Abstracts
Crohn's disease is a multisystem chronic granulomatous inflammatory disease that primarily affects the gastrointestinal tract. In the majority of the cases, the cutaneous manifestations follow the intestinal disease, but occasionally dermatological lesions are the inaugural event and may constitute the only sign of the disease. Vulvoperineal involvement is rare, may precede bowel symptoms by months to years and may go unrecognized. Due to the paucity of reports of Crohn's disease at this location and in the absence of randomized trials, there are no standard treatments for the cutaneous disease. We describe the case of a 47 year-old woman with vulvoperineal Crohn's disease without digestive involvement, that was successfully managed with metronidazole.
Crohn disease; Metronidazole; Therapeutics
A doença de Crohn é uma doença granulomatosa multissistêmica inflamatória crónica que afecta primariamente o tracto gastrointestinal. Na maioria dos casos, as manifestações cutâneas sucedem a doença intestinal, mas, ocasionalmente, as lesões dermatológicas são o primeiro evento e podem constituir o único sinal da doença. O envolvimento vulvoperineal é raro, pode preceder os sintomas intestinais em meses ou anos, e pode passar despercebido. Devido à escassez de relatos de doença de Crohn com esta localização e na ausência de ensaios clínicos randomizados, não há nenhum tratamento padrão para a doença cutânea. Descrevemos um caso de uma mulher de 47 anos com doença de Crohn vulvoperineal sem envolvimento digestivo, que foi tratada com sucesso com metronidazol.
Doença de Crohn; Metronidazol; Terapêutica
INTRODUCTION
Crohn's disease is a multisystem chronic granulomatous inflammatory disease that primarily affects the gastrointestinal tract. In the majority of cases, cutaneous manifestations follow the intestinal disease, but occasionally dermatological lesions are the inaugural event and may constitute the only sign of the disease. Vulvoperineal involvement is rare, may precede bowel symptoms by months to years and may go unrecognized. Due to the paucity of reports of Crohn's disease at this location and in the absence of randomized trials, there are no standard treatments for the cutaneous disease. Numerous therapies (including surgery, use of antibiotics and immunosuppression) have been used with variable results. There are only anecdotal reports that support the use of metronidazole. We describe a case of a 47 year-old woman with vulvoperineal Crohn's disease without digestive involvement that was successfully managed with metronidazole and without side effects. Oral metronidazole seems to be effective in the treatment of vulvoperineal Crohn's disease and cutaneous flares also respond rapidly to repeated treatment.
CASE REPORT
A 47-year-old woman presented for evaluation of multiple persistent painful vulvoperineal lesions that had appeared in the last 5 years. She went on several antibiotic courses without any improvement. She denied bowel complaints or weight loss. Her past medical history was only remarkable for hypertension. On physical examination, an exuberant inflammation of the vulva with aftoid ulcers of the labia minor and majora, and linear ulcerations in the inguinocrural folds were observed. A deep linear fissure above the clitoris and a "knife-cut" ulcer with sharp margins on the buttocks fold were also present (Figure 1). A skin biopsy revealed an ulcerated epidermis with a fistulous tract and aspects of chronic inflammation with lymphocytes, hystiocytes and multinucleated giant cells in a non- caseating granulomatous pattern on the dermis (Figure 2). Fungal and mycobacterial elements were not detected by histology or in tissue culture. Laboratory investigations were normal except for C-reactive protein of 41 mg/dl (<5). Syphilis, HIV serologies and Mantoux test were negative. PCR testing for herpes simplex virus was negative. Chest X-ray showed no abnormalities. Based on the clinical and histological findings a vulvoperineal cutaneous Crohn's disease (CD) diagnosis was made. The patient was referred to gastroenterology for evaluation of bowel involvement. Endoscopic studies of the digestive tract and biopsies from the ileum, colon and rectum showed no abnormalities, so that a diagnosis of vulvoperineal cutaneous CD without digestive involvement was assumed. The patient went on daily metronidazole (1000 mg) and ciprofloxacin (1000 mg) with a striking improvement. Antibiotherapy was discontinued at 3 months and azathioprine (50 mg daily) was introduced. However, the condition worsened and metronidazole (1000 mg daily) was added to azathioprine and marked improvement was observed after 12 days. At 2 months of combined therapy (metronidazole 1000 mg plus azathioprine 150 mg daily) sustained clinical improvement was observed (Figure 3).
H&E (10x): ulcerated epidermis with a fistulous tract (left). PAS (40x): aspects of chronic inflammation in a granulomatous pattern in the dermis (right)
DISCUSSION
In CD the mucocutaneous lesions usually follow the intestinal disease and exceptionally
occur prior to bowel involvement.11. Eames T, Landthaler M, Karrer S. Crohn's disease: an important
differential diagnosis of granulomatous skin diseases. Eur J Dermatol.
2009;19:360-4. In the latter
case, a high index of suspicion may be required to reach the accurate diagnosis. Most of
the lesions are a result of direct extension of the intestinal disease (perineal
abscesses and fistula) and more rarely they occur in a noncontiguous extraintestinal
spread (metastatic CD). Genitalia involvement in CD is rare.22. Andreani SM, Ratnasingham K, Dang HH, Gravante G, Giordano P. Crohn's
disease of the vulva. Int J Surg. 2010;8:2-5.,33. Madnani NA, Desai D, Gandhi N, Khan KJ. Isolated Crohn's disease of
the vulva. Indian J Dermatol Venereol Leprol. 2011;77:342-4. Andreani
et al, reported that 25% of vulvar CD did not have any previous
intestinal symptoms and patients had not been diagnosed as having CD.22. Andreani SM, Ratnasingham K, Dang HH, Gravante G, Giordano P. Crohn's
disease of the vulva. Int J Surg. 2010;8:2-5. Vulvar swelling, erythema and pain that evolve to
vulvar hypertrophy, ulceration and abscesses are the typical clinical picture.
"Knifecut" ulcers (as in our case) are almost pathognomonic of CD, although they have
been described in cutaneous tuberculosis and herpetic infections in immunocompromised
patients.33. Madnani NA, Desai D, Gandhi N, Khan KJ. Isolated Crohn's disease of
the vulva. Indian J Dermatol Venereol Leprol. 2011;77:342-4. The histological examination
characteristically shows non-caseating granulomas. The differential diagnoses include
other granulomatous diseases that can cause vulvar ulceration such as sarcoidosis,
tuberculosis, fungal infections, lymphogranuloma venereum, granuloma inguinale and
actinomycosis. Sometimes pyoderma gangrenosum can clinically mimic cutaneous Crohn's
disease. Ruling out infections usually requires bacteriological and mycological workup.
Due to a paucity of reports with this topography the treatment remains
nonstandardized.44. Khaled A, Ezzine-Sebai N, Fazaa B, Zeglaoui F, Zermani R, Kamoun MR.
Vulvoperineal Crohn's disease: response to metronidazole. Skinmed.
2010;8:240-1. Several medical treatments
for cutaneous disease have been proposed with variable results and include: topical,
intralesional and systemic corticosteroids, sulfasalazine, azathioprine, cyclosporine,
methotrexate, thalidomide, metronidazole, infliximab, adalimumab and surgical excision.
Only few small studies and anecdotal reports have evaluated the use of
metronidazole.22. Andreani SM, Ratnasingham K, Dang HH, Gravante G, Giordano P. Crohn's
disease of the vulva. Int J Surg. 2010;8:2-5.,33. Madnani NA, Desai D, Gandhi N, Khan KJ. Isolated Crohn's disease of
the vulva. Indian J Dermatol Venereol Leprol. 2011;77:342-4.,44. Khaled A, Ezzine-Sebai N, Fazaa B, Zeglaoui F, Zermani R, Kamoun MR.
Vulvoperineal Crohn's disease: response to metronidazole. Skinmed.
2010;8:240-1.
5. Abide JM. Metastatic Crohn disease: clearance with metronidazole. J
Am Acad Dermatol. 2011;64:448-9.
6. Thukral C, Travassos WJ, Peppercorn MA. The role of antibiotics in
inflammatory bowel disease. Curr Treat Options Gastroenterol.
2005;8:223-8.-77. Fernandes MD, Fernandes HD, Deliza R, Pires CE, Bortoncello AC.
Metastatic Crohn's disease without intestinal clinical manifestation. An Bras
Dermatol. 2009;84:651-4. As supported by our
case, it seems to be effective with resolution of almost all the lesions. In combination
with oral corticotherapy a success rate of 87.5% has been reported.22. Andreani SM, Ratnasingham K, Dang HH, Gravante G, Giordano P. Crohn's
disease of the vulva. Int J Surg. 2010;8:2-5. Its efficacy is probably due to its anti-inflammatory,
antibacterial and immunosuppressive action.44. Khaled A, Ezzine-Sebai N, Fazaa B, Zeglaoui F, Zermani R, Kamoun MR.
Vulvoperineal Crohn's disease: response to metronidazole. Skinmed.
2010;8:240-1. In
the study of Brandt LJ et al, the lesions of all 26 patients with
perineal CD cleared, and an optimal dose of 20 mg/kg/day for 12 to 36 months was
required.88. Brandt LJ, Bernstein LH, Boley SJ, Frank MS. Metronidazole therapy
for perineal Crohn's disease: a follow-up study. Gastroenterology.
1982;83:383-7. The tapering of this dose often
leads to recurrences, however cutaneous lesions promptly respond to repeated treatment
with the drug.55. Abide JM. Metastatic Crohn disease: clearance with metronidazole. J
Am Acad Dermatol. 2011;64:448-9.,88. Brandt LJ, Bernstein LH, Boley SJ, Frank MS. Metronidazole therapy
for perineal Crohn's disease: a follow-up study. Gastroenterology.
1982;83:383-7. Reversible paresthesia is the major complication reported with
long-term metronidazole therapy.44. Khaled A, Ezzine-Sebai N, Fazaa B, Zeglaoui F, Zermani R, Kamoun MR.
Vulvoperineal Crohn's disease: response to metronidazole. Skinmed.
2010;8:240-1. Minor
complications include a metallic taste and darkening of the urine together with
gastrointestinal upset. In our patient the treatment was well-tolerated without any side
effects. We report an extremely atypical presentation of CD that was successfully
managed with metronidazole with no significant adverse effects. Physicians should be
aware of such presentation as it may precede gastrointestinal involvement and be a cause
of high morbidity if not promptly recognized.
REFERENCES
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1Eames T, Landthaler M, Karrer S. Crohn's disease: an important differential diagnosis of granulomatous skin diseases. Eur J Dermatol. 2009;19:360-4.
-
2Andreani SM, Ratnasingham K, Dang HH, Gravante G, Giordano P. Crohn's disease of the vulva. Int J Surg. 2010;8:2-5.
-
3Madnani NA, Desai D, Gandhi N, Khan KJ. Isolated Crohn's disease of the vulva. Indian J Dermatol Venereol Leprol. 2011;77:342-4.
-
4Khaled A, Ezzine-Sebai N, Fazaa B, Zeglaoui F, Zermani R, Kamoun MR. Vulvoperineal Crohn's disease: response to metronidazole. Skinmed. 2010;8:240-1.
-
5Abide JM. Metastatic Crohn disease: clearance with metronidazole. J Am Acad Dermatol. 2011;64:448-9.
-
6Thukral C, Travassos WJ, Peppercorn MA. The role of antibiotics in inflammatory bowel disease. Curr Treat Options Gastroenterol. 2005;8:223-8.
-
7Fernandes MD, Fernandes HD, Deliza R, Pires CE, Bortoncello AC. Metastatic Crohn's disease without intestinal clinical manifestation. An Bras Dermatol. 2009;84:651-4.
-
8Brandt LJ, Bernstein LH, Boley SJ, Frank MS. Metronidazole therapy for perineal Crohn's disease: a follow-up study. Gastroenterology. 1982;83:383-7.
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* Work performed at the Dermatology Service; Hospital de Santo António - Hospital Center at Porto, E.P.E - Porto, Portugal.
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Financial Support: none
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Conflict of Interests: none
Publication Dates
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Publication in this collection
Nov-Dec 2013
History
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Received
21 Nov 2012 -
Accepted
11 Jan 2013