Acute Generalized Exanthematous Pustulosis Induced by Dexamethasone Injection

Demitsu, Toshio; Kosuge, A.; Yamada, Tetsutaro; Usui, Kae; Katayama, Hiroki; Yaoita, Hideo

doi:10.1159/000246204

Cited by 45 publications

(24 citation statements)

References 3 publications

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“…To further prove the involvement of drugs in eliciting AGEP, we performed patch tests in patients AP, JS, and EB. In agreement with previous reports (7,(21)(22)(23), application of the drug resulted in erythema, induration, and vesicle formation (Figure 4, a-f, h) in all three patients.…”

supporting

confidence: 93%

“…As another report on patch-test reaction of AGEP patients describes pustule formation after longer skin test application (96 hours) (22), the biopsy that was taken at 48 hours might reflect the early events. This would suggest that the drug-specific CD4 + (and probably also some CD8 + ) T cells are reacting first, and they may be responsible for vesicle formation.…”

Section: Discussionmentioning

confidence: 97%

“…Indeed, various studies have documented a high IL-5 production by tissueinfiltrating T cells in exanthema as well as drug-specific T cells from the circulation (19,20) and an enhanced eotaxin production by endothelial cells and infiltrating T cells (19). Interestingly, previous studies in patients with AGEP have revealed a high rate of strongly positive patch tests to drugs compared with patients with other drug eruptions (21)(22)(23)(24). This suggests that T cells are involved in AGEP as well.…”

Section: Introductionmentioning

confidence: 99%

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T-cell involvement in drug-induced acute generalized exanthematous pustulosis

Britschgi¹,

Steiner²,

Schmid³

et al. 2001

J. Clin. Invest.

331

287

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Acute generalized exanthematous pustulosis (AGEP) is an uncommon eruption most often provoked by drugs, by acute infections with enteroviruses, or by mercury. It is characterized by acute, extensive formation of nonfollicular sterile pustules on erythematous background, fever, and peripheral blood leukocytosis. We present clinical and immunological data on four patients with this disease, which is caused by different drugs. An involvement of T cells could be implied by positive skin patch tests and lymphocyte transformation tests. Immunohistochemistry revealed a massive cell infiltrate consisting of neutrophils in pustules and T cells in the dermis and epidermis. Expression of the potent neutrophil-attracting chemokine IL-8 was elevated in keratinocytes and infiltrating mononuclear cells. Drug-specific T cells were generated from the blood and skin of three patients, and phenotypic characterization showed a heterogeneous distribution of CD4/CD8 phenotype and of T-cell receptor Vβ-expression. Analysis of cytokine/chemokine profiles revealed that IL-8 is produced significantly more by drug-specific T cells from patients with AGEP compared with drug-specific T cells from patients that had non-AGEP exanthemas. In conclusion, our data demonstrate the involvement of drug-specific T cells in the pathomechanism of this rather rare and peculiar form of drug allergy. In addition, they indicate that even in some neutrophil-rich inflammatory responses specific T cells are engaged and might orchestrate the immune reaction. T cells from the circulation (19,20) and an enhanced eotaxin production by endothelial cells and infiltrating T cells (19). Interestingly, previous studies in patients with AGEP have revealed a high rate of strongly positive patch tests to drugs compared with patients with other drug eruptions (21)(22)(23)(24). This suggests that T cells are involved in AGEP as well. They may contribute to the accumulation of polymorphonuclear neutrophils (PMN) at the site of the lesions by the preferential release of PMN-attractive chemokines, mainly CXC chemokines such as 26).To understand the function of T cells in AGEP patients we generated drug-specific TCLs and TCCs from the circulation and skin biopsy specimens and analyzed their phenotypes, specificities, and cytokine and chemokine profiles in vitro. Immunohistochemical analysis of the acute and patch-test lesions ex vivo was performed to determine the nature of the inflammatory cell infiltrate in vivo and to supplement the in vitro studies. The data point to an important role of drug-specific T cells in AGEP, which clearly exert distinct functions compared with other cutaneous drug eruptions. MethodsPatients. A summary of the patients' clinical characteristics is given in Table 1. Patient AP developed a generalized erythema after oral administration of Augmentin (amoxicillin and clavulanic acid; SmithKline Beecham Pharmaceuticals, Irvine, United Kingdom), which was given to treat an otitis media. She had fever (40°C) and developed pustules on the back, arms, and f...

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supporting

confidence: 93%

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

T-cell involvement in drug-induced acute generalized exanthematous pustulosis

Britschgi¹,

Steiner²,

Schmid³

et al. 2001

J. Clin. Invest.

331

287

View full text Add to dashboard Cite

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“…Prednisolone and its derivatives (corticosteroids of group A, hydrocortisone type) have frequently been identified as the causative agents [9]. So far only 2 cases of AGEP elicited by corticosteroids (methylprednisolone, dexamethasone) and confirmed by positive patch test results have been published [10, 11]. However, the proof that corticosteroids are the causative drug is difficult due to their inherent immunosuppressive properties.…”

Section: Discussionmentioning

confidence: 99%

Oral Prednisolone Induced Acute Generalized Exanthematous Pustulosis due to Corticosteroids of Group A Confirmed by Epicutaneous Testing and Lymphocyte Transformation Tests

Buettiker

Keller²,

Pichler³

et al. 2006

Dermatology

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Background:Acute generalized exanthematous pustulosis (AGEP) is a rare cutaneous eruption which is often provoked by drugs. Case Report:We report 2 cases of AGEP which showed rapidly spreading pustular eruptions accompanied by malaise, fever and neutrophilia after the administration of systemic prednisolone (corticosteroid of group A, hydrocortisone type). The histological examination showing neutrophilic subcorneal spongiform pustules was consistent with the diagnosis of AGEP. In both cases the rash cleared within a week upon treatment with topical steroids (corticosteroid of group D1, betamethasonedipropionate type and corticosteroid of group D2, hydrocortisone-17-butyrate type). Three months after recovery, the sensitization to corticosteroids of group A was confirmed by epicutaneous testing and positive lymphocyte transformation tests. Conclusion: These cases show that systemic corticosteroids can induce AGEP and demonstrate that epicutaneous testing and lymphocyte transformation tests may be helpful in identifying the causative drug. Our data support previous reports indicating an important role for drug-specific T cells in inducing neutrophil inflammation in this disease.

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“…Pathogenetically, positive sometimes pustular patch tests are demonstrated in over 50% of cases and provide indirect evidence of an underlying immunological process involving T cells [13,14,15,16]. The crucial role of T cells is additionally supported by positive lymphocyte transformation test results as has recently been shown by Beltraminelli et al [unpubl.…”

Section: Discussionmentioning

confidence: 94%

Ciprofloxacin-Induced Acute Generalized Exanthematous Pustulosis Mimicking Bullous Drug Eruption Confirmed by a Positive Patch Test

Häusermann¹,

Scherer

Weber³

et al. 2005

Dermatology

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We report the case of an 80-year-old woman presenting with ciprofloxacin-induced acute generalized exanthematous pustulosis (AGEP) confirmed by a positive patch test. Cutaneous morphology, course and histological findings were consistent with a definite diagnosis according to the AGEP validation score of the EuroSCAR study group. We point to the rarity of quinolone-induced AGEP and discuss immunological mechanisms, the value of in vivo and in vitro tests as well as the main differential diagnosis. Furthermore, we highlight in this particular case the challenging differentiation from bullous drug eruption.

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Acute Generalized Exanthematous Pustulosis Induced by Dexamethasone Injection

Cited by 45 publications

References 3 publications

T-cell involvement in drug-induced acute generalized exanthematous pustulosis

T-cell involvement in drug-induced acute generalized exanthematous pustulosis

Oral Prednisolone Induced Acute Generalized Exanthematous Pustulosis due to Corticosteroids of Group A Confirmed by Epicutaneous Testing and Lymphocyte Transformation Tests

Ciprofloxacin-Induced Acute Generalized Exanthematous Pustulosis Mimicking Bullous Drug Eruption Confirmed by a Positive Patch Test

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