Behcet’s disease without oral ulcers presenting with erythema nodosum and deep venous thrombosis

Introduction

Behcet’s disease (BD) is a rare systemic inflammatory disease of unknown aetiology. ¹ Although the commonest presentation is with oral ulcers, with or without genital ulcers, about 2% of patients can present without oral ulcers. ² We report a young man with erythema nodosum, deep venous thrombosis and a history of genital ulcers, without oral ulcers. Although the 1990 International Study Group (ISG) criteria ³ for diagnosis of BD mandate the presence of oral ulcers, the new International Criteria for Behcet’s Disease (ICBD) criteria does not. ⁴ This case highlights the need to consider BD in the differential diagnosis of a patient with deep vein thrombosis (DVT) and skin lesions.

Case report

A 17-year-old boy presented with recurrent erythematous nodular lesions on both legs for 5 months, intermittent fever for 3 months and left lower limb swelling for 3 days. He had three episodes of erythematous tender nodules on the extensor surface of the legs, each time lasting for 2–3 weeks, healing with hyperpigmentation without ulceration or scarring (consistent with erythema nodosum). In addition, he reported intermittent fever to 39℃ for the past 3 months, without chills or rigors and without any localising symptoms. Over 3 days, he developed a sudden onset of painful swelling involving the entire left lower limb below the groin. He also reported a scrotal ulcer for the previous 15 days and a similar ulcer 3 months before. He had no weight loss, night sweats, loss of appetite, oral ulcers, swellings anywhere in the body, neither cough, abdominal swelling, acneiform rash, joint pain, altered sensorium nor headache. There was no past history of similar leg swelling, stroke or thrombosis, nor family history to suggest a hypercoagulable state. Examination revealed hyperpigmented macules on the extensor surfaces of the legs consistent with healed erythema nodosum. The left lower limb (Figure 1) was diffusely swollen and tender. There was a shallow scrotal ulcer (1 × 1 cm) with an erythematous border with healthy granulation tissue at its base (Figure 2). The remainder of the general physical and systemic examination was unremarkable. OPEN IN VIEWER

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Figure 2.

Scrotal ulcer.

Venous Doppler revealed thrombosis of bilateral femoral, external iliac and common iliac veins. The haemoglobin level was 94 g/L (normocytic normochromic), total leucocyte count 11.9 × 10⁹/L (neutrophils 72%, lymphocytes 28%), platelet count 362 × 10⁹/L. Renal and liver function tests were normal. He had markedly elevated acute phase reactants ([ESR, 30 mm/h; C-reactive protein, 203 mg/L [normal <6 mg/L]). Coagulation profile was normal. IgM and IgG anticardiolipin antibodies, anti-β2GPI antibody and lupus anti-coagulant were negative. No evidence of malignancy was found on computed tomography of the chest and abdomen. The pathergy test was negative: this test refers to a hyper-reactivity to trauma, and is relatively specific for BD, with sensitivity around 70%. It can also be positive in pyoderma gangrenosum and Sweet’s syndrome. It is elicited by pricking the skin with a sterile needle on the flexor aspect of the forearm to a depth in the range of 3–5 mm. The test is read at 48 h, and a positive test is indicated by presence of either a papule or pustule at the site of injection, surrounded by an erythematous halo. ⁵ It is considered a variant of the Koebner phenomenon. ⁵

The unusual pairing of erythema nodosum with DVT along with recurrent genital ulcers led us to consider BD as the diagnosis. Even in the absence of oral ulcers, the diagnosis of BD as per ICBD criteria was tenable, especially in the absence of a plausible alternative. Other differential diagnoses which could readily be excluded were inflammatory bowel disease and malignancy.

Treatment was started with 1 mg/kg of prednisolone, gradually tapered to 0.15 mg/kg over 4 months. Anticoagulants (heparin followed by warfarin) were given for 6 months and then stopped. Mycophenolate mofetil was added for maintenance immunosuppression. A recurrence of erythema nodosum necessitated addition of colchicine. At follow-up after 6 months, the left lower limb swelling had completely resolved with no recurrence of venous thrombosis. A follow-up Doppler study showed partial canalization of the involved vessels. The scrotal ulcer had healed.

Discussion

Our patient fulfilled the diagnostic criteria of BD as per ICBD. Numerous diagnostic criteria have been proposed for BD. The most commonly used are the 1990 ISG criteria, which mandates the presence of oral ulcers with any two of the following: recurrent genital ulceration, eye lesion (anterior or posterior uveitis), skin lesions (erythema nodosum, pseudofolliculitis, papulopustular lesions, acneiform nodules) and a positive pathergy test. The ICBD criteria were proposed to increase sensitivity, and provide a weighted score for the various manifestations of BD. Ocular lesions, oral aphthosis and genital aphthosis are each assigned 2 points, while skin lesions, central nervous system involvement, vascular manifestations and pathergy test score 1 point each. A score of at least 4 points allows classification as BD. A comparative study showed a higher sensitivity of the ICBD criteria (94.8%) against the ISG criteria (85%), with a lower specificity 90.5 versus 96.0%. ⁴ In the absence of oral ulcers, our patient fulfilled the ICBD criteria but not the ISG criteria. As previously mentioned, it is important to note that 1–2% of patients with BD can present without oral ulcers. ²

Venous involvement in BD is more common than arterial; up to 11% patients may have one or more large vessel thrombosis. ⁶ Since pathogenesis of thrombosis is endothelial inflammation, immunosuppression is warranted to prevent further DVT. Long-term anti-coagulation is controversial. ⁷ Inflammatory venous thrombi rarely embolise due to their tendency to stick to the endothelium. Retrospective data suggest decreased risk of recurrence of venous thrombosis in patients with BD treated with immunosuppressants. ⁷ We decided to add anticoagulants during the initial 6 months in view of the extensive venous thrombosis with renal vein involvement. Although there are no randomised control trials on the subject, most rheumatologists prefer oral anti-coagulation for the initial 6 months. ⁸

This case reiterates the need to consider BD even in absence of oral ulcers. Timely diagnosis enabled institution of appropriate therapy and a favourable outcome.