CASE REPORT

Acute Generalized Exanthematous Pustulosis

(AGEP) due to Dapsone in a patient with leprosy

P. NARASIMHARAO*, D.V.S. PRATAP**

& SUJAI SUNEETHA***

*BhaskarMedicalCollege,RangaReddydistrict, AndhraPradesh, India

**Gandhi Medical College, Secunderabad, India

***Nireekshana-ACET, Hyderabad, India

Accepted for publication 05 February 2009

Introduction

Acute Generalized Exanthematous Pustulosis (AGEP) is a dermatosis characterised by an

acute episode of appearance of sub-corneal sterile pustules over erythematous-edematous

skin. AGEP is often associated with systemic symptoms such as high grade fever and is usually

considered to be an adverse drug reaction, although a viral etiology is sometimes implicated.

Here we report a case of AGEP following the intake of dapsone in a patient with leprosy.

Case Report

A 22 year-old male presented with a single slightly raised hypopigmented and hypoaesthetic

skin lesion on his left knee to the Department of Dermatology, Gandhi Medical College,

Hyderabad, India, and was diagnosed clinically as having Borderline Tuberculoid (BT)

leprosy. No major nerve trunk was involved. He did not give any past history of skin disorders

including psoriasis. A skin biopsy showed histopathological features consistent with BT

leprosy. The patient was started on dapsone (100 mg daily) and rifampicin (600 mg monthly)

as specified for the WHO MDT PB regimen. However, on the 9th day after starting therapy,

the patient developed a generalised macular erythematous eruption all over the body, on

which within the next 2 days, very superficial groups of tiny pustules developed,

predominantly on the trunk and limbs. These pustules were more marked on the back and

sides of the trunk. The patient was afebrile and denied taking any other drugs except MDT

PB. A full blood count was normal except for moderate leucocytosis. Liver function tests

were within normal limits. The patient was diagnosed as having AGEP based on clinical

findings. A skin biopsy was taken from affected skin on the trunk, and it showed classical

Correspondence to: P. NarasimhaRao, B-48, Income Tax Colony, Mehdipatnam, Hyderabad 500 028, India(Tel: þ091 4023514566; e-mail: dermarao@gmail.com)

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features of AGEP, which are subcorneal vesicles containing dense neutrophil infiltrate, and

inflammatory changes and mild vasculitis in the papillary dermis (Figures 1 and 2). The MDT

had been stopped when the skin eruption appeared and the patient was put on 20 mg of

prednisolone daily, and supportive therapy. Prednisolone was tapered over the next 2 weeks.

The generalised exanthematous pustulosis while subsiding presented as generalised

exfoliation and entire eruption regressed within the next 2 weeks. When drug therapy was

reintroduced after 4 weeks, rifampicin was given first. It did not bring back the eruption. By

exclusion, dapsone was considered the offending drug although re-challenge was not done.

Dapsone was substituted with clofazimine in the regimen. Both clofazimine and rifampicin

were well tolerated.

Discussion

AGEP, as the name suggests is characterised by the appearance of generalised exanthemaous

macular eruption accompanied by non-follicular subcorneal sterile pustules all over the skin and is

predominantly a drug induced dermatosis. Until the early 1990s AGEP was considered a variant

of pustular psoriasis. However, it was later recognised as a distinct drug eruption and in effect,

some cases previously reported as ‘drug-induced pustular psoriasis’ were actually AGEP.1,2

The onset of AGEP is always acute, accompanied by an episode of fever, which regresses

in a few days. Resolution of the pustules occurs spontaneously within 4–10 days after

discontinuing the suspected drug. AGEP appears to be a drug-induced, T lymphocyte cell-

mediated disease, wherein the effector function of T cells leads to a neutrophil-rich

Figure 1. AGEP eruption in skin: Photomicrograph of skin showing sub-corneal vesicles containing a denseneutrophilic infiltrate and a few lymphohistiocytic cell collections in the dermis with mild vasculitis (H& Estain 100 X).

P. NarasimhaRao et al.82

inflammation.3 T lymphocytes are involved in some neutrophilic inflammatory responses,

and may orchestrate the immune reaction by high CXCL8 (formerly known as interleukin-8)

chemokine production directly or indirectly via interleukin-17 production. AGEP may

provide a useful model for characterising T cells with this particular function leading to a

neutrophilic inflammation.4

The main triggering drugs implicated in AGEP are antibiotics, mostly beta-lactams. Other

medications, such as anti fungal drugs, non steroid anti-inflammatory drugs, analgesics, anti-

arrhythmic, anticonvulsant and antidepressant drugs are also reported to induce AGEP.5

Triggering agents may be administered orally or topically. A case of AGEP provoked by a

patch test with acetaminophen has been described.6 Three cases of AGEP occurring 24 to 48

hours after a spider bite have been reported.7 AGEP is presently considered as an adverse

drug reaction that can occur in any age group.8

Dapsone Hypersensitivity syndrome (DHS) is a well documented adverse drug eruption

observed in patients of leprosy, with the reported incidence ranging from 1·3% to 3·6%.9 DHS

typically presents with a triad of fever, erythema and inflammation of skin, and internal organ

involvement especially of the lungs and liver. However, it is not associated with eruption of

sub-corneal pustules, which is the hallmark of AGEP and its characteristic histopathology.

DHS must be promptly identified, as untreated the disorder could be potentially fatal. In

comparison, AGEP is a benign cutaneous adverse drug reaction, which resolves spontaneously

on discontinuation of the offending drug with no significant systemic involvement.

We have not found any previous published reports of AGEP in patients with leprosy on

treatment. This could be the first reported case of AGEP attributable to dapsone in a leprosy

patient.

Figure 2. AGEP eruption in skin: Photomicrograph of skin showing a dense neutrophilic infiltrate within the stratumcorneum (H& E stain 400 X).

Acute Generalized Exanthematous Pustulosis secondary to Dapsone 83

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