Clinically differentiating Behcet's syndrome from Crohn's disease

Abstract

Lesson

We aim to highlight the diagnostic challenges in differentiating Behcet's syndrome from Crohn's disease, in patients presenting with overlapping clinical features, highlighting the importance of comprehensive clinical evaluation for appropriate management and prognostication.

Case presentation

A 56-year-old Caucasian woman presented with a 15-year history of recurrent oral ulcers, inflammatory arthritis, a history of cerebrovascular accident (CVA) involving the right globus pallidus, skin lesions (suspected to be pseudofolliculitis), and occasional episodes of bloody diarrhoea. Of note, the patient denied experiencing episodes of uveitis or skin pathergy. Over the years, the patient received various diagnoses from various providers, including inflammatory bowel disease and Behcet's syndrome. Initially treated with cyclophosphamide and later azathioprine, she achieved clinical remission in 2020 and discontinued her medications due to sustained improvement.

In 2023, the patient presented to the clinic with complaints of bloody diarrhoea and leg swelling. She was hospitalised for severe gastrointestinal bleeding and a lower extremity venous thrombosis confirmed on ultrasound duplex scanning. On examination, the patient had unilateral leg swelling with a temperature differential. Notably, she had stasis dermatitis of her bilateral lower extremities, but she did not have synovitis on joint examination, conjunctival erythema, or tenderness to palpation on abdominal examination. Colonoscopy revealed nonspecific inflammation, raising concern for inflammatory bowel disease once again. After detailed multidisciplinary discussions between rheumatology, haematology, and gastroenterology, it was concluded that her constellation of symptoms favoured a diagnosis of Behcet's syndrome over Crohn's disease. Given the compelling clinical picture, HLA B51 was not tested. She was restarted on immunosuppression with azathioprine as well as apixaban for deep vein thrombosis (DVT). At her follow-up clinic visit six weeks post-discharge, she reported doing well, and thus, the planned addition of apremilast therapy was not implemented.

Discussion

Behcet's syndrome is a chronic, inflammatory disorder that affects multiple organ systems and is characterised by diverse clinical symptoms. In contrast, Crohn's disease primarily involves inflammation of the gastrointestinal system and may present with various extra-intestinal symptoms. Due to their pleomorphic presentations and overlapping features, distinguishing between the two diseases can be challenging. It is hypothesised that Behcet's syndrome is an autoinflammatory disease with a strong acute-phase response. Similarly, the pathogenesis of Crohn's disease is likely driven by the innate immune system. ¹

There are many diagnostic criteria sets for Behcet's syndrome, but no pathognomonic laboratory tests exist. Behcet's syndrome is typically diagnosed based on the presence of recurrent oral ulcers plus any two of the following: genital ulcers, eye inflammation, skin lesions, or a positive pathergy test. Similarly, multiple sets of diagnostic criteria have been proposed for Crohn's disease. Crohn's disease is typically diagnosed based on clinical symptoms such as abdominal pain, diarrhoea, or weight loss, supported by imaging studies showing characteristic bowel wall thickening, and confirmed by endoscopic findings of ulcerations or inflammation in the gastrointestinal tract and biopsy. ¹

As shown in Table 1, nearly all patients with Behcet's syndrome suffer from recurrent oral ulcers (approximately 100%) compared to less than 10% of patients with Crohn's Disease. ¹ Vascular manifestations occur in 30% of cases of Behcet's syndrome, with 87% of vascular complications being DVT. ² Roughly 0.314% of patients with Crohn's disease develop DVT. ³ Inflammation in the gastrointestinal tract is a defining diagnostic criterion for Crohn's disease, but the rates of enteritis in Behcet's syndrome vary from as low as 3% to as high as 60%. ⁴ Biopsy can aid in diagnosing both conditions: granulomas found in mucosal biopsy samples are indicative of Crohn's disease, whereas the presence of vasculitis suggests Behcet's syndrome. ¹ Inflammatory arthritis is more common in patients with Behcet's syndrome (30% to 57%) than in those with Crohn's disease (2% to 24.7%). ¹ Uveitis occurs more frequently in Behcet's syndrome (pan-uveitis and posterior uveitis), while Crohn's disease patients can have anterior uveitis, however, they are more prone to developing episcleritis or conjunctivitis. ¹

Table 1.

Comparison of the prevalence of various clinical manifestations in Behcet's syndrome and Crohn's disease.^1–4

Feature	Behcet's syndrome	Crohn's disease
Oral ulcers	∼100%	<10%
Deep venous thrombosis (DVT)	Vascular manifestations occur in 30% of cases, with DVT being the most common (87%)	0.314%
Intestinal inflammation/enteritis	3% to 60%	100%
Inflammatory arthritis	30% to 57%	2% to 24.7%
Neurologic disorders (i.e. basal ganglia lesions)	9.3%	3%
Uveitis	57% to 69% (pan-uveitis and posterior uveitis are seen more commonly)	<10% (anterior uveitis is usually seen)
Mucosal biopsy	Vasculitis	Granulomas

A notable and rare presentation in this case was the basal ganglia lesion observed on magnetic resonance imaging. Neurological findings, including basal ganglia lesions, are observed in less than 10% of Behcet's syndrome patients and approximately 3% of Crohn's disease patients.^2,5 Basal ganglia lesions are amongst the most commonly seen in Behcet's patients with CVA.^4,6 However, most central nervous system strokes in Behcet's syndrome, when they occur, are located in the basal ganglia.

Patients with Behcet's syndrome, particularly those with intestinal involvement, are at risk of being misdiagnosed with inflammatory bowel disease. While treatment can be similar for both conditions, it is not always the case, especially in resistant cases. Accurate diagnosis is crucial as it also impacts prognosis.

Conclusion

In this case, the patient's presentation posed a diagnostic dilemma between Behcet's syndrome and Crohn's disease. The overlap of symptoms, such as gastrointestinal inflammation and vascular complications, complicated the differential diagnosis (see Table 1). Table 1 will help clinicians in better understanding the similarities and differences between the two and being more cognizant of these differences when treating similar patients. This case underscores the importance of a thorough clinical evaluation, including interdisciplinary and comprehensive diagnostic approaches, to guide appropriate management decisions in complex autoimmune disorders.