Do Behçet's syndrome patients with acne and arthritis comprise a true subset? Comment on the article by Hatemi et al.

To the Editor: The issue of whether Behçet’s syndrome should be classified among the spondylarthritides (SpA) has become the subject of lively debate, with some groups completely opposed to the hypothesis (1,2) and others strongly supporting it (3,4). In their recent article, Hatemi and colleagues took the latter position (5). Using ultrasound (US) to evaluate the enthesis in Behçet’s syndrome, the authors demonstrated an increased presence of enthesitis, a typical feature of SpA, in a subgroup of patients from Turkey with Behçet’s syndrome with acne and arthritis (BS-AA). Other features of SpA, such as inflammatory low back pain and radiologically evident sacroiliitis, along with family medical history, were not considered in the study by Hatemi et al. Within the past decade, musculoskeletal US has been recognized as a fundamental imaging technique for the diagnosis and followup of patients with rheumatic diseases (6,7), and it has already been used for the assessment of joint involvement in Behçet’s syndrome. In fact, we have recently used US to evaluate knee involvement in a series of 30 consecutive Italian Behçet’s syndrome patients, and the results demonstrated a high prevalence of signs of synovitis even among patients without symptoms (8). These evaluations confirmed the high sensitivity of US for the detection of joint alterations in rheumatic diseases and its role in detecting subclinical inflammation. We subsequently extended this investigation to 43 Behçet’s syndrome patients (13 women, 30 men; mean age 44.9 years, range 20–72), 26 (60.4%) of whom had signs of synovitis, confirming the previous results. Even though joint involvement in Behçet’s syndrome is generally considered mild, we demonstrated an erosive form in 6.9% of patients, suggesting that bone surface can also be affected in Behçet’s syndrome. Interestingly, we could not demonstrate a statistically significant association between arthritis as detected by US and skin manifestations, even though among patients with arthritis, acneiform skin lesions (papules and pustules) were more frequent in those with a higher sonographic score. Furthermore, in order to investigate the presence of sacroiliitis, we performed conventional pelvic radiography and magnetic resonance imaging (MRI) of the sacroiliac (SI) joints in 5 consecutive patients with BS-AA (3 women, 2 men; mean age 44.8 years, range 26–54). MRI, now considered a powerful tool for the detection of sacroiliitis (9), was performed using a Magnetom Avanto 1.5T scanner (Siemens, Erlangen, Germany). Before contrast medium injection, coronal oblique (parallel to the long axis of the sacrum) and axial T1-weighted turbo spin-echo (TSE) sequences (time to recovery [TR] 734 msec, time to echo [TE] 20 msec), inversion recovery TSE sequences (TR 5,000 msec, TE 27 msec), and T2-weighted TSE sequences (TR 3,320 msec, TE 90 msec) were examined; after intravenous administration of gadopentate dimeglumine, fat-suppressed contrast-enhanced T1-weighted TSE sequences (TR 1,030 msec, TE 20 msec) and standard T1-weighted TSE sequences, both on the axial plane, were examined. For evaluating the results of conventional radiography, the SI joints were scored using the modified New York criteria for diagnosing ankylosing spondylitis (10); a similar system for the scoring of structural changes (erosions, sclerosis, and ankylosis) was used for the evaluation of MRI results, for which inflammatory changes (e.g., enhancement and subchondral bone marrow edema) were also considered. One of the 5 patients with recent-onset inflammatory low back pain (20%) exhibited active grade 2 sacroiliitis in both SI joints on MRI, in the absence of significant abnormalities seen on conventional radiography. This observation is consistent with the greater sensitivity of MRI compared with conventional radiography for the detection of early sacroiliitis (9). In another 4 patients with Behçet’s syndrome without past or present peripheral arthritis (BS-WA) (2 women, 2 men; mean age 42 years, range 33–58) but with inflammatory low back pain and/or double positivity for HLA–B51 and HLA–B27 (found in 2 of the 4), MRI revealed signs of bilateral sacroiliitis. Folliculitis was also recorded in 2 of these 4 patients. Though preliminary and limited to only a few Italian patients, these findings suggest that, while the hypothesis that BS patients with acne and arthritis form a distinct cluster carrying features of SpA is very intriguing, the evidence is still limited. Also, patients with BS-WA can fall within the spectrum of SpA, especially if they are positive for HLA–B27. The significance of folliculitis is still to be determined, since it is not necessarily associated with arthritis but is detectable in a relevant percentage of patients with BS-WA (87% in the group considered by Hatemi et al [5]). Larger cohorts of patients of different ethnic origins need to be examined in order to clearly define arthritis, assess SI joints and the enthesis with reproducible techniques such as MRI and US, and evaluate the association with HLA–B27. More importantly, as the presence of HLA–B27 in Behçet’s syndrome seems to be a good prognostic factor for uveitis (11), an attempt should be made to ascertain whether different subsets of patients (i.e., the patients with BS-AA proposed by Hatemi et al) also have a different prognosis with regard to vision outcomes.