Pediatric Dermatology Vol. 9 No. 3 288-292
Sweet Syndrome in a Neonate with Aseptic Meningitis Terris R. Dunn, M.D., Harry W. Saperstein, M.D., Aviva Biederman, M.D., and Richard P. Kaplan, M.D. Division of Dermatology. University of California at Los Angeles and Cedars-Sinai Medical Center, and Department of Pediatrics, Cedars-Sinai Medical Center, Los Angeles, California
Abstract: A 7-week-old Infant with arstecedent otitis media, upper respiratory infection, and aseptic meningitis was diagnosed as having Sweet syndrome. Although this disease usually affects adults, it has been reported in 17 children. This is the youngest reported patient with the disorder to date, and the first In whom the syndrome was associated with aseptic meningitis.
Sweet syndrome (SS), acute febrile neutrophilic dermatosis, first described by Sweet in 1964(1), is charactedzed by painful plaques, fever, and peripheral leukocytosis. Histopathology shows a dense dermal infiltrate of polymorphonuclear leukocytes without evidence of vasculitis (2). The pathogenesis of this syndrome remains unknown, although it is believed to represent a hypersensitivity reaction to an infection or malignancy. It is characterized by a rapid therapeutic response to systemic corticosteroids. It is most common in adults, with only 17 reported pediatric cases (3). We report the youngest patient with SS to date and the first associated with aseptic meningitis. CASE REPORT A 7-week-old white boy was admitted to the hospital with a four-day history of fever, upper respiratory infection symptoms of mild congestion, decreased appetite, increased irritability, and rash. The rash initially was limited to his cheeks, but two days prior to admission it spread to the scalp, eyelids, trunk, and extremities, with one lesion on his Address correspondence to Richard P. Kaplan. M.D., 200 UCLA Medical Plaza, Suite 465. Los Angeles, CA 90024.
right palm. The lesions were slightly indurated, erythematous papules and plaques that progressed to buliae that crusted over (Fig. 1). Two days before admission the infant was seen by his primary physician who diagnosed otitis media and prescribed amoxicillin, which was discontinued on admission to the hospital. The infant was admitted to the hospital with a temperature of 103°F. Initial complete blood cell count showed white blood cell count of 17,200/til with 58% polys, 5% bands, 22% lymphocytes, 15% monocytes, and 1% eosinophils. Hemoglobin was 10.0 g/dl and hematocdt 29.7%. Chest radiograph showed no infiltrates. Routine urinaiysis was negative. Cerebrospinal fluid (CSF) showed protein 46 mg/dl, glucose 55 mg/dl, no red blood cells, 34 white blood cells, 13 polys, 67 lymphocytes, and 19 monocytes; this was consistent with aseptic meningitis. Pending cultures, the infant was given ampicillin and cefotoxime. The antibiotics were discontinued after three days, secondary to negative bacterial blood and CSF cultures. Herpes simplex virus (HSV) titers were elevated for IgG, with HSV 1 titer of 1:1024 and HSV 2 titer of 1:512, indicative of
Dunn et al: Sweet Syndrome in a Neonate
289
Figure 1. Lesions of Sweet syndrome.
maternal antibody being passed. The IgM titers were negative, indicative of no current infection. The infant was given acyclovir empidcally due to the possibility of a herpes meningitis. Before starting acyclovir, HSV cultures of the CSF were performed. Viral cultures remained negative over the infant's hospitalization. Serum vadcella titers were also negative. Acyclovir was discontinued four days after admission. A skin biopsy specimen taken four days after admission was diagnostic of SS. The lesion, noted to be in the dermis, was an acute suppurative process with microabscess formation in some foci. There was a heavy neutrophilic infiltrate with some eosinophils with marked edema but no epithelial separation. Leukocyte nuclear fragmentation was also present (Fig. 2). The infant was administered prednisone 1 mg/kg/ day for three days and then switched to 0.5 mg/kg/ day for three days. On day 2 of 0.5 mg/kg new lesions began to form; the dosage was increased to the initial level and the lesions began to subside within a day. Because of eyelid lesions, the infant was evaluated by an ophthalmologist pdor to discharge and found to have no evidence of ocular disease. The infant was discharged 14 days after admission taking prednisone 1.0 mg/kg/day for 7 days then 0.5 mg/kg/day for 7 days. The lesions had regressed considerably by discharge. To date, 3! months after admission, they had not recurred. DISCUSSION The infant fulfills the criteda for the diagnosis of SS as evidenced by his acute febrile illness, characteristic skin lesions, and biopsy fmdings of intradermal neutrophilic infiltrate and leukocytosis. He is the
Figure 2. Histopathology revealed dense collection of neutrophils in the dermis.
first reported case of the syndrome associated with aseptic meningitis. In adults SS primadly affects women in their midthirties to midfifties, with a femaie:male ratio of 15:1 as reported by Sweet (1,2). Of the 17 reported pediatdc cases, 10 were males and 7 females, and they ranged in age from 3 months to 12 years (3). To date, no specific etiology has been found for SS. It is postulated to be a hypersensitivity reaction lo a bacterial, viral, or tumor antigen (4), or the response to an inappropriate secretion of endogenous cytokines such as interleukin-1 (epidermal cell thymocyte-activating factor), and/or granulocyte colony-stimulating factor (G-CSF) (5). In one study, a 42-year-old woman with hairy cell leukemia, complicated by neutropenia and cutaneous vasculitis, developed SS manifestations after two weeks of therapy with G-CSF. When the agent was discontinued, fevers and skin lesions persisted for two weeks, then gradually improved (6). It was believed that the SS manifestations were secondary to an increase in tissue granulocytes induced by G-CSF. Studies of neutrophilic chemotaxis and phagocytosis showed increased or normal levels of neutrophilic activity in SS (7). Neutrophilic hyperproduction of superoxide anion also was demonstrated in a
290
Pediatric Dermatology Vol. 9 No. 3 September 1992
patient with SS and myelodysplastic syndrome (8). This superoxide anion hyperproductiori may cause the damage to cutaneous tissues associated with the syndrome. As with our patient, in many adults and children with SS, a febrile upper respiratory infection, otitis media, pharyngitis, tonsillitis, or influenzalike illness may precede the skin lesions by one to three weeks (1,2,9-11), which suggests a crossreactive immunologic process with microbial antigens. Approximately 15% of adults with SS have associated malignancy, with hematologic malignancies such as acute myelogenous leukemia being the most common (5,12,13). Again, a cross-reactive immunologic process with tumor antigens is likely. In approximately two thirds of adult patients the diagnosis of SS preceded the diagnosis of malignancy. Other conditions associated with SS in adults include Sjogren syndrome (14), lymphoma (15), ulcerative colitis (1), and inflammatory arthdtis (16). Drugs and vaccinations have rarely been implicated in inducing SS (11,17). Mucosal lesiotis involving the eyes, mouth, or oral pharynx may accompany the characteristic skin lesions (1,2,18). Of the reported SS childhood cases (Table 1). all patients had erythematous papular and plaque-type lesions involving the face, trunk, and/or extremities. Two had associated leukemias. One child with juvenile chronic myelogenous leukemia was diagnosed with leukemia one year preceding SS manifestations (19). The other was diagnosed with acute promyeiocytic leukemia during hospitalization for SS (20). Two children had associated otitis media (21,22). Four had associated osteomyelitis (23-25). Five cases of SS were associated with anemia. Two were brothers with congenital dyserythropoietic anemia (23). Two had Fanconi anemia, an autosoma! recessive pancytopenia that carries an increased risk for malignancy. The last child with SS associated with anemia had a transient hypochromic microcytic anemia. Our patient also had mild anemia (hemoglobin 10.0 g/dl, hematocdt 29.7%), which subsequently returned to normal. Five children had associated respiratory problems. One had a persistent right middle lobe infiltrate on chest radiograph accompanied by coughing and wheezing (26). Two had history of recurrent respiratory tract infections (22,26). One child had left basal pneumonia on chest radiograph, accompanied by coughing (3), and one had expiratory wheezing (22). Two children had evidence of panniculitis (neutrophilic infiltration of the subcutaneous tissues)
TABLE 1. Pediatric Cases of Sweet Syndrome Age
Sex
4 mo
M
9 mo 3.5 yrs 10 yrs 21 mo iO mo
F M M M M
9 mo
M
30 mo 3 yrs
M M
23 mo 7 yrs
M
12 yrs
F
17 mo
F F
32 mo 8 mo 24 mo 3 mo 7 wks
M M F M
Associated conditions (reference) Hypochroniic microcytic anemia, pneumonia (3) Tonsillitis, cutis laxa (11) Juvenile chronic myelogenous leukemia, cutis laxa (19) Actue promyeiocytic leukemia (20) Otitis media (21) Otitis niedia, recurrent respiratory tract infections, pathergy, atrophic scarring (22) Wheezing, pathergy, atrophic scarring (22) Congenital dyserythropoietic aneniia. recurrent multifocal osteomyelitis (23) Congenital dyserythropoietic aneniia, recurrent multifocal osteomyelitis (23) Multifocal osteomyelitis (24) Osteomyelitis, Fanconi anemia, pathergy, panniculitis (25) Fanconi anemia, pannicuiitis, esophageal atresia (25) Congestion, cough, wheezing, persistent right middle lobe infiltrate, cutis laxa; death from cardiac involvement at age 30 mo (26, 31) Recurrent respiratory tract infections (26) Cutis laxa (28) None (29) None (30) Upper respiratory tract infection, otitis media, aseptic meningitis (this report)
(25). Panniculitis is not a common manifestation of SS (25,27). Three children had evidence of pathergy at intravenous catheter sites (22,25). Four had secondary cutis laxa localized to sites of healed lesions (11,19,26,28) and two had healing with atrophic scar formation (22). Two children had SS without other associated conditions (29,30). Two of the children died. One was a 12-year-old with esophageal atresia (25). The second was a 17month-old who died at 30 months of age after cardiac catheterization for associated coronary vasoocclusive disease. A neutrophilic infiltrate was found in her coronary arteries (26,31). The majority of children were treated with oral steroids, although spontaneous remission occurred in one (23) and the syndrome resolved with antibiotics in another (11). Oral corticosteroid treatment results in a rapid response, with symptoms and signs cleadng in one to three days (5,24,26). Three children required maintenance steroids (25,26).
Dunn et al: Sweet Syndrome in a Neonate
Aside from the patient reported by Saxe and Gordon (11) in whom antibiotics apparently cleared the syndrome, antibiotics in general do not alter the course of the disease. Most likely this is because SS appears to be an inflammatory reaction and not primadly an infectious process. The etiology of aseptic meningitis includes infectious and noninfectious causes such as viruses, neoplastic diseases, systemic diseases, and certain medications (i.e., penicillin), as well as unknown causes (32). Our patient's viral cultures remained negative throughout his hospital stay, and neither systemic nor neoplastic disease was discovered. He was taking amoxicillio two days before hospital admission (for presumed otitis media), and it is possible amoxicillin led to the development of druginduced aseptic meningitis. However, the boy developed SS manifestations before taking the antibiotics, and it is our belief that the aseptic meningitis and SS manifestations were directly related. Also, all antibiotics were discontinued three days after hospital admission, and symptoms persisted. Therefore, drug-induced aseptic meningitis seems unlikely. Consistent with the theory that SS may be the response to an inappropriate secretion of endogenous cytokines, it has been shown that the levels of vadous cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF) (33). interleukin-1 beta (IL-lp) (34). and interferon gamma (35) are increased in the CSF of patients with aseptic meningitis. It is possible that our patient developed aseptic meningitis (unknown etiology) that led to an increased level of one or more of these cytokines. ultimately resulting in SS. Conversely, it is also possible that an increased secretion of endogenous cytokines. possibly a resuh of hypersensitivity to an unknown antigen, led to the development of SS and aseptic meningitis simultaneously. REFERENCES 1. Sweet RD. An acute febrile neutrophilic dermatosis. BrJ Dermatol 1964:76:349-356. 2. Sweet RD. Acute febrile neutrophilic dcrmatosis1978. BrJ Dermatol 1979; 100:93-99. 3. Collins P. Rogers S, Keenan P, McCabe M. Acute febrile neutrophilic dermatosis in childhood (Sweet's syndrome). BrJ Dermatol !991;124:203-206. 4. Honigsmann H, Wolff K. Acute febrile neutrophilic dermatosis (Sweet's syndrome). In: Wolff K, Winkelmann RK, eds. Major problems in dermatology, vol 10. Vasculitis. Linden: Lloyd-Luke, 1980: 307.
291
5. Cohen PR, Taipaz M, Kurzrock R. Malignancy associated Sweet's syndrome: review of world literature. J Clin Oncol 1988;6:1887-1897. 6. Glaspy JA, Baldwin GC, Robertson PA, et al. Therapy for neutropenia in hairy cell leukemia with recombinant human granulocyte colony-stimulating factor. Ann Intern Med 1988;109:789-79'5. 7. Storer JS, Nesbitt LT, Galen WK, Deleo VA. Sweet's syndrome. Int J Dermatol 1983;22:8-12. 8. Komiya I, Tanoue K, Kakinuma K. et al. Superoxide anion hyperproduction by neutrophils in a case of myelodysplastic syndrome. Association with Sweet's syndrome and interstitial pneumonia. Cancer 1991; 67:2337-2341. 9. Crow KD, et al. Acute febrile neutrophilic dermatosis: Sweet's syndrome. Dermatologica 1969;139;123. 10. Cohen PR, Almeida L. Kurzrock R. Acute febrile neutrophilic dermatosis. Am Fam Physician 1989.39(3): 199-204. 11. Saxe N, Gordon W. Acute febrile neutrophilic dermatosis (Sweet's syndrome!. S Afr Med J 1978;53: 253-256. 12. Cohen PR. Kurzrock R. Sweet's syndrome and malignancy. Am J Med 1987;82:1220-1226. 13. Goette DK. Acute myelogenous leukemia presenting as Sweet's syndrome. J Assoc Milit Dermatol 1984;10(l):24-25. 14. Prystowsky SD, Fye KH. Goette KD, Daniels TE. Acute febrile neutrophilic dermatosis associated with Sjogren's syndrome. Arch Dermatol 1978;114:1234— 1235. 15. Schwartz RA. French SW. Rubenstein DJ. Lambert WC. Acute neutrophilic dermatosis with diffuse histiocytic lymphoma. J Am .\cad Dermatol 1984; 10: 350-354. 16. Krauser RE. Schumacher HR. The arthritis of Sweet's syndrome. Arthritis Rheum 1975;18:35-41. 17. Cobb MW. Furosemide-induced eruption simulating Sweet's syndrome. J Am Acad Dermatol 1989;21: 339-343. 18. Duban NE, Alvarez MA. Oral manifestations of Sweet's syndrome. Dermatologica 1984;!69:102-103. 19. Krilov LR, Jacobson M. Shende A. Acute febrile neutrophilic dermatosis (Sweet's syndrome) presenting as facial cellulitis in a child with juvenile chronic myelogenous leukemia. Pediatr Infect Dis J 19'87;6:77-79. 20. Klock JC, Okun RL. Febrile neutrophilic dermatosis in acute myelogenous leukemia. Cancer 1976;37:922. 21. Litt R, Branski D, Gross-Kieselsstein E. et al. Sweet syndrome in eariy childhood. EurJ Pediatr 1986;145: 303-305. 22. Hazen PG, Kark EC, Davis BR, et al. Acute febrile neutrophilic dermatosis in children, .^rch Dermatol 1983;119:998-1002. 23. Majeed AH. Kalaawi M. Mohanty D. et al. Congenital dyserythropoietic anemia and chronic recurrent multifocal osteomyelitis in three related children and the association with Sweet's syndrome in two siblings. J Pediatr 1989;!15:730-734. 24. Edwards TC, Stapleton FB. Bond MJ, Barrett FF. Sweet's syndrome with multifocal sterile osteomyelitis. Am J Dis Child 1986;140:817-818.
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25. Baron F, Sybert VP, Andrews RG. Cutaneous and extracutaneous neutrophilic infiltrates (Sweet's syndrome) in three patients with Fanconi anemia. J Pediatr 1989;] 15:726-729. 26. Levin DL, Esterly NB, Herman JI, Boxall LHB. The Sweet syndrome in children. J Pediatr 198! ;99:73-78. 27. Leibowitz MR, Rippey JJ, Bezwoda WR, Carman HA. Unusual aspects of febrile neutrophilic dermatosis (Sweet's syndrome). S Afr Med J 1982;62(ll); 375-378. 28. Kibbi AG, Zaynoun ST, Kurban AK, et al. Acute febrile neutrophilic dermatosis (Sweet's syndrome): case report and review of the literature. Pediatr Dermatol 1985;3:40-44. 29. Atili R'V, Hira SK, Dube MK. Sweet's syndrome in a child. Med J Zambia 1983;17:92-93. 30. Itami S, Nishioka K. Sweet's syndrome in infancy. BrJ Dermatol 1980;103:449-451.
31. Muster AJ, Bharati S, Herman JJ, et al. Fatal cardiovascular disease and cutis laxa following acute febrile neutrophilic dermatosis. J Pediatr 1983; 102:243-248. 32. Chaudhry H, Cunha B. Drug-induced aseptic meningitis. Diagnosis leads to quick resolution. Postgrad Med 1991;90(7):65-70. 33. Shimoda K, Okamura S, Omori F, et al. Detection of granulocyte-macrophage colony-stimulating factor in cerebrospinal fluid of patients with aseptic meningitis. Acta Haematol 1991 ;86;36-39. 34. Ramiio O. Mustafa M, Porter J, et al. Detection of interleukin-lp but not tumor necrosis factor-alpha in cerebrospinal fluid of children with aseptic meningitis. Am J Dis Child 1990;S44:349-352. 35. Minamishima I, Ohga S. Ishii E, et al. Aseptic meningitis in children: correlation between fever and interferon-gamma level. Eur J Pediatr 1991:150:722725.
Sweet Syndrome in a Neonate with Aseptic Meningitis Terris R. Dunn, M.D., Harry W. Saperstein, M.D., Aviva Biederman, M.D., and Richard P. Kaplan, M.D. Division of Dermatology. University of California at Los Angeles and Cedars-Sinai Medical Center, and Department of Pediatrics, Cedars-Sinai Medical Center, Los Angeles, California
Abstract: A 7-week-old Infant with arstecedent otitis media, upper respiratory infection, and aseptic meningitis was diagnosed as having Sweet syndrome. Although this disease usually affects adults, it has been reported in 17 children. This is the youngest reported patient with the disorder to date, and the first In whom the syndrome was associated with aseptic meningitis.
Sweet syndrome (SS), acute febrile neutrophilic dermatosis, first described by Sweet in 1964(1), is charactedzed by painful plaques, fever, and peripheral leukocytosis. Histopathology shows a dense dermal infiltrate of polymorphonuclear leukocytes without evidence of vasculitis (2). The pathogenesis of this syndrome remains unknown, although it is believed to represent a hypersensitivity reaction to an infection or malignancy. It is characterized by a rapid therapeutic response to systemic corticosteroids. It is most common in adults, with only 17 reported pediatric cases (3). We report the youngest patient with SS to date and the first associated with aseptic meningitis. CASE REPORT A 7-week-old white boy was admitted to the hospital with a four-day history of fever, upper respiratory infection symptoms of mild congestion, decreased appetite, increased irritability, and rash. The rash initially was limited to his cheeks, but two days prior to admission it spread to the scalp, eyelids, trunk, and extremities, with one lesion on his Address correspondence to Richard P. Kaplan. M.D., 200 UCLA Medical Plaza, Suite 465. Los Angeles, CA 90024.
right palm. The lesions were slightly indurated, erythematous papules and plaques that progressed to buliae that crusted over (Fig. 1). Two days before admission the infant was seen by his primary physician who diagnosed otitis media and prescribed amoxicillin, which was discontinued on admission to the hospital. The infant was admitted to the hospital with a temperature of 103°F. Initial complete blood cell count showed white blood cell count of 17,200/til with 58% polys, 5% bands, 22% lymphocytes, 15% monocytes, and 1% eosinophils. Hemoglobin was 10.0 g/dl and hematocdt 29.7%. Chest radiograph showed no infiltrates. Routine urinaiysis was negative. Cerebrospinal fluid (CSF) showed protein 46 mg/dl, glucose 55 mg/dl, no red blood cells, 34 white blood cells, 13 polys, 67 lymphocytes, and 19 monocytes; this was consistent with aseptic meningitis. Pending cultures, the infant was given ampicillin and cefotoxime. The antibiotics were discontinued after three days, secondary to negative bacterial blood and CSF cultures. Herpes simplex virus (HSV) titers were elevated for IgG, with HSV 1 titer of 1:1024 and HSV 2 titer of 1:512, indicative of
Dunn et al: Sweet Syndrome in a Neonate
289
Figure 1. Lesions of Sweet syndrome.
maternal antibody being passed. The IgM titers were negative, indicative of no current infection. The infant was given acyclovir empidcally due to the possibility of a herpes meningitis. Before starting acyclovir, HSV cultures of the CSF were performed. Viral cultures remained negative over the infant's hospitalization. Serum vadcella titers were also negative. Acyclovir was discontinued four days after admission. A skin biopsy specimen taken four days after admission was diagnostic of SS. The lesion, noted to be in the dermis, was an acute suppurative process with microabscess formation in some foci. There was a heavy neutrophilic infiltrate with some eosinophils with marked edema but no epithelial separation. Leukocyte nuclear fragmentation was also present (Fig. 2). The infant was administered prednisone 1 mg/kg/ day for three days and then switched to 0.5 mg/kg/ day for three days. On day 2 of 0.5 mg/kg new lesions began to form; the dosage was increased to the initial level and the lesions began to subside within a day. Because of eyelid lesions, the infant was evaluated by an ophthalmologist pdor to discharge and found to have no evidence of ocular disease. The infant was discharged 14 days after admission taking prednisone 1.0 mg/kg/day for 7 days then 0.5 mg/kg/day for 7 days. The lesions had regressed considerably by discharge. To date, 3! months after admission, they had not recurred. DISCUSSION The infant fulfills the criteda for the diagnosis of SS as evidenced by his acute febrile illness, characteristic skin lesions, and biopsy fmdings of intradermal neutrophilic infiltrate and leukocytosis. He is the
Figure 2. Histopathology revealed dense collection of neutrophils in the dermis.
first reported case of the syndrome associated with aseptic meningitis. In adults SS primadly affects women in their midthirties to midfifties, with a femaie:male ratio of 15:1 as reported by Sweet (1,2). Of the 17 reported pediatdc cases, 10 were males and 7 females, and they ranged in age from 3 months to 12 years (3). To date, no specific etiology has been found for SS. It is postulated to be a hypersensitivity reaction lo a bacterial, viral, or tumor antigen (4), or the response to an inappropriate secretion of endogenous cytokines such as interleukin-1 (epidermal cell thymocyte-activating factor), and/or granulocyte colony-stimulating factor (G-CSF) (5). In one study, a 42-year-old woman with hairy cell leukemia, complicated by neutropenia and cutaneous vasculitis, developed SS manifestations after two weeks of therapy with G-CSF. When the agent was discontinued, fevers and skin lesions persisted for two weeks, then gradually improved (6). It was believed that the SS manifestations were secondary to an increase in tissue granulocytes induced by G-CSF. Studies of neutrophilic chemotaxis and phagocytosis showed increased or normal levels of neutrophilic activity in SS (7). Neutrophilic hyperproduction of superoxide anion also was demonstrated in a
290
Pediatric Dermatology Vol. 9 No. 3 September 1992
patient with SS and myelodysplastic syndrome (8). This superoxide anion hyperproductiori may cause the damage to cutaneous tissues associated with the syndrome. As with our patient, in many adults and children with SS, a febrile upper respiratory infection, otitis media, pharyngitis, tonsillitis, or influenzalike illness may precede the skin lesions by one to three weeks (1,2,9-11), which suggests a crossreactive immunologic process with microbial antigens. Approximately 15% of adults with SS have associated malignancy, with hematologic malignancies such as acute myelogenous leukemia being the most common (5,12,13). Again, a cross-reactive immunologic process with tumor antigens is likely. In approximately two thirds of adult patients the diagnosis of SS preceded the diagnosis of malignancy. Other conditions associated with SS in adults include Sjogren syndrome (14), lymphoma (15), ulcerative colitis (1), and inflammatory arthdtis (16). Drugs and vaccinations have rarely been implicated in inducing SS (11,17). Mucosal lesiotis involving the eyes, mouth, or oral pharynx may accompany the characteristic skin lesions (1,2,18). Of the reported SS childhood cases (Table 1). all patients had erythematous papular and plaque-type lesions involving the face, trunk, and/or extremities. Two had associated leukemias. One child with juvenile chronic myelogenous leukemia was diagnosed with leukemia one year preceding SS manifestations (19). The other was diagnosed with acute promyeiocytic leukemia during hospitalization for SS (20). Two children had associated otitis media (21,22). Four had associated osteomyelitis (23-25). Five cases of SS were associated with anemia. Two were brothers with congenital dyserythropoietic anemia (23). Two had Fanconi anemia, an autosoma! recessive pancytopenia that carries an increased risk for malignancy. The last child with SS associated with anemia had a transient hypochromic microcytic anemia. Our patient also had mild anemia (hemoglobin 10.0 g/dl, hematocdt 29.7%), which subsequently returned to normal. Five children had associated respiratory problems. One had a persistent right middle lobe infiltrate on chest radiograph accompanied by coughing and wheezing (26). Two had history of recurrent respiratory tract infections (22,26). One child had left basal pneumonia on chest radiograph, accompanied by coughing (3), and one had expiratory wheezing (22). Two children had evidence of panniculitis (neutrophilic infiltration of the subcutaneous tissues)
TABLE 1. Pediatric Cases of Sweet Syndrome Age
Sex
4 mo
M
9 mo 3.5 yrs 10 yrs 21 mo iO mo
F M M M M
9 mo
M
30 mo 3 yrs
M M
23 mo 7 yrs
M
12 yrs
F
17 mo
F F
32 mo 8 mo 24 mo 3 mo 7 wks
M M F M
Associated conditions (reference) Hypochroniic microcytic anemia, pneumonia (3) Tonsillitis, cutis laxa (11) Juvenile chronic myelogenous leukemia, cutis laxa (19) Actue promyeiocytic leukemia (20) Otitis media (21) Otitis niedia, recurrent respiratory tract infections, pathergy, atrophic scarring (22) Wheezing, pathergy, atrophic scarring (22) Congenital dyserythropoietic aneniia. recurrent multifocal osteomyelitis (23) Congenital dyserythropoietic aneniia, recurrent multifocal osteomyelitis (23) Multifocal osteomyelitis (24) Osteomyelitis, Fanconi anemia, pathergy, panniculitis (25) Fanconi anemia, pannicuiitis, esophageal atresia (25) Congestion, cough, wheezing, persistent right middle lobe infiltrate, cutis laxa; death from cardiac involvement at age 30 mo (26, 31) Recurrent respiratory tract infections (26) Cutis laxa (28) None (29) None (30) Upper respiratory tract infection, otitis media, aseptic meningitis (this report)
(25). Panniculitis is not a common manifestation of SS (25,27). Three children had evidence of pathergy at intravenous catheter sites (22,25). Four had secondary cutis laxa localized to sites of healed lesions (11,19,26,28) and two had healing with atrophic scar formation (22). Two children had SS without other associated conditions (29,30). Two of the children died. One was a 12-year-old with esophageal atresia (25). The second was a 17month-old who died at 30 months of age after cardiac catheterization for associated coronary vasoocclusive disease. A neutrophilic infiltrate was found in her coronary arteries (26,31). The majority of children were treated with oral steroids, although spontaneous remission occurred in one (23) and the syndrome resolved with antibiotics in another (11). Oral corticosteroid treatment results in a rapid response, with symptoms and signs cleadng in one to three days (5,24,26). Three children required maintenance steroids (25,26).
Dunn et al: Sweet Syndrome in a Neonate
Aside from the patient reported by Saxe and Gordon (11) in whom antibiotics apparently cleared the syndrome, antibiotics in general do not alter the course of the disease. Most likely this is because SS appears to be an inflammatory reaction and not primadly an infectious process. The etiology of aseptic meningitis includes infectious and noninfectious causes such as viruses, neoplastic diseases, systemic diseases, and certain medications (i.e., penicillin), as well as unknown causes (32). Our patient's viral cultures remained negative throughout his hospital stay, and neither systemic nor neoplastic disease was discovered. He was taking amoxicillio two days before hospital admission (for presumed otitis media), and it is possible amoxicillin led to the development of druginduced aseptic meningitis. However, the boy developed SS manifestations before taking the antibiotics, and it is our belief that the aseptic meningitis and SS manifestations were directly related. Also, all antibiotics were discontinued three days after hospital admission, and symptoms persisted. Therefore, drug-induced aseptic meningitis seems unlikely. Consistent with the theory that SS may be the response to an inappropriate secretion of endogenous cytokines, it has been shown that the levels of vadous cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF) (33). interleukin-1 beta (IL-lp) (34). and interferon gamma (35) are increased in the CSF of patients with aseptic meningitis. It is possible that our patient developed aseptic meningitis (unknown etiology) that led to an increased level of one or more of these cytokines. ultimately resulting in SS. Conversely, it is also possible that an increased secretion of endogenous cytokines. possibly a resuh of hypersensitivity to an unknown antigen, led to the development of SS and aseptic meningitis simultaneously. REFERENCES 1. Sweet RD. An acute febrile neutrophilic dermatosis. BrJ Dermatol 1964:76:349-356. 2. Sweet RD. Acute febrile neutrophilic dcrmatosis1978. BrJ Dermatol 1979; 100:93-99. 3. Collins P. Rogers S, Keenan P, McCabe M. Acute febrile neutrophilic dermatosis in childhood (Sweet's syndrome). BrJ Dermatol !991;124:203-206. 4. Honigsmann H, Wolff K. Acute febrile neutrophilic dermatosis (Sweet's syndrome). In: Wolff K, Winkelmann RK, eds. Major problems in dermatology, vol 10. Vasculitis. Linden: Lloyd-Luke, 1980: 307.
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25. Baron F, Sybert VP, Andrews RG. Cutaneous and extracutaneous neutrophilic infiltrates (Sweet's syndrome) in three patients with Fanconi anemia. J Pediatr 1989;] 15:726-729. 26. Levin DL, Esterly NB, Herman JI, Boxall LHB. The Sweet syndrome in children. J Pediatr 198! ;99:73-78. 27. Leibowitz MR, Rippey JJ, Bezwoda WR, Carman HA. Unusual aspects of febrile neutrophilic dermatosis (Sweet's syndrome). S Afr Med J 1982;62(ll); 375-378. 28. Kibbi AG, Zaynoun ST, Kurban AK, et al. Acute febrile neutrophilic dermatosis (Sweet's syndrome): case report and review of the literature. Pediatr Dermatol 1985;3:40-44. 29. Atili R'V, Hira SK, Dube MK. Sweet's syndrome in a child. Med J Zambia 1983;17:92-93. 30. Itami S, Nishioka K. Sweet's syndrome in infancy. BrJ Dermatol 1980;103:449-451.
31. Muster AJ, Bharati S, Herman JJ, et al. Fatal cardiovascular disease and cutis laxa following acute febrile neutrophilic dermatosis. J Pediatr 1983; 102:243-248. 32. Chaudhry H, Cunha B. Drug-induced aseptic meningitis. Diagnosis leads to quick resolution. Postgrad Med 1991;90(7):65-70. 33. Shimoda K, Okamura S, Omori F, et al. Detection of granulocyte-macrophage colony-stimulating factor in cerebrospinal fluid of patients with aseptic meningitis. Acta Haematol 1991 ;86;36-39. 34. Ramiio O. Mustafa M, Porter J, et al. Detection of interleukin-lp but not tumor necrosis factor-alpha in cerebrospinal fluid of children with aseptic meningitis. Am J Dis Child 1990;S44:349-352. 35. Minamishima I, Ohga S. Ishii E, et al. Aseptic meningitis in children: correlation between fever and interferon-gamma level. Eur J Pediatr 1991:150:722725.
