18. Jakobiec FA, Austin P, Iwamoto T, Trokel SL, Marquardt MD,

Harrison W. Primary infiltrating signet ring carcinoma of the

eyelids. Ophthalmology 1983;90:291-9.

19. Thomas JW, Fu YS, Levine MR. Primary mucinous sweat gland

carcinoma of the eyelid simulating metastatic carcinoma. Am J

Ophthalmol 1979;87:29-33.

20. Kuno Y, Numata T, Kanzaki T. Adenocarcinoma with signet

ring cells of the axilla showing apocrine features: a case report.

Am J Dermatopathol 1999;21:37-41.

21. Kuno Y, Tsuji T, Yamamoto K. Adenocarcinoma with signet

ring cells of the axilla: two case reports and review of the

literature. J Dermatol 1999;26:390-5.

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Perineal ulcers in an infant: An unusual presentationof postnatal cytomegalovirus infection

John G. Hancox, MD,a Avinash K. Shetty, MD,b Omar P. Sangueza, MD,c and Gil Yosipovitch, MDa,d

Wake Forest, NC

Cytomegalovirus (CMV) disease can cause significant morbidity and mortality in neonates and immunosup-pressed patients. Cutaneous disease is rare, even in at-risk patients. We report a case of CMV with perinealpapules, erosions, and ulcers in a preterm but presumably immunocompetent patient, whose diagnosiswas first suggested by skin biopsy and confirmed with serologic testing. The mode of transmission of CMVwas unclear. The lesions resolved without CMV-specific therapy, and the child had no apparent systemicsequelae of infection. CMV disease should be considered in the differential diagnosis of perineal erosionsand ulcers in infancy. In addition to the case, we briefly review the literature on cutaneous manifestationsof CMV disease. ( J Am Acad Dermatol 2006;54:536-9.)

Congenital cytomegalovirus (CMV) infectionis a well-recognized cause of perinatal mor-bidity and mortality, occurring in 0.5% to 2%

of live births.1 Approximately 10% of infants withcongenital CMV infection are symptomatic and maydevelop hepatosplenomegaly, pneumonitis, micro-cephaly, deafness, and thrombocytopenia.1 Long-term serious sequelae such as mental retardation,seizures, sensorineural deafness, and visual defectscan occur.1,2 In contrast, perinatal/postnatal CMVinfection has received considerably less attentionalthough infection rates up to 40% have beenreported in the first 6 months of life.1,3 PerinatalCMV infection, often acquired at delivery via expo-sure to genital secretions or transmitted through

From the Departments of Dermatology,a the Department of

Pediatrics, Section of Infectious Diseases,b the Department of

Pathology,c and the Neuroscience Program,d Wake Forest

University School of Medicine.

Funding sources: None.

Conflicts of interest: None identified.

Reprint requests: Gil Yosipovitch, MD, Associate Professor, Wake

Forest University School of Medicine, Department of Derma-

tology, Medical Center Blvd, Winston-Salem, NC 27157. E-mail:

gyosipov@wfubmc.edu.

0190-9622/$32.00

ª 2006 by the American Academy of Dermatology, Inc.

doi:10.1016/j.jaad.2005.04.037

breast-feeding, is usually asymptomatic with nolong-term sequelae; however, serious disease hasbeen reported in preterm infants.4,5

Numerous cutaneous findings have been de-scribed in infants with congenital CMV infectionincluding jaundice, petechiae, purpura, and ‘‘blue-berry muffin’’ lesions, which represent extramed-ullary (dermal) hematopoiesis and appear asviolaceous, dark blue to purple papules and nodulesthat can last for weeks.6 Perineal ulcers caused byCMV are very rare in neonates with perinatal orpostnatal CMV infection. We describe an unusualpresentation for CMV infection in a preterm butotherwise immunocompetent neonate with erodedand ulcerated papulonodules on the perineal andgluteal regions. This case is interesting in terms of itscutaneous presentation, which is usually seen inpatients with systemic sequelae and/or severeimmunocompromise.

CASE REPORTThe patient was born at 33 and 3/7 weeks’

gestation via cesarean section with a birth weightof 6 lb, 4 oz. The child’s prenatal history wassignificant for supraventricular tachycardia (SVT),abdominal ascites, and pericardial effusion. Themother was RPR nonreactive, hepatitis B negative,

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Case reports 537

rubella immune, and HIV negative. She receivedbetamethasone before delivery, and had artificialrupture of membranes at delivery. The child’s Apgarscores were 4 at 1 minute, 6 at 5 minutes, and 8 at10 minutes; because of apnea, he was intubated.Eventually, the child’s heart rate required controlwith propanolol. The child was breast-fed for thefirst 2 weeks of life. At approximately 4 weeks afterdelivery, the child developed a ‘‘diaper rash’’ thatwas initially and unsuccessfully treated with zincoxide paste and over-the-counter steroid agents. Thefamily reported frequent diaper changes using dis-posable diapers. At approximately 12 weeks of age,physical examination revealed a well-appearinginfant with normal vital signs. No lymphadenopathyor hepatosplenomegaly was noted. Examination ofthe skin revealed erythematous, umbilicated pap-ules and nodules on the buttocks, perineum,medial thighs, and proximal scrotum (Fig 1). Manyof the lesions were eroded. A background of ery-thema was present. The rest of the skin examinationwas unremarkable.

A 3-mm punch biopsy was performed; it dis-played hyperkeratosis overlying pseudoepitheliom-atous hyperplasia (Fig 2, A). Within the dermis, therewas a moderately heavy superficial perivascular andinterstitial inflammatory infiltrate composed mostlyof lymphocytes, histiocytes, and scant plasma cells.In some dermal vessels, endothelial cells were en-larged and contained intranuclear inclusions (Fig 2,

Fig 1. Eroded, excoriated, and umbilicated papules andnodules on the buttocks, perineum, medial thighs, andproximal scrotum.

B). CD1a stain was negative, ruling out Langerhanscell histiocytosis. Immunoperoxidase stain of thetissue for CMV was positive (Fig 3).

Serum CMV IgM and IgG (16 AU/mL) were bothpositive, but urine culture was negative. Liver trans-aminases, albumin, alkaline phosphatase, and bili-rubin were within normal limits, as was a completeblood cell count with platelets with differential. HIVtesting was negative. A computed tomographic scanof the head without contrast showed no intracranialabnormality, and a chest radiograph was normal. Anophthalmologic examination elucidated no evidence

Fig 2. A, Punch biopsy displaying hyperkeratosis overly-ing pseudoepitheliomatous hyperplasia. (Hematoxylin-eosoin stain; original magnification: 32.) B, Superficialperivascular and interstitial inflammatory infiltrate com-posed mostly of lymphocytes, histiocytes, and scantplasma cells. Enlarged endothelial cells (black arrow) ofsome dermal vessels contained intranuclear inclusionstypical of CMV. (Hematoxylin-eosoin stain; original mag-nification: 320.)

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538 Case reports

of retinal involvement or other ocular abnormality,and no hearing deficit was elicited. Serologic studiesof the mother were not performed. At his 2-monthfollow-up, the patient’s lesions had resolved with nospecific therapy, and there were no obvious physicalsequelae.

DISCUSSIONAlthough rare, cutaneous disease caused by CMV

has been reported in immunocompetent patients;uncommon cutaneous presentations in infants andchildren with CMV infection include scleredema7

and papular acrodermatitis of childhood (Gianotti-Crosti syndrome).8 A wide spectrum of cutaneousmanifestations of CMV infection has been reported inimmunocompromised pediatric and adult patients,including transplant recipients and patients withacquired immune deficiency syndrome (AIDS).9-12

Presentations of disseminated CMV disease from theliterature include perianal and rectal ulceration,13

indurated hyperpigmented nodules or plaques,14

papular and pruritic eruptions, and vesiculobullouslesions.15 CMV-associated ulcerative diaper derma-titis was reported in a 6-month-old AIDS patient. Inthis case, the eruption on the perineum was theinitial manifestation of a disseminated and subse-quently fatal infection.16 The patient in that case hadvesicles, bullae, pustules, and signs and symptomsof systemic disease. Our patient had no evidence ofextracutaneous sequelae, and the lesions spontane-ously resolved without any specific treatment forthe CMV infection. Finally, perineal ulcers havebeen reported in immunocompromised adults aswell.10,13,17-21 The precise mode of acquisition ofCMV in our patient is not clear although breast milk isa possibility. Besides breast milk, other sources ofCMV include exposure to maternal cervical secre-tions, transmission from other people, or transmis-sion by blood.22 Because our patient was born viacesarean section, transmission via maternal fluids

Fig 3. Immunoperoxidase stain of the tissue for CMV waspositive in scattered cells. (Original magnification: 340.)

during labor is less likely. Also, the infant did notreceive any blood transfusions. CMV has beenshown in the breast milk of 32% to 96% of seropos-itive mothers with a transmission rate of 37%.23

Transmission of CMV through breast-feeding couldresult in symptomatic CMV infections, includingsepsis-like syndromes.23 Breast milk viral load andduration of breast-feeding may influence the rate ofacquiring CMV infection.24 Severe disease is uncom-mon in term infants when CMV is contracted by thismeans because the child has passive immunity byacquired maternal antibodies.25 Transfer of the ma-jority of protective antibodies occurs at 28 weeks,and thus severely premature neonates are muchmore susceptible.25 Although premature, our patientwas born at 33 3/7 weeks and may have acquiredsuch antibodies, thus decreasing the risk of severedisease. Confirming the decreased risk of postdeliv-ery infection even in preterm infants, Vollmer et al26

suggested that CMV acquired postnatally via breastmilk does not have a negative affect on neuro-development, even in neonates born at 28 weeksgestation.26 Since the virus is ubiquitous and we donot have serologic evidence of acute CMV infectionin the mother, it is very possible that our patientacquired CMV through horizontal transmissionby direct contact with virus-containing secretionsfrom older siblings at home or from day-carecontacts.

With regard to the infant’s arrhythmia, no reportsof CMV-associated arrhythmia to our knowledgeexist in the literature. CMV pericarditis has beenreported, including in an infant with congenital heartdisease,27 and, in a series of 26 viral myocarditiscases, CMV was detected in 1 case by polymerasechain reaction.28 Respiratory syncytial virus has beenreported in association with supraventricular tachy-cardia, and, in those cases with structurally normalhearts, the tachycardiaswere self-limited.29Wedoubtthe supraventricular tachycardia and CMV infec-tion are related in our patient.

The differential diagnosis of erythematous,eroded and ulcerated papules and nodules in theperineum of an infant includes Jacquet’s erosivediaper dermatitis, irritant or contact dermatitis, inter-trigo, candida infection, viral causes (herpes simplexvirus, human papilloma virus, CMV, human immu-nodeficiency virus, molluscum contagiosum),Langerhans cell histiocytosis, granuloma glutealeinfantum and nutritional deficiencies such as acro-dermatitis enteropathica. Jacquet’s diaper dermatitisdeserves mention as it displays well-demarcatedpunched-out ulcers and is often the result of infre-quent diaper changes; therefore, it responds toexcellent diapering practices.30 Because several of

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Case reports 539

the entities in the above differential diagnosis areworsened by poor skin care, frequent diaperchanges should be part of the first step in themanagement of any such eruption.

Treatment options for perinatal/postnatal CMVinfection are limited. Although ganciclovir, a guano-sine analogue that selectively inhibits CMV DNApolymerase, has been used in the treatment of symp-tomatic congenital CMV infection,31,32 the role ofganciclovir in treating perinatal/postnatal CMV-infected infants is yet to be determined, and thereare no published controlled studies. Diagnosis ofCMV disease can be difficult; histopathologic evalu-ation is extremely valuable in difficult cases.

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