- Email: [email protected]
An Infant with Pulmonary-Cutaneous Sweet Syndrome
An Infant with Pulmonary-Cutaneous Sweet Syndrome Ryan Arakaki, BS1, Joshua D. Shofner, MD2, and Daniela Kroshinsky, MD2 We report the case of a 31-day-old girl presenting with severe respiratory distress and cutaneous lesions from Sweet syndrome. Pulmonary symptoms unresponsive to antibiotics in patients with Sweet syndrome should raise suspicion for neutrophilic infiltration. (J Pediatr 2012;161:959-61).
S
weet syndrome, or acute febrile neutrophilic dermatosis, is characterized by a constellation of 4 primary features: fever, erythematous, edematous to violaceous plaques and nodules, peripheral leukocytosis, and infiltration of mature neutrophils into the dermis.1 A common unifying characteristic is the prompt resolution of symptoms following corticosteroid administration. On presentation, patients with Sweet syndrome can appear dramatically ill. The majority of patients have disease localized exclusively to the skin; however, there are reports of extracutaneous manifestations affecting nearly all organs of the body.2 The scope of these rare manifestations includes sterile osteomyelitis, acute myositis, necrotizing fasciitis, aseptic meningitis, hepatitis, pancreatitis, myocardial infiltration, and renal involvement.3 Of these extracutaneous manifestations, pulmonary disease was the first described; it has been seen in a small number of patients and is characterized histologically by dense neutrophilic infiltration. Like cutaneous Sweet syndrome, prompt resolution of pulmonary symptoms occurs with steroid administration. Pulmonary Sweet syndrome remains a rare diagnosis.4
Clinical Course A 31-day-old girl, born healthy at term via cesarean delivery, was taken to an outside hospital with a 2-day history of fever, a rash, and intermittent cough and increasing irritability. Approximately 2 weeks earlier, her mother noted small bumps over the face. The child was admitted for possible sepsis and transferred to the pediatric intensive care unit after her respiratory status declined, despite broad-spectrum antibiotic and antiviral coverage. Chest radiograph demonstrated hyperinflation of the lungs and no infiltrate. She remained tachycardic and febrile, and 8 days into her hospital course, dermatology was consulted to evaluate the facial rash. On examination, her rash was notable for numerous 3- to 4-mm, firm, erythematous to yellow, edematous papules and nodules overlying the chin, cheeks, neck, both arms, and trunk (Figure 1). A 3-mm punch biopsy of a facial lesion was performed, demonstrating a pustular folliculitis with associated dense dermal neutrophilic infiltrate. Preliminary diagnosis at the time was an atypical form of Sweet syndrome. The patient continued to worsen from a respiratory standpoint. Due to the profound concern for an undiagnosed underlying infection, the intensive care unit team was apprehensive about starting steroids.
Two days later, there was a significantly increased number and size of the cutaneous lesions, with extension and umbilication of the largest most edematous papulo-nodules, especially on the face and hands (Figure 2). The lesion that had undergone biopsy on the face was noted to be larger and more edematous. The cutaneous picture was more consistent with Sweet syndrome; a repeat skin biopsy was performed and demonstrated scale crust with a dense dermal neutrophilic infiltrate, pustular involvement of the hair follicles and eccrine ducts, and deep dermal and subcutaneous abscess formation. The pathology again confirmed Sweet syndrome, and it was suspected that the patient’s respiratory findings represented neutrophilic infiltration of the lungs, given her failed response to broadspectrum antibiotic coverage for infection. As such, she was started on intravenous solumedrol. Over the next 48 hours, the patient’s skin lesions rapidly cleared and her respiratory findings resolved. The patient was switched to oral prednisone after 3 days of intravenous steroids and was placed on a 10-week steroid taper at discharge.
Discussion Sweet syndrome was originally described by Dr Robert Sweet in 1964.1 Pediatric cases account for 8% of cases of Sweet syndrome, usually in children younger than 3 years.5 In the pediatric population, its onset is most often preceded by upper respiratory tract infection or recent illness.6 The diagnostic guidelines to diagnose Sweet syndrome are the presence of 2 major criteria: (1) abrupt onset of painful erythematous plaques; and (2) histopathologic evidence of dense neutrophilic infiltrate into the dermis without evidence of leukocytoclastic vasculitis—and 2 of 4 minor criteria: (1) fever $38 C; (2) association with underlying trigger; (3) rapid response to systemic steroids; and (4) leukocytosis with neutrophilia. Sweet syndrome can mimic sepsis, as in our case. Patients can also experience arthralgias, malaise, headache, and myalgias.7-9 Fever with a duration of days to weeks
From the 1Harvard Medical School; and 2Department of Dermatology, Massachusetts General Hospital, Boston, MA The authors declare no conflicts of interest. This case has been submitted to the Society of Pediatric Dermatology (SPD) as an abstract for a case presentation at the SPD Annual Pre-American Academy of Dermatology Meeting. 0022-3476/$ - see front matter. Copyright ª 2012 Mosby Inc. All rights reserved. http://dx.doi.org/10.1016/j.jpeds.2012.07.035
959
THE JOURNAL OF PEDIATRICS
www.jpeds.com
Figure 1. Numerous firm edematous papules and nodules on the patient’s chin and neck.
may precede cutaneous manifestations. As with other neutrophilic dermatoses, patients with Sweet syndrome have pathergy, or a condition in which new papular or pustular lesions are forms at sites of prior trauma, as occurred in our patient over her sites of biopsy, blood draws, and intravenous line placement.7,8,10 The finding of pathergy is a helpful diagnostic tool as there is a limited number of conditions in which it is found, namely Sweet syndrome, Behc¸et disease, pyoderma gangrenosum, bowel-associated dermatosisarthritis syndrome, and rheumatoid arthritis. The parallel course of our patient’s pulmonary symptoms with her skin disease suggests a relationship between her dermatosis and pulmonary function.2 The presentation of pul-
Vol. 161, No. 5 monary Sweet syndrome includes dry cough, dyspnea, and general respiratory deterioration.4 Chest radiographic findings may show unilateral or bilateral infiltrates, as well as pleural effusions. In the rare instances when lung biopsy is performed, histologic examination reveals dense neutrophilic infiltration of the lung tissue. Of note, in patients with pulmonary Sweet syndrome, there appears to be a higher frequency of hematologic malignancy, which was not identified in our patient.4 Pediatric Sweet syndrome presents similarly to its adult variant. The onset of symptoms can be associated with malaise, episcleritis, conjunctivitis, and polyarthritis.11 Although there are approximately only 70 cases of pediatric Sweet syndrome described to date in the English-language literature, a growing body of literature associates approximately one-half of the cases to preceding illness, typically an upper respiratory infection or flulike illness.6,12 Sweet syndrome has also been associated with the use of specific medications. In adults, a wide variety of medications have been implicated; however, there are only 4 medications that have been reported as potential causes of pediatric drug–induced Sweet syndrome. These medications include granulocyte colonystimulating factor, all-trans-retinoic acid, trimethoprimsulfamethoxazole, and azathioprine.12 The youngest cases of Sweet syndrome to date are described in 10-day-old and 15-day-old siblings.5 Significant disease associations have included chronic granulomatous disease, primary immunodeficiency, aseptic meningitis, myelodysplastic syndrome, and chronic myelogenous leukemia.13-17 Two reported cases of pediatric Sweet syndrome with respiratory involvement occurred in a 4-month-old and a 12-month-old.12,18,19 The presence of such striking pulmonary symptoms in our patient that rapidly responded to steroid therapy highlights an underrecognized component of Sweet syndrome that should be considered in the workup of acute febrile neutrophilic dermatosis with respiratory symptoms. n Submitted for publication Apr 18, 2012; last revision received Jun 11, 2012; accepted Jul 13, 2012. Reprint requests: Ryan Arakaki, 28 Saint Albans Rd, #2, Boston, MA 02115. E-mail: [email protected]
References
Figure 2. Extension and umbilication of hand lesions with formation of new lesions at prior intravenous line sites. 960
1. Sweet RD. An acute febrile neutrophilic dermatosis. Br J Dermatol 1964; 76:349-56. 2. Cohen PR. Sweet’s syndrome: a comprehensive review of an acute febrile neutrophilic dermatosis. Orphanet J Rare Dis 2007;2:34. 3. Kroshinsky D, Alloo A, Rothschild B, Cummins J, Tan J, Montecino R, et al. Necrotizing Sweet syndrome: a new variant of neutrophilic dermatosis mimicking necrotizing fasciitis. J Am Acad Dermatol 2012. 4. Astudillo L, Sailler L, Launay F, Josse AG, Lamant L, Couret B, et al. Pulmonary involvement in Sweet’s syndrome: a case report and review of the literature. Int J Dermatol 2006;45:677-80. 5. Parsapour K, Reep MD, Gohar K, Shah V, Church A, Shwayder TA. Familial Sweet’s syndrome in 2 brothers, both seen in the first 2 weeks of life. J Am Acad Dermatol 2003;49:132-8. 6. Collins P, Rogers S, Keenan P, McCabe M. Acute febrile neutrophilic dermatosis in childhood (Sweet’s syndrome). Br J Dermatol 1991;124: 203-6.
Arakaki, Shofner, and Kroshinsky
November 2012 7. Cohen PR, Kurzrock R. Sweet’s syndrome revisited: a review of disease concepts. Int J Dermatol 2003;42:761-78. 8. Cohen PR. Sweet’s syndrome. Orphanet Encyclopedia [updated 2012 Jun 9; cited 2012 Jan 10]. Available from: http://www.orpha.net/data/ patho/GB/uk-Sweet.pdf. 9. Cohen PR, Kurzrock R. Sweet’s syndrome: a neutrophilic dermatosis classically associated with acute onset and fever. Clin Dermatol 2000; 18:265-82. 10. Awan F, Hamadani M, Devine S. Paraneoplastic Sweet’s syndrome and the pathergy phenomenon. Ann Hematol 2007;86:613-4. 11. Cuende Quintana E, Gomez R de Mendarozqueta M, Gorospe Arrazuria MA, Saracibar Oyon N, Atares Pueyo B, Pena MV, et al. Concurrent Sweet’s syndrome and Lofgren’s syndrome. J Rheumatol 1996;23: 1995-8. 12. Hospach T, von den Driesch P, Dannecker GE. Acute febrile neutrophilic dermatosis (Sweet’s syndrome) in childhood and adolescence: two new patients and review of the literature on associated diseases. Eur J Pediatr 2009;168:1-9.
An Infant with Pulmonary-Cutaneous Sweet Syndrome
CLINICAL AND LABORATORY OBSERVATIONS 13. Elliott SP, Mallory SB. Sweet syndrome: an unusual presentation of chronic granulomatous disease in a child. Pediatr Infect Dis J 1999;18: 568-70. 14. Satra K, Zalka A, Cohen PR, Grossman ME. Sweet’s syndrome and pregnancy. J Am Acad Dermatol 1994;30:297-300. 15. Dunn TR, Saperstein HW, Biederman A, Kaplan RP. Sweet syndrome in a neonate with aseptic meningitis. Pediatr Dermatol 1992;9:288-92. 16. Bajwa RP, Marwaha RK, Garewal G, Rajagopalan M. Acute febrile neutrophilic dermatosis (Sweet’s syndrome) in myelodysplastic syndrome. Pediatr Hematol Oncol 1993;10:343-6. 17. 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 1987;6:77-9. 18. Brady RC, Morris J, Connelly BL, Boiko S. Sweet’s syndrome as an initial manifestation of pediatric human immunodeficiency virus infection. Pediatrics 1999;104:1142-4. 19. Eghrari-Sabet JS, Hartley AH. Sweet’s syndrome: an immunologically mediated skin disease? Ann Allergy 1994;72:125-8.
961
S
weet syndrome, or acute febrile neutrophilic dermatosis, is characterized by a constellation of 4 primary features: fever, erythematous, edematous to violaceous plaques and nodules, peripheral leukocytosis, and infiltration of mature neutrophils into the dermis.1 A common unifying characteristic is the prompt resolution of symptoms following corticosteroid administration. On presentation, patients with Sweet syndrome can appear dramatically ill. The majority of patients have disease localized exclusively to the skin; however, there are reports of extracutaneous manifestations affecting nearly all organs of the body.2 The scope of these rare manifestations includes sterile osteomyelitis, acute myositis, necrotizing fasciitis, aseptic meningitis, hepatitis, pancreatitis, myocardial infiltration, and renal involvement.3 Of these extracutaneous manifestations, pulmonary disease was the first described; it has been seen in a small number of patients and is characterized histologically by dense neutrophilic infiltration. Like cutaneous Sweet syndrome, prompt resolution of pulmonary symptoms occurs with steroid administration. Pulmonary Sweet syndrome remains a rare diagnosis.4
Clinical Course A 31-day-old girl, born healthy at term via cesarean delivery, was taken to an outside hospital with a 2-day history of fever, a rash, and intermittent cough and increasing irritability. Approximately 2 weeks earlier, her mother noted small bumps over the face. The child was admitted for possible sepsis and transferred to the pediatric intensive care unit after her respiratory status declined, despite broad-spectrum antibiotic and antiviral coverage. Chest radiograph demonstrated hyperinflation of the lungs and no infiltrate. She remained tachycardic and febrile, and 8 days into her hospital course, dermatology was consulted to evaluate the facial rash. On examination, her rash was notable for numerous 3- to 4-mm, firm, erythematous to yellow, edematous papules and nodules overlying the chin, cheeks, neck, both arms, and trunk (Figure 1). A 3-mm punch biopsy of a facial lesion was performed, demonstrating a pustular folliculitis with associated dense dermal neutrophilic infiltrate. Preliminary diagnosis at the time was an atypical form of Sweet syndrome. The patient continued to worsen from a respiratory standpoint. Due to the profound concern for an undiagnosed underlying infection, the intensive care unit team was apprehensive about starting steroids.
Two days later, there was a significantly increased number and size of the cutaneous lesions, with extension and umbilication of the largest most edematous papulo-nodules, especially on the face and hands (Figure 2). The lesion that had undergone biopsy on the face was noted to be larger and more edematous. The cutaneous picture was more consistent with Sweet syndrome; a repeat skin biopsy was performed and demonstrated scale crust with a dense dermal neutrophilic infiltrate, pustular involvement of the hair follicles and eccrine ducts, and deep dermal and subcutaneous abscess formation. The pathology again confirmed Sweet syndrome, and it was suspected that the patient’s respiratory findings represented neutrophilic infiltration of the lungs, given her failed response to broadspectrum antibiotic coverage for infection. As such, she was started on intravenous solumedrol. Over the next 48 hours, the patient’s skin lesions rapidly cleared and her respiratory findings resolved. The patient was switched to oral prednisone after 3 days of intravenous steroids and was placed on a 10-week steroid taper at discharge.
Discussion Sweet syndrome was originally described by Dr Robert Sweet in 1964.1 Pediatric cases account for 8% of cases of Sweet syndrome, usually in children younger than 3 years.5 In the pediatric population, its onset is most often preceded by upper respiratory tract infection or recent illness.6 The diagnostic guidelines to diagnose Sweet syndrome are the presence of 2 major criteria: (1) abrupt onset of painful erythematous plaques; and (2) histopathologic evidence of dense neutrophilic infiltrate into the dermis without evidence of leukocytoclastic vasculitis—and 2 of 4 minor criteria: (1) fever $38 C; (2) association with underlying trigger; (3) rapid response to systemic steroids; and (4) leukocytosis with neutrophilia. Sweet syndrome can mimic sepsis, as in our case. Patients can also experience arthralgias, malaise, headache, and myalgias.7-9 Fever with a duration of days to weeks
From the 1Harvard Medical School; and 2Department of Dermatology, Massachusetts General Hospital, Boston, MA The authors declare no conflicts of interest. This case has been submitted to the Society of Pediatric Dermatology (SPD) as an abstract for a case presentation at the SPD Annual Pre-American Academy of Dermatology Meeting. 0022-3476/$ - see front matter. Copyright ª 2012 Mosby Inc. All rights reserved. http://dx.doi.org/10.1016/j.jpeds.2012.07.035
959
THE JOURNAL OF PEDIATRICS
www.jpeds.com
Figure 1. Numerous firm edematous papules and nodules on the patient’s chin and neck.
may precede cutaneous manifestations. As with other neutrophilic dermatoses, patients with Sweet syndrome have pathergy, or a condition in which new papular or pustular lesions are forms at sites of prior trauma, as occurred in our patient over her sites of biopsy, blood draws, and intravenous line placement.7,8,10 The finding of pathergy is a helpful diagnostic tool as there is a limited number of conditions in which it is found, namely Sweet syndrome, Behc¸et disease, pyoderma gangrenosum, bowel-associated dermatosisarthritis syndrome, and rheumatoid arthritis. The parallel course of our patient’s pulmonary symptoms with her skin disease suggests a relationship between her dermatosis and pulmonary function.2 The presentation of pul-
Vol. 161, No. 5 monary Sweet syndrome includes dry cough, dyspnea, and general respiratory deterioration.4 Chest radiographic findings may show unilateral or bilateral infiltrates, as well as pleural effusions. In the rare instances when lung biopsy is performed, histologic examination reveals dense neutrophilic infiltration of the lung tissue. Of note, in patients with pulmonary Sweet syndrome, there appears to be a higher frequency of hematologic malignancy, which was not identified in our patient.4 Pediatric Sweet syndrome presents similarly to its adult variant. The onset of symptoms can be associated with malaise, episcleritis, conjunctivitis, and polyarthritis.11 Although there are approximately only 70 cases of pediatric Sweet syndrome described to date in the English-language literature, a growing body of literature associates approximately one-half of the cases to preceding illness, typically an upper respiratory infection or flulike illness.6,12 Sweet syndrome has also been associated with the use of specific medications. In adults, a wide variety of medications have been implicated; however, there are only 4 medications that have been reported as potential causes of pediatric drug–induced Sweet syndrome. These medications include granulocyte colonystimulating factor, all-trans-retinoic acid, trimethoprimsulfamethoxazole, and azathioprine.12 The youngest cases of Sweet syndrome to date are described in 10-day-old and 15-day-old siblings.5 Significant disease associations have included chronic granulomatous disease, primary immunodeficiency, aseptic meningitis, myelodysplastic syndrome, and chronic myelogenous leukemia.13-17 Two reported cases of pediatric Sweet syndrome with respiratory involvement occurred in a 4-month-old and a 12-month-old.12,18,19 The presence of such striking pulmonary symptoms in our patient that rapidly responded to steroid therapy highlights an underrecognized component of Sweet syndrome that should be considered in the workup of acute febrile neutrophilic dermatosis with respiratory symptoms. n Submitted for publication Apr 18, 2012; last revision received Jun 11, 2012; accepted Jul 13, 2012. Reprint requests: Ryan Arakaki, 28 Saint Albans Rd, #2, Boston, MA 02115. E-mail: [email protected]
References
Figure 2. Extension and umbilication of hand lesions with formation of new lesions at prior intravenous line sites. 960
1. Sweet RD. An acute febrile neutrophilic dermatosis. Br J Dermatol 1964; 76:349-56. 2. Cohen PR. Sweet’s syndrome: a comprehensive review of an acute febrile neutrophilic dermatosis. Orphanet J Rare Dis 2007;2:34. 3. Kroshinsky D, Alloo A, Rothschild B, Cummins J, Tan J, Montecino R, et al. Necrotizing Sweet syndrome: a new variant of neutrophilic dermatosis mimicking necrotizing fasciitis. J Am Acad Dermatol 2012. 4. Astudillo L, Sailler L, Launay F, Josse AG, Lamant L, Couret B, et al. Pulmonary involvement in Sweet’s syndrome: a case report and review of the literature. Int J Dermatol 2006;45:677-80. 5. Parsapour K, Reep MD, Gohar K, Shah V, Church A, Shwayder TA. Familial Sweet’s syndrome in 2 brothers, both seen in the first 2 weeks of life. J Am Acad Dermatol 2003;49:132-8. 6. Collins P, Rogers S, Keenan P, McCabe M. Acute febrile neutrophilic dermatosis in childhood (Sweet’s syndrome). Br J Dermatol 1991;124: 203-6.
Arakaki, Shofner, and Kroshinsky
November 2012 7. Cohen PR, Kurzrock R. Sweet’s syndrome revisited: a review of disease concepts. Int J Dermatol 2003;42:761-78. 8. Cohen PR. Sweet’s syndrome. Orphanet Encyclopedia [updated 2012 Jun 9; cited 2012 Jan 10]. Available from: http://www.orpha.net/data/ patho/GB/uk-Sweet.pdf. 9. Cohen PR, Kurzrock R. Sweet’s syndrome: a neutrophilic dermatosis classically associated with acute onset and fever. Clin Dermatol 2000; 18:265-82. 10. Awan F, Hamadani M, Devine S. Paraneoplastic Sweet’s syndrome and the pathergy phenomenon. Ann Hematol 2007;86:613-4. 11. Cuende Quintana E, Gomez R de Mendarozqueta M, Gorospe Arrazuria MA, Saracibar Oyon N, Atares Pueyo B, Pena MV, et al. Concurrent Sweet’s syndrome and Lofgren’s syndrome. J Rheumatol 1996;23: 1995-8. 12. Hospach T, von den Driesch P, Dannecker GE. Acute febrile neutrophilic dermatosis (Sweet’s syndrome) in childhood and adolescence: two new patients and review of the literature on associated diseases. Eur J Pediatr 2009;168:1-9.
An Infant with Pulmonary-Cutaneous Sweet Syndrome
CLINICAL AND LABORATORY OBSERVATIONS 13. Elliott SP, Mallory SB. Sweet syndrome: an unusual presentation of chronic granulomatous disease in a child. Pediatr Infect Dis J 1999;18: 568-70. 14. Satra K, Zalka A, Cohen PR, Grossman ME. Sweet’s syndrome and pregnancy. J Am Acad Dermatol 1994;30:297-300. 15. Dunn TR, Saperstein HW, Biederman A, Kaplan RP. Sweet syndrome in a neonate with aseptic meningitis. Pediatr Dermatol 1992;9:288-92. 16. Bajwa RP, Marwaha RK, Garewal G, Rajagopalan M. Acute febrile neutrophilic dermatosis (Sweet’s syndrome) in myelodysplastic syndrome. Pediatr Hematol Oncol 1993;10:343-6. 17. 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 1987;6:77-9. 18. Brady RC, Morris J, Connelly BL, Boiko S. Sweet’s syndrome as an initial manifestation of pediatric human immunodeficiency virus infection. Pediatrics 1999;104:1142-4. 19. Eghrari-Sabet JS, Hartley AH. Sweet’s syndrome: an immunologically mediated skin disease? Ann Allergy 1994;72:125-8.
961