Pediatric Dermatology Vol. 33 No.

2 172–177, 2016

Penile and Scrotal Swelling: An Underrecognized

Presentation of Crohn’s Disease
Benjamin J. Barrick, D.O.,* Megha M. Tollefson, M.D.,*,† Jennifer J. Schoch, M.D.,*
Marian T. McEvoy, M.D.,*,† Jennifer L. Hand, M.D.,*,†,‡ Carilyn N. Wieland, M.D.,*,§ and
Dawn M. R. Davis, M.D.*,†
Departments of *Dermatology, †Pediatric and Adolescent Medicine, and ‡Medical Genetics, and §Division of
Anatomic Pathology, Mayo Clinic, Rochester, Minnesota

Abstract:
Background: Penile and scrotal swelling can occur as an extraintestinal
manifestation of Crohn’s disease (CD) and is thought to be an uncommon form
of metastatic CD (MCD). Because of the rarity of this manifestation, much is
unknown concerning the presentation, treatment, and response to therapy in
children with genital MCD.
Methods: Boys ages 1 to 17 years presenting with genital edema and a
confirmed diagnosis or strong suspicion of CD who were evaluated at the Mayo
Clinic between 1996 and 2014 were included for review. We sought to
characterize the clinical and pathologic features of genital MCD and response to
treatment in our cohort of patients.
Results: Eight patients with genital MCD were identified from our institution
(mean age 11.4 yrs, range 7–16yrs). Seven (88%) patients experienced
cutaneous symptoms before a formal diagnosis of CD was made, and two of
the seven had no adverse gastrointestinal symptoms at that time. Patients were
prescribed an average of 3.4 medications (topical and systemic) for manage-
ment of their gastrointestinal CD and MCD.
Conclusions: Penile and scrotal swelling can occur as an extraintestinal
manifestation of CD and is thought to be an uncommon form of MCD. In boys,
genital swelling typically precedes intestinal CD. Treatment of the underlying CD
with systemic medications was most helpful in this series. An evaluation for CD
is necessary in all patients presenting with unexplained genital swelling.

Crohn’s disease (CD) is an autoimmune inflamma- aphthous ulcers, pyodermatitis-pyostomatitis vege-

tory disease of the gastrointestinal (GI) tract. Cuta- tans, necrotizing vasculitis, and metastatic CD
neous manifestations are common in CD and may (MCD). Rarely, unexplained penile or scrotal swelling
include erythema nodosum, pyoderma gangrenosum, (Fig. 1A) occurs as an extraintestinal manifestation of

Address correspondence to Dawn M. R. Davis, M.D., Depart-

ment of Dermatology, Mayo Clinic, 200 First Street SW, Rochester,
MN 55905, or e-mail: davis.dawnmarie@mayo.edu.

DOI: 10.1111/pde.12772

172 © 2016 Wiley Periodicals, Inc.

 Barrick et al: Penile and Scrotal Swelling as Metastatic Crohn Disease 173

A B

Figure 1. (A) Marked scrotal and penile swelling in a patient with metastatic Crohn’s disease. Histopathologic findings in
the perianal area of a patient with genital swelling and Crohn’s disease: (B) epidermal papillomatosis and hyperplasia with
dilated vessels, edema, and a mixed inflammatory infiltrate in the superficial dermis (hematoxylin and eosin, 409), (C) focal
dermal granulomatous inflammation with collections of histiocytes and multinucleated giant cells scattered within dermal
inflammatory infiltrate (hematoxylin and eosin, 4009).

CD and is thought to be an uncommon type of MCD
(1,2). Reports are limited to case studies, and much is
unknown about the presentation, treatment, and
response to therapy in children.
METHODS
Following approval by the Mayo Clinic Institutional
Review Board, a data retrieval specialist identified
relevant patient records based on search criteria of the
diagnosis codes of the International Classification of
Diseases, Ninth Revision, for inflammatory bowel
disease and variations of keywords for genital
swelling. Boys ages 1 to 17 years presenting with
genital swelling and a confirmed diagnosis or strong
suspicion of CD who were evaluated at the Mayo
Clinic between 1996 and 2014 were included for
review. We sought to characterize the temporal
relationship between symptoms of genital swelling
and diagnosis of CD, clinical and pathologic features,
and response to treatment in our cohort of patients.
RESULTS
Eight boys were identified (mean age 11.4 yrs, range 7–
16 yrs) at the onset of cutaneous symptoms. Data for
each case are listed in Table 1. Seven (88%) patients
experienced cutaneous symptoms before a formal
diagnosis of CD was made, although GI symptoms
were variably present at the time of evaluation (n = 6
[75%]). Two patients (25%) presented without any GI
symptoms and were subsequently suspected to have
MCD without gastrointestinal CD. Cutaneous find-
ings included penile (n = 7[88%]), scrotal (n = 7
[88%]), or perianal swelling (n = 4[50%]). GI symp-
toms throughout the follow-up period included diar-
rhea (n = 2[25%]), constipation (n = 3[38%]), hema
tochezia (n = 4[50%]), anal fissures (n = 4[50%]), and
anal skin tags (n = 2[25%]). A skin biopsy specimen
was obtained in five of the eight cases, and all were
compatible with MCD. Three patients declined cuta-
neous biopsy. Two of the three patients were diagnosed
with biopsy-proven gastrointestinal CD. The third
patient had a negative colonoscopy, but he experienced
genital edema, hematochezia, and constipation and
was treated empirically for CD. The cutaneous clinical
presentation was consistent with genital MCD in all
patients.
Patients were evaluated in the departments of
pediatrics (n = 7[88%]), gastroenterology (n = 8
[100%]), dermatology (n = 8[100%]), and urology
(n = 7[88%]) and by lymphedema specialists (n = 3
[38%]). Pediatricians were typically first to evaluate
these patients (n = 6[75%]), and patients were most
often first referred to a urologist for specialist care
(n = 4[50%]). One international patient with MCD
TABLE 1. Data for Eight Boys With Genital Swelling and CD
Known
Age, history
yrs of CD Findings at presentation
12 No Asymptomatic, isolated
penile and scrotal swelling
without adverse GI
symptoms
16 No 1-yr history of frequent
bowel movements,
hematochezia with
subsequent perianal and
scrotal swelling
16 Yes Diagnosed with intestinal
CD 1 yr before onset of
scrotal swelling with prior,
concurrent, and
subsequent history of anal
fissures, loose stools, and
abdominal cramping
8 No Penile and scrotal swelling
without adverse GI
symptoms
8 No Penile swelling with history
of perianal skin tags and
preceding, concurrent, and
subsequent episodes of
scant hematochezia and
constipation
11 No Marked penile, perianal,
and perineal swelling with
subsequent episodes of
hematochezia and fecal
incontinence
Biopsy findings Treatment according to result
Duration of
Cutaneous Gastrointestinal No improvement Improvement follow-up, mos
Consistent with cutaneous Consistent with Cephalexin, desonide Scrotal swelling 10
CD and negative for CD ointment, topical dramatically improved
microorganisms (scrotum) tacrolimus, infliximab with ciprofloxacin, but
infusions penile swelling was
persistent
Consistent with cutaneous Consistent with Azathioprine, mesalamine Azathioprine, mesalamine 1
CD and negative for CD (insufficient follow-up) (insufficient follow-up)
microorganisms (perianal
region)
Consistent with cutaneous Consistent with Prednisone and mesalamine Infliximab and azathioprine 30
CD and negative for CD improved GI symptoms, combined significantly
microorganisms (scrotum) but genital MCD improved scrotal swelling
worsened; doxycycline and and intestinal CD;
manual lymph massage sporadic, correlating
techniques provided no cutaneous and GI flares
benefit continued between
infliximab infusions
Consistent with cutaneous No biopsy Prednisone, antihistamines Near-total improvement in 4
CD and negative for specimen scrotal swelling with
174 Pediatric Dermatology Vol. 33 No. 2 March/April 2016
microorganisms obtained desonide ointment, but
(scrotum) swelling relapsed after
cessation; further topical
corticosteroids prescribed
without further follow-up
None Biopsy results Prednisone Infliximab infusions 11
negative for CD empirically prescribed with
modest improvement of
erythema and acute
inflammation associated
with genital MCD;
redundant tissue and
swelling of scrotal skin
treated with compression;
intermittent constipation
continues despite therapy
None Consistent with Prednisone, 6- Initial improvement of 78
CD mercaptopurine, topical intestinal CD and scrotal
tacrolimus swelling but persistent
penile swelling with
infliximab infusions;
adalimumab was given
because of lack of
sustained intestinal
response and adverse
effects of infliximab;
TABLE 1. Continued

Known Biopsy findings Treatment according to result

Age, history Duration of
yrs of CD Findings at presentation Cutaneous Gastrointestinal No improvement Improvement follow-up, mos

genital symptoms best

13 No Scrotal and penile swelling
with concurrent
alternating episodes of
diarrhea and constipation
7 No Scrotal and penile swelling
with preceding and
concurrent constipation
CD, Crohn’s disease; GI, gastrointestinal; MCD, metastatic Crohn’s disease; TNF-a, tumor necrosis factor alpha.
None Consistent with
Consistent with cutaneous Biopsy specimens
CD; negative for
microorganisms (base of
penis)
Topical tacrolimus
CD
Topical tacrolimus with
negative for CD plans to start TNF-a
inhibitor (insufficient
follow-up)
controlled when
underlying intestinal CD
was quiescent; nearly
complete improvement in
genital swelling obtained
with methotrexate and
adalimumab combination
therapy
Modest improvement in 15
scrotal swelling and
resolution of GI symptoms
with adalimumab and
prednisone; cutaneous
flares decreased,
lymphedema persisted,
remission of GI symptoms
sustained with
subcutaneous
methotrexate and
infliximab infusions
Topical tacrolimus with 1
plans to start TNF-a
inhibitor (insufficient
follow-up)
Barrick et al: Penile and Scrotal Swelling as Metastatic Crohn Disease
175
176 Pediatric Dermatology Vol. 33 No. 2 March/April 2016
was lost to follow-up, and in one patient, genital
MCD was diagnosed just before this report; response
to treatment was not available in these patients. All
patients were prescribed an average of 3.4 medications
(topical and systemic) for the management of their
gastrointestinal CD and MCD, which were often
treated concurrently. Dermatologists most frequently
prescribed topical corticosteroids (n = 2, 50%
response) and calcineurin inhibitors (n = 4, 0%
response); one patient who was prescribed a topical
calcineurin inhibitor has had insufficient time for
assessment of response. Four of five patients (80%)
found clinical benefit of MCD from systemic tumor
necrosis factor alpha (TNF-a) inhibitors, but results
were variable, unpredictable, and often not long-
lasting. Two of the five patients later experienced
lasting benefit from systemic TNF-a inhibitor and
methotrexate combination therapy.
DISCUSSION
Genital MCD in boys is a rare clinical manifestation
of CD. Our findings highlight the importance of early
suspicion for this entity and multidisciplinary care for
evaluation and treatment. Similar to our findings, a
recent single case report with literature review of boys
with penile and scrotal MCD reported cutaneous
symptom onset preceding the diagnosis of CD in 71%
of cases (n = 17; mean age 9.7 yrs) (3). This finding is
in contrast to that in adults; a previous review
reported that 82% of adults with genital MCD had
known CD (4).
The current series evaluated only boys, but vulvar
MCD has been reported in girls (5). In a recent review
of the literature, 15 of 19 girls (79%) with MCD had
labial or vulvar swelling and 9 of 15 (60%) had no
adverse GI symptoms at presentation (6). Childhood-
onset CD has a male predominance and is known to
progress rapidly with more extensive involvement
than in adults and girls (7). Therefore, prompt
recognition of genital edema may be beneficial for
early diagnosis and treatment of CD.
The differential diagnosis for penile or scrotal
edema is broad and has been described previously
(Table 2) (8). Skin biopsy may be helpful for estab-
lishing the diagnosis. Biopsy site selection often
depends upon patient involvement but should include
sufficient sampling of the dermis. In cases in which
scrotal and penile swelling were present, we preferred
obtaining the biopsy from the scrotum to prevent
biopsy site manipulation during urination, scar
formation, and injury of underlying tissue.
Histopathologic findings are not specific and may be
TABLE 2. Differential Diagnosis of Acute and Chronic
Genital Swelling (8)
Acute genital swelling Chronic genital swelling
Allergic contact dermatitis Congenital lymphatic obstruction
Angioedema Sarcoidosis
Hair tourniquet Mycobacterial infections
Herpes simplex virus Pyoderma gangrenosum
Gonorrhea Actinomycosis
Chlamydia Lymphogranuloma venereum
Other sexually transmitted Granuloma inguinale
infections
Balanoposthitis Recurrent erysipelas
Peritonitis Pelvic neoplasms
Parental fluid overload Filariasis
Idiopathic scrotal edema Foreign body reaction
Metastatic Crohn’s disease
subtle. Therefore the pathologist should be alerted to
the clinical suspicion of CD. Typical histopathologic
findings of MCD include noncaseating granuloma-
tous inflammation involving the papillary and
reticular dermis, and the subcutaneous fat may be
involved (1) (Fig. 1B, C), but the granulomas may be
small, focal, and intermixed with surrounding lym-
phoplasmacytic inflammation and therefore may be
easily overlooked if attention is not paid to the clinical
suspicion of CD. Granulomatous lymphangitis is
often observed with secondary obstruction and
destruction of lymphatic channels, which probably
causes the resultant genital swelling. Other causes of
granulomatous inflammation, including infection,
must be excluded.
Therapy described in a prior review of the literature
(n = 17) predominantly consisted of oral prednisone
therapy (n = 7[41%]), oral metronidazole (n = 6
[35%]), and circumcision (n = 5[29%]) (3). Although
genital swelling improved early in a few cases, no
lasting resolution was obtained. In our patient pop-
ulation and those previously described, genital MCD
frequently relapsed (3). No patients from our institu-
tion underwent circumcision for redundant penile
tissue and swelling, but this therapeutic strategy was
used in five patients described in the literature, four
(80%) of whom had complete resolution of penile
swelling (9–12).
In patients from our series and prior case reports,
the symptoms of genital MCD were not necessarily
associated with activity of the underlying intestinal
CD. In our cohort, the therapeutic response of genital
MCD and intestinal CD most often improved with
systemic TNF-a inhibitors, although relapse was
common. Combination therapy with methotrexate
and systemic TNF-a inhibitors was helpful in two
patients. It is possible that this combination therapy
may decrease the formation of anti-TNF-a antibodies
 Barrick et al: Penile and Scrotal Swelling as Metastatic Crohn Disease
and increase clinical efficacy. (13) Topical treatment
alone was usually insufficient. Treatment of the
underlying CD was most helpful in this series.
Approximately 25 cases of genital MCD in boys
younger than 18 years have been described in the
literature. Our series adds an additional eight patients
and is the largest case series of genital MCD in boys
reported. Although the differential diagnosis for penile
or scrotal edema is broad, MCD must be considered.
ACKNOWLEDGMENTS
This study was supported financially by the Mayo
Clinic Department of Dermatology.
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