Erythema Nodosum with Oral and Genital Ulcers

A Case of Behçet's Disease

Abstract

Behçet's disease (BD) is a chronic, relapsing, multisystemic disorder characterized by mucocutaneous, ocular, vascular, and central nervous system manifestations. The clinical spectrum includes oral and genital ulcerations, uveitis, and vascular, neurological, articular, renal, and gastrointestinal manifestations. The etiopathogenesis of the disease remains unknown although genetic predisposition, environmental factors, and immunological abnormalities have been implicated. It usually affects young adults. The case of a 22-year-old female who presented with fever, recurrent oral ulcers, genital ulcers, arthralgia, and erythema nodosum is presented here. A diagnosis of BD based on clinical criteria was made. The patient was treated with colchicine 1 mg/day which had beneficial effects on the reduction in size and recurrence of mucocutaneous ulcers.

INTRODUCTION

Behçet's disease (BD) was described by Hulusi Behçet in 1937 as an inflammatory process of unknown etiology, characterized by recurrent aphthous ulcers, genital ulcers, uveitis, and cutaneous lesions. BD is a chronic, systemic inflammatory disorder at the crossroad between autoimmune and autoinflammatory syndromes.[¹] It is also associated with other less frequent systemic manifestations, such as gastrointestinal, central nervous system, vascular, and joint infections. Cases of BD seem to cluster along the ancient Silk Road, which extends from Eastern Asia to the Mediterranean Basin. The prevalence is 80–370 cases per 100,000 population in Turkey, 10/100,000 in Japan, and 0.6/100,000 in Yorkshire. Only a few cases have been reported from Northern India – possibly the disease has been under-diagnosed. BD occurs mainly between 18 and 40 years. Men are more frequently affected than women. The prevalence of HLA-B5 in North Indians is high. There are few reports of BD from India. Only two major studies from North India and one from South India exist.

The etiopathogenesis seems to be related to an alteration of the immunoregulation set-off by one or various infectious agents in genetically susceptible individuals. HLA-B51 is the most strongly associated known genetic factor to BD but is of no diagnostic value. The diagnosis is made based on the clinical criteria. The specific criteria proposed by the International Study Group for BD specify those recurrent aphthous or herpetiform ulcers observed in a minimum of three episodes during a period of 12 months and two of any of the following manifestations: recurrent genital ulcers (ulcers or genital ulcer scars); joint manifestations; ocular lesions (anterior or posterior uveitis, or presence of cells in the vitreous during ocular examination, or also retinal vasculitis); cutaneous lesions (erythematous nodules, pseudo folliculitis, papulopustular lesions, or acneiform nodules in postadolescent patients not on corticosteroids); and analysis of pathergy test (after 24–48 h).[^2,3] International criteria of classification have been defined with a sensitivity of 85% and specificity of 96%.

Colchicine (1–2 mg/day) has beneficial effects on the mucocutaneous symptoms decreasing the number, size, and recurrence of aphthous ulcers.[⁴] Steroids are the cornerstone of the anti-inflammatory agents administered in case of ocular and/or central nervous system involvement. Immunosuppressive drugs have been shown to be effective in association with corticosteroids. They are prescribed in cases of severe organ involvement. The prognosis is severe due to the ocular, neurological, and arterial involvement.

CASE REPORT

A 22-year-old female with a history of recurrent oral ulcers for 1 year presented with low-grade fever, polyarthralgias, genital ulcers, and painful lesions over shin of both lower limbs of 7 days duration. The oral ulcers were painful and used to heal spontaneously over a period of 1–2 weeks. There was no history of rash elsewhere on the body. Polyarthralgias were not associated with swelling of joints. There were no complaints of photosensitivity or blurring of vision. There were no neurological symptoms. Menstrual and obstetric history was uneventful. On examination, she had stable vitals. There were no lymph nodes palpable on general physical examination. On clinical intraoral examination, a single aphthous ulcer was observed, measuring approximately 0.5–1.2 cm in diameter, with the presence of an erythematous halo and fibrinolytic bed on the buccal mucosa [Figure 1]. There were deep-seated tender nodules with blanchable dusky erythema on the bilateral lower limbs, suggestive of erythema nodosum [Figure 2]. A single superficial nonindurated ulcer of 0.5 cm diameter was noted on the labia minora on genital examination. Rest of the systemic examination was normal.

Figure 1: Oral aphthous ulcer

Figure 2: Erythema nodosum on both lower limbs

Her hemogram was normal. Erythrocyte sedimentation rate was 45 mm/h. C-reactive protein was positive. Renal and liver function tests were normal. Uric acid level was normal. Hepatitis B surface antigen, HIV 1/2, venereal disease research laboratory were nonreactive. Anti-HCV antibody, rheumatoid factor (<12 IU/ml), anti-streptolysin O antibody (<200 IU/ml), and anti-nuclear antibody were negative. HLA-B51 was also negative. Pathergy skin test was done by injecting saline intradermally and was read at 24–48 h as negative. Slit-lamp examination of both the eyes revealed normal anterior and posterior segments and no aqueous flare. X-rays of the chest, elbows, knees, and ankles were normal. A diagnosis of BD was made based on the clinical criteria. The patient was treated with oral colchicine 0.5 mg twice daily and topical ointment for her mucocutaneous symptoms which responded well over a period of 2–3 weeks.

DISCUSSION

BD is primarily a systemic vasculitis syndrome.[^5,6] It is characterized by recurrent episodes of oral and genital ulcers, iritis, and cutaneous lesions. It may lead the patient to blindness and even death due to the complications of systemic manifestations, mainly ophthalmological, neurological, and pulmonary.[⁷]

The mucocutaneous lesions constitute the hallmark of BD. Oral aphthae occur in 98% of cases and are mandatory in the international criteria of classification. Oral ulceration is not specific of BD as it may occur in 30%–40% of the general population. Oral ulcerations may also be associated with HIV, Crohn's disease, lupus, or vitamin deficiencies.

Genital aphthae occur in 60%–65% of cases and are very suggestive of the diagnosis of BD. The most frequent skin manifestations are pseudofolliculitis and erythema nodosum-like lesions. Arthralgia and/or arthritis occur in 45% of cases which is nonerosive. Venous involvement seen in 30% cases should exclude antiphospholipid syndrome or thrombophilia. Neuro-BD observed in 20%–40% of cases [⁸] is sometimes difficult to distinguish from multiple sclerosis or tuberculosis. Pathergy test is positive in about 40%–80% cases.[³] The positivity of HLA-B51 allele is of no diagnostic value. The diagnosis of BD is only supported by clinical criteria that require the exclusion of other diagnoses based on clinical presentation. Due to its broad clinical spectrum, multidisciplinary treatment is important to make an early and efficient diagnosis so as to prevent the aggravation of disease manifestations.

CONCLUSION

The disease occurs in a much milder form in India and is primarily mucocutaneous and arthritic. Only a few cases have been reported from Northern India. These cases occur sporadically [⁹] and can be detected if the index of suspicion is high. Early diagnosis is essential to prevent complications of BD. Treatment of patients with BD is guided by organ involvement. Topical steroids are usually effective for mucocutaneous involvement. Colchicine is an effective and safe therapeutic option for mucocutaneous and joint involvement. Pentoxifylline is effective in reducing the frequency and severity of oral and vaginal ulcers. Cyclosporine and dapsone are alternative treatment for mucocutaneous involvement. Tumor necrosis factor blockers represent a novel regimen of drugs in the treatment of refractory mucocutaneous lesions, severe gastrointestinal or neurological involvement, and ocular disease.

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Conflicts of interest

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