This article elucidates the diagnostic and therapeutic challenges, as well as the implications of rare extraintestinal manifestations, through a three-year longitudinal follow-up of a 19-year-old female with metastatic Crohn’s disease (MCD) co-occurring with vulvar Crohn’s disease (VCD). The patient exhibited asynchronous progression of intestinal symptoms and vulvar lesions. Initial treatment with mesalazine proved ineffective; however, significant improvement was observed following infliximab therapy (5-10 mg/kg) in combination with surgical intervention for anal fistulas, as evidenced by normalization of inflammatory markers (CRP/ESR/HGB). Despite this, VCD persisted, underscoring the limitations of anti-TNFα therapy in modulating the gut-skin axis. Key insights include: ? VCD, as a rare manifestation independent of intestinal activity, necessitates accurate diagnosis via multimodal imaging and histopathological biopsy to prevent misclassification; ? The integration of biologics with surgical interventions can effectively manage complex fistulas and inflammation but requires personalized long-term strategies; ? Investigating the immune-microbial interactions within the skin-gut axis may pave the way for novel targeted therapies for MCD; ? Holistic physical and psychological management is essential for optimizing outcomes in chronic conditions. This case provides valuable empirical data for guiding clinical decision-making and advancing mechanistic understanding of MCD.

• Metastatic Crohn’s disease; Vulvar Crohn’s disease; Intestine-skin axis; Infliximab; Anal fistula surgery.

Zhao R (2026) A 3-Year Evolution of Metastatic Crohn’s Disease-Related Vulvar Crohn’s Disease. JSM Gastroenterol Hepatol 13(1): 1136.

Crohn’s disease (CD) is a chronic nonspecific inflammatory disease of the intestine. The cutaneous manifestations of CD outside the intestine can be categorized as follows: (1) CD-specific lesions, where skin lesions exhibit histological features similar to those of the underlying gastrointestinal lesions. (2)CD-reactive lesions, which are inflammatory in nature and typically occur in association with gastrointestinal diseases but display histological characteristics distinct from those of gastrointestinal lesions. (3)CD-related skin lesions, which arise as a result of sequelae caused by human leukocyte antigen (HLA) or chronic inflammation. (4) Treatment related skin lesions, which emerge as a consequence of CD therapy and may overlap with the aforementioned three types, making them challenging to differentiate. A patient may present with varying cutaneous manifestations at different stages of the disease. Vulvar Crohn’s Disease (VCD) represents a rare extraintestinal manifestation of CD and constitutes a form of Metastatic Crohn’s Disease (MCD), which can occur independently or concurrently with gastrointestinal Crohn’s Disease (GCD). This article comprehensively documents the 3-years dynamic evolution of a 19-year-old female patient who has VCD associated with MCD, aiming to enhance understanding of the rare dermatological manifestations of CD and provide insights into clinical management strategies.

First stage: In April 2022, the patient began experiencing diarrhea with mucoid stools occurring approximately 3–5 times per day, the symptoms were not considered serious. By November 2022, due to worsening diarrhea, the patient sought medical attention at our outpatient clinic. A colonoscopy revealed multiple longitudinal and fissure-like ulcers in the Transverse colon, descending colon, sigmoid colon. Biopsy results indicated active colitis characterized by local cryptitis, crypt abscesses, and focal granulomas that were suspicious for CD. An anal ultrasound demonstrated changes in the rectal and anal mucosa as well as submucosal layers. Laboratory tests showed significantly elevated levels of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Tests for tuberculosis (T-spot), Clostridium difficile, Epstein-Barr virus, and cytomegalovirus yielded no significant abnormalities. The patient was impression diagnosed with CD. Initially, the patient agreed only to oral treatment with mesalamine, bifidobacteria, and Kangfuxin liquid (a traditional Chinese medicine); however, these interventions failed to significantly alleviate the diarrhea symptoms (Figure 1).

Figure 1 First Stage: Biopsy results indicated active colitis characterized by local cryptitis, crypt abscesses, and focal granulomas that were suspicious for CD.

Second Stage: The patient went to Peking Union Medical College Hospital for medical treatment an abdominal enhanced CT scan December 30, 2022revealed a thickened colonic wall and narrowed intestinal lumen, with enhancement observed in the enhanced imaging small intestinal CTE January 5, 2023 demonstrated segmental thickening of both the ileum and colon accompanied by mucosal enhancement. Additionally, comb-like changes were noted in the mesentery of the small intestine, suggestive of inflammatory bowel disease (specifically CD). The patient was subsequently diagnosed with CD. In January 2023, the patient experienced an exacerbation characterized by diarrhea accompanied by fever reaching up to 38.5°C, bright red bloody stool estimated at approximately 800 ml, and episodes of syncope. Following treatment with corticosteroids and fluid replacement at a local hospital, gastrointestinal bleeding subsided; however, she was admitted to our facility for further management. Over the past six months, there has been a significant weight loss of 15 kg. The patient has no history of hypertension or diabetes mellitus; there is also no record indicating coronary heart disease or drug allergies. Furthermore, there is no documented history of tuberculosis or hepatitis. Temperature: 36.5°C; Pulse: 80 beats/minute; Respiratory Rate: 18 breaths/min; Blood Pressure: 120/80 mmHg. The patient presents with poor nutritional status characterized by pallor and mucosal congestion as well as edema around both the anus and perineum. The abdomen is soft upon palpation without tenderness or palpable masses present; bowel sounds are normal. Hemoglobin (HGB) level at 79 g/L; Platelet count (PLT) at579×10^9/L. Albumin level measured at 30.6 g/L; serum potassium recorded at 3.21 mmol/L. Antinuclear antibody (ANA) test positive at a dilution ratio of 1:100; CRP level found to be 3.13 mg/L. Skin biopsy findings: Site 1 Right Labia: Mild hyperplasia observed in epidermis alongside vascular hyperplasia and dilation within dermis layers exhibiting moderate lymphocytic infiltration surrounding widened collagen fiber spaces containing significant mucoid material deposition—alcian blue staining recommended for further analysis. Site 2 Clitoral glans skin lesion: Notable irregular hyperplasia coupled with thickening in epidermis along loose arrangement patterns seen in superficial dermal collagen fibers alongside vascular hyperplasia dilation presenting moderate lymphocytic infiltration nearby. The Department of Pathology at the Institute of Dermatology, Chinese Academy of Medical Sciences conducted a consultation. The findings indicate mild hyperplasia in the epidermal spinous cell layer, slight edema in the superficial dermis, and scattered infiltration of inflammatory cells surrounding blood vessels. Furthermore, focal infiltration of inflammatory cells is noted in the deep dermis, predominantly comprising lymphocytes. Based on clinical considerations and diagnostic results, vascular edema—whether inflammatory or resulting from venous obstruction—should be taken into account; it is essential to rule out early-stage cutaneous CD. Clinical diagnosis: CD (A2L3B1) CDAI21; VCD; anemia; hypokalemia; hypoalbuminemia. Initiate treatment with Infliximab biologics (5mg/kg), provide enteral nutrition support, correct electrolyte imbalances, regulate gut microbiota with bifidobacteria, and promote mucosal repair with Kangfuxin liquid (Figure 2).

Figure 2 Second Stage: An abdominal enhanced CT scan December 30, 2022 revealed a thickened colonic wall and narrowed intestinal lumen, with enhancement.

The third stage: The patient’s diarrhea was alleviated following infliximab treatment, and enteral nutrition was well tolerated; however, perineal swelling persisted without relief. It is recommended to continue the infliximab biologic therapy. The patient subsequently sought further treatment at the Second Hospital of Zhejiang University on March 27, 2023: during the enteroscopy procedure there, only a straight second endoscopy was performed based on the condition observed. A finer endoscope (0.9 cm in diameter) was selected for insertion. Upon advancing the endoscope approximately 20 cm from the anus, an increased amount of mucus was noted. After irrigation, deeper longitudinal ulcers were identified along with congested, swollen, and brittle mucosa, also swelling around the anal canal. The colonoscopy had to be terminated due to significant pain experienced by the patient. Diagnosis: colon ulcer with slight swelling and narrowing of the anal canal. An anal MRI indicated the same day, an anal fistula characterized by a single internal opening located 20 mm from the anal opening; it exhibited a six-point fistula or sinus shape with bifurcated sphincter penetration through both internal and external sphincters measuring approximately 3 mm in width at its external orifice alongside evidence of perianal abscesses. Imaging diagnosis confirmed an anal fistula classified according to St James’ Classification as Grade 2 - intersphincteric fistula with associated abscess or secondary sinus tract. Treatment involved administering infliximab at a dosage of 10 mg/ kg for intensive management purposes. Re-examination after one month Number of internal openings of anal fistula: single, Position of inner mouth: 30mm away from anal opening, 9 o’clock, Flaccid path or sinus path: strip, Sphincter penetration: the internal sphincter penetrates and runs between the internal and external sphincters, Lane or lane width and diameter: 5mm,External orifice of anal fistula: None, Perianal abscess: None, Diagnosis: Anal fistula (St James’ Classification: Grade 2 - intersphincteric fistula with secondary sinus tract); Attached: extensive inflammatory lesions in perineum, rectum and anal canal, and multiple inflammatory enlarged lymph nodes in the groin. Note: Widespread inflammatory lesions in the perineum, rectum, and anal canal, multiple inflamed lymph nodes in the inguinal region (Figure 3).

Figure 3 Third Stage: MRI Scan revealing one internal opening associated with an anal fistula located at approximately nine o’clock position.

Fourth Stage: The patient exhibits no abdominal symptoms, and no significant swelling is observed in either the perineal or perianal regions, both CRP, HGB and ESR levels have been restored to within the normal range, January 2024 Gastroscopy Diagnosis: Chronic gastritis (Miyamoto-Takasaki classification CO), with no suspicion of Helicobacter pylori infection. Colonoscopy reached the terminal ileum where the ileocecal valve displayed a lip-like appearance and an appendix fossa was identified. Scattered white scar formations were evident throughout the colon, alongside polypoid hyperplasia observed in the descending colon. Slight congestion of sigmoid colon mucosa was noted; however, other segments of intestinal mucosa appeared normal with no traces of blood found within the intestinal cavity. The endoscopic procedure progressed smoothly without any complications. Boston Colonoscopy Cleanliness Score: 7, Diagnosis: Findings consistent with CD treatment (SES CD score 0) based on medical history. Small Intestinal CT Enhancement: Adequate filling was observed across small intestine segments; local or segmental thickening and enhancement were noted particularly in groups 4, 5, and 6 of the small intestine with group 4-5 exhibiting more pronounced changes. No significant dilation or narrowing of the lumen was observed, and no definite new biological or abnormal contents were seen within the lumen. No abnormal thickening of the mesentery, omentum, or peritoneum was noted. No enlarged lymph nodes were seen in the retroperitoneal or pelvic regions. No ascites was present in the abdomen or pelvis. Additional findings: Multiple low-density shadows in the liver, please refer to liver MRI for further evaluation. Accessory spleen. Diagnosis: Thickening and enhancement of the small intestine segments 4-6, consistent with CD. Anorectal MRI: Anal fistula: One internal opening, located at 9 o’clock, fistula or sinus tract course: No fistula tract or sinus tract penetration of the sphincter, external diameter of the fistula tract: 2mm. No external opening of the fistula. No perianal abscess. Diagnosis: Significant improvement in the anal fistula compared to (2023-04-22). Improvement in inflammatory lesions of the perineum and anal canal compared to before. The patient was originally treated with sequential biologic agents due to increased perianal pain and rectal stricture and underwent an anal fistula surgery on March 28, 2024 (Figure 4).

Figure 4 Fourth Stage: The patient exhibits no abdominal symptoms, and no significant swelling is observed in either the perineal or perianal regions, both CRP, HGB and ESR levels have been restored to within the normal range.

Stage Five: Anal MRI (2025-01-08) revealed one internal opening associated with an anal fistula located at approximately nine o’clock position without evidence indicating penetration into either sphincter by a potential sinus track—the external diameter measured two millimeters without any visible external openings related to this condition as well as absence confirmed regarding any perianal abscesses. Small intestine enhanced MRI (2025 01-09) reveals some poorly filled segments within small intestine along with local/segmental thickening observed in intestinal wall situated at middle/lower abdomen exhibiting slightly elevated DWI signals that enhance significantly post-enhancement.” Revised Text: “The examination revealed a more pronounced involvement in groups four through five. There were no significant dilations nor narrowings detected within the lumen, nor were any definitive new biological materials or abnormal contents identified therein. Additionally, there was no notable thickening observed in either mesenteric tissue, omentum, or peritoneum structures. Enlarged lymph nodes were not evident within retroperitoneal or pelvic areas while ascites remained absent from both abdominal and pelvic cavities. Diagnosis: The imaging indicated thickening and enhancement across segments four through six of the small intestine consistent with a diagnosis of CD. Gastroscopy Diagnosis: Chronic gastritis (Moriyama Takasaki classification CO). Colonoscope advanced to the terminal ileum where a lip-shaped ileocecal valve was identified alongside a cecal fossa. Multiple aphthous ulcers were present in both the rectum and sigmoid colon, accompanied by scattered white scar formations; polypoid hyperplasia was noted in the descending colon. The remaining intestinal mucosa appeared normal, with no traces of blood detected within the intestinal cavity. The endoscopy procedure proceeded smoothly without any complications (Boston score 8). Diagnosis: CD (SES-CD1 score); Infliximab administered at a dosage of 400 mg for a patient weighing 55 kg (Figure 5).

Figure 5 Fifth Stage: Anal MRI (2025-01-08) revealed one internal opening associated with an anal fistula located at approximately nine o’clock position.

For Metastatic Crohn’s Disease (MCD), the main manifestations are abscess, fistula, ulcer or nodule, and the skin lesions can appear anywhere but in the continuous part of the digestive tract (cutaneous CD), mostly involving the end of the lower limbs and vulnerable to friction, while the face and genitals are rare [1,2]. MCD does not parallel enteropathic activity [3,4]. This is similar to our current medical case: her skin lesions precede the exacerbation of intestinal symptoms in GCD and follow the alleviation of these intestinal symptoms. The MCDs pertinent to the differential diagnosis of this medical record primarily encompass VCD and genital lymphedema. VCD is characterized by a granulomatous lesion that directly involves the vulva and is attributable to CD. Confirmation of this condition necessitates a biopsy [5,6]. In contrast, genital lymphedema represents a chronic swelling resulting from lymphatic reflux disorder; although it may be associated with CD, it is not exclusive to this condition [7]. There are notable differences between these two entities regarding their pathological mechanisms, clinical manifestations, and treatment strategies. A thorough analysis and comprehensive evaluation should be carried out by considering this patient’s symptoms, pathological characteristics, the specific categorization of treatment reactions, and the clinical doctor’s insights documented in this medical case.

VCD is rare in both adults and children. A study on adults (n=22) showed that 64% of VCD patients also had GCD, with 65% of these patients experiencing GCD before VCD; while 36% of patients had isolated VCD [5]. Pediatric cases: A systematic review (2000-2017) included 22 cases of VCD in children, all of which were case reports or small sample reports, highlighting its rarity [6]. The clinical manifestations of VCD are diverse and non specific, often leading to misdiagnosis as infections or inflammatory diseases. The concept of the Gut-Skin Axis has revealed the complex interactions between the gut and skin through immunological, microbiological, metabolic, and neuroendocrine pathways, which are particularly crucial in the development of MCD [8,9]. Characteristics of adult patients: Common symptoms include labial fissures, ulcers, and scars, which are more pronounced in patients with isolated VCD. Treatment options are also limited, including the local or systemic application of corticosteroids, immunomodulators, biologics, and other agents, but their efficacy is often uncertain [5,10,11]. Due to its diverse clinical manifestations, the actual incidence may be underestimated [12,13], leading to misdiagnosis and underreporting [8,7]. Case reports include patients of all age groups. Younger individuals seem to be more prone to the disease, which may reflect the age distribution of CD (Crohn’s disease), although the incidence of MCD in children is lower than in adults [4].

Even if GCD achieves remission through anti-TNFα therapy, vascular CD (VCD) may still persist. Regular assessment of vulvar lesions and gastrointestinal symptoms is needed to adjust treatment plans [5,11]. VCD can lead to impairments in patients’ body image and contribute to mental health issues; therefore, it is essential to address patients’ psychological and social well-being as part of the treatment process. This patient did not experience the above-mentioned problems after receiving supportive care and showed a high level of cooperation with continuous follow-up.

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