Abstract

Crohn's disease is a chronic relapsing, granulomatous, and inflammatory bowel disorder. Variable extra-intestinal manifestations may occur, which include erythema nodosum, erythema multiforme, pyoderma gangrenosum, and other non-specific skin lesions. Here, we present a case of metastatic penile Crohn's disease without scrotal involvement, which was initially approached as a balanoposthitis with penile cellulitis, and completely treated with infliximab infusion in a short time.

Introduction

Crohn's disease (CD) is a chronic relapsing, granulomatous, inflammatory bowel disorder that can affect the gastrointestinal tract from mouth to anus.1 Clinical manifestations of CD are highly variable, with significant diversity in disease phenotypes.2 Cutaneous manifestations may occur as non-specific lesions, including erythema nodosum, erythema multiforme and pyoderma gangrenosum, and these lesions must be distinguished from skin lesions with the characteristic histological pattern of CD.3 We report a case of metastatic penile CD (PCD) that was initially approached as a balanoposthitis with penile cellulitis and completely treated with infliximab infusion.

Case report

A 15-year-old boy visited the emergency room complaining of a 12-day history of a tender and swollen penis without trauma history. The patient had concurrently been suffering from 4–5 episodes of bloody diarrhea per day and yellowish penile discharge. The patient had been diagnosed with CD 2 years previously and was being treated with azathiopurine and mesalazine. Six months ago, the patient had received treatment for a perianal abscess, consisting of incision and drainage.

The patient's body temperature was 39.7 °C and other vital signs were unremarkable. On initial physical examination, erythematous swollen penile shaft with tenderness and discharge was observed but there was no scrotal edema. Anal examination revealed an indolent fistula at the 4 o'clock direction. Laboratory findings showed marked leukocytosis (23,120/μL, neutrophiles 82.1%) and elevated C-reactive protein (10.57 mg/dL), which suggested an acute infection. Penile Doppler sonography revealed cellulitis with a presumed small abscess in the superficial fascia of the penis (Fig. 1 A). Cultures of urine and penile discharge were performed and systemic intravenous antibiotics (metronidazol + cefotaxime) were started. After 10 days of treatment with the antibiotics, the penile lesion became ulcerative with scant penile discharge (Fig. 1 B). Initial urine and penile discharge culture did not isolate any clinically relevant organisms. Pediatric urology consultation recommended circumcision if the penile lesion did not improve. Along with the penile symptoms, the patient's pediatric Crohn's disease activity index4(PCDAI) was 37.5, and mild fever and bloody diarrhea were sustained, which suggested uncontrolled moderate-to-severe CD. An abdominopelvic computed tomography scan was performed, which revealed diffusely enhanced wall thickening from rectum to the mid-transverse colon with suspicious skipped lesions and diffuse soft tissue swelling with multifocal air density at the dorsum of the penis. A punch biopsy was performed on the penile lesion and histology showed dermal ulcer with granulomatous inflammation consistent with cutaneous manifestations of CD (Fig. 1 C). Intravenous infliximab was administered and both gastrointestinal symptoms and penile lesion were soon ameliorated after two infusions at a 2-week interval. The penile ulceration completely resolved after three infusions at 2 months.

Discussion

CD, an idiopathic granulomatous disorder, commonly presents in adolescents and young adults. Insidious symptoms include diarrhea, hematochezia, weight loss, anorexia, abdominal pain, and perianal lesions. However, extraintestinal manifestations are less frequent than anorectal involvement.5 Metastatic PCD is a rare complication of CD that has been infrequently reported in the literature.6 According to another report,7 there was only a single case of metastatic CD of the penis in the 207 cases of CD in one hospital. In our 10-year experience at the Samsung Medical Center, Seoul, South Korea, this is the first case of 150 pediatric CD patients. In 1997, Chiba et al.8 reported a case of adult PCD and reviewed seven previously reported cases of adult metastatic PCD. Lehrnbecher9 and Gonzalez Gomez10 each reported a case of PCD in Germany and Spain, respectively. Recently, Lane3 reported two pediatric cases in the United Kingdom. In an appreciable number of cases, penile or scrotal lesions are the first symptom of CD.3,5,9,1114 The aforementioned pediatric cases involved both the penis and the scrotum. However, in the present case, no definite scrotal lesion was observed, which made diagnosis difficult.

Currently, no confirmed standard treatment for penile metastatic CD exists. Therefore, the conventional medical and surgical treatments for CD have been performed. The treatment responses are variable and usually take time (Table 1). Among the cases of PCD, there has been 1 case reported as using infliximab for systemic CD treatment,15 however, the case demonstrated symptomatic improvement of PCD itself from using infliximab, and is the very first one to our knowledge. In our case antibiotic therapy was partially effective. But, the penile ulcer completely resolved after infliximab infusions. Infliximab is a tumor necrosis factor monoclonal antibody that is currently widely-used in moderate-to-severe pediatric CD control, since receiving Food and Drug Administration approval for pediatric use in May 2006.16 Considering that a penile lesion is an extraintestinal manifestation of CD, it is plausible that a penile ulcer can concomitantly resolve as gastrointestinal CD activity decreases. In the present case, PCD rapidly responded to infliximab, compared with previous conventional treatments.

Conflict of interest statement

All authors report no conflicts.

Acknowledgment

There was no grant support for this article.

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Figure 1

(A) Ultrasound imaging shows penile superficial fascial layer thickening with heterogeneous echogenicity, which suggests cellulitis. Ill-defined anechoic portion in the soft tissue swelling (white arrow) could be a small abscess. (B) After 10 days of antibiotic treatment, penile lesion became ulcerative with scant penile discharge. (C) A punch biopsy on the penile lesion was performed and histology showed dermal ulcer with granulomatous inflammation consistent with cutaneous manifestations of Crohn's disease.

Figure 1

(A) Ultrasound imaging shows penile superficial fascial layer thickening with heterogeneous echogenicity, which suggests cellulitis. Ill-defined anechoic portion in the soft tissue swelling (white arrow) could be a small abscess. (B) After 10 days of antibiotic treatment, penile lesion became ulcerative with scant penile discharge. (C) A punch biopsy on the penile lesion was performed and histology showed dermal ulcer with granulomatous inflammation consistent with cutaneous manifestations of Crohn's disease.

Table 1

Clinical features of metastatic Crohn's disease involving penis with/without scrotum involvement.

Authors Age (years) Crohn's disease diagnosis Perineal Crohn's disease 
Penile lesion Scrotal lesion Treatment Response 
Lehrnbecher, T.9 Diagnosis at the same time Erythematous plaque Scrotal swelling Prednisone/metronidazole 2 weeks 
→ Azathioprine added → Relapse after 2 years 
Goh, M.1 35 No information Subcoronal ulcer None Topical steroid 6 months 
Corazza, M.17 37 18 Penile shaft doral side ulcer Superficial ulcers Methyl prednisolone/metronidazole After surgery 
→ A surgical plastic reconstructive operation 
Martinez-Salamanca, J. I.18 27 1 year before Subcoronal non-healing ulcer Scrotal ulcer Doxycycline 6 months 
→ Mesalamine/prednisone/metronidazole 
Aviles-Izquierdo, J. A.11 27 Diagnosis at the same time Penile dorsal ulcer Scrotal ulcer Prednisone/metronidazole/5-aminosalicylic acid A few months 
Zelhof, B.19 22 7 years before penile lesion Painless penile swelling Left hemiscrotal involvement Oral steroid/topical Elocon oint 18 months 
→ Azathioprine 
Gonzalez-Guerra, E12 26 Diagnosis at the same time Inflammation and deformity Present Deflazacort Not fully improved 
Rajpara, S. M.14 73 Diagnosis at the same time Penile and perianal ulcers None Oral antibiotics/methotrexate/cyclosporine/acyclovir/prednisolone/topical clobetasol propionate 0.05% ointment 9-month hospitalization 
→ Oral thalidomide/minocycline and topical tacrolimus 
→ Excision and reconstruction operation 
Saha, M.13 27 Diagnosis at the same time Edema with inguinal lymphadenopathy None Oral antibiotics After surgery 
→ Mesalazine 
→ Circumcision 
Kaess, H.15 23 16 Penile edema Present Antibiotics/prednisonea 10 days 
→ Relapse 3 months after 
Lopez, V.20 39 13 years before penile lesion Penile edema Present Oral prednisone A year 
→ Relapse after tapering 
→ Topical tacrolimus 
Lane, V. A.3 Diagnosis at the same time Penile edema Present Oral cephalosporine/metronidazol 6 months 
→ Topical tacrolimus → Relapse 3 years after 
→ Circumcision 
No information Erythematous edema Present Antihistamine/flucloxacillin No information 
→ Azathioprine 
Vint, R21 25 24 Penile edema None Azathioprine/steroid One year 
→ Cyclosporine 
→ Circumcision/slazopyrin, intra lesional steroid injection 
24 12 Gross penile edema Present Triamcinolone injection for 8 months 8 months 
→ Circumcision 
Present case 15 2 years before penile lesion Penile swelling None Azathioprine/mesalazine/metronidazol/cefotaxim One month 
→ Infliximab (2 weeks after infliximab) 
Authors Age (years) Crohn's disease diagnosis Perineal Crohn's disease 
Penile lesion Scrotal lesion Treatment Response 
Lehrnbecher, T.9 Diagnosis at the same time Erythematous plaque Scrotal swelling Prednisone/metronidazole 2 weeks 
→ Azathioprine added → Relapse after 2 years 
Goh, M.1 35 No information Subcoronal ulcer None Topical steroid 6 months 
Corazza, M.17 37 18 Penile shaft doral side ulcer Superficial ulcers Methyl prednisolone/metronidazole After surgery 
→ A surgical plastic reconstructive operation 
Martinez-Salamanca, J. I.18 27 1 year before Subcoronal non-healing ulcer Scrotal ulcer Doxycycline 6 months 
→ Mesalamine/prednisone/metronidazole 
Aviles-Izquierdo, J. A.11 27 Diagnosis at the same time Penile dorsal ulcer Scrotal ulcer Prednisone/metronidazole/5-aminosalicylic acid A few months 
Zelhof, B.19 22 7 years before penile lesion Painless penile swelling Left hemiscrotal involvement Oral steroid/topical Elocon oint 18 months 
→ Azathioprine 
Gonzalez-Guerra, E12 26 Diagnosis at the same time Inflammation and deformity Present Deflazacort Not fully improved 
Rajpara, S. M.14 73 Diagnosis at the same time Penile and perianal ulcers None Oral antibiotics/methotrexate/cyclosporine/acyclovir/prednisolone/topical clobetasol propionate 0.05% ointment 9-month hospitalization 
→ Oral thalidomide/minocycline and topical tacrolimus 
→ Excision and reconstruction operation 
Saha, M.13 27 Diagnosis at the same time Edema with inguinal lymphadenopathy None Oral antibiotics After surgery 
→ Mesalazine 
→ Circumcision 
Kaess, H.15 23 16 Penile edema Present Antibiotics/prednisonea 10 days 
→ Relapse 3 months after 
Lopez, V.20 39 13 years before penile lesion Penile edema Present Oral prednisone A year 
→ Relapse after tapering 
→ Topical tacrolimus 
Lane, V. A.3 Diagnosis at the same time Penile edema Present Oral cephalosporine/metronidazol 6 months 
→ Topical tacrolimus → Relapse 3 years after 
→ Circumcision 
No information Erythematous edema Present Antihistamine/flucloxacillin No information 
→ Azathioprine 
Vint, R21 25 24 Penile edema None Azathioprine/steroid One year 
→ Cyclosporine 
→ Circumcision/slazopyrin, intra lesional steroid injection 
24 12 Gross penile edema Present Triamcinolone injection for 8 months 8 months 
→ Circumcision 
Present case 15 2 years before penile lesion Penile swelling None Azathioprine/mesalazine/metronidazol/cefotaxim One month 
→ Infliximab (2 weeks after infliximab) 

a Penile Crohn's disease has been treated successfully with antibiotics and prednisone, but this patient received infliximab treatment twice for systemic Crohn's disease control, one year before and one month after penile involvement.