J AM ACAD DERMATOL

APRIL 2010

718 Letters

and food allergy. Ann Allergy Asthma Immunol

2005;94:398-401.

5. Kuhl J, Davis MD, Kalaaji AN, Kamath PS, Hand JL, Peine CJ. Skin

signs as the presenting manifestation of severe nutritional

deficiency: report of 2 cases. Arch Dermatol 2004;140:521-4.

doi:10.1016/j.jaad.2008.10.018

Fig 1. Numerous 2- to 3-cm erythematous plaques stud-ded with pustules covering the right anterior surface of thechest.

Phenytoin-induced acute generalizedexanthemous pustulosis

To the Editor: A 57-year-old African American malewith a history of a seizure disorder caused by atraumatic head injury presented to the emergencydepartment with a recent onset of multiple pustularlesions that started on his face and spread to his trunkand upper extremities. He had presented to the sameemergency department 5 days earlier in status epi-lepticus. He was treated with 1 g phenytoin for thefirst time in addition to increased doses of his othermedicines (lorazepam and levetiracetam). His sei-zure resolved and he was discharged 2 days later onincreased doses of levetiracetam and valproic acid.

The physical examination revealed a febrile pa-tient with numerous 1- to 3-mm nonfollicular roundpustules covering his entire face. The chest, back, andupper extremities had numerous 2- to 3-cm erythem-atous plaques studded with pustules (Fig 1). The righteye was severely edematous. The right hand showedirregular macular erythema with diffuse edema. Notargetoid, mucosal, or genital lesions were observed.

Laboratory examinations revealed leukocytosiswith an increase in band neutrophils. Hypocalcemiawas also noted. Pathologic examination of alesional punch biopsy with hematoxylineeosin stainshowed areas of neutrophilic spongiosis in theepidermis and patchy intraepidermal neutrophilicinfiltrates with slight aggregation in the upper epider-mis consistent with pustules. The superficial dermisshowed signs of edema and sparse perivascularlymphoid infiltrates. This was consistent with acutegeneralized exanthemous pustulosis (AGEP).

As the index of suspicion for AGEP was high onpresentation, the patient was immediately started on20 mg prednisone four times daily for 4 days. Within48 hours, the patient showed signs of improvement,and on the fourth day of prednisone therapy, most ofthe pustules had ruptured, leaving exfoliated areas.The patient was subsequently discharged on day 6on a prednisone taper.

The present case is noteworthy in that it implicatesphenytoin as a cause of AGEP. The antiepilepticdrugs mentioned in the literature have mainly fo-cused on carbamezapine and phenobarbital.1

Phenytoin was the likely etiologic agent because itwas the only new drug introduced to the patient.

Although he had recently taken lorazepam, levetir-acetam, and valproic acid, these were drugs he hadbeen taking for years without a history of adversereactions. Phenytoin was administered in a one-timedose 5 days before the onset of symptoms, whichfalls within the normal interval between drug inges-tion and onset of AGEP.2,3 Confirmation with patchtesting was not possible because the patient’s dimin-ished mental capacity made him a poor candidate.However, when performed, patch testing is by nomeans definitive, because only 50% of AGEP casesdemonstrate positive patch tests results.4

This case is the first of its kind to implicate phen-ytoin as a cause of AGEP. Although not a commonetiology, antiepileptics should be scrutinized as acause of AGEP and in particular, phenytoin shouldnow be considered in the differential of drugs causingAGEP. Fortunately, the condition is largely self-limitedand most patients go on to a full recovery.

Nasir Aziz, MD,a Samantha Toerge, MD,b andThomas Nigra, MDb

Riverside Regional Medical Center,a Newport News,Virginia and the Department of Dermatology,b

Washington Hospital Center, Washington, DC

Funding sources: None.

Conflicts of interest: None declared.

Reprint requests: Samantha Toerge, MD, Depart-ment of Dermatology, Washington Hospital Cen-ter, 110 Irving St, NW, Washington, DC 20010

E-mail: staoerge@gmail.com

REFERENCES

1. Noce R, Paredes B, Pichler W, Krahenbuhl S. Acute generalized

exanthematic pustulosis (AGEP) in a patient treated with

furosemide. Am J Med Sci 2000;320:331-3.

2. Belda Junior W, Ferolla AC. Acute generalized exanthema-

tous pustulosis (AGEP). Rev Inst Med Trop Sao Paulo

2005;47:171-6.

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3. Pattee S, Silvis N, Ellsworth L. Diffuse pustular eruption after

treatment of dog bite. Arch Dermatol 2002;138:1091-6.

4. Teixeira M, Silva E, Selores M. Acute generalized exanthematous

pustulosis induced by nimesulide. Dermatol Online J 2006;12:20.

doi:10.1016/j.jaad.2008.10.057

Fig 2. A, Superficial spindle cell proliferation (not ex-tending into the fat). B, Diffuse CD341 staining. (A,Hematoxylineeosin stain; B, CD34 immunohistochemicalstain; original magnification: A, 3100; B, 3200.)

Fig 1. Connective tissue nevus located on the left suboc-cipital neck.

CD341 connective tissue nevi: Are theyunusual?

To the Editor: A 1-year-old white male with a 6-monthhistory of ‘‘raised bumps’’ overlying the dorsal sur-face of his neck was brought to our dermatologyclinic for evaluation. An agminated patch of whitepapules was identified on the suboccipital neck(Fig 1). Nuchal ultrasound was unremarkable. A 3-mm punch biopsy demonstrated spindle cell prolif-eration within the papillary dermis, without signifi-cant atypia (Fig 2, A). Vascularity was slightlyincreased. The overlying epidermis was unremark-able. Laboratory tests for Ulex europaeus, S-100,CD68, muscle-specific actin, and smooth muscleactin were negative. The spindle cells and visualizedvascular structures stained strongly positive for CD34(Fig 2, B). After a thorough Web-based literaturesearch, we were unable to find any reports of CD341

staining with connective tissue nevus (CTN), but wedecided that the final pathologic diagnosis was mostconsistent with this diagnosis. In lieu of repeat biopsyor excision, the mother opted for a reevaluation in1 year. The patient had no other medical history,family history, or clinical findings suggestive orsuspicious for the diagnosis of tuberous sclerosis.

This CD341 staining pattern prompted us to deter-mine if this pattern was similarly present in other CTN.By reviewing our log of previous dermatopathologycases over the last 5 years, we identified six additionalpatients (Table I) who had specimens identified asCTN. Six of the seven total patients (5 males and 2females) showed diffuse immunoreactivity for CD34.Ages ranged from 4 months to 13 years.

When it comes to spindle cell neoplasms, CD34staining is classically associated with the histopatho-logic diagnosis of dermatofibrosarcoma protuberans(DFSP).1 Other spindle cell neoplasms associated withCD34 expression include cases of sclerotic fibromas,nuchal fibromas, solitary fibrous tumors, cellular bluenevi, nerve sheath tumors, stromal cells surroundingtrichoepitheliomas, and Kaposi sarcoma1-5 (Table II).In nephrogenic systemic fibrosis, there is an increasednumber of spindle-shaped dermal fibroblastelikecells that are CD341 and procollagen-1epositive.6

A basic immunohistochemistry panel for highmolecular weight cytokeratin, melanocytic markers(S100 protein, HMB-45, and Melan-A), smooth mus-cle actin, desmin, and endothelial markers (CD31 and

CD34) is effective in diagnosing most cutaneousspindle cell tumors.7 Pathologic differential diagnosesfor CD341, U europeausenegative, and S-100enega-tive spindle cell tumors include DFSP, hemangio-pericytoma, Kaposi sarcoma, and lymphangioma( fibrous/hemangioblastic). The histologic appear-ance of the cases presented here does not fit DFSP,nuchal fibromas (both aredeeper processes involvingfat1,2), sclerotic fibroma (hypocellular nodule withmarkedly sclerotic ’’plywood’’ stroma2), or solitary