Pediatric Dermatology Vol. 11 No. 3 237-240

Sweet Syndrome as the PresentingManifestation of Chronic Granulomatous

Disease in an Infant

D. Sedel,* P. Huguet,t C. Lebbe4 J. Donadieu,§ M. Odievre,t and Ph. Labrunet

*Consultation de Dermatologie, fService de Pediatrie, Hopital Antoine Beclere, Clamart; tService deDermatologie, Hopital St. Louis, Paris; §Service de Pediatrie, Hopital de Bicetre, Bicetre, France

Abstract: A 2.5-month-oid infant had Sweet s^idrome. Chronic granu-iomatous disease was suiasequentiy diagn<»ed by the nitrobiue tetrazo-iium reduction test. To date, this infant is ttte youngest reported wiHiSweet syndrome. Moreover, the association of chronic granuicHnatousdisease with this syndrome has not iseen previousiy described. The pre-cise relationship between the conditions remains to ise determined. Gran-uiocyte function shouid be evaiuated in any infant with Sweet syndrome.

Sweet syndrome is a well-identified condition inadults. It is often associated with infection, immu-nologic dysfunction, or malignancy, and is thusconsidered to be a hypersensitivity reaction thatmight be driven by several factors such as cyto-kines. The syndrome is rare in infants and children.We report a 10-week-old infant in whom Sweet syn-drome was the initial manifestation of chronic gran-ulomatous disease (CGD). To our knowledge, thisassociation has not been previously reported.

CASE REPORT

A male infant, bom to unrelated parents after a full-term, uneventful pregnancy, was first seen at age 3weeks for cutaneous infection related to Klebsiellaon local samples, and successfully treated with oralcefixime and local synergistins. At 5 weeks, bilat-eral otitis due to Staphylococcus aureus was treatedwith oral amoxicillin, then erythromycin. At age 2.5

months, seborrheic dermatitis of the scalp wasnoted, preceding a rapidly generalized skin eruptionaccompanied by fever.

Physical examination showed disseminated skinlesions, involving the head, in particular the fore-head and scalp, the lower part of the abdomen andback (Fig. lA), buttocks, and dorsal surfaces ofboth hands. Most of the lesions were large, raised,round, 2-cm plaques, sharply defined, with edema-tous edges and a depressed gray or violaceous cen-ter; at each venipuncture site, they first looked likewaxy papules etnd then rapidly enlai^ed. They be-came confluent on both forehead and scalp, result-ing in large annular and gyrate plaques (Fig. IB).Palms and soles were spared. The itifant's tempera-ture was 38.7°C. His physical examination provedotherwise normal.

The diagnosis of Sweet syndrome was confirmedby light microscopic examination of the skin (Fig.2). Bacterial cultures of forehead cutaneous lesionsyielded 5. aureus. A total blood cell count showed

Address correspondence to Ph. Labnine, M.D., Service dePidiatrie, Hdpital Antoine Bfcl^re, 157 me de la Porte deTrivaux, 92141 CUunait Cedex, France.

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238 Pediatric Dermatology Vol. 11 No. 3 September 1994

Figure 1. (A) Large, raised, round plaques over the lower part of the abdomen. (B) Confluent skin lesions on theforehead resulting in annular, squamous plaques.

lets 395,000/mm'. Serum C-reactive protein levelwas normal and fibrinogeti concentration was 5.5g/L.

The patient was given a combination of intrave-nous cefotaxime and fosfomycin, followed by oraloxacillin, even though no infectious foci could bedetected on chest roentgenogram and tomodensi-tometry, abdominal ultrasound examination, or re-peated blood, urine, and throat cultures. Eight daysafter admission, the skin lesions had dramaticallyspread to both knees, inguinal folds, and scrotum.Positive bacterial cultures from the forehead hadled us to delay corticosteroid therapy. Now, how-ever, oral prednisone (1 mg/kg body weight) wasstarted and resulted in rapid improvement of the cu-taneotis lesions. These resolved within 10 days,leaving discrete areas of secondary cutis laxa. Bonemarrow smears were normal. Serum immunoglobu-lin concentrations and lymphocyte subpopulationswere normal. Granulocyte functions were studiedafter interruption of oral prednisone. Chemotaxisand phagocytosis were both normal. An abnormalnitroblue tetrazolium (NBT) reduction test identi-fied CGD: 4% of polymorphonuclear cells (PMN)reducted NBT with either endotoxin or Staphylo-coccus albus (normal >60%). Cytochrome B-558concentration was 6.78 pmol/lO' PMN (normal7-12). Myeloperoxidase activity was normal. Bothparents' NBT reduction tests and cytochromeB-558 concentrations were normal, suggesting anautosomal recessive form of CGD.

The infant was discharged taking a combinationof oral trimethoprimsulfamethoxazole and itracona-zole. Eighteen months later he was doing well,without recurrence of Sweet syndrome.

Figure 2. Diffuse dermal infiltration by intact polymor-phonuclear leukocytes. (Hematoxylin and eosin stain.)

17,100 !eukocytes/mm' with 54% neutrophils, 26%lymphocytes, 14% monocytes, and 6% eosinophils;hematocrit 27.7%; hemoglobin 9.4 g/dl; and plate-

Sedel et al: Sweet Syndrome and Chronic Granulomatotis Disease 239

DISCUSSIONIn this infant Sweet syndrome was the first manifes-tation of CGD. To date, he is the youngest patientreported with Sweet syndrome. Moreover, the as-sociation of the syndrome with CGD has not beenpreviously described.

Since the original description of the syndrome bySweet (1), several hundred cases have been re-ported in adults (2,3). Pediatric reports are morescarce, with only 17 children identified so far, al-though the real frequency may be underestimated(4-9). In all cases, the cutaneous lesions are sugges-tive (3). The diagnosis is confirmed by light micro-scopic examination of a skin biopsy specimen,showing subepidermal edema, diffuse dermal infil-tration by ititact polymorphonuclear leukocytes,and no evidence of necrotizing vasculitis (10). Inadults this condition may appear after infectious ep-isodes (11,12), or be associated with general inflam-matory disorders such as lupus erythematosus (3).Moreover, Sweet syndrome is associated in 10% to15% of patients with malignaticies or premalignan-cies, in particular myeloproliferative or myelodys-plaslic syndromes (13,14). Oral corticosteroids arethe only efficient treatment for this condition, re-sulting in dramatic improvement in both generalsymptoms and cutaneous eruption within a fewdays.

Among the 18 patients (including this infant) withinfantile Sweet syndrome, two groups nnay be dis-tinguished. The first consists of 12 patients agedless than 3 years (mean 16 mo) in whom skin mani-festations occurred after infectious episodes, espe-cially upper respiratory tract infection. Our patientis the youngest infant of this group. The secondgroup consists of patients whose ages range from 3to 12 years. In this group, skin manifestations areless suggestive of Sweet syndrome (e.g., facial cel-lulitis), and there may be some histologic similari-ties with pyoderma gangrenosum. Furthermore, inthis group, several children had severe heoiatologicdisorders stich as chronic myelogenous leukemia(15), congenital dyserythropoietic anemia (16), andFanconi anemia (17). A characteristic feature ofCGD is defective granulocyte bactericidial activity.Skin manifestations such as eczematous reactionsand infectious lesions such as impetigo and/or puru-lent reactions secondary to minimal skin trauma areoften diagnostic (18).

Our report emphasizes the possible associationbetween Sweet syndrome and CGD, thus illustrat-ing the importance of sttidying granulocyte functionin such patients. Ftirthermore, this association

combines granuiocyte dysfunction (the pathophysi-ologic basis of CGD) with the syndrome in whichneutrophils are deeply involved. Indeed, the molec-ular basis of CGD is well known, even though it is agenetically heterogenous condition. Conversely,the pathogenesis of Sweet syndrome is still notclear, but most studies consider the condition to bea hypersensitivity reaction to bacterial or viral in-fection or to other types of antigens including tumorantigens. In support of this, changes in neutrophilfunction have been reported (19,20), but data arecontroversial: chemotaxis may be decreased (21) orrarely increased (22); phagocytosis was decreasedby 50% in a patient with Fanconi anemia (17) but isusually normal; and intracellular killing of S. aureuswas slightly reduced in one patient (20). Thus somedegree of neutrophil dysfunction may be encoun-tered in Sweet syndrome. Furthermore, the syn-drome has been reported during therapy with gran-ulocyte colony-stimulating factor, suggesting therole of cytokines in its development (22). Finally,abnormal regulation of inflammatory skin responsein patients with CGD was described (23). Thus, theprecise relationship between CGD and Sweet syn-drome is still to be determined, but it may well de-pend OB granulocyte dysfunction, the nature ofwhich requires further studies.

ACKNOWLEDGMENT

We are thankful to Alan Strickland for his help inthe preparation of the manuscript.

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