Index of Suspicion in the Nursery
2 Newborn with Hemorrhagic Skin Reaction
AUTHOR DISCLOSURE Drs Redford and
Trachimowicz have disclosed no financial
relationships relevant to this article. This
commentary does not contain a discussion of
an unapproved/investigative use of a
commercial product/device.
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Katherine Redford, DO,* Gina M. Trachimowicz, MD*
*Barbara Bush Children’s Hospital, Portland, ME
PRESENTATION
A female infant is born via emergent repeat cesarean section because of a
maternal abruption. The mother is a 34-year-old woman whose history includes
3 prior preterm cesarean deliveries and polysubstance abuse with recent use of
crack cocaine a few hours before delivery. The infant was born at 27 2/7 weeks
weighing 920 g.
After delivery, the infant had a spontaneous cry with poor tone, color, and
respiratory effort. She was briefly given positive pressure ventilation and sup-
ported on continuous positive pressure ventilation. Apgar scores are 3 and 7 at 1
and 5 minutes, respectively. Physical examination findings were unremarkable.
She was placed in a plastic bag for thermoregulation and reduction of insensible
water losses.
As per routine procedure, she received erythromycin eye ointment and pro-
phylaxis against hemorrhagic disease of the newborn with an intramuscular
injection of 0.5 mg vitamin K in her upper left thigh (vastus lateralis muscle)
using a 26-gauge, 5/8” needle approximately 90 minutes after birth. Intravenous
access was established, and she was started on treatment with ampicillin and
gentamicin for presumed early-onset sepsis. Her respiratory distress worsened,
and she underwent endotracheal intubation with a 2.5-mm tube and was given 1
endotracheal dose of surfactant for the treatment of respiratory distress syn-
drome. Because of hypotension, she received a normal saline bolus (10 mL/kg)
with improvement in her blood pressure.
Approximately 45 minutes after the vitamin K injection, she developed a well-
defined ecchymotic area measuring 42.5 cm (Fig 1 and Fig 2). Within a few
hours, edema, skin splitting, and serosanguinous drainage developed, mostly on
the proximal edge.
DISCUSSION
Differential Diagnosis
Differential diagnosis for an evolving ecchymotic skin lesion includes infiltrate of
intravenous medication, cutaneous reaction to injection (Nicolau syndrome),
birth or intrauterine trauma, subcutaneous opportunistic fungal infection, and
compartment syndrome.
Actual Diagnosis
Given the close temporal relationship to the vitamin K injection, Nicolau
syndrome was thought to be the most likely diagnosis. Examination demonstrated
adequate peripheral perfusion, reassuring against compartment syndrome, a rare
complication of Nicolau syndrome. Given that it evolved further after birth,
Vol. 21 No. 1 JANUARY 2020 e49
 Figure 1. Initial skin changes seen at about 1 hour after vitamin K
injection.
intrauterine and delivery trauma seemed less likely. Devel-
opment on the first day after birth made opportunistic
fungal infection less likely, even in a premature neonate.
The Condition
Nicolau syndrome (also called “embolia cutis medicamen-
tosa” or “livedoid dermatitis”) is a cutaneous reaction to an
injection that is given in an intravascular or perivascular
route rather than intramuscular, as intended. Many agents
have been implicated in Nicolau syndrome. Some examples
include immunotherapy (allergy injections), (1) benzathine
penicillin, and (2) triple diphtheria-tetanus-pertussis vac-
cine, (3) among others. Pathophysiology is not definitively
known but likely involves occlusion or damage to arterioles
causing necrosis of the surrounding tissue. (4) Immuno-
logic response is not thought to be a contributing factor
because of its occurrence in the premature infant with an
immature immune system. (5)
When the patient is old enough to verbalize symptoms,
Nicolau syndrome is associated with immediate and severe
pain at the time of injection and subsequent exquisite
tenderness at the injection site. (1) The initial skin changes
of pallor and edema are almost immediate and are followed
by a red-violet hemorrhagic plaque and eventual varying
e50 NeoReviews
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Figure 2. Initial skin changes seen at about 1 hour after vitamin K
injection.
degrees of necrosis, ulcers, erosions, crusts, and bullae. (3)
Skin biopsies demonstrate necrosis of the epidermis and
thrombosis of small and medium blood vessels. (3) Mag-
netic resonance imaging demonstrates a small stellate
region of signal change consistent with fibrotic granulation
tissue. (1)
Treatment/Management
Conservative management is first-line option for this diag-
nosis. Antibiotics should only be used in the setting of
secondary infection. (6) Topical anesthetic and steroid
creams have been described to help with discomfort in
older children. (3) Surgical intervention, particularly debride-
ment and skin grafting, are rarely required.
These skin lesions heal in weeks to months and have an
atrophic scar. (3) Case reports have described the use of
hyperbaric oxygen to avoid scarring. (4) In 1 case report, a
pediatric patient developed subsequent compartment syn-
drome, kidney dysfunction, seizure, and cardiorespiratory
failure leading to death. (2)
Methods of prevention include aspiration before injec-
tion to decrease likelihood of perivascular or intravascular
injection, sufficient depth to reach intramuscular space, and
the Z-track method to decrease subcutaneous irritation. (6)

Figure 3. Skin changes a few days after birth.
Patient Course
Because of the evolving nature of the lesion and a high
suspicion for an infiltrate of inadvertent medication, in the
current case, hyaluronidase was given to aid in the dispersion of
the unknown medication and to reduce the local concentration.
Pediatric surgery was consulted, and an additional liter-
ature search revealed the clinical diagnosis. Erythema
decreased, and the skin began to slough off in the days
after birth (Fig 3). The lesion slowly decreased in size and
within 3 weeks, a scar remained at the site of injection.
Lessons for the Clinician
• The very sudden onset of skin changes and evolution
consistent with necrosis are suggestive of the diagnosis of
Nicolau syndrome. Imaging and skin biopsy are not
required to make the diagnosis with the appropriate
exposure history and evolution of symptoms.
• Supportive care is indicated and aside from scarring,
long-term complications and escalation of interventions
are rare. This should reassure clinicians that the benefit of
adequate vitamin K far outweighs the risk of this potential
complication of injection.
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• We hope to raise awareness of this potential complication
among clinicians caring for newborns and preterm
newborns to avoid unneeded diagnostic tests or thera-
peutic interventions.
American Board of Pediatrics
Neonatal-Perinatal Content
Specifications
• For therapeutic drugs commonly used in the neonate (eg,
opiates, methylxanthines, barbiturates, etc), know indications for
their use, clinical effects, side effects, and toxicity.
• Know the complications and management of various neonatal
skin injuries including IV infiltrates and chemical and thermal
burns.
• Know the potential toxicity of various drugs applied topically to
newborn skin, including antiseptics, lidocaine, and mydriatic
agents.
References
1. Tierce ML IV, Schultz SM, Lanier BQ. Tissue loss with subcutaneous
immunotherapy--Nicolau syndrome. J Allergy Clin Immunol Pract.
2016;4(1):154–155
2. De Sousa R, Dang A, Rataboli PV. Nicolau syndrome following
intramuscular benzathine penicillin. J Post Med. 2008;54(4):332–334
3. Erkek E, Torrelo A, Sanli C, et al. Nicolau’s syndrome in a newborn
caused by triple DTP (diphtheria-tetanus-pertussis) vaccination. J Am
Acad Dermatol. 2006;54(suppl 5):S241–S242
4. Ruffieux P, Salomon D, Saurat JH. Livedo-like dermatitis (Nicolau’s
syndrome): a review of three cases. Dermatology. 1996;193(4):368–371
5. Koklu E, Sarici SU, Altun D, Erdeve O. Nicolau syndrome induced by
intramuscular vitamin K in a premature newborn. Eur J Pediatr.
2009;168(12):1541–1542
6. Puvabanditsin S, Garrow E, Weerasethsiri R, Joshi M, Brandsma E.
Nicolau’s syndrome induced by intramuscular vitamin K injection in
two extremely low birth weight infants. Int J Dermatol.
2010;49(9):1047–1049
Vol. 21 No. 1 JANUARY 2020 e51
 Case 2: Newborn with Hemorrhagic Skin Reaction
Katherine Redford and Gina M. Trachimowicz
NeoReviews 2020;21;e49
DOI: 10.1542/neo.21-1-e49

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 Case 2: Newborn with Hemorrhagic Skin Reaction
Katherine Redford and Gina M. Trachimowicz
NeoReviews 2020;21;e49
DOI: 10.1542/neo.21-1-e49

The online version of this article, along with updated information and services, is
located on the World Wide Web at:
http://neoreviews.aappublications.org/content/21/1/e49

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