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Year : 2014  |  Volume : 59  |  Issue : 2  |  Page : 210
Rare case of phenytoin induced acute generalized exanthematous pustulosis with cerebellar syndrome

1 Department of Medicine, Government Medical College and Hospital, Nagpur, India
2 Department of Skin and V. D., Government Medical College and Hospital, Nagpur, India

Date of Web Publication21-Feb-2014

Correspondence Address:
Pravin U Shingade
Department of Medicine, Government Medical College and Hospital, Nagpur
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0019-5154.127715

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Acute generalized exanthematous pustulosis (AGEP) is a rare drug induced cutaneous hypersensitivity reaction characterized by sudden onset of fever with sterile pustules overlying an erythematous skin occurring all over the body. The offending drugs are usually B-lactams and macrolides.Among anticonvulsants carbamazepine and Phenobarbital are commonly associated with AGEP. Only one case of phenytoin induced AGEP has been reported in literature. We present a rare case of AGEP with cerebellar syndrome occurring after receiving loading dose of phenytoin.

Keywords: Acute generalized exanthematous pustulosis, cerebellar syndrome, phenytoin

How to cite this article:
Shingade PU, Wankhede V, Kataria PS, Sonone N. Rare case of phenytoin induced acute generalized exanthematous pustulosis with cerebellar syndrome. Indian J Dermatol 2014;59:210

How to cite this URL:
Shingade PU, Wankhede V, Kataria PS, Sonone N. Rare case of phenytoin induced acute generalized exanthematous pustulosis with cerebellar syndrome. Indian J Dermatol [serial online] 2014 [cited 2021 Dec 1];59:210. Available from:

What was known?
1. Among antiepileptics carbamazepine is commonly associated with AGEP. 2. Cerebellar syndrome and DRESS are known adverse effect of phenytoin.

   Introduction Top

AGEP also known as toxic pustuloderma and pustular drug reaction [1] is an uncommon drug reaction with an incidence of one to five cases per million per year. In a recent eight year study of clinical types of drug eruptions in 106 patients by Fatima Akpinar et al. only two patients had AGEP. [2] The term AGEP was coined by Beylot, a French dermatologist, in 1980. [3] Typical rash of AGEP has an acute onset occurring within 24 hours after drug ingestion. Initially there is scarlantiform erythema which usually begins on the face or in the intertriginous areas accompanied by fever above 38 degree Celsius and leucocytosis. The rash rapidly spreads and consists of multiple non follicular sterile pustules. Facial oedema, purpura and erythema multiforme like lesions are also seen. [4] Transient renal failure is seen in 32% of cases. The rash resolves within 15 days with residual desquamation.

   Case Report Top

An 18-year-old male was admitted to infectious disease ward for fever and generalized erythematous rash since one day. A diagnosis of viral exanthem was made. On detailed history taking patient was found to be a known case of seizure disorder on regular levetiracetam since three years. Patient gave past history of an allergic rash to phenytoin three years ago. Patient had received loading intravenous dose of phenytoin (1000 mg) one day prior to admission. On examination patient was febrile and was having facial edema [Figure 1] with predominant involvement of lips. There was total sparing of oral mucosa. Patient had generalized erythematous macular rash along with multiple non follicular pustules more pronounced on chest [Figure 2] and back [Figure 3] but also involved the axilla [Figure 4] and neck. There was no involvement of palm and soles. In addition, patient had cerebellar signs in the form of horizontal, up beating and down beating nystagmus along with bilateral swaying while walking suggestive of signs of acute phenytoin toxicity. Rest of general and systemic examination was unremarkable. In view of clinical presentation and history, diagnosis of acute drug reaction was kept and dermatologist opinion was taken. A provisional diagnosis of acute generalized exanthematouspustulosis was made and skin biopsy and gram stain of the pustule was done. His investigations revealed leucocytosis (TLC-11,500) and deranged kidney function test (Urea-55 mg/dl; Creatinine-2.2 mg/dl) with normal liver function test. Skin biopsy revealed spongiosis with dermal neutrophilic and eosinophilic infiltrate [Figure 5] which are features of acute generalized exanthematous pustulosis. Gram staining of smear from the pustule showed no organism. Patient was treated with tapering doses 40 mg of oral corticosteroids along with antihistaminics. Patient responded dramatically with total subsidence of rash with desquamation [Figure 6] and [Figure 7]. Facial edema subsided completely. His cerebellar signs disappeared and kidney function test was normal within 15 days and patient was discharged with no sequelae.
Figure 1: Facial edema

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Figure 2: Pustular lesions over the chest

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Figure 3: Pustular lesions over back

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Figure 4: Pustular lesions in axilla

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Figure 5: H and E stain showing spongiosis

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Figure 6: Healing by desquamation

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Figure 7: Pin point desquamation over back

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   Discussion Top

After analysis of 63 cases Roujeau et al. concluded that most common causes of AGEP is drug induced, acute infections with enteroviruses and hypersensitivity to mercury. [5] Most frequently mentioned drugs causing AGEP are antibiotics namely beta lactams and macrolides, antifungal agents like terbinafine and nystatin, anticonvulsants mainly carbamazepine and Phenobarbital. [6] Drugs rarely causing AGEP are chloroquine, acetylsalicylic acid, [6] hydroxyzine. [7] The exact pathogenesis is unknown. It is thought to be a delayed type four hypersensitivity reaction involving both CD4 and CD8 cells. Histopathology shows dermal edema, intraepidermal/subcornealpustules, perivascular eosinophils and neutrophils. Differential diagnosis to be considered includes pustular psoriasis, subcorneal pustular dermatosis drug reactions with eosinophilia and systemic symptoms (DRESS) and erythema multiforme/TEN. [6] In Pustular psoriasis lesions are confluent and polycyclic erythematous patches with pinhead size pustules at the periphery and central area of desquamation. [6] Histopathology will show papillomatosis and acanthosis which is absent in AGEP. Subcorneal pustular dermatosis is chronic pustular disease in which pustules are arranged in annular and serpiginious pattern. DRESS in addition to eosinophilia has associated systemic involvement in the form of hepaosplenomegaly, interstitial nephritis.TEN has a positive Nicholky's sign alongwith significant mucosal involvement.

Following five criteria has been suggested for the definition of AGEP. [8] (1) several dozens of nonfollicular pustules arising on a widespread edematous erythema. (2) typical histopathological changes. (3) fever > 38°C. (4) leucocytosis (5) acute evolution with spontaneous resolution in less than 15 days. Our patient satisfied all the criteria. After receiving loading dose of phenytoin he developed ataxia with nystagmus which are known acute signs of phenytoin toxicity along with fever and rapidly spreading erythematous rash with sterile pustules. Histopathology showed spongiosis with dermal eosinophilic and neutrophilic infiltrate consistent with diagnosis with AGEP. To the best of our knowledge there is only one case report of phenytoin induced AGEP. [9] Ours probably is the first report of simultaneous occurrence of phenytoin induced AGEP with cerebellar syndrome. Physicians should be aware of this uncommon cutaneous side effect of a commonly prescribed antiepileptic drug.

   References Top

1.Contact dermatitis and drug eruptions. In: James JD, Berger TG, Elston DM, editors. Andrew's siseases of the skin clinical dermatology. 11 th ed, Philadelphia: W.B. Saunders Company: 2011. p. 119-20.  Back to cited text no. 1
2.Akpinar F, Dervis E. Drug Eruptions: An 8-year Study Including 106 Inpatients at a Dermatology Clinic in Turkey. Indian J Dermatol 2012;57:194-8.  Back to cited text no. 2
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3.Beylot C, Bioulac P, Doutre MS. [Acute generalized exanthematic pustuloses (four cases) (author's transl)]. [in French]. Ann Dermatol Venereol 1980;107:37-48.  Back to cited text no. 3
4.Guevara-Gutierrez E, Uribe-Jimenez E, Diaz-Canchola M, Tlacuilo-Parra A. Acute generalized exanthematouspustulosis.Report of 12 cases and literature review. Int J Dermatol 2009;48:253-8.  Back to cited text no. 4
5.Roujeau JC, Bioulac-Sage P, Bourseau C, Guillaume JC, Bernard P, Lok C, et al. Acute generalized exanthematouspustulosis. Analysis of 63 cases. Arch Dermatol 1991;127:1333-8.  Back to cited text no. 5
6.Speeckaert MM, Speeckaert R, Lambert J, Brochez L. Acute generalized exanthematouspustulosis: An overview of the clinical, immunological and diagnostic concepts. Eur J Dermatol 2010;20:425-33.  Back to cited text no. 6
7.Kumar SL, Rai R.Hydroxyzine induced acute generalized exanthematouspustulosis: An uncommon side effect of a common drug. Indian J Dermatol 2011;56;447-8.  Back to cited text no. 7
8.Sidoroff A, Halevy S, Bavinck JN, Vaillant L, Roujeau JC. Acute generalized exanthematouspustulosis (AGEP): A clinical reaction pattern. J Cutan Pathol 2001;28:113-9.  Back to cited text no. 8
9.Aziz N, Toerge S, Nigra T. Phenytoin-induced acute generalized exanthemouspustulosis. J Am Acad Dermatol 2010;62:718-9. Report of 12 cases and literature review. Int J Dermatol 2009;48:253-8.  Back to cited text no. 9

Whats is new?
1. Phenytoin a widely prescribed antiepileptic drug should be considered in the etiology of AGEP. 2. The simultaneous occurrence of phenytoin induced AGEP and cerebellar syndrome is not yet reported.


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]

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