantially toxic for humans. The well-known exceptions are brown spiders (Loxosceles spp.) and widow spiders (Lactodectus spp.) (4). Induction of AGEP after a spider bite is extremely rare, and the mechanism responsible is unknown (3,4).

In AGEP pathogenesis, interleukin-8 (IL-8) and granulocyte-macrophage colony-stimulating factor (GM-CSF) are implicated for the recruitment of poly-morphonuclear cells into the epidermis; thus, they contribute to neutrophilic infiltration and ensure neutrophil survival. IL-8 is produced by keratinocytes and T cells (9).

To the best of our knowledge, there are only 2 reports in the literature describing a total of 4 AGEP cases due to a spider bite (3,4). Our patient is the fifth one; our case is quite interesting because she also had lymphangitis.

With this very rare and interesting case, we propose that spider bites may cause AGEP.

Acknowledgements

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

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9. Britscghi 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.

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