Review

Pediatric pyoderma gangrenosum: a systematic review and

update
Elio Kechichian1,2, MD, Roger Haber1,2, MD, Nadim Mourad1,2, MD, Rana El Khoury1,2,
2,3 2,4
MD, Samer Jabbour , MD, and Roland Tomb , PhD

1
Department of Dermatology, Hotel Dieu de Abstract
France University Hospital, Beirut, Pyoderma gangrenosum (PG) is a sterile neutrophilic disorder that rarely affects children.
Lebanon, 2Faculty of Medicine, Saint
Clinical, epidemiological, and therapeutic data on pediatric PG is poor as there are many
Joseph University, Beirut, Lebanon,
3
Department of Plastic and Reconstructive
newly reported associated diseases and drugs. This paper aims to review all recent
Surgery, Hotel Dieu de France University available data on pediatric PG. A systematic review of the literature was conducted using
Hospital, Beirut, Lebanon, and 4Chief of Embase, Medline, and Cochrane databases. A total of 132 articles were included in the
Department of Dermatology, Hotel Dieu de review. The most commonly reported underlying diseases in pediatric PG are inflammatory
France University Hospital, Beirut, Lebanon
bowel diseases followed by hematologic disorders, vasculitis, immune deficiencies and
Pyogenic Arthritis, Pyoderma gangrenosum and Acne (PAPA) syndrome. More than half of
Correspondence
Elio Kechichian, MD the cases occur with no underlying disease. The most frequently reported clinical
Hotel Dieu De France Hospital University presentation is multiple disseminated ulcers. Treatment should be tailored according to the
Hospital underlying etiology. It includes systemic steroids, corticosteroid sparing agents such as
Alfred Naccache St., PO BOX: 166830
dapsone and cyclosporine, and TNF-alpha inhibitors such as adalimumab and infliximab.
Achrafieh
Beirut
Response to treatment is high with cure rates reaching 90%. A high index of suspicion and
Lebanon a thorough workup are mandatory in the management of pediatric PG.
E-mail: elio.kechichian@net.usj.edu.lb

Funding: This article has no funding source.

Conflicts of interest: The authors have no

conflict of interest to declare.

No prior presentation.

doi: 10.1111/ijd.13584

trauma.7,10–12 Visceral involvement is also possible and has

Introduction
Pyoderma gangrenosum (PG) is a primarily sterile inflammatory
neutrophilic dermatosis that was first described by Brunsting
et al. in 1930.1 Lesions typically present as painful, erythematous
pustules, bullae, or nodules that demonstrate pathergy and
enlarge concentrically. They may evolve into necrotic plaques
with raised edges or into violaceous deep ulcers with undermined
bluish borders, healing with atrophic or cribriform scars.2 Clinical
subtypes include ulcerative, pustular, bullous, and vegetating
3,4
lesions. Pathophysiology may include aberrant integrin oscilla-
tions on neutrophils and abnormal neutrophil chemotaxis.5,6
The peak of incidence occurs between the ages of 20 and
50 years with women being more often affected than men.7–9
Cases in infants and adolescents account for only 4% of PG,
with a higher incidence of head and perineal involvement, pre-
ponderance of pustular lesions, and a frequent history of
been reported in both adults and pediatric PG.13,14
Diagnosis is based on the typical clinical appearance of the
lesion and the course of the disease; histological findings are
nonspecific and consist of neutrophilic aggregates, mononuclear
cells, fibrosis, hemorrhage, necrosis, ulceration, and giant
cells.15 Differential diagnosis includes vascular occlusive or
venous disease, thrombophilic conditions, vasculitis, malignan-
cies, infectious disease, exogenous tissue injury, factitious pan-
niculitis, insect or spider bites, and pustular drug reactions.16,17
Pyoderma gangrenosum has been reported in the pediatric
population in association with ulcerative colitis, leukemia, IgA
gammopathy, Crohn’s disease, rheumatoid arthritis,10 Takayasu
disease,18 and various immunodeficiencies including HIV,19
chronic granulomatous disorder,20 leukocyte adherence glyco-
protein deficiency,21 hyper IgE syndrome,20 and selective IgA
deficiency.22 More recently, PG has been associated with novel
1

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2 Review Pediatric pyoderma gangrenosum
drug therapies like pegfilgrastim – a granulocyte-stimulating fac-
tor,23 and gefitinib – an inhibitor of epidermal growth factor
receptor24 and with autoinflammatory syndromes like Pyogenic
Arthritis, Pyoderma gangrenosum and Acne (PAPA) syndrome25
and Majeed syndrome.26
In addition to oral10 and intralesional corticosteroids,27 pulse
intravenous dexamethasone,28 cyclosporine,29 colchicine,18
thalidomide,30 sulfa drugs,31 azathioprine,18 mycophenolate
mofetil,32 tumor necrosis alpha inhibitors,33–36 calcineurin inhibi-
tors,37 IL-1,38 intravenous immunoglobulin,39 and surgery27
have recently been shown to be effective in the treatment of
adult and pediatric PG.9,40 Still, to date, there is currently no
gold standard of treatment or published algorithm for choice of
therapy for pediatric PG.40
Considering the relatively poor clinical, epidemiological, and
therapeutic data on pediatric PG, and in view of the newly
reported association with emerging drugs and inflammatory dis-
eases, the aim of this paper is to review all recent available
data on pediatric PG with a particular focus on clinical features,
associated medical conditions, and available treatments.
Materials and methods
On the June 28, 2016, we conducted a systematic search of
the English and French literature using the MEDLINE, Embase,
and Cochrane collaboration databases. The search was done
with the following combination of keywords: (“pyoderma
gangrenosum” or “pyostomatitis vegetans”) AND (“child” or
“children” or “childhood” or “paediatric” or “adolescent” or
“adolescence” or “toddler” or “infant” or “infancy”). Candidate
studies were selected by two independent authors (EK and RH)
based on titles and abstracts. These candidate studies were
obtained and read in full. Corresponding authors of unavailable
articles were contacted by email. Due to the presence of a
systematic review done in March 1994, we included all articles
published from March 1994 to the search date. To be included
in our review, patients had to be younger than 18. Studies that
did not clearly report the age or the clinical evolution and
outcome were excluded. The bibliography of included articles
was manually screened for additional pertinent articles. Based
on the inclusion and exclusion criteria, the two main authors
(EK and RH) agreed on the final selection of studies, and any
disagreement was solved by discussion. The Cohen’s kappa
statistic for the inclusion of studies was 0.8.
The following outcomes were obtained from the included
studies for analysis: underlying disease, age, gender, clinical
characteristics, treatment used, treatment outcome (clearing of
the lesions and lesion recurrence), treatment side effects, and
follow-up time. PG lesions were considered cured when the
primary authors of the articles clearly stated significant clinical
improvement and both main authors (EK and RH) agreed on it
when reviewing the pictures and/or the clinical description in the
texts. To compare the cure rate of the most commonly used
International Journal of Dermatology 2017
Kechichian et al.
corticosteroid-sparing drugs and TNF-alpha inhibitors, 2 9 2
online contingency tables were used.41 To reach statistical
significance, the P value must be lower than 0.05.
Results
The initial search of databases yielded 1223 studies of which
333 were duplicates; 203 were selected as candidate studies.
Based on the inclusion and exclusion criteria, 132 were included
in the systematic review. They are compiled according to the
underlying disorder with the corresponding outcomes in Table 1.
The stepwise approach for study selection is summarized in
Figure 1. All of the included studies are case series and case
reports as no clinical trials were found.
A total of 170 patients were included (Table 1). In the largest
group (n = 77), no underlying disease was found. Underlying eti-
ologies were ulcerative colitis (17), Crohn’s disease (18),
Takayusu’s arteritis (6), Behcet’s disease (5), leukocyte adhe-
sion deficiency type 1 (LAD1)21,42–45 (8), recombination-activat-
ing gene 1 (RAG1) mutation (1), common variable immune
deficiency (CVID) (1), PAPA syndrome (6), myelodysplastic syn-
drome (5), chronic recurrent multifocal osteomyelitis (3), leuke-
mia (2), anablastic lymphoma (2), juvenile idiopathic arthritis (2),
and Pyogenic Arthritis, Pyoderma gangrenosum, Acne, and Sup-
purative Hidradenitis (PAPASH) syndrome, Pyoderma gangreno-
sum, Acne, and Suppurative Hidradenitis (PASH) syndrome,
pure red blood cell aplasia, autoimmune neutropenia of infancy,
autoimmune lymphoproliferative syndrome, trauma-induced,
hyperzincemia and hypercalprotectinemia, sickle cell anemia,
isotretinoin-induced, Wilson’s disease, type 1 diabetes, heredi-
tary spherocytosis, systemic lupus erythematosus (SLE), Sjo-
gren’s disease, and varicella (1 for each, respectively). The six
most common underlying diseases are represented in Figure 2.
The average age of all included patients was 9.5 years with
a standard deviation of 6.3 years. Disease distribution according
to age in the six most reported etiologies is illustrated in
Figure 3. Fifty percent were male. Median time from initial
symptom to diagnosis is 2 months. Most commonly, lesions
were disseminated (46.5%). When localized, lesions mostly
occurred on the lower extremity (29.7%), followed by the per-
ineum (7.8%), head (3.9%), oral mucosa (3.9%), back (3.2%),
peristomal skin (2.6%), upper extremity (2%), and chest (1.3%).
All of the peristomal lesions were found in the inflammatory
bowel disease (IBD) group. This particular location accounts for
12.5% of cases associated with ulcerative colitis and 24.9% of
cases associated with Crohn’s disease (Table 2). Four types of
PG were identified with ulcerative being the most frequent
(83.6%) (Table 3). Multiple lesions were more commonly found
than single lesions in 79.4 and 20.6%, respectively. The most
frequently used treatments were systemic steroids alone
(42.3%) followed by the combination of systemic steroids and
corticosteroid sparing agent (16.7%) (Table 4). The doses of
systemic steroids ranged from 0.5 to 3 mg/kg of body weight
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Kechichian et al. Pediatric pyoderma gangrenosum Review 3

Table 1 Patient characteristics compiled according to the underlying disease

Patients Age in Male Number of Rate of clinical

Underlying disease (n) years (mean) (%) lesions (%) improvementa

Anaplastic lymphoma 2.0 10.0 50.0 M (100) 50.0

Autoimmune lymphoproliferative syndrome 1.0 16.0 0.0 S (100) 100.0
Autoimmune neutropenia of infancy 1.0 0.8 0.0 S (100) 100.0
Chronic recurrent multifocal osteomyelitis 3.0 1.2 66.7 M (66.7) 100.0
S (33.34)
Crohn’s disease 18.0 13.4 53.3 M (53.34) 100.0
S (46.65)
Hereditary spherocytosis 1.0 15.0 100.0 M (100) 100.0
Hyperzincemia and hypercalprotectinemia 1.0 10.0 0.0 M (100)
Idiopathic 77.0 7.0 45.5 M (79.2) 92.9
S (20.8)
Immune deficiency: 10.0 9.3 50.0 M (90) 100.0
LAD 1 deficiency (80%) S (10)
RAG 1 mutation (10%)
CVID (10%)
Isotretinoin-induced 1.0 17.0 100.0 M (100) 100.0
Juvenile idiopathic arthritis 2.0 16.0 50.0 S (100) 100.0
Leukemia 3.0 4.3 50.0 M (100) 100.0
Myelodysplastic syndrome 5.0 8.2 40.0 M (100) 100.0
PAPA 7.0 11.3 83.3 M (66.67) 100.0
S (33.34)
PAPASH 1.0 16.0 0.0 M (100) 100.0
PASH 1.0 16.0 0.0 M (100) 100.0
Pure red blood cell aplasia 1.0 4.0 100.0 M (100) 100.0
Sickle cell anemia 1.0 12.0 100.0 M (100)
Sjogren 1.0 17.0 0.0 M (100) 100.0
SLE 1.0 1.2 0.0 M (100) 0.0
Trauma 1.0 9.0 100.0 M (100) 100.0
Type 1 diabetes 1.0 15.0 0.0 M (100) 100.0
Ulcerative colitis 17.0 14.5 37.5 M (85.72) 69.2
S (14.29)
Varicella 1.0 2.5 100.0 M (100) 100.0
Vasculitis: 11.0 9.1 54.6 M (90.8) 66.7
Behcet (45.46%) S (10.2)
Takayusu’s arteritis (54.56%)
Wilson’s disease 1.0 17.0 0.0 M (100) 100.0
Total 170.0 10.4 50.4 M (79.4) 90.1
S (20.6)

CVID, common variable immune deficiency; LAD 1, leukocyte adhesion deficiency, type 1; M, multiple; PAPA, pyogenic arthritis, pyoderma
gangrenosum and acne; PAPASH, pyogenic arthritis, pyoderma gangrenosum, acne, and suppurativa hidradenitis; PASH, pyoderma grangre-
nosum, acne, suppurativa hidradenitis; RAG 1, recombination-activating gene 1; S, single; SLE, systemic lupus erythematosus.
a
Clinical improvement is defined by a significant healing of lesions reported by the authors of the primary articles.

per day. Corticosteroid pulses were used with doses ranging
from 15 to 30 mg/kg of body weight per day. Corticosteroid-
sparing agents, alone or in combination with systemic steroids,
were used in 29% of cases. The most frequently used drug was
dapsone (34.9%) (at a dose of 12–100 mg/d) followed by
cyclosporine (30.1%) (at a dose of 0.3–10 mg/kg of body weight
per day) (Table 2). TNF-alpha inhibitors, alone or in combina-
tion with systemic steroids, were used in 13.4% of cases: 5 mg/
kg of body weight of infliximab being the most common (63.4%)
followed by 40 mg of adalimumab every other week (33.3%)
and etanercept in one case only.
Clinical improvement defined as significant healing of lesions
reported by the authors of the primary articles was found in
90.14% of all included cases. Among the corticosteroid-sparing
drugs, dapsone had a clinical improvement rate of 82.6%, which
was not statistically different from that of cyclosporine (80% with
P = 0.32). Among the TNF-alpha inhibitors, adalimumab had
the highest cure rate (60%) but was not statistically different
from that of infliximab (57.9% with P = 0.91).
Follow-up was reported in 76 patients. Mean follow-up time
was 22.1 months, median was 12 months, and range
0.5–186 months. Four patients died, due to the gravity of their

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4 Review Pediatric pyoderma gangrenosum Kechichian et al.

hypertrichosis with gingival hyperplasia in another. Dyspnea

Records identified through
database searching and other
and rash were reported in only one patient following infliximab
sources injection.
(n = 1223)

Discussion

Pyoderma gangrenosum is relatively rare in the pediatric popula-

Records after duplicates removed tion with only four percent of PG occurring in children.10 In
(n = 890) adults, PG most commonly occurs on lower extremities.46 Con-
cordantly, we found that the most common presentation of PG in
children is disseminated ulcerative lesions with lower extremities
Records excluded most frequently affected when lesions are localized. Peristomal
Records screened
(n = 687)
(n = 890) skin is a particular location reported in IBD.47 Extracutaneous
manifestations include but are not limited to lungs, eyes, and
Full-text articles
excluded, based on musculoskeletal system.48 In contrast with what has been
Full-text articles inclusion and exclusion reported by Graham et al.,10 we found that the ulcerative sub-
criteria type is the most common presentation in children. PG lesions
assessed for eligibility (n = 71)
could have begun as pustules and ulcerated at a later stage.
The pathophysiology of PG is still poorly understood. It is
Studies included in thought to be a neutrophilic disorder characterized by metabolic
oscillations and increased cytokine production, resulting in tis-
the systematic review (n = 132)
sue destruction. The current understanding of the disease
pathogenesis has recently evolved with advances in immunol-
Figure 1 Stepwise approach for study selection
ogy and biologic therapies. Il-18, a leukocyte chemotactic agent
overexpressed in PG, and Il-16, another chemotactic agent
increased in auto-inflammatory syndromes such as PAPA, play
underlying disorder: LAD1 deficiency in one patient, Takayusu’s an important role in inducing PG lesions.5,6 Other possible
arteritis in one patient, RAG1 mutation in one patient, and immunologic triggers are Il-1 and TNF alpha, which are potential
anaplastic lymphoma in one patient each. Treatment side therapeutic targets as illustrated in our review.
effects were not reported in most of the included studies. Diagnosis of pediatric PG is often delayed, with an average
Adverse events were mentioned in only nine reports. In patients of 2 months; this can be explained by the low prevalence of the
treated with systemic steroids, cushingoid features were found disease among children and the fact that PG can be misdiag-
in three patients, growth retardation in one patient, hypertricho- nosed with other causes of ulcerative disease (infectious,
sis and striae distensae in one patient, and minor infections in vasculitis, etc.).
one patient. Among the patients treated with cyclosporine, ane- The diagnosis of PG is, in fact, a diagnosis of exclusion.49
mia and hypertension were reported in one patient and Clinical presentation, along with repeatedly negative cultures,

MOST COMMON UNDERLYING DISEASES IN

PEDIATRIC PYODERMA GANGRENOSUM
(NUMBER OF CASES)
77

34

14

11

10

Figure 2 The most common underlying

IDIOPATHIC INFLAMATORY HEMATOPATHY VASCULITIS IMMUNE PAPA, PAPASH, diseases in pediatric pyoderma
BOWEL DISEASE DEFICIENCY PASH gangrenosum

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Kechichian et al. Pediatric pyoderma gangrenosum Review 5

AVERAGE AGE OF PATIENTS WITH PG

(YEARS)

14
12.88
9.09

9.3
7.43
7

IDIOPATHIC HEMOPATHY VASCULITIS IMMUNE PAPA, PAPASH, INFLAMATORY

Figure 3 Disease distribution according to DEFICIENCY PASH BOWEL
age in pediatric pyoderma gangrenosum DISEASE

Table 2 Body area affected according to the underlying disease

Body area affected expressed in percentage

Upper Lower
Generalized Head Oral Trunk extremity extremity Perineum Peristomal

Underlying disease
Anablastic lymphoma 50.0 50.0
Autoimmune lymphoproliferative syndrome 100.0
Autoimmune neutropenia of infancy 100.0
Chronic recurrent multifocal osteomyelitis 66.7 33.3
Crohn’s disease 6.7 12.5 24.9 18.7 12.5 24.9
Hyperzincemia and hypercalprotectinemia 100.0
Idiopathic 31.3 60.0 12.5
Immune deficiency 60.0 10.0 30.0
Isotretinoin-induced 100.0
Juvenile idiopathic arthritis 100.0
Leukemia 50.0 50.0
Myelodysplastic syndrome 60.0 20.0 20.0
PAPA 16.7 50.0 16.7 16.7
PAPASH 100.0
PASH 100.0
Pure red blood cell aplasia 100.0
Pyodermatitis-pyostomatitis vegetans 100.0
Sickle cell anemia 100.0
SLE 100.0
Trauma 100.0
Ulcerative colitis 60.0 12.5
Varicella 100.0
Vasculitis 71.4 28.6
Total 46.5 3.9 3.9 4.5 2.0 29.7 7.8 2.6

PAPA, pyogenic arthritis, pyoderma gangrenosum and acne; PAPASH, pyogenic arthritis, pyoderma gangrenosum, acne, and suppurativa
hidradenitis; PASH, pyoderma grangrenosum, acne, suppurativa hidradenitis; SLE, systemic lupus erythematosus.

nonresponse to antibiotics, pathergy phenomenon, and a histol- Once the diagnosis of pediatric PG is confirmed, the search
ogy showing nonspecific aseptic neutrophilic infiltration, are all for an underlying etiology should be undertaken as pediatric PG
suggestive of PG. can be the initial presentation of a systemic disorder. The most

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6 Review Pediatric pyoderma gangrenosum Kechichian et al.

Table 3 Pyoderma gangrenosum type according to the underlying disease

Lesion type expressed in percentage

Ulcerative Ulcerative Ulcerative

Ulcerative Pustular Bullous Vegetative and vegetative and pustular and bullous

Underlying disease
Anablastic lymphoma 50.0 50.0
Autoimmune lymphoproliferative syndrome 100.0
Autoimmune neutropenia of infancy 100.0
Chronic recurrent multifocal osteomyelitis 100.0
Crohn’s disease 80.0 6.7 6.7 6.7
Hyperzincemia and hypercalprotectinemia 100.0
Idiopathic 83.2 1.3 1.3 3.9 3.9 3.9 3.9
Immune deficiency 90.0 10.0
Isotretinoin-induced 100.0
Juvenile idiopathic arthritis 100.0
Leukemia 100.0
Myelodysplastic syndrome 50.0 25.0 25.0
PAPA 66.7 33.3
PAPASH 100.0
PASH 100.0
Pure red blood cell aplasia 100.0
Pyodermatitis-pyostomatitis vegetans 100.0
Sickle cell anemia 100.0
SLE 100.0
Trauma 100.0
Ulcerative colitis 100.0
Varicella 100.0
Vasculitis 89.6 10.4
Total 83.6 0.7 0.7 1.4 5.3 5.3 3.3

PAPA, pyogenic arthritis, pyoderma gangrenosum and acne; PAPASH, pyogenic arthritis, pyoderma gangrenosum, acne, and suppurativa
hidradenitis; PASH, pyoderma grangrenosum, acne, suppurativa hidradenitis; SLE, systemic lupus erythematosus.

common underlying etiology is IBD. Minute inquiry about
gastrointestinal symptoms is crucial, completed by endoscopic
evaluation if judged necessary by the clinician.50,51 While pyos-
tomatitis vegetans is often referred to as “PG of the mouth,”
recent reports indicate that it is a distinct entity that is frequently
associated with IBD and primary sclerosing cholangitis.52 Tissue
eosinophilia may be helpful in distinguishing pyostomatitis vege-
tans from PG.52 We found that peristomal PG is also frequently
associated with IBD,53,54 as it represents 12.5% of cases associ-
ated with ulcerative colitis and 24.9% of cases associated with
Crohn’s disease. The second most common underlying disorder
is hemopathies such as myelodysplastic syndrome, leukemias,
and lymphomas. In such cases, the child commonly presents
with general status alteration with hepatosplenomegaly and pal-
pable lymph nodes on physical exam. A complete blood count,
blood smear, and bone marrow aspiration are to be done. Pedi-
atric vasculitis can present with PG, with Behcet and Takayusu’s
arteritis being the most commonly reported. Recurrent infections
and delayed wound healing suggest immune deficiencies and,
more specifically, LAD 1 deficiency.21 Personal or family history
of auto-inflammatory syndromes, pyogenic arthritis, and severe
acne +/ hidradenitis suppurativa raise the possibility of PAPA,
PASH, or PAPASH syndromes. PG along with arthritis can also
occur in juvenile idiopathic arthritis and chronic multifocal recur-
rent osteomyelitis. In contrast with the previous findings of Gra-
ham et al. in 1994,10 idiopathic PG proved to be the largest
subgroup. This may be due to a publication bias. Thorough his-
tory taking, physical exam and workup, combined with a close
follow-up, are paramount when faced with PG with no obvious
underlying disease.
In this review, lymphoma-and-leukemia-associated PG along
with idiopathic PG tended to occur in the young pre-adolescent
child (7 and 7.4 years of average age, respectively), whereas
IBD and PAPA associated PG affected older children (14 and
12.9 years of average age, respectively). This can be due to the
fact that pediatric leukemias and lymphomas tend to occur in
relatively younger patients compared to PAPA syndrome and
IBD.
Identifying and aggressively treating the underlying disorder
is imperative. The goal is to obtain stable, long-term control of
the primary disease. Corticosteroids with or without steroid-
sparing therapy remain the cornerstone of management of pedi-
atric PG as they are used in 60% of all reported cases
(Table 5). Gulliver’s sign is an important prognostic sign to look

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Kechichian et al. Pediatric pyoderma gangrenosum Review 7

Table 4 Treatments used in pediatric pyoderma gangrenosum

Systemic Corticosparing Topical TNF alpha Bone marrow High dose

Treatment steroids agent treatment Anakinra inhibitor transplant chemotherapy IVIG Isotretinoin

Underlying disease
PAPASH xxx
PASH xxx xxx
PAPA xx xx
Immune deficiency xxx x x
Vasculitis xx x xx
Leukemia xxx
Anaplastic lymphoma xxx xxx
Myelodysplastic xx x x
syndrome
Pure red blood cell xxx
aplasia
Autoimmune xxx
Neutropenia of
infancy
Autoimmune xxx
Lymphoproliferative
syndrome
Crohn’s disease x xx x xxx
Ulcerative colitis xx xx x xxx
Idiopathic xx x x xx x
Chronic recurrent xxx
multifocal
osteomyelitis
Juvenile idiopathic xx xx
arthritis
Trauma x
Pyodermatitis- xxx xxx
pyostomatitis
vegetans
Acne conglobata xxx
SLE xxx
Hyperzincemia and xxx
hypercalprotectinemia
Sickle cell anemia xxx
Isotretinoin-induced xxx
Varicella xxx
Hereditary xxx xxx
spherocytosis
Type 1 diabetes xxx

PAPA, pyogenic arthritis, pyoderma gangrenosum and acne; PAPASH, pyogenic arthritis, pyoderma gangrenosum, acne, and suppurativa
hidradenitis; PASH, pyoderma grangrenosum, acne, suppurativa hidradenitis; SLE, systemic lupus erythematosus.
xxx this treatment has been used in 51–100%.
xx this treatment has been used in 25–50%.
x this treatment has been used in 1–24%.

for as it indicates the decrease in inflammation and the begin-
ning of the healing of lesions.55 In fact, raised, erythematous
and sometimes necrotic edges are signs of active inflammation
and expansion of the PG lesion. On the other hand, epithelial
growth and evening of the edges between the ulcer center and
the surrounding skin are signs of wound healing. At this point,
tapering of the systemic steroids can be initiated. We found that
dapsone and cyclosporine were the most commonly prescribed
steroid-sparing drugs with a fairly high success rate (around
80%). In IBD, both adalimumab and infliximab were shown to
control both the gastrointestinal tract inflammation and the asso-
ciated PG. As in adults, aggressive surgery is to be avoided as
pathergy phenomenon worsens the disease. In fact, while sur-
gery has been frequently used in the past to treat PG,10 at the
present time the key element in management is the pharmaco-
logic control of the inflammation.
Adverse events, although relatively rarely mentioned in the
reports, were comparable to the ones observed in adults taking

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8 Review Pediatric pyoderma gangrenosum Kechichian et al.

Table 5 Corticosteroid sparing agents used in pediatric clinically-oriented workup is mandatory to make the correct
pyoderma gangrenosum diagnosis and prescribe the appropriate treatment. As it is not
known whether children with PG might, in the long-term,
Frequency of using the drug as Frequencya develop other disorders such as ulcerative colitis, Crohn’s dis-
a corticosteroid sparing drug (%) ease, leukemia, or arthritis, large clinical trials with long follow-
up periods are mandatory to determine the exact prognosis of
Dapsoneb 34.9
Cyclosporineb 30.4 PG in children.
Mycophenolate mofetil 9.1
Methotrexate 4.6
Colchicine 4.6 Questions (answers found after references)
Azathioprine 4.6
Sulfasalazine 4.6 (1) What is the most common underlying disorder in pediatric
6 mercaptopurine 4.6
pyoderma gangrenosum?
Oral tacrolimus 3
a) Ulcerative colitis
a
Frequency of using the drug among all cases where a corticos-
b) Crohn’s disease
teroid sparing drug was used. c) Myelodysplastic syndrome
b
Both Dapsone and cyclosporine were the most commonly used d) PASH syndrome
corticosteroid spearing drugs with the highest clinical efficacy (82.6 e) Leukemia
and 80%, respectively with a P value of 0.32).
(2) True or False: The six main disorders reported with pedia-
tric PG are: inflammatory bowel disease (IBD); PAPA,
systemic steroids and steroid-sparing drugs. One expected PASH, and PAPASH; Immune deficiency, vasculopathies,
exception is growth retardation in children. Therefore, clinical and hemopathies.
and biological follow-up with a pediatric endocrinologist, if avail- (3) Among the most common underlying disorders of pediatric
able, is crucial with special focus on growth and height/weight PG, which ones have the lowest and highest average age
curves. of onset?
In our pooled analysis, we found multiple differences between a) Hemopathies and IBD
pediatric PG and adult PG. While being commonly located on b) Hemopathies and PASH
the lower extremities in adults,46 pediatric PG tends to be more c) IBD and PASH
disseminated with no specific location pattern. Lesions are more d) PASH and immune deficiencies
commonly multiple in children. The associated diseases are dif- e) Immune deficiencies and IBD
ferent as auto-inflammatory syndromes such as PAPA, PASH, (4) What is the most common clinical presentation of pediatric
and PAPASH, as well as hematologic malignancies, are over- PG?
represented in the pediatric population. Finally, special attention a) Unique ulcer on the upper extremity
should be made regarding the follow-up of children treated with b) Multiple ulcers on the upper extremities
steroids and steroid-sparing drugs as they can effect their c) Unique ulcer on the lower extremity
growth and development. d) Multiple ulcers on the lower extremities
There are several limitations to this systematic review. Due e) Multiple disseminated ulcers
to the rarity of pediatric PG, all the included studies are case (5) True or False: The diagnosis of pediatric PG is one of
reports and case series. In addition, the lack of trials limited our exclusion.
review to a pooled analysis. The relatively short follow-up time (6) True or False: The recommended workup in pediatric PG is
in many reports could overestimate the relatively high reported standardized and applicable to all patients.
cure rates. In addition, the idiopathic subgroup may be over- (7) What is the goal of treatment in patients with pediatric PG?
represented as PG can precede the underlying disorder by a) Wound healing
many months and sometimes years. The large amount of vari- b) Long-term sustainable response
ability of evolution between underlying diseases restricted the c) Prevention of recurrence
inter-study comparison and integrated analysis. Finally, publica- d) All are true
tion bias is another limitation, as only published articles were (8) What is the most commonly used treatment in pediatric
evaluated. patients with PG?
In conclusion, generalized and ulcerative lesions are the most a) TNF alpha inhibitors
frequent initial presentation of pediatric PG. The most common b) Systemic steroids +/ seroid sparing drugs
underlying etiologies in pediatric PG are IBD, hematologic c) Topical steroids
malignancies, immune deficiencies, vasculitis, and PAPA syn- d) Antibiotics
drome; idiopathic cases account for 49% of cases. A thorough e) Steroid sparing drugs alone

International Journal of Dermatology 2017 ª 2017 The International Society of Dermatology

Kechichian et al.
(9) When are the systemic steroids tapered?
a) After 2 weeks
b) After 1 month
c) After 1 year
d) After complete healing of the lesion
e) Once Gulliver’s sign is noted
(10) What are the most commonly used steroid-sparing agents?
a) Dapsone
b) Cyclosporine
c) Azathioprine
d) Mycophenolate mofetil
e) Cyclophosphamide
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Answers
1. b Pediatric pyoderma gangrenosum is most commonly idio-
pathic. When present, the most frequent underlying disorder
is Crohn’s disease.
2. True.
3. a. Pediatric PG is associated with hemopathies earlier in life
(at the age of 7 years) and with IBD later in life (average
age of 14 years).
4. e. The most common clinical presentation of pediatric PG is
multiple disseminated ulcers.
5. True. The diagnosis of pediatric PG is, in fact, a diagnosis of
exclusion. Clinical presentation, along with repeatedly nega-
tive cultures, nonresponse to antibiotics, pathergy phe-
nomenon and a histology showing nonspecific aseptic
neutrophilic infiltration are all suggestive of PG. The major
diagnostic criteria are: (i) rapid progression of a painful,
necrolytic cutaneous ulcer with an irregular, violaceous, and
undermined border and (ii) other causes of cutaneous ulcer-
ation have been excluded.
6. False. The workup largely depends on the clinical presenta-
tion and the first step of management is to look for an under-
lying disorder. Blood tests, endoscopies and cultures can be
helpful in revealing the causative disease.
7. d. The goal of therapy is to obtain a long-term sustainable
response of the underlying disorder, as well as total wound
healing of the pediatric PG lesions.
8. b
9. e. The systemic steroids can be tapered once Gulliver’s sign
is noted: ulcer edges begin to heal and re-epithelialization
occur.
10. a and b.
ª 2017 The International Society of Dermatology