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

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. Dur-
ing admission, the infant developed violaceous skin lesions with edema in inguinal and ax- WHAT IS YOUR DIAGNOSIS?
illary regions (Figure). Lesions became ulcerated within 3 to 4 days, with infarcted necrotic
areas. Blood tests showed leukopenia (white blood cell A. Pyoderma gangrenosum
count, 2460/μL) with neutropenia (neutrophil count,
Quiz at jamapediatrics.com 220/μL) (to convert both to ×109 per liter, multiply by B. Ecthyma gangrenosum
0.001). The lesions were biopsied and samples were sent
for cultures and histopathological analysis. Intravenous floxacillin was started, followed by
C. Wegener granulomatosis
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
D. Meningococcemia
pregnancy was unsupervised. Thirteen days before delivery, she visited the emergency de-
partment with flulike symptoms. Routine infectious screening revealed negative serology
for syphilis, hepatitis B virus, and human immunodeficiency virus (HIV) types 1 and 2 by en-
zyme-linked immunosorbent assay (ELISA). The infant was born at 40 weeks’ gestation by
forceps delivery.

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 Clinical Review & Education JAMA Pediatrics Clinical Challenge

Diagnosis tropenia (chemotherapy, primary causes, or neutrophil functional de-

B. Ecthyma gangrenosum
Discussion
A pediatric infectious diseases specialist gave a clinical diagnosis of
ecthyma gangrenosum and probable immunodeficiency. Antibiot-
ics 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 hem-
orrhage and surrounding edema, suggestive of ecthyma gangreno-
sum. Blood cultures and skin biopsy showed P aeruginosa. Skin le-
sions 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 con-
vert IgA and IgM to milligrams per liter, multiply by 10]) were nor-
mal. Fourth-generation ELISA for HIV was performed (the first as-
say 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 re-
duced 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, Burk-
holderia cepacia, Klebsiella species, Escherichia coli, Neisseria men-
ingitidis, Proteus species, Aeromonas hydrophila, Sternotroph-
omonas maltophilia, Aspergillus species, and Candida species.1,2
Most commonly seen in patients who are critically ill and immu-
nocompromised, 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 neu-
fects), hypogammaglobulinemia, malignant neoplasms, or severe
burns.2,6 It is necessary to determine whether neutropenia is second-
ary to the infection, a persistent condition, or a transient phenom-
enon (eg, viral induced) in previously healthy children.2 Considering
this diagnosis, a thorough search for any underlying immune defi-
ciency should be undertaken. It is mandatory to exclude HIV infec-
tion, 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 sur-
rounded by an erythematous halo.7 These lesions result from peri-
vascular bacterial invasion of media and adventitia of vessels into
dermis and subcutaneous tissues, with secondary thrombosis, giv-
ing rise to necrotizing vasculitis (due to protease and endotoxin A
produced by P aeruginosa). There is bacterial invasion of the adven-
titia and media of dermal veins but not arteries.1 The main sites af-
fected 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 distin-
guishes it from pyoderma gangrenosum as well as external inocu-
lation with group A Streptococci, which produces a crusted ulcer-
ated 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 neutrope-
nia are poor prognostic indicators.9
For routine HIV screening during pregnancy, fourth-
generation ELISA should be preferred, especially in high-risk
groups.10 Fourth-generation assays test for both antibodies and an-
tigens simultaneously, being better able to detect recent infection
than first-generation tests that detect only antibodies. The win-
dow period could be reduced from 4 weeks to 1 week with fourth-
generation tests.

ARTICLE 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.
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.
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