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This is a rare skin rash, usually secondary to a drug reaction. This disease is characterized by several features:

Numerous small, mostly nonfollicular pustules arising on an erythematous base
Intraepidermal or subcorneal pustules associated with dermal edema with focal necrosis of the keratinocytes
Fever (38C)
Blood neutrophil count >7000/mm3
Acute evolution with spontaneous resolution of pustules in less than 15 days

Most of the pustules last an average of 9-10 days and usually occurs within 2 days of drug exposure.


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ANTIBIOTICS Beta lactams
DRUGS Calcium channel blockers

Acute generalized exanthematous pustulosis induced by dexamethasone injection.

Demitsu T, Kosuge A, Yamada T, Usui K, Katayama H, Yaoita H.

Department of Dermatology, Jichi Medical School, Tochigi-ken, Japan.

Dermatology 1996;193(1):56-8 Abstract quote

A 52-year-old woman, without a history of psoriasis, developed a widespread, sterile pustular eruption on the trunk and extremities 2 days after subcutaneous injection of dexamethasone solution.

Skin biopsy revealed subcorneal pustules filled with neutrophils and moderate lymphohistiocytic infiltrate with a few eosinophils in the dermis. There was no evidence of vasculitis. Patch testing showed positive pustular reactions to dexamethasone solution. Histology of this pustule also resembled that of the original eruption.

To our knowledge, acute generalized exanthematous pustulosis due to corticosteroid has not been previously reported.


Diltiazem-induced acute generalised exanthematous pustulosis.

Wakelin SH, James MP.

Department of Dermatology, Royal Berkshire Hospital, Reading, UK.

Clin Exp Dermatol 1995 Jul;20(4):341-4 Abstract quote

Pustulation is a major feature in several different dermatoses, and it may also occur as a manifestation of drug hypersensitivity. Acute generalized exanthematous pustulosis (AGEP) is an uncommon eruption characterized by acute, extensive formation of sterile pustules, fever and peripheral blood leucocytosis. It shares several clinical and histological features in common with pustular psoriasis. Most reported cases have been triggered by ingestion of broad spectrum antibiotics, particularly betalactams and macrolides. There is usually rapid resolution of the eruption on drug withdrawal.

We report the case of a 58 year-old woman who developed AGEP shortly after commencing treatment with the calcium channel blocker diltiazem hydrochloride. The eruption followed a biphasic course, and improved following treatment with systemic corticosteroids and methotrexate. AGEP appears to be a rare adverse cutaneous reaction to diltiazem, whereas a wide range of other skin eruptions have been reported more commonly with this drug.


Acute generalized exanthematous pustulosis due to doxycycline.

Trueb RM, Burg G.

Department of Dermatology, University Hospital, Zurich, Switzerland.

Dermatology 1993;186(1):75-8 Abstract quote

Sterile epidermal neutrophilic pustulation can be observed in a variety of diseases. Though drug hypersensitivity is an uncommon cause, it is yet a known entity to be considered in the differential diagnosis of generalized pustulosis.

In a 40-year-old woman, who developed a generalized pustular eruption after starting on doxycycline therapy of bronchitis, the rash was concluded to be drug induced after exclusion of other pustular dermatoses.

Sensitization to doxycycline was demonstrated by in vitro lymphocyte testing and correlated with clinical drug hypersensitivity after recurrence of the pustular eruption on nonintentional rechallenge with doxycycline.


Acute generalized exanthematous pustulosis following oral nystatin therapy: a report of three cases.

Kuchler A, Hamm H, Weidenthaler-Barth B, Kampgen E, Brocker EB.

Department of Dermatology, University Hospital, University of Wurzburg.

Br J Dermatol 1997 Nov;137(5):808-11 Abstract quote

We report three cases of acute generalized exanthematous pustulosis (AGEP) following oral administration of nystatin. All cases showed similar clinical features and histopathological findings, and a delayed-type hypersensitivity to nystatin could be demonstrated in patch and prick testing.

Drug eruptions to nystatin are extremely rare, and, to our knowledge. AGEP has not been reported previously.


Acute generalized exanthematous pustulosis induced by paracetamol. A case with severe hemodynamic disturbances.

De Coninck AL, Van Strubarq AS, Pipeleers-Marichal MA, Huyghens LP, Suys ET, Roseeuw DI.

Department of Dermatology, Academic Hospital, Vrije Universiteit Brussel, Belgium.

Dermatology 1996;193(4):338-41 Abstract quote

We report on a 28-year-old Bangladesh man with acute generalized exanthematous pustulosis, induced by paracetamol. The patient presented with an erythematous and pustular eruption after taking 1 tablet of paracetamol for a sore throat. After intravenous administration of propacetamol hydrochloride (which is a prodrug of paracetamol), the rash became worse, showing a toxic epidermal necrolysis-like appearance and the patient suffered from severe hemodynamic disturbances.

After discontinuation of propacetamol hydrochloride, the eruption cleared within 2 days. Prick testing performed in the patient revealed a positive reaction for propacetamol hydrochloride.


Acute generalized exanthematous pustulosis associated with STI571 in a patient with chronic myeloid leukemia.

Brouard MC, Prins C, Mach-Pascual S, Saurat JH.

Department of Dermatology, University Hospital, Geneva, Switzerland

Dermatology 2001;203(1):57-9 Abstract quote

The tyrosine kinase inhibitor STI571 is a novel promising class of anticancer drugs. We report a case of cutaneous adverse reactions to STI571 in a young woman with blast crisis of chronic myeloid leukemia. She had first typical acute generalized exanthematous pustulosis mimicking mercury rash and then urticarial eruption.

We suggest that cell pathways mediated by some tyrosine kinases might be involved in the pathogenesis of these skin eruptions.


Acute generalized exanthematous pustulosis induced by salazosulfapyridine in a patient with ulcerative colitis.

Kawaguchi M, Mitsuhashi Y, Kondo S.

Department of Dermatology, Yamagata University School of Medicine, Japan.

J Dermatol 1999 Jun;26(6):359-62 Abstract quote

We report a case of acute generalized exanthematous pustulosis (AGEP) induced by salazosulfapyridine in a patient with ulcerative colitis. A 26-year-old Japanese man, who had been receiving medical attention for ulcerative colitis for one year, presented with diffuse erythema and pustules on his face and trunk, malaise, and fever up to 39 degrees C one day after the administration of salazosulfapyridine.

A skin biopsy specimen disclosed intracorneal pustule composed of neutrophils and lymphohistiocytic infiltrate in the dermis. A drug lymphocyte stimulation test for salazoslufapyridine was positive, but the patch test was negative. Immunological mechanisms are suggested in the pathogenesis of psoriasis and ulcerative colitis.

We suspect that a similar immunological pathway played a role in the pathogenesis of AGEP appearing in psoriasis and ulcerative colitis.



Acute generalized exanthematous pustulosis, a clue to neutrophil-mediated inflammatory processes orchestrated by T cells.

Britschgi M, Pichler WJ.

Division of Allergology, Clinic of Rheumatology and Clinical Immunology/Allergology, Inselspital, University of Bern, Bern, Switzerland.

Curr Opin Allergy Clin Immunol 2002 Aug;2(4):325-31 Abstract quote

PURPOSE OF REVIEW: Circumstantial evidence exists that certain neutrophilic inflammatory processes are regulated by T cells, but how this occurs is not well understood. The present review presents data on how T cells may directly orchestrate a neutrophilic inflammation by specific release of the neutrophil-attracting chemokine CXCL8 (formerly known as interleukin-8).

RECENT FINDINGS: Acute generalized exanthematous pustulosis (AGEP) is an uncommon cutaneous eruption that is 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 an erythematous background, fever and elevated numbers of blood neutrophils. Involvement of T cells in drug-induced AGEP was suggested by positive patch tests and lymphocyte transformation tests. Moreover, drug-specific CD4+ and CD8+ T cells could be isolated and propagated in vitro from patch test sites and blood from AGEP patients. Their main characteristic is a high level of CXCL8 production.

SUMMARY: T cells are involved even in some neutrophil-rich inflammatory responses, and they may orchestrate the immune reaction directly by high CXCL8 production or indirectly via interleukin-17 production, which induces CXCL8 production in various cell types. AGEP serves as a valuable model for characterizing T cells with a particular function - namely production of CXCL8 - leading to neutrophilic inflammation. It is tempting to speculate that elucidation of this pathomechanism will help to improve our understanding of similar neutrophilic eruptions (e.g. pustular psoriasis) and may reveal new targets for pharmacotherapeutic interventions in such diseases.




Drug induced acute generalized exanthematous pustulosis.

Katagiri K, Takayasu S.

Department of Dermatology, Oita Medical University, Japan.

J Dermatol 1996 Sep;23(9):623-7 Abstract quote

A 62-year-old woman with diabetic triopathy developed widespread erythematous macules, numerous pustules, and a high fever after she underwent electric coagulation for vitreous hemorrhage. She was administered several drugs at that time.

After discontinuation of the drugs, the eruption disappeared, and the fever returned to normal within two weeks. A positive patch test with isepamicin sulfate highly suggested that the symptoms described above were due to drug allergy. Cadralazine, which was positive in the drug lymphocyte stimulation test (DLST), could not be excluded from the causative drugs. A false-positive DLST with ofloxacin was confirmed by an accidental challenge test.

To our knowledge, this is the first report of acute generalized exanthematous pustulosis due to isepamicin sulfate and/or cadralazine.



Acute generalized exanthematous pustulosis. Analysis of 63 cases.

Roujeau JC, Bioulac-Sage P, Bourseau C, Guillaume JC, Bernard P, Lok C, Plantin P, Claudy A, Delavierre C, Vaillant L, et al.

Department of Dermatology, University of Creteil, France.

Arch Dermatol 1991 Sep;127(9):1333-8 Abstract quote

We retrospectively analyzed 63 observations collected in nine French departments of dermatology of an acute pustular dermatosis, recently named in the French literature acute generalized exanthematous pustulosis (AGEP). Even though 11 of these cases occurred in patients with a history of psoriasis, AGEP appeared distinct from pustular psoriasis based on several slight pathologic differences, drug induction in most cases, and a more acute course of fever and pustulosis, with rapid spontaneous healing.

We, therefore, suggest that AGEP is a reaction pattern, perhaps favored by a "psoriatic background." The most frequent causes of AGEP seem to be drug reactions, acute infections with enteroviruses, and hypersensitivity to mercury. With 55 (87%) of 63 cases attributed to drugs in this series, AGEP should be added to the list of cutaneous adverse drug reactions. Among drug-induced skin eruptions, AGEP is remarkable by its short time to onset after the administration of the suspected drug (less than 24 hours in half of our cases) and the great predominance (80%) of antibiotics as causative agents.

It is suggested that some cases previously reported as "drug-induced pustular psoriasis" were in fact AGEP.

Acute generalized exanthematous pustulosis.

Beylot C, Doutre MS, Beylot-Barry M.

Department of Dermatology, Hopital du Haut Leveque, France.

Semin Cutan Med Surg 1996 Dec;15(4):244-9 Abstract quote

Acute generalized exanthematous pustulosis (AGEP) is now a well-known clinical entity, characterized by acute onset with associated fever, and numerous non-follicular pin-head sterile pustules on erythematous background.

The biopsy evidences subcorneal pustules resembling those of pustular psoriasis. However, polymorphic aspects such as pseudo-erythema multiforme purpuric lesions, and edema are often associated, and with the rapid self-healing course of this impressive pustulosis, allow the differential diagnosis with pustular psoriasis. Most cases of AGEP are drug induced, particularly by antibiotics and mainly beta-lactams.

However, a number of other drugs, of which the list is increasing, may be responsible. Few cases are related to other causative factors such as viral infections or ultraviolet radiation.



Acute generalized exanthematous pustulosis (AGEP) – A clinical reaction pattern

Alexis Sidoroff, etal.

J Cutan Pathol 2001;28 (3):113-119 Abstract quote

Background: A wide range of diseases or reactions can cause pustular eruptions of the skin. In this spectrum there seems to be a subgroup with characteristic clinical features and a typical course which is mostly caused by drugs for which the term acute generalized exanthematous pustulosis (AGEP) has been established.

Objective: To describe the clinical features of AGEP.

Methods: The authors’ experience from a multinational epidemiological study on severe cutaneous adverse reactions and a comprehensive review of the literature were used to provide an overview of the disease and it’s possible causes. An algorithm for validating cases which was established for this study is also presented.

Results: AGEP typically presents with at least dozens of non follicular sterile pustules occurring on a diffuse, edematous erythema predominalty in the folds and/or on the face. Fever and elevated blood neutrophils are common. Histopathology typically shows spongiform subcorneal and/or intraepidermal pustules, a marked edema of the papillary dermis, and eventually vasculitis, eosinophils and/or focal necrosis of keratinocytes. Onset is acute, most often following drug intake, but viral infections can also trigger the disease. Pustules resolve spontaneously in less than 15 days.

Conclusion: The diagnosis AGEP should be considered in cases of acute pustular rashes and detection of the causative drug should be strived for. Knowledge of the clinical features and usual course of this disease can often prevent unnecessary therapeutical measures.



Pustular skin disorders: diagnosis and treatment.

Mengesha YM, Bennett ML.

Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.

Am J Clin Dermatol 2002;3(6):389-400 Abstract quote

The differential diagnosis for pustular skin disorders is extensive. The distribution of the lesions and the age of the patient are characteristics that may provide strong clues to the etiology of cutaneous pustular eruptions.

In adults, generalized pustular dermatoses include pustular psoriasis, Reiter's disease and subcorneal pustular dermatosis. Medications can cause generalized pustular eruptions, such as in the case of acute generalized exanthematous pustulosis; or more localized reactions, such as acneiform drug eruptions, which usually involve the face, chest and back. Localized pustular eruptions are seen on the hands and feet in adults with pustulosis palmaris et plantaris and acrodermatitis continua (both of which may be variants of psoriasis); on the face in patients with acne vulgaris, rosacea, and perioral dermatitis; and on the trunk and/or extremities in patients with folliculitis. A seperate condition known as eosinophilic folliculitis occurs in individuals with advanced human immunodeficiency disease. Severely pruritic, sterile, eosinophilic pustules are found on the chest, proximal extremities, head and neck. Elevated serum immunoglobulin E and eosinophilia are often concurrently found. In neonates, it is especially important to make the correct diagnosis with respect to pustular skin disorders, since pustules can be a manifestation of sepsis or other serious infectious diseases. Generalized pustular eruptions in neonates include erythema toxicum neonatorum and transient neonatal pustular melanosis, both of which are non-infectious. Pustules are seen in infants with congenital cutaneous candidiasis, which may or may not involve disseminated disease. Ofuji's syndrome is an uncommon generalized pustular dermatosis of infancy with associated eosinophilia. As in adults, neonates and infants may develop acne or scabies infestations.

In this article, we review the most common pustular dermatoses and offer a systematic approach to making a diagnosis. We also report the most up-to-date information on the treatment of these various cutaneous pustular conditions.


Pustulosis acuta generalisata is a post-streptococcal disease and is distinct from acute generalized exanthematous pustulosis.

Auer-Grumbach P, Pfaffenthaler E, Soyer HP.

Department of Dermatology, University of Graz, Austria.

Br J Dermatol 1995 Jul;133(1):135-9 Abstract quote

Generalized pustular eruptions with fever present a diagnostic and therapeutic problem. Based on a case of pustulosis acuta generalisata and a review of the literature, this entity can be regarded as an exclusively post-streptococcal disorder with an elevated antistreptolysin titre. It has a distinct clinical presentation of isolated pustules on normal skin, predominantly in an acral location.

We propose criteria for the clear separation of this disease from acute generalized exanthematous pustulosis and from pustular psoriasis.



TREATMENT Usually self-limited and resolves spontaneously with discontinuation of the drug
  May consider systemic prednisone therapy

Weedon D. Weedon's Skin Pathology. Churchill Livingstone. 1997.
Fitzpatrick's Dermatology in General Medicine. 5th Edition. McGraw-Hill. 1999.

Commonly Used Terms

Skin Drug Reactions

Skin Rash

Last Updated 8/21/2002

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