Pediatric Dermatology Vol. 11 No. 2 156-159

Persistent Erythema Infectiosum-Like Rashas a Prodrome of AcuteLymphocytic Leukemia

Seung Min Lee, M.D., Dong Gun Kim, M.D., and Dongsik Bang, M.D.

[Department of Dermatology, Yonsei University College of Medicine, Seoul, Korea\

Abstract: A 7-year-old boy had erythema infectiosum with typical man-ifestations. Over more than 40 days, these iesions showed no sign of re-gression, and chronic anemia became progressiveiy more severe. Elec-tron microscopic examination performed 20 days after onset showedabnormal Sezary-like lymphocytes. Bone marrow biopsy, which was per-formed to evaluate the anemia, was consistent with acute lymphocyticleukemia. Persistent parvovirus B19 infection may be connected with im-munosuppression. Therefore, early electron microscopic study and bonemarrow biopsy may be helpfui for early diagnosis of hematologic malig-nancies. .

Erythema infectiosum, first described in 1886 byTschamer, is a benign infectious exanthem. Thisusually asymptomatic disease begins abruptly witherythema of the cheeks, referred to as a slappedcheck appearance, and extends to the trunk and ex-tremities. The periora! area, eyelids, and chin areusually spared. A characteristic feature of erythemainfectiosum is the evanescent nature of the rash,which fades within a week but subsequently brieflyrecurs several times (1).

Human parvovirus B19 is now known to be theetiologic agent of erythema infectiosum (2-5) aswell as other disorders such as postinfectious ar-thropathy in adults (6-7), transient aplastic crisis as-sociated with various hemoiytic anemias, and im-munosuppressive states (8-14).

We present a patient with persistent erythema in-fectiosum and chronic anemia lasting more than 40

days, who subsequently was diagnosed as havingacute lymphocytic leukemia.

CASE REPORT

A 7-year-old boy had a 7-day history of an erythem-atous. maculopapular eruption and a 20-day historyof mild fever, headache, and arthralgia of bothknees. Physical examination revealed a warm, indu-rated, erythematous. maculopapular rash on theface, prominent on the malar eminences, with cir-cumoral pallor and lacelike erythema on the exten-sor surfaces and trunk (Figs. 1 and 2). Hepato-splenomegaly and small, coin-sized, cervical lymphnodes were noted on palpation. His temperaturewas 37.3°C. The white blood cell count was 12500/mm" . with 43% polymorphonuclear cells, 52% lym-phocytes. 3% monocytes, 1% basophils, and 1%eosinophils. and platelet count of 238,000/mm"'. The

Address correspondence to Seung Min Lee, M.D.. YongdongSeverence Hospital. Yonsei University College of Medicine. De-partment of Dermatology, Young Dong P.O. Box 1217, Seoul,Korea.

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Lee et al: Erythema Infectiosum-Like Rash 157

Figure 1. trythematous maculopapular rash on bothcheeks (slapped cheek appearance) and foreheadwith circumoral pallor.

hemoglobin level was 10.2 g/dl, the hematocrit was29.9%. Erythrocyte sedimentation rate was 55 mm/hour and antistreptolysin titer was 400 IU. Resultsof antinuclear antibody. C-reactive proteins, andLE cell studies were negative. The levels of immu-noglobulins and C and C4 were normal. Peripheralblood smear showed no abnormal blasts.

A skin biopsy specimen from an erythematouspatch on the arm showed a perivascular infiltrate ofmononuclear cells with spongiosis of the epidermis(Fig. 3). The patient was treated symptomaticallywith acetaminophen and antihistamines, but the dif-fuse morbiliform eruption on his face, trunk, andextremities lasted for 40 days. At that time the boyappeared anemic and had a great deal of joint pain.His hemoglobin was 7.3 g/dl, and hematocrit 22.7%.A bone marrow examination showed abnormal lym-phoblast proliferation and erythroid hypoplasia(Fig. 4). Reevaluation of electron microscopic find-ings of a previous biopsy specimen 20 days after on-set revealed classic Sezary-like cells showing mark-edly convoluted nuclei with poor cytoplasm (Fig.5). The patient began chemotherapy with predniso-lone, vineristine. and L-asparaginase, and centralnervous system prophylaxis with methotrexate,cytosine-arabinoside, and hydrocortisone. He has

Figure 2. Maculopapular erythema with lacelike ap-pearance on both legs.

received maintenance therapy for two years afterremission without relapse.

DISCUSSION

Erythema infectiosum has long been presumed tobe due to a virus, and occurs in epidemics in thespring and summer (1). After the publication of areport by Anderson et al (2), Plummer et al testedserum taken from 12 patients with erythema infec-tiosum during a miniepidemic in 1980 and identifiedparvovirus BI9 in 11. Human parvovirus B19 is asingle-stranded DNA virus that has been associatedwith erythema infectiosum (2-5), poly arthralgia andarthritis, aplastic crisis in patients with hemoglobu-linopathies. immunosuppression (8-14), hydropsand fetal death (15). The most common manifesta-tion of parvovirus B19 infection is erythema infec-tiosum (16). The illness usually begins with the sud-den appearance of livid erythema of the cheeks.The rash lasts 2 to 39 days (mean 11 days) (20).

Our patient had the characteristic slapped cheek

158 Pediatric Dermatology Vol. 11 No. 2 June 1994

Figure 3. Biopsy specimen from the forearm showsspongiotic epidermis and perivascular infiltration ofmononuclear cells. (Hematoxylin & eosin magnifica-tion lOOx,)

Figure 4. Bone marrow examination shows abnormallymphoblast proliferation and erythroid hypoplasia.(Giemsa; magnification 400x.)

appearance and lacelike erythema on both extremi-ties and trunk, and also a mild fever with generalweakness. Laboratory findings revealed chronicanemia without evidence of leukemia at the time ofonset. Morbiliform eruption and anemia lastedabout 40 days, at which time his anemia became se-vere.

In parvovirus B19 infection, anemia, aplastic cri-sis, and chronic bone marrow failure may result.The virus lytically infects erythroid precursors inthe bone marrow and inhibits erythropoiesis (11,17,18); there is also virus-induced perturbation of hu-man megakaryocytopoiesis (19). Chronic bone mar-row failure resulting from parvovirus B!9 infectionwas reported in a child with Nezelof syndrome (10),and children with acute lymphocytic leukemia andchronic parvovirus B19 infection are described inthe literature (11.12).

In an immunocompromised host, infection withparvovirus B19 can persist and cause chronic bonemarrow failure, usuaiiy manifested as anemia(10,12). Those patients had no characteristic skinmanifestations, and the infection was detected byserologic assay with specific antibodies and DNAdetection in serum and organ specimens.

Our patient provides several points for consider-ation. His preceding persistent parvovirus Bt9 in-fection with characteristic skin manifestations ledto acute lymphocytic leukemia (ALLl FAB classi-fication). Infection with parvovirus has been impli-cated in affecting rapidly dividing bone marrowcells and causing chronic bone marrow failure in im-munocompromised hosts. Whether the parvovirus

Figure 5. Electron microscopy demonstrates cells with marked convoluted nuclei and poor cytoplasm (Sezary-likecell). (Magnification (A) 5850x, (B) 17,250x.)

Lee et al: Erythema Infectiosum-Like Rash 159

infection is an etiologic agent of ALL is not clear atthis point. An electron microscopic specimen taken20 days after onset revealed Sezary-like lympho-cytes with marked folded nuclei. Definitive diagno-sis of ALL could not be established by clinical andlaboratory tests at this time. Incubation of normalhuman lymphocytes with pokeweed mitogen orphytohemagglutinin results in the presence of 5% to11% of cells with light microscopic and ultrastruc-tural appearance indistinguishable from that ofSezary cells. Therefore Sezary cells are simulatedor transformed lymphocytes (21). Their presence isnot indicative of malignancy, but we assumed theultrastructural environment already might bechanged.

We suggest persistent parvovirus B19 infectionmay indicate an immunosuppressed status. Per-forming early electron microscopic studies andbone marrow examination may therefore be helpfulin early diagnosis of hematologic malignancies inchildren.

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