Andreas Altenburg

Epidemiology and clinical manifestations of Adamantiades-Behçet disease in Germany – Current pathogenetic concepts and therapeutic possibilities

© Blackwell Verlag GmbH • www.blackwell.de • 1610-0379/2006/0401-0049 JDDG | 1 2006 (Band 4) Introduction Historical background and nomenclature In his third book of “Epidimion” Hippocrates of Kos (460–377 BC) described a disease with symptoms comparable to the cardinal symptoms of Adamantiades-Behcet disease (ABD): “Many patients had aphthous ulcerations in the mouth. There were numerous purulent genital ulcers, as well as furuncles, which were external and internal, as well as in the groins. There was a watery inflammation of the eye that was chronic and painful as well as growths on the eyelids – external and internal – which impaired eyesight in many patients. (...) There were also larger ecthymata and large herpetic lesions in many patients. “ In 1930 Benediktos Adamantiades (1875–1965), a Greek ophthalmologist, presented a lecture describing findings in an 18-year-old patient, for the first time grouping ocular symptoms, oral aphthae, and genital ulcers together as symptoms of a single clinical entity. He later added vascular involvement as a fourth cardinal symptom and in a review article presented the first classification of the disease by describing its ocular, mucocutaneous, and systemic forms [1]. The chief symptom, which according to Adamantiades was hypopyon, appears at various intervals, causing more or less lasting permanent damage and ultimately resulting in blindness. Hulusi Behcet (1889–1948), a Turkish dermatologist, first described in 1937 patients with recurrent lesions affecting the mouth, genitals, and eyes, adding a catalogue of symptoms including periodontitis, jaw cysts, acneiform skin changes, and erythema nodosum as well as arthralgia. Behcet’s intense work on the disease and his conviction about its autonomous character finally brought this puzzling clinical picture to the attention of the scientific community. CME

Practical aspects of management of recurrent aphthous stomatitis

Treatment of recurrent aphthous stomatitis (RAS) remains, to date, empirical and non‐specific. The main goals of therapy are to minimize pain and functional disabilities as well as decrease inflammatory reactions and frequency of recurrences. Locally, symptomatically acting modalities are the standard treatment in simple cases of RAS. Examples include topical anaesthetics and analgesics, antiseptic and anti‐phlogistic preparations, topical steroids as cream, paste or lotions, antacids like sucralfate, chemically stable tetracycline suspension, medicated toothpaste containing the enzymes amyloglucosidase and glucoseoxidase in addition to the well‐known silver nitrate application. Dietary management supports the treatment. In more severe cases, topical therapies are again very useful in decreasing the healing time but fail to decrease the interval between attacks. Systemic immunomodulatory agents, like colchicine, pentoxifylline, prednisolone, dapsone, levamisol, thalidomide, azathioprine, methotrexate, cyclosporin A, interferon alpha and tumour necrosis factor (TNF) antagonists, are helpful in resistant cases of major RAS or aphthosis with systemic involvement.

The treatment of chronic recurrent oral aphthous ulcers.

BACKGROUND Chronic recurrent oral aphthous ulcers are the most common type of inflammatory efflorescence of the oral mucosa, with a prevalence of 2% to 10% in Caucasian populations. To treat them properly, physicians should know their clinical appearance and course, conditioning factors, underlying causes, and differential diagnosis. METHOD This review is based on pertinent articles that were retrieved by a selective search in PubMed and in the Cochrane Central Register of Controlled Trials. RESULTS Hard, acidic, and salty foods and toothpastes containing sodium lauryl sulfate should be avoided, along with alcohol and carbonated drinks. In Germany, the only drugs that have been approved to treat oral aphthous ulcers are corticosteroids, topical antiseptic/anti-inflammatory agents such as triclosan and diclofenac, and local anesthetics such as lidocaine. Antiseptic agents and local anesthetics should be tried first; if these are ineffective, topical cortico steroids should be used. In severe cases, local measures can be combined with systemic drugs, e.g., colchicine, pentoxifylline, or prednisolone. The efficacy of systemic treatment is debated. Other immunosuppressive agents should be given systemically only for refractory or particularly severe oral aphthous ulcers due to Adamantiades-Behçet disease. CONCLUSION The treatment of chronic recurrent oral aphthous ulcers is symptomatic, mainly with topically applied agents. It is tailored to the severity of the problem in the individual case, i.e., the frequency of ulcers, the intensity of pain, and the responsiveness of the lesions to treatment. Effective treatment relieves pain, lessens functional impairment, and lowers the frequency and severity of recurrences.

Ocular involvement is associated with HLA-B51 in Adamantiades–Behçet's disease

PurposeTo evaluate the association of HLA-B51 and ocular involvement in Adamantiades–Behçets disease.MethodsWe retrospectively analysed all patients with Adamantiades–Behçets disease examined in our Department of Ophthalmology since 1982. All patients fulfilled the criteria of the International Study Group for Behçets disease. We included 140 patients (63 female and 77 male) with a mean follow-up of 6.4 years.ResultsThe mean age at the first manifestation was 23 years; full disease was noted at 32 years. The mean age at the time of eye involvement was 30 years. Most of the patients were of Turkish (n=73) or German (n=34) origin. A total of 56% patients developed eye involvement. Forty-nine out of 76 HLA-B51-positive patients (64.5%) and 26 out of 60 HLA-B51-negative patients (43.3%; P=0.014) developed ocular involvement.ConclusionMore than the half of the patients with Adamantiades–Behçets disease evaluated in our department developed ocular involvement. There was a statistically significantly higher frequency of HLA-B51 in these patients.

[Epidemiology and clinical aspects of Adamantiades-Behçet disease in Gemany. Current data].

Of the 721 documented patients in the German Registry for Adamantiades-Behçet disease (registered charity), 258 were of German and 308 of Turkish descent, along with 30 other countries of origin. The prevalence in Germany is 0.9:100,000. Manifestation of the disease was predominantly in the third decade of life (median age: 26.5 years) and in 10.7% the disease onset was under 16 years of age. The full clinical picture developed on average in 2.9 years (median 3 months). Patients of Turkish descent showed androtopism in contrast to those of German descent (female:male  1.9:1), which was also detected in the whole collective in a ratio of 1.4:1. In 12.4% there was a family history with differences between German and Turkish patients (3.8% versus 14.6%) as well as in patients with disease onset in young and adult age (25.0% versus 7.3%). Most frequent features included oral aphthae (98.5%), cutaneous lesions (81%), genital ulcers (64.7%), ocular manifestations (51.6%), arthritis (52.4%) and positive pathergy test (30.8%). Turkish patients suffered significantly more often from eye manifestations compared with Germans, while in German patients prostatitis/epididymitis and gastrointestinal involvement were more frequently documented. As serious complications arose blindness 6.8%, meningoencephalitis 4.0%, severe arthritis 2.6%, fatal outcome 1.2%, hemoptysis 1.1% and gastrointestinal perforation 0.5%. The HLA-B5 antigen was positive in 58.1% and showed an association with eye manifestations. The relative risk of HLA-B5 positive individuals is high in both Germans (6.57) and Turks (5.81).

Reactive hyperplasias,precancerous and malignant lesions of the oral mucosa

The oral cavity contains many organs and tissues compressed in a small area. Accordingly oral tumors have a wide variety of appearances. Reactive hyper‐plastic lesions include epulis,morsicatio,traumatic ulcer or palatal hyperplasia. These benign lesions must be separated clinically and histologically from precancerous and neoplastic lesions. In leukoplakia,the individual risk can be estimated by clinical signs. Nevertheless histopathology is mandatory because precancerous lesions usually precede or accompany most oral cancers. Amalgam tattoo,oral nevi and melanoacanthoma have to be considered as differential diagnoses of oral melanoma. Accurate clinico‐pathological diagnosis is mandatory to insure appropriate therapy. Oral soft tissue tumors such as Kaposi sarcoma and multiple mucosal neuromas in MEN 2b require interdisciplinary management. Diseases affecting the minor salivary glands which may be encountered by dermatologists include mucocele, necrotizing sialometa‐plasia,and tumors such as pleomorphic adenoma.

Epidemiologie und Klinik des Morbus Adamantiades-Behçet in Deutschland

Of the 721 documented patients in the German Registry for Adamantiades-Behçet disease (registered charity), 258 were of German and 308 of Turkish descent, along with 30 other countries of origin. The prevalence in Germany is 0.9:100,000. Manifestation of the disease was predominantly in the third decade of life (median age: 26.5 years) and in 10.7% the disease onset was under 16 years of age. The full clinical picture developed on average in 2.9 years (median 3 months). Patients of Turkish descent showed androtopism in contrast to those of German descent (female:male  1.9:1), which was also detected in the whole collective in a ratio of 1.4:1. In 12.4% there was a family history with differences between German and Turkish patients (3.8% versus 14.6%) as well as in patients with disease onset in young and adult age (25.0% versus 7.3%). Most frequent features included oral aphthae (98.5%), cutaneous lesions (81%), genital ulcers (64.7%), ocular manifestations (51.6%), arthritis (52.4%) and positive pathergy test (30.8%). Turkish patients suffered significantly more often from eye manifestations compared with Germans, while in German patients prostatitis/epididymitis and gastrointestinal involvement were more frequently documented. As serious complications arose blindness 6.8%, meningoencephalitis 4.0%, severe arthritis 2.6%, fatal outcome 1.2%, hemoptysis 1.1% and gastrointestinal perforation 0.5%. The HLA-B5 antigen was positive in 58.1% and showed an association with eye manifestations. The relative risk of HLA-B5 positive individuals is high in both Germans (6.57) and Turks (5.81).

Non-infectious ulcerating oral mucous membrane diseases

Non‐infectious ulcerative oral mucous membrane diseases are difficult to separate at first glance: they can appear as aphthous, bullous, lichenoid, drug‐induced or toxic‐irritative reactions. The overall considerations of history, localization of lesions, clinical and histological features, as well as direct and indirect immunofluorescence examination are required for the correct diagnosis. Some disorders start preferably at the oral mucosa, like pemphigus vulgaris and Adamantiades‐Behçet disease, while others, such as cicatricial pemphigoid and habitual aphthosis generally are confined to the mucous membranes. This overview summarizes clinical and diagnostic features, differential diagnoses and current therapeutic possibilities of non‐infectious inflammatory stom‐atopathies, which possess a specific position among skin diseases in distinction to infectious or neoplastic oral ulcers. This group of diseases includes aphthous lesions, lichen planus mucosae, lupus erythematosus, disorders with intraepi‐dermal or subepidermal formation of blisters including pemphigus, bullous pemphigoid, erythema multiforme and variants as well as allergic or toxic contact stomatitis.

Epidemiologie der Augenbeteiligung beim Morbus Adamantiades-Behçet

Epidemiological studies demonstrate a prevalence of Adamantiades-Behçets disease (MAB) in the range of 0.12-420 per 100,000 inhabitants with the highest rates in Istanbul, Turkey and the lowest rates in the USA. Ophthalmological data on the prevalence of ocular involvement are limited for MAB in Germany because most epidemiological studies are based on rheumatological or dermatological data. Berlin is the city with the highest number of non-native German inhabitants and its multiethnic character renders it uniquely appropriate for epidemiological studies on MAB. This article summarizes the most important epidemiological data of 140 patients (63 female and 77 male) with a mean follow-up of 6.4 years (range 0.5-22 years) which we have recently published. The mean age was 23 years at the first manifestation and 32 years when the fully developed disease was recorded. The mean age at onset of ocular involvement was 30 years, 56% of patients developed ocular involvement, which was the first manifestation in 8.6% and the second manifestation in 19.3%. More than half the patients developed ocular involvement. The calculated prevalence of ocular involvement in MAB is 1.77/100,000 inhabitants for the population of Berlin.

[Epidemiology of ocular involvement in Adamantiades-Behçets disease].

Epidemiological studies demonstrate a prevalence of Adamantiades-Behçets disease (MAB) in the range of 0.12-420 per 100,000 inhabitants with the highest rates in Istanbul, Turkey and the lowest rates in the USA. Ophthalmological data on the prevalence of ocular involvement are limited for MAB in Germany because most epidemiological studies are based on rheumatological or dermatological data. Berlin is the city with the highest number of non-native German inhabitants and its multiethnic character renders it uniquely appropriate for epidemiological studies on MAB. This article summarizes the most important epidemiological data of 140 patients (63 female and 77 male) with a mean follow-up of 6.4 years (range 0.5-22 years) which we have recently published. The mean age was 23 years at the first manifestation and 32 years when the fully developed disease was recorded. The mean age at onset of ocular involvement was 30 years, 56% of patients developed ocular involvement, which was the first manifestation in 8.6% and the second manifestation in 19.3%. More than half the patients developed ocular involvement. The calculated prevalence of ocular involvement in MAB is 1.77/100,000 inhabitants for the population of Berlin.