We report a patient with metastatic Crohn’s disease (MCD) who presented with vulvar swelling preceding the diagnosis of gastrointestinal disease. Vulvar involvement of Crohn’s disease (CD) is rare and difficult to diagnose, especially when it precedes the onset of overt gastrointestinal symptoms. In our case, the diagnosis was enigmatic because no radiological and laboratory examinations gave a clue for diagnosis. Here, we suggest two diagnostic clues which may help early diagnosis of vulvar MCD after reviewing reported cases of MCD in children whose vulvar swelling or edema preceded gastrointestinal symptoms in the English-language published work.
A 10-year-old girl presented to our dermatological clinic with a 1-month history of unilateral, non-tender, vulvar swelling. Before visiting our clinic, she had been treated with empirical antibiotics for 2 weeks at local pediatric and gynecological clinics under the impression of infectious disease but her vulvar swelling had not improved. She and her parent denied any trauma, sexual abuse or a history of infectious disease. She had no notable medical history and did not have any systemic symptom. Physical examination revealed non-tender, erythematous swelling on the left vulva (Fig. 1a,b) and small skin tags on the anal orifice (Fig. 1c). Height and weight percentiles were normal for her age. Laboratory test results were within normal range except for a slightly increased erythrocyte sedimentation rate of 18 mm/h (reference range 0–15 mm/h). Magnetic resonance imaging of the pelvis showed focally enhancing subcutaneous tissue on the anterior portion of the left labia majora which primarily suggested focal cellulitis (Fig. 1d). We prescribed cefprozil 250 mg/day for 10 days under the impression of infection of the vulva.
Ten days later, the lesion did not improve, so we decided to perform skin biopsy. The histopathological finding revealed non-caseating granulomatous inflammation throughout the dermis. The granulomas were composed of epithelioid histiocytes, a few giant cells and lymphocytes (Fig. 1e). Neither special stains and cultures for bacteria, fungus and mycobacterium nor polarizing light microscopy for foreign bodies were positive. Chest X-ray and tuberculin skin test were also normal. Even though the patient did not have overt abdominal symptom, diagnostic colonoscopy was performed to rule out CD. It disclosed multiple aphthous ulcers ranging from rectosigmoid colon to ascending colon with ileal involvement and biopsy specimens of the colon revealed granulomatous inflammation, consistent with CD. Treatment was commenced with oral corticosteroid and metronidazole with marked improvement in 2 months’ treatment. During one and half year follow up, several diarrheal episodes occurred but her symptom was generally tolerable.
Crohn’s disease is a chronic relapsing, multisystemic, inflammatory disorder of uncertain etiology, characterized by non-caseating granulomatous inflammation that can affect any part of the gastrointestinal tract from mouth to anus. Twenty-two to forty-four percent of CD patients present four types of cutaneous manifestations: (i) direct extension from involved bowel leading to perioral or perianal diseases; (ii) MCD; (iii) nutritionally-associated skin lesions; and (iv) reactive lesions like pyoderma gangrenosum and erythema nodosum.1
Metastatic Crohn’s disease is defined as non-caseating, granulomatous skin lesions that are not contiguous to the gastrointestinal tract. It usually presents as solitary or multiple papules, nodules or plaques that are red to purple or violaceous and commonly involves the limbs, especially legs, vulva, penis and face.2 MCD on the vulva in children is rare and difficult to diagnose. Furthermore, if a dermatological manifestation precedes gastrointestinal symptoms, the diagnosis becomes enigmatic. Only several cases of which vulvar swelling or edema antedates the clinical appearance of intestinal CD in children have been reported in the English-language published work.3–9
The diseases which can cause vulvar swelling include pregnancy, hidradenitis suppurativa, sexual abuse, tumor, vascular malformation, lymphedema, genital cheilitis granulomatosa, factitial dermatitis, contact dermatitis, CD, mastocytosis and various infectious diseases. For differential diagnosis of vulvar swelling, prudent history taking and physical examinations are important. Laboratory and radiological examinations could also give some diagnostic clues. When clinical diagnosis cannot be made easily, skin biopsy is necessary. MCD is distinguished histologically by granulomatous inflammation. However, because various conditions can also cause granulomatous inflammation, diverse investigations are necessary.7 After common infectious or inflammatory diseases are excluded, performing diagnostic colonoscopy is warranted to check for CD. In our case, as the dermatological manifestation antedated the onset of typical intestinal symptoms, the diagnosis was difficult because no laboratory and radiological examinations gave a hint for MCD.
After reviewing reported MCD cases in children including the present case whose vulvar swelling or edema preceded gastrointestinal symptoms of Crohn’s disease (Table 1), we suggest two diagnostic characteristics which may help early diagnosis of MCD on the vulva. First, if the vulvar swelling is non-tender or painless, MCD rather than infectious diseases should be included in the differential diagnosis. MCD represents another “great imitator” and it resembles many other dermatoses.1 Most of the reported cases have been clinically misdiagnosed as cellulitis, erysipelas, lichenoid eruptions and various sexually transmitted diseases1 and vulvar swelling as a manifestation of CD commonly misdiagnosed as cellulitis or sexual abuse.10 So, non-tenderness or painlessness in MCD could be an important clinical feature in the differential diagnosis with infectious diseases. Many reported vulvar CD were painless, especially when occurring in children.4–6,8–11 In Table 1, pain was not observed in six out of nine cases, and in the remaining three cases, vulvar symptom was not described. We speculate that those three cases would have been painless because the authors would have probably stated the symptom if there was pain or tenderness. In addition, many reported MCD cases in male patients presenting penile and scrotal swelling or edema did not accompany pain.12–19 In perianal CD, Alexander-Williams et al.20 previously suggested that the relative lack of pain, multiplicity of lesions and edema of skin tags can be important clinical indicators if perianal CD occurred as the first manifestation. We do not think that every vulvar CD shows lack of pain but we assume that most genital swelling in MCD at its first manifestation without secondary lesions such as fissure, erosion, ulcer or abscess would be painless or non-tender. We suggest that following MCD cases need to address the presence of tenderness or pain because such a clinical feature can be a useful information for clinicians. Second, if a patient has perianal lesions such as skin tags, anal fissures, ulcers, fistulas, perianal abscesses and anorectal strictures with vulvar swelling, MCD should be considered. In our case, anal skin tags were small and asymptomatic, and were not of clinical interest in the first place. Presence of perianal disease was noted on presentation in 81% of pediatric patients with MCD.10 Therefore, if a patient presents vulvar swelling, careful examination of the anus as well as the vulva is needed.
|Reference||Age (years)||Presentation||Initial diagnosis||Vulvar symptom||Concomitant perianal lesion||Vulvar pathology|
|Mountain3||14||Edema and inflammation of labia||Tuberculosis†||N/D||Anal fistula||Chronic inflammatory changes without tubercules or caseation|
|Lally et al.4||8||Vulvar erythema and edema||Contact dermatitis, candidiasis and sexual abuse||Non-tender||Anal fistula||Noncaseating granulomatous inflammation|
|Werlin et al.5||8||Erythematous, firm, unilateral, labial hypertrophy||Foreign body reaction||Non-tender||Skin tags||Non-caseating granulomatous inflammation|
|Guerrieri et al.6||11||Swelling of right labium majus||Vulvitis granulomatosa||Non-tender||Anal tags||Non-necrotizing granulomatous inflammation|
|Ploysangam et al.7||6||Erythema and edema of the labial majora||Cellulitis||N/D||Skin tags and fissures with anal hemorrhoids||Granulomatous inflammation|
|Ploysangam et al.7||10||Swelling of lower lip, vulvar swelling and perivaginal abscess||N/D||N/D||None||Granulomatous inflammation|
|Porzionato et al.8||7||Swelling and induration of the labia majora||Sexual abuse||Genital itching||Perianal fissures and skin tags||Non-caseating granulomatous inflammation|
|Pinna et al.9||10||Erythematous, firm tumescence of left labial majora||Infectious disease||Asymptomatic||Rose-grayish vegetations||Non-caseating granulomatous inflammation|
|Present case||10||Left vulvar swelling||Cellulitis||Non-tender||Skin tags||Non-caseating granulomatous inflammation|
Because vulvar CD is very rare, there is no consistent treatment for genital CD. The most effective treatment for cutaneous CD seems to be oral metronidazole, and other treatments such as systemic corticosteroids, topical corticosteroids, azathioprine, cyclosporine, sulfasalazine and tetracycline have been used sucessfully.1
Metastatic Crohn’s disease usually postdates or coincides with gastrointestinal symptoms, but in 25% of cases, dermatological lesions precede the onset of overt intestinal symptoms.1 Without intestinal manifestations, the diagnosis is extremely difficult. So we suggest that if vulvar swelling or edema is non-tender or painless and accompanies perianal diseases, CD should be taken into consideration. For definite diagnosis, skin biopsy and colonoscopy need to be performed. Vulvar CD has been a diagnostic challenge not only for dermatologists but also for gastroenterologists, gynecologists, pediatricians and urologists. Delayed diagnosis of CD can result in many complications such as malnutrition, delayed pubertal development, intestinal obstruction, hemorrhage and emotional issues. In this context, our suggestion for early diagnosis has clinical significance.