Clinical Review & Education
JAMA Pediatrics Clinical Challenge
Newborn With Unexpected Skin Lesions Lia Oliveira, MD; Isabel Castro Esteves, MD; Filipa Prata, MD; Cristina Tapadinhas, MD; Cristina Guerreiro, MD; José Gonçalo Marques, MD
A
B
Figure. Axillary inflammatory nodule (A) and inguinal inflammatory plaques with violaceous hue (B).
A 25-day-old newborn was admitted to our hospital with a diagnosis of bronchiolitis. During admission, the infant developed violaceous skin lesions with edema in inguinal and axillary regions (Figure). Lesions became ulcerated within 3 to 4 days, with infarcted necrotic areas. Blood tests showed leukopenia (white blood cell count, 2460/μL) with neutropenia (neutrophil count, Quiz at jamapediatrics.com 220/μL) (to convert both to ×109 per liter, multiply by 0.001). The lesions were biopsied and samples were sent for cultures and histopathological analysis. Intravenous floxacillin was started, followed by surgical debridement due to progression of the major lesions. His mother was addicted to drugs, she had a known hepatitis C virus infection, and the pregnancy was unsupervised. Thirteen days before delivery, she visited the emergency department with flulike symptoms. Routine infectious screening revealed negative serology for syphilis, hepatitis B virus, and human immunodeficiency virus (HIV) types 1 and 2 by enzyme-linked immunosorbent assay (ELISA). The infant was born at 40 weeks’ gestation by forceps delivery.
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WHAT IS YOUR DIAGNOSIS?
A. Pyoderma gangrenosum B. Ecthyma gangrenosum C. Wegener granulomatosis D. Meningococcemia
JAMA Pediatrics January 2014 Volume 168, Number 1
Copyright 2014 American Medical Association. All rights reserved.
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91
Clinical Review & Education JAMA Pediatrics Clinical Challenge
Diagnosis B. Ecthyma gangrenosum
Discussion A pediatric infectious diseases specialist gave a clinical diagnosis of ecthyma gangrenosum and probable immunodeficiency. Antibiotics were changed to piperacillin sodium and tazobactam sodium to cover Pseudomonas aeruginosa, and the HIV type 1 viral load was determined. Skin biopsy revealed a necrotizing vasculitis with hemorrhage and surrounding edema, suggestive of ecthyma gangrenosum. Blood cultures and skin biopsy showed P aeruginosa. Skin lesions improved with antipseudomonal antibiotic therapy. The HIV type 1 viral load was higher than 7.0 log10 copies/mL. The CD4+ cell count (4770/μL [to convert to ×109 per liter, multiply by 0.001]) and immunoglobulin levels (IgG, 735 mg/dL; IgA, 37 mg/dL; and IgM, 55 mg/dL [to convert IgG to grams per liter, multiply by 0.01; to convert IgA and IgM to milligrams per liter, multiply by 10]) were normal. Fourth-generation ELISA for HIV was performed (the first assay was first generation) using the blood sample collected from the mother before delivery, and the result was positive. Six weeks after beginning highly active antiretroviral therapy, the viral load was reduced to 2403 copies/mL (3.38 log10 copies/mL), the CD4+ cell count was 1191/μL, and the neutrophil count increased to 2810/μL. Ecthyma gangrenosum is a rare cutaneous manifestation most often associated with a P aeruginosa bacteremia or septicemia. It occurs in up to 6% of patients with systemic P aeruginosa infection,1 but it also occurs as a primary cutaneous infection by inoculation. Clinically similar lesions may develop as a result of infection with other agents such as Staphylococcus aureus, Serratia marcescens, Burkholderia cepacia, Klebsiella species, Escherichia coli, Neisseria meningitidis, Proteus species, Aeromonas hydrophila, Sternotrophomonas maltophilia, Aspergillus species, and Candida species.1,2 Most commonly seen in patients who are critically ill and immunocompromised, occasional cases of ecthyma gangrenosum have been reported in otherwise healthy children.3-5 Patients at high risk include those with any kind of immunodeficiency associated with neuARTICLE INFORMATION Author Affiliations: Pediatric Department, Hospital de Santa Maria, Lisbon, Portugal (Oliveira); Pediatric Infectious Diseases, Pediatric Department, Hospital de Santa Maria, Lisbon, Portugal (Esteves, Prata, Marques); Dermatology Department, Hospital de Santa Maria, Lisbon, Portugal (Tapadinhas); Gynecology-Obstetrics Department, Alfredo da Costa Maternity Hospital, Lisbon, Portugal (Guerreiro). Corresponding Author: Lia Oliveira, MD, Pediatric Department, Hospital de Santa Maria, Av Egas Moniz, 1649-035 Lisbon, Portugal (lcfoliveira @gmail.com). Section Editor: Samir S. Shah, MD, MSCE Accepted for Publication: July 9, 2013. Author Contributions: Drs Oliveira and Marques had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Oliveira, Esteves, Prata, Marques. Acquisition of data: All authors.
92
tropenia (chemotherapy, primary causes, or neutrophil functional defects), hypogammaglobulinemia, malignant neoplasms, or severe burns.2,6 It is necessary to determine whether neutropenia is secondary to the infection, a persistent condition, or a transient phenomenon (eg, viral induced) in previously healthy children.2 Considering this diagnosis, a thorough search for any underlying immune deficiency should be undertaken. It is mandatory to exclude HIV infection, as it is more frequent than any primary immunodeficiency. The characteristic clinical appearance is a red, painless macule that enlarges to become an elevated papule; this evolves in 12 to 18 hours into hemorrhagic pustules or infarcted-appearing areas surrounded by an erythematous halo.7 These lesions result from perivascular bacterial invasion of media and adventitia of vessels into dermis and subcutaneous tissues, with secondary thrombosis, giving rise to necrotizing vasculitis (due to protease and endotoxin A produced by P aeruginosa). There is bacterial invasion of the adventitia and media of dermal veins but not arteries.1 The main sites affected include the apocrine areas (gluteal or perineal region [55%]), but these lesions can spread to other sites (limbs [30%] and face and trunk [12%]).8 The absence of suppuration and slough distinguishes it from pyoderma gangrenosum as well as external inoculation with group A Streptococci, which produces a crusted ulcerated plaque.9 This is a severe infection associated with a high mortality rate, requiring prompt diagnosis. Once the diagnosis is established, early treatment must include antibiotic coverage against P aeruginosa. If lesions fail to respond to antimicrobials, surgical debridement should be performed. Multiple lesions, delay in treatment, and neutropenia are poor prognostic indicators.9 For routine HIV screening during pregnancy, fourthgeneration ELISA should be preferred, especially in high-risk groups.10 Fourth-generation assays test for both antibodies and antigens simultaneously, being better able to detect recent infection than first-generation tests that detect only antibodies. The window period could be reduced from 4 weeks to 1 week with fourthgeneration tests.
Analysis and interpretation of data: Oliveira, Prata, Marques. Drafting of the manuscript: Oliveira. Critical revision of the manuscript for important intellectual content: All authors. Administrative, technical, or material support: Oliveira, Esteves, Prata. Study supervision: Esteves, Prata, Tapadinhas, Guerreiro, Marques. Conflict of Interest Disclosures: None reported. REFERENCES 1. Morelli G. Cutaneous bacterial infections. In: Kliegman R, Behrman R, Jenson H, Stanton B, eds. Nelson Textbook of Pediatrics. 18th ed. Philadelphia, PA: Saunders; 2007:2740. 2. Chan YH, Chong CY, Puthucheary J, Loh TF. Ecthyma gangrenosum. Singapore Med J. 2006;47(12):1080-1083. 3. Martins P, Pedroso H, Marques JG. Neutropénia transitória na criança previamente saudável. Acta Med Port. 2001;14(3):285-291.
4. Huang YC, Lin TY, Wang CH. Communityacquired Pseudomonas aeruginosa sepsis in previously healthy infants and children. Pediatr Infect Dis J. 2002;21(11):1049-1052. 5. Zomorrodi A, Wald ER. Ecthyma gangrenosum. Pediatr Infect Dis J. 2002;21(12):1161-1164. 6. Singh TN, Devi KM, Devi KS. Ecthyma gangrenosum. Indian J Med Microbiol. 2005;23(4):262-263. 7. Marques SA, Fioretto JR, Martins JG, Sato CM, Martins DS. Ectima gangrenoso. Diagn Tratamento. 2009;14(3):108-110. 8. Habif TP. Clinical Dermatology. 4th ed. St Louis, MO: Mosby; 2004. 9. Goolamali SI, Fogo A, Killian L, et al. Ecthyma gangrenosum. Clin Exp Dermatol. 2009;34(5):e180-e182. 10. British HIV Association; British Association of Sexual Health and HIV; British Infection Society. UK national guidelines for HIV testing 2008. http://www.bhiva.org/documents/Guidelines /Testing/GlinesHIVTest08.pdf. Accessed December 2012.
JAMA Pediatrics January 2014 Volume 168, Number 1
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archpedi.jamanetwork.com/ by a J H Quillen College User on 05/31/2015
jamapediatrics.com
JAMA Pediatrics Clinical Challenge
Newborn With Unexpected Skin Lesions Lia Oliveira, MD; Isabel Castro Esteves, MD; Filipa Prata, MD; Cristina Tapadinhas, MD; Cristina Guerreiro, MD; José Gonçalo Marques, MD
A
B
Figure. Axillary inflammatory nodule (A) and inguinal inflammatory plaques with violaceous hue (B).
A 25-day-old newborn was admitted to our hospital with a diagnosis of bronchiolitis. During admission, the infant developed violaceous skin lesions with edema in inguinal and axillary regions (Figure). Lesions became ulcerated within 3 to 4 days, with infarcted necrotic areas. Blood tests showed leukopenia (white blood cell count, 2460/μL) with neutropenia (neutrophil count, Quiz at jamapediatrics.com 220/μL) (to convert both to ×109 per liter, multiply by 0.001). The lesions were biopsied and samples were sent for cultures and histopathological analysis. Intravenous floxacillin was started, followed by surgical debridement due to progression of the major lesions. His mother was addicted to drugs, she had a known hepatitis C virus infection, and the pregnancy was unsupervised. Thirteen days before delivery, she visited the emergency department with flulike symptoms. Routine infectious screening revealed negative serology for syphilis, hepatitis B virus, and human immunodeficiency virus (HIV) types 1 and 2 by enzyme-linked immunosorbent assay (ELISA). The infant was born at 40 weeks’ gestation by forceps delivery.
jamapediatrics.com
WHAT IS YOUR DIAGNOSIS?
A. Pyoderma gangrenosum B. Ecthyma gangrenosum C. Wegener granulomatosis D. Meningococcemia
JAMA Pediatrics January 2014 Volume 168, Number 1
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archpedi.jamanetwork.com/ by a J H Quillen College User on 05/31/2015
91
Clinical Review & Education JAMA Pediatrics Clinical Challenge
Diagnosis B. Ecthyma gangrenosum
Discussion A pediatric infectious diseases specialist gave a clinical diagnosis of ecthyma gangrenosum and probable immunodeficiency. Antibiotics were changed to piperacillin sodium and tazobactam sodium to cover Pseudomonas aeruginosa, and the HIV type 1 viral load was determined. Skin biopsy revealed a necrotizing vasculitis with hemorrhage and surrounding edema, suggestive of ecthyma gangrenosum. Blood cultures and skin biopsy showed P aeruginosa. Skin lesions improved with antipseudomonal antibiotic therapy. The HIV type 1 viral load was higher than 7.0 log10 copies/mL. The CD4+ cell count (4770/μL [to convert to ×109 per liter, multiply by 0.001]) and immunoglobulin levels (IgG, 735 mg/dL; IgA, 37 mg/dL; and IgM, 55 mg/dL [to convert IgG to grams per liter, multiply by 0.01; to convert IgA and IgM to milligrams per liter, multiply by 10]) were normal. Fourth-generation ELISA for HIV was performed (the first assay was first generation) using the blood sample collected from the mother before delivery, and the result was positive. Six weeks after beginning highly active antiretroviral therapy, the viral load was reduced to 2403 copies/mL (3.38 log10 copies/mL), the CD4+ cell count was 1191/μL, and the neutrophil count increased to 2810/μL. Ecthyma gangrenosum is a rare cutaneous manifestation most often associated with a P aeruginosa bacteremia or septicemia. It occurs in up to 6% of patients with systemic P aeruginosa infection,1 but it also occurs as a primary cutaneous infection by inoculation. Clinically similar lesions may develop as a result of infection with other agents such as Staphylococcus aureus, Serratia marcescens, Burkholderia cepacia, Klebsiella species, Escherichia coli, Neisseria meningitidis, Proteus species, Aeromonas hydrophila, Sternotrophomonas maltophilia, Aspergillus species, and Candida species.1,2 Most commonly seen in patients who are critically ill and immunocompromised, occasional cases of ecthyma gangrenosum have been reported in otherwise healthy children.3-5 Patients at high risk include those with any kind of immunodeficiency associated with neuARTICLE INFORMATION Author Affiliations: Pediatric Department, Hospital de Santa Maria, Lisbon, Portugal (Oliveira); Pediatric Infectious Diseases, Pediatric Department, Hospital de Santa Maria, Lisbon, Portugal (Esteves, Prata, Marques); Dermatology Department, Hospital de Santa Maria, Lisbon, Portugal (Tapadinhas); Gynecology-Obstetrics Department, Alfredo da Costa Maternity Hospital, Lisbon, Portugal (Guerreiro). Corresponding Author: Lia Oliveira, MD, Pediatric Department, Hospital de Santa Maria, Av Egas Moniz, 1649-035 Lisbon, Portugal (lcfoliveira @gmail.com). Section Editor: Samir S. Shah, MD, MSCE Accepted for Publication: July 9, 2013. Author Contributions: Drs Oliveira and Marques had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Oliveira, Esteves, Prata, Marques. Acquisition of data: All authors.
92
tropenia (chemotherapy, primary causes, or neutrophil functional defects), hypogammaglobulinemia, malignant neoplasms, or severe burns.2,6 It is necessary to determine whether neutropenia is secondary to the infection, a persistent condition, or a transient phenomenon (eg, viral induced) in previously healthy children.2 Considering this diagnosis, a thorough search for any underlying immune deficiency should be undertaken. It is mandatory to exclude HIV infection, as it is more frequent than any primary immunodeficiency. The characteristic clinical appearance is a red, painless macule that enlarges to become an elevated papule; this evolves in 12 to 18 hours into hemorrhagic pustules or infarcted-appearing areas surrounded by an erythematous halo.7 These lesions result from perivascular bacterial invasion of media and adventitia of vessels into dermis and subcutaneous tissues, with secondary thrombosis, giving rise to necrotizing vasculitis (due to protease and endotoxin A produced by P aeruginosa). There is bacterial invasion of the adventitia and media of dermal veins but not arteries.1 The main sites affected include the apocrine areas (gluteal or perineal region [55%]), but these lesions can spread to other sites (limbs [30%] and face and trunk [12%]).8 The absence of suppuration and slough distinguishes it from pyoderma gangrenosum as well as external inoculation with group A Streptococci, which produces a crusted ulcerated plaque.9 This is a severe infection associated with a high mortality rate, requiring prompt diagnosis. Once the diagnosis is established, early treatment must include antibiotic coverage against P aeruginosa. If lesions fail to respond to antimicrobials, surgical debridement should be performed. Multiple lesions, delay in treatment, and neutropenia are poor prognostic indicators.9 For routine HIV screening during pregnancy, fourthgeneration ELISA should be preferred, especially in high-risk groups.10 Fourth-generation assays test for both antibodies and antigens simultaneously, being better able to detect recent infection than first-generation tests that detect only antibodies. The window period could be reduced from 4 weeks to 1 week with fourthgeneration tests.
Analysis and interpretation of data: Oliveira, Prata, Marques. Drafting of the manuscript: Oliveira. Critical revision of the manuscript for important intellectual content: All authors. Administrative, technical, or material support: Oliveira, Esteves, Prata. Study supervision: Esteves, Prata, Tapadinhas, Guerreiro, Marques. Conflict of Interest Disclosures: None reported. REFERENCES 1. Morelli G. Cutaneous bacterial infections. In: Kliegman R, Behrman R, Jenson H, Stanton B, eds. Nelson Textbook of Pediatrics. 18th ed. Philadelphia, PA: Saunders; 2007:2740. 2. Chan YH, Chong CY, Puthucheary J, Loh TF. Ecthyma gangrenosum. Singapore Med J. 2006;47(12):1080-1083. 3. Martins P, Pedroso H, Marques JG. Neutropénia transitória na criança previamente saudável. Acta Med Port. 2001;14(3):285-291.
4. Huang YC, Lin TY, Wang CH. Communityacquired Pseudomonas aeruginosa sepsis in previously healthy infants and children. Pediatr Infect Dis J. 2002;21(11):1049-1052. 5. Zomorrodi A, Wald ER. Ecthyma gangrenosum. Pediatr Infect Dis J. 2002;21(12):1161-1164. 6. Singh TN, Devi KM, Devi KS. Ecthyma gangrenosum. Indian J Med Microbiol. 2005;23(4):262-263. 7. Marques SA, Fioretto JR, Martins JG, Sato CM, Martins DS. Ectima gangrenoso. Diagn Tratamento. 2009;14(3):108-110. 8. Habif TP. Clinical Dermatology. 4th ed. St Louis, MO: Mosby; 2004. 9. Goolamali SI, Fogo A, Killian L, et al. Ecthyma gangrenosum. Clin Exp Dermatol. 2009;34(5):e180-e182. 10. British HIV Association; British Association of Sexual Health and HIV; British Infection Society. UK national guidelines for HIV testing 2008. http://www.bhiva.org/documents/Guidelines /Testing/GlinesHIVTest08.pdf. Accessed December 2012.
JAMA Pediatrics January 2014 Volume 168, Number 1
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archpedi.jamanetwork.com/ by a J H Quillen College User on 05/31/2015
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