CUSTOM DERMATOLOGY SEARCH:
Current Therapy in BehÁetís Disease
T. Sakane, MD, PhD and Mitsuhiro Takeno MD, PhD
BehÁetís disease (BD) is an inflammatory disorder, characterized by recurrent oral aphthous ulcers, genital ulcers, uveitis, and skin lesions1. BD patients cluster along the ancient Silk-Road, which extends from eastern Asia to the Mediterranean basin. The prevalence of BD in the countries along the Silk-Road ranges from 13.5 to 380 cases per 100,000, whereas the prevalence in western countries is less than one per 100,0001. This unique geographic distribution suggests possible genetic and environmental factors in the development of BD. It is well established that susceptibility of BD is strongly associated with the HLA-B51 allele2. There is also accumulating evidence that microbial infections trigger cross-reactive autoimmune responses, leading to overt BD. Thus, BD is neither a hereditary disease nor an infectious disease, but is multifactorial.
Diagnosis of BehÁetís Disease
Because BD does not have any specific symptoms and laboratory findings, the diagnosis is made on the basis of the criteria proposed by the International Study Group for BehÁetís Disease in 1990. These criteria require recurrent oral ulceration as an essential symptom, plus any two or more of the following symptoms: genital ulceration, eye lesions, skin lesions, and a positive pathergy test. The pathergy test is performed by piercing a sterile needle subcutaneously into the forearm. It is judged as positive when the puncture leaves an aseptic erythematous nodule or pustule of more than 2mm in diameter after 24-48 hours. The differential diagnosis includes chronic oral aphthosis, herpes simplex virus infection, Sweetís syndrome and HLA-B27-related syndromes such as ankylosing spondylitis. Analysis of HLAphenotypes and the measurement of serum IgD levels may help to make a diagnosis (patients with active BD often have elevated levels of serum IgD)1.
Oral ulceration is usually an initial symptom that is seen in all patients during the course of the disease. This symptom may be a genetic predisposition, because it frequently precedes other manifestations and is often seen in some of the patientís family members. Painful oral ulcers appear in the gingiva, tongue, buccal, and labial mucosal membranes. The typical lesion is round, with a sharp, erythematous border and the surface is covered with a yellowish pseudomembrane. The lesions heal within 10 days and do not leave scars.
Therapeutic priority is given to the treatment of vital organ lesions, which requires high dose corticosteroids and/or immunosuppressants, and sometimes needs surgical intervention. Treatment of ocular lesions requires more careful consideration than that of the mucocutaneous symptoms.
Mucocutaneous lesions, especially genital ulcers, must be kept clean to avoid contaminated secondary infection. Oral and genital ulcers are treated with topical corticosteroids (i.e., triamcinalone acetonide, and corticosteroids in combination with antibiotics). Another topical approach would be the use of a tetracycline solution, which is made by dissolving in the contents of a 250mg capsule in 5ml of water, for aphthous lesions.
Colchicine 1-1.5mg/day has beneficial effects for the mucocutaneous symptoms, presumably by inhibiting neutrophil functions. Systemic corticosteroids are prescribed for erythema nodosum refractory to colchicine. Furthermore, the following drugs have been documented to be effective for treating mucocutaneous lesions: thalidomide1,3, dapsone1, pentoxifylline1, azathioprine1, interferon-alpha1,4, and rebamipide5. However, the mucocutaneous symptoms of BD are self-limiting, and overtreatment should be avoided.
Colchicine is first prescribed to prevent both anterior and posterior uveitis. Topical mydriatics and corticosteroid drops are given for the treatment of anterior uveitis. Topical injection, in some cases with systemic administration, of corticosteroids is used for the acute attacks of posterior uveitis. Cyclosporin A becomes the first line therapy for uveitis1,6, while conventional cytotoxic agents such as azathioprine, chlorambucil and cyclophosphamide are other alternatives1. Recent trials using interferon-alpha (IFN-alpha) to treat BD have produced encouraging results1,4.
Involvement of Vital Organs
The treatments for inflammatory bowel diseases are also applicable for the gastrointestinal lesions found in BD. Sulfasalazine and corticosteroids are the principal drugs. High doses of corticosteroids with cytotoxic immunosuppressants are administered for neurological involvement. A combination therapy of corticosteroids and cytotoxic agents, supplemented with anticoagulants and antiplatelet agents is used for vascular lesions.
Local treatment with corticosteroids is satisfactory in most of the mucocutaneous lesions. Colchicine is useful to prevent the attacks of individual symptoms. Overtreatment should be avoided for mucocutaneous lesions unless they are complicated by more serious symptoms.
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Last modified: Thursday, 20-Feb-2014 18:03:54 MST