DOI: 10.1111/pde.

13389

Pediatric
BRIEF REPORT Dermatology

Isotretinoin-induced acne fulminans without systemic

symptoms with concurrent exuberant granulation tissue
Abstract
Acne fulminans is a severe form of acne characterized by painful,
inflammatory nodules that progress into ulcers and concurrent sys-
temic symptoms. Treatment of acne with isotretinoin can precipitate
a syndrome called isotretinoin-induced acne fulminans without sys-
temic symptoms. An exuberant granulation tissue response, another
known adverse event associated with isotretinoin, can occur concur-
rently, inhibiting wound repair and complicating treatment. We
report a case of isotretinoin-induced acne fulminans without sys-
temic symptoms with exuberant granulation tissue response that
was treated successfully with topical clobetasol ointment.
1 | INTRODUCTION
with granulation tissue. He did not report fever, change in bowel
habits, or joint or bone pain.
On examination, there were several irregularly shaped, 1- to
10-cm, well-demarcated ulcers scattered on the upper torso with
overlying red, hypertrophic granulation tissue (Figure 1). On the left
dorsal forearm, was a 1-cm oval-shaped ulcer with hypertrophic granu-
lation tissue protruding approximately 1 to 2 mm above the skin base.
The patient was treated with clobetasol 0.05% ointment once daily to
affected areas for 1 week, which resulted in marked improvement of
the ulcers and regression of the hypergranulation tissue. He reported
significantly reduced bleeding and pain. The clobetasol was subse-
quently decreased to one application every other day. At 1-month fol-
low-up, the majority of ulcers were re-epithelializing, and after
5 months of treatment, all ulcers had healed completely (Figure 2).

Acne fulminans (AF) is a severe form of acne characterized by pain-

ful, inflammatory nodules that progress into ulcers accompanied by 3 | DISCUSSION
systemic symptoms, including fever, arthralgia, and weight loss.
Treatment of acne with isotretinoin can cause severe worsening of IIAF-WOSS and hypergranulation tissue are two rare adverse events
acne, resulting in painful ulcerating lesions without associated sys- of isotretinoin that can occur together. The pathophysiology driving
temic symptoms. This reaction has been named isotretinoin-induced
acne fulminans without systemic symptoms (IIAF-WOSS).1-3 Another
known adverse effect of isotretinoin therapy, an exuberant granula-
tion tissue response, can occur concurrently, inhibiting wound
repair.4 We report a case of IIAF-WOSS with exuberant granulation
tissue response that was treated successfully with topical clobetasol
ointment.

2 | BRIEF REPORT

A 16-year-old boy with a 1-year history of cystic acne presented for

evaluation of numerous, large, nonhealing ulcers on the neck, back,
chest, and upper extremities. Five months before, he had developed
a severe cystic flare of acne involving his arms, chest, and back, and
an outside dermatologist started him on isotretinoin 40 mg/d
(0.75 mg/kg/d). While on this regimen, several of the acne cysts
evolved into ulcers, some with overlying hypergranulation tissue.
Because of these complications, isotretinoin was discontinued after
3 months of treatment. Despite having been off of isotretinoin for
2 months at the time of this current presentation, the ulcers and
hypergranulation tissue had persisted. The ulcers were nonhealing,
bleeding, and exquisitely painful, prohibiting him from attending F I G U R E 1 Irregularly shaped, well-demarcated ulcers on the
school and interfering with sleep. Biopsy results were compatible upper right back with overlying red, hypertrophic granulation tissue

Pediatric Dermatology. 2018;1–2. wileyonlinelibrary.com/journal/pde © 2018 Wiley Periodicals, Inc. | 1

2 | Pediatric BRIEF REPORT
Dermatology
CONFLICT OF INTEREST

Dr. Antaya has been a consultant or performed research for Promius,

Anacor, Astellas, Leo, Ferndale, Ranbaxy, Pierre Fabre, and Hoffman-
LaRoche Pharmaceuticals. Mr. Li has no conflicts of interest to
declare.

Keywords
acne, corticosteroid, drug reaction, inflammatory disorders, topical

ORCID

Alvin W. Li http://orcid.org/0000-0003-2591-838X

Alvin W. Li BS1
F I G U R E 2 Atrophic scarring remains in place of resolved
Richard J. Antaya MD2,3
ulcerative lesions and granulation tissue after 5 months of treatment 1
with clobetasol 0.05% ointment School of Medicine, Yale University, New Haven, CT, USA
2
Department of Dermatology, School of Medicine, Yale University, New
Haven, CT, USA
either process is unclear. Some authors have hypothesized that an 3
Department of Pediatrics, School of Medicine, Yale University, New
overwhelming immunologic reaction against Propionibacterium acnes
Haven, CT, USA
antigen, which is released in large quantities after initiation of isotre-
tinoin therapy, drives the former.1 The latter process, some hypothe- Correspondence
size, is driven though the stimulatory effects of retinoids on wound Alvin W. Li, BS, School of Medicine, Yale University, New Haven, CT,
healing and collagen synthesis.5 Retinoids also enhance angiogenic USA.
activity, further facilitating the formation of granulation tissue.5 Email: Alvin.li@yale.edu
Because isotretinoin is commonly used to treat acne vulgaris, clini-
cians should be aware of the potential risk of rare but serious adverse REFERENCES
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