Giuseppe Stinco

Giusto Trevisan

Nicola di Meo

Sara Trevisini

Serena Bergamo

Serena Bonin

English

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295Adamantiades-Behçet Disease at the Beginning of the Silk Route: North-East Italian ExperienceActa Dermatovenerol Croat  2017;25(4):295-297                           LETTER TO THE EDITORDear Editor,Adamantiades-Behçet’s disease (ABD) is an inflam-matory disease classified as vasculitis, which was origi-nally diagnosed in patients with aphthous stomatitis, genital ulcerations, and ocular manifestations. Howev-er, any organ or system may be involved, particularly the central and peripheral nervous systems, joints, as well as the gastrointestinal tract. The etiology of ABD is still not fully understood, but some evidence indicates that an autoimmune process could be triggered by an infectious or environmental agent specific for the geo-graphic region (1). Although BD can occur worldwide, it is most prevalent in the region along the ancient commercial route called the “Silk Road”. In Italy, stud-ies on the precise prevalence of ABD are lacking (2). As there are no specific diagnostic laboratory tests or his-topathologic findings which confirm the preliminary diagnosis, the final diagnosis should be based on clini-cal criteria (3). Skin and mucosae are the target organs of this disease, and therefore their involvement has been considered in the numerous diagnostic criteria developed over the years (4). The first most important and popular criteria were created in 1990 by the In-ternational Study Group (ISG) (5). Because of their low sensitivity, the new International Criteria for Behçet’s Disease (ICBD) were established, and were presented at the International Conference of Behçet’s Disease in Lisbon in 2006 (6,7). In 2014, the International Team for the Revision of the International Criteria for BD submit-ted new criteria assigning 2 points to ocular lesions, oral aphthosis, and genital aphthosis, and 1 point to skin lesions, central nervous system involvement, and vascular manifestations. The pathergy test, when used, was assigned 1 point. A patient scoring ≥4 points is classified as having BD (8). We performed a single cen-ter, case-control study on a cohort of patients of Friuli Venezia Giulia, enrolled from January 2010 to Septem-ber 2015 in the Dermatology Unit of the University of Trieste. The aim was to analyze the clinical features and compare the sensitivity, specificity, and accuracy of the three diagnostic criteria for ABD presented above in patients born in this particular region which is located at the very start of the “Silk Route”. We enrolled 153 consecutive patients (74 cases and 79 controls) in the study. The characteristics and clinical features of patients and controls are summa-rized in Table 1. The most common diagnoses in the control group were recurrent oral aphtosis, lichen planus, mucous-membrane pemphigoid, and lupus erythematosus. The inclusion criterion was the pres-ence of at least one principal clinical feature of ABD (oral aphtosis, genital aphtosis, skin lesions, ocular in-volvement) properly recorded in clinical records. Pa-tient recruitment was done in a consecutive manner. Exclusion criteria were incomplete clinical records and absence of follow-up data.The diagnosis of ABD was established by expert dermatologists, without the use of any particular diagnostic criterion. For ABD, diagnosis agreement among dermatologists was required. The study was conducted according to the Declaration of Helsinki protocols. Possible associations between categorical vari-ables were detected by the use of Fisher’s exact test or Pearson χ2 test, depending on the sample size. Lo-gistic regression was performed in order to identify which symptoms are of higher impact in the diagno-sis of ABD. A comparison in terms of sensitivity, speci-ficity, and accuracy among the three diagnostic crite-ria (ISG 1990, ITR 2006, and ITR 2014) was performed. The receiver operator characteristic (ROC) curve was obtained for each diagnostic criterion.Data were produced with a 95% confidence inter-val; P values <0.05 were considered statistically sig-nificant. Statistical analysis was done using Stata SE12 software (Stata Corporation, Tx, USA). According to our data, patients with ABD had a significantly lower age at diagnosis compared with controls (P=0.0001); this was confirmed for both men (P=0.0006) and women (P=0.004). The presence of oral aphtosis was not necessarily pathognomonic of ABD (P=0.005) as it was found in 97.3% of patients with ABD and in 83.5% of controls. Genital aphtosis was directly associated with ABD diagnosis (P<0.001), ACTA DERMATOVENEROLOGICA CROATICA296Table 2. Results of logistic regressionClinical Features Odds ratio P valueYounger age 0.8950334 0.000Oral aphtosis 145.3229 0.004Genital aphtosis 12947.7 0.000Skin involvement 104.5625 0.002Neurological inolvement 819.263 0.001Vacular involvement 240.2573 0.000Table 1. Comparison between the clinical characteristics of patients and controlsBehçet Disease (n=74, M=21, F=53)    Controls (n=79, M=13, F=66)                P valueAge 45.79 ± 13.25 56.09 ± 17.78 0.0001Age if Male 42.78 ± 11.71 62.43 ± 20.55 0.0006Age if Female 46.98 ±13.73 54.84 ± 17.08 0.0038Oral aphtosis 72 (97.30%) 66 (83.54%) 0.005Genital aphtosis 59 (79.73%) 7 (8.86%) 0.000Skin manifestations 46 (62.16%) 22 (27.85%) 0.000Pseudofolliculitis 33 (44.59%) 13 (16.46%) 0.000Erythema nodosum 18 (24.32%) 10 (12.66%) 0.093Cutaneous aphtosis 1 (1.35%) 0 (0.00%) 0.484Ocular lesions 16 (21.62%) 4 (5.06%) 0.003Anterior uveitis 14 (18.92%) 2 (2.53%) 0.001Posterior uveitis 4 (5.41%) 2 (2.53%) 0.0431Retinal vasculitis 1 (1.35%) 1 (1.27%) 0.963Joint manifestations 34 (45.95%) 32 (40.51%) 0.518Arthralgia 27 (36.49%) 25 (31.65%) 0.609Arthritis 7 (9.46%) 7 (8.86%) 0.898Spondylitis 1 (1.35%) 1 (1.27%) 0.963Neurological manifestations 11 (14.86%) 4 (5.06%) 0.056Peripheral 5 (6.76%) 4 (5.06%) 0.740Central 6 (8.11%) 0 (0%) 0.011Vascular manifestations 10 (13.51%) 3 (3.80%) 0.042Arterial thrombosis 1 (1.35%) 0 (0%) 0.484Venous thrombosis 3 (4.05%) 1 (1.27%) 0.354Phlebitis 7 (9.46%) 3 (3.80%) 0.1999Gastrointestinal manifestations 11 (14.86%) 0 (0.00%) 0.000Epididymitis 2 (2.70%) 0 (0.00%) 0.232Pathergy test positive 17 (36.17%) 1 (4.76%) 0.007HLA B51 test positive 26 (70.27%) 9 (34.62%) 0.009as it was present in 79.7% of patients with ABD, but in only 8.9% of controls. Furthermore, even skin mani-festations and ocular lesions were observed at differ-ent rates in patients with ABD and controls (P<0.001 and P=0.003, respectively). The presence of pseu-dofolliculitis was significantly more frequent in pa-tients than in controls (P<0.001), whereas erythema nodosum and skin aphtosis did not differ consider-ably between ABD and controls. Joint manifestations were as common in patients with ABD as in controls (P=0.6): arthralgia and arthritis alone do not indicate a diagnosis of ABD. Neurological symptoms as well as vascular involvement, if present, can be suggestive of ABD, but their absence does not exclude an ABD di-agnosis (P=0.06 and P=0.04). Positive pathergy tests and positive HLA B51 tests were significantly more frequent in patients than in controls (P=0.007 and Figure 1. Results of receiver operator characteristic (ROC) areas.Acta Dermatovenerol CroatLetter to the editor     2017;25(4):295-297ACTA DERMATOVENEROLOGICA CROATICA297ACTA DERMATOVENEROLOGICA CROATICAP=0.009, respectively), although if negative they did not exclude a diagnosis of ABD.Logistic regression showed that genital aph-tosis (odds ratio (OR)=12948, P<0.001), neurologi-cal manifestations (OR=819.263, P=0.001), vascular manifestations (OR=240.2573, P=0.001), cutaneous manifestations (OR=104.5625, P=0.002), oral aphtosis (OR=145.3229, P=0.004), and younger age at diag-nosis (OR=0.8950334, P=0.000) were associated with ABD diagnosis (Table 2). There was no single pathog-nomonic symptom of ABD.We found that the ITR criteria –both from 2006 and 2014 – had a higher sensitivity (98.7% and 100%, respectively), specificity (94.9% and 97.9%, respec-tively), and accuracy (96.7% and 98.7%, respectively) compared with the ISG 1990 criterion, which scored 66% sensitivity, 100% specificity, and 83.7% accuracy. Area Under Roc Curve (AUC) was significantly differ-ent between ISG 1990 and ITR 2006 and between ISG 1990 and ITR 2014 (Figure 1). Even though no statis-tically significant difference was found between the ITR 2014 and ITR 2006 criteria, the former had a better performance according to our records.  The clinical features reported in our retrospective case-control study are comparable to data found in the literature from European and international re-ports.A recent study (8) found a similar organ involve-ment percentage to our study, although we found a higher prevalence of HLA B51 positive patients and a lower percentage of ocular manifestations in our re-cords. The results of the logistic regression performed based on our records indicate genital aphtosis, oral aphtosis, ocular involvement, neurological signs, and vascular features are more strongly linked to the di-agnosis of ABD. According to our data, the presence of oral aphtosis is not paramount for the diagnosis of ABD, which fits well with the intent of the ITR 2006 and 2014 diagnostic criteria. The new ITR 2014 criteria added neurological signs to the diagnostic symptoms of ABD, emphasizing the importance of a multidisci-plinary approach to patients suspected to have ABD.References:1. di Meo N, Quaranta L, Crisman G, Trevisan G. Ada-mantiades Behçet Disease triggered by a tick bite and or Borrelia infection. J Eur Acad Dermatol Ve-nereol. 2009;23:1198-9.2. Davatchi F, Jamshidi AR, Banihashemi AT, Gholami J, Forouzanfar MH, Moradi M, et al. Prevalence of Behcet’s disease in Iran: a WHO-ILAR COPCORD st-age I study. APLAR J Rheumatol. 2007;10:239-43. 3. Woźniacka A, Sysa-Jędrzejowska A, Jurow-ski P, Jabłkowski M, Kot M. Morbus Behçet - a rare disease in Central Europe. Arch Med Sci. 2015;11:1189-96. 4. Davatchi F, Sadeghi Abdollahi B, Chams-Davatchi C, Shahram F, Shams H, Nadji A, et al. The saga of diagnostic/classification criteria in Behcet’s di-sease. Int J Rheum Dis. 2015;18:594-605.5. International study group for Behçet’s disease. Criteria for diagnosis of Behçet’s disease. Lan-cet.1990; 335: 1078–80.  6. Davatchi F, Sadeghi Abdollahi B, Shahram F, Nadji A, Chams-Davatchi C, Shams H, et al. Validation of the international criteria for Behçet’s disease (ICBD) in Iran. Int J Rheumat Dis. 2010; 13: 55–60. 7. di Meo N, Bergamo S, Vidimari P, Bonin S, Trevisan G. Analysis of diagnostic criteria in Adamiantia-des-Behçet disease: a retrospective study. Indian J Dermatol. 2013;58:275-7. 8. International Team for the Revision of the Interna-tional Criteria for Behçet’s Disease (ITR-ICBD). The International Criteria for Behçet’s Disease (ICBD): a collaborative study of 27 countries on the sensiti-vity and specificity of the new criteria. J Eur Acad Derm Venereol. 2014;28:338-47.Serena Bergamo1, Nicola di Meo1, Giuseppe Stinco2, Serena Bonin1, Sara Trevisini1, Giusto Trevisan11Dermatology Department, University of Trieste, Trieste, Italy2Department of Experimental and Clinical Medicine, Institute of Dermatology, University of Udine, Udine, ItalyCorresponding author:Nicola di Meo, MDDermatology Department, University of TriesteOspedale Maggiore di TriestePiazza Ospedale 1, IV Piano Palazzina Infettivi34100 TriesteItalynickdimeo@libero.itReceived: October 28, 2016Accepted: November 15, 2017Acta Dermatovenerol CroatLetter to the editor     2017;25(4):295-297

Adamantiades-Behcet disease at the beginning of the Silk Route: North-East Italian experience.

Bergamo, Serena

di Meo, Nicola

Stinco, Giuseppe

Bonin, Serena

Trevisini, Sara

Trevisan, Giusto

Archivio istituzionale della ricerca - Università degli Studi di Udine

Adamantiades-BehÃ§et disease at the beginning of the silk route: North-East Italian experience

Bergamo S.

di Meo N.

Stinco G.

Bonin S.

Trevisini S.

Trevisan G.

Archivio istituzionale della ricerca - Università di Trieste

Adamantiades-Behçet disease at the beginning of the silk route: North-East Italian experience

Adamantiades-Behcet disease at the beginning of the Silk Route: North-East Italian experience.

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