Cem Mat

The long-term mortality and morbidity of Behçet syndrome: a 2-decade outcome survey of 387 patients followed at a dedicated center.

We surveyed the 20-year outcome of a cohort of patients with Behçet syndrome with emphasis on both mortality and morbidity. During 1999 and 2000, we collected outcome information on 387/428 (90.4%) of a cohort of patients (262 male, 125 female) who had registered in a dedicated outpatient clinic between July 1977 and December 1983. In 245/345 (71.0%) patients, outcome information was based on a formal hospital reevaluation, and in the remaining patients, on detailed telephone interviews.Forty-two patients (9.8%) (39 male, 3 female) had died, mainly due to major vessel disease and neurologic involvement. Mortality, as measured by standardized mortality ratios (SMR), was specifically increased among young males, among whom morbidity was also the highest. However, the SMR tended to decrease significantly with the passage of time. The same was also true for all mucocutaneous and articular manifestations. Both the onset of eye disease and its greatest damage were also usually within the first few years of disease onset. These suggest that the “disease burden” of Behçet syndrome is usually confined to the early years of its course, and in many patients the syndrome “burns out.” However, central nervous system involvement and major vessel disease are exceptions. They can have their onset late (5–10 yr) during the disease course. As reflected in the mortality figures, the disease was less severe among the females for almost each disease manifestation. There were no female patients with arterial aneurysms.Severely impaired vision did not always mean an eventual loss of useful vision, and those patients with a late onset of eye disease had a better visual prognosis.

A double-blind trial of colchicine in Behçet's syndrome.

OBJECTIVE Colchicine is a widely used treatment for Behçets syndrome, even though in a previous 6-month controlled study, it was shown to be effective only in controlling erythema nodosum and arthralgias. We reassessed the effect of colchicine in Behçets syndrome in a study conducted among a larger group of patients for 2 years. METHODS We randomized 116 patients with Behçets syndrome (60 male/56 female), who had active mucocutaneous disease without eye or major organ involvement, to receive either placebo or colchicine (1-2 mg/day, adjusted to body weight) in a double-blind trial for 2 years. The primary outcome measure was the sustained absence of any lesions during treatment (complete response). The secondary outcome measure was the difference in the number of mucocutaneous lesions or arthritic joints between the active drug and placebo arms. Women and men were analyzed separately. RESULTS Eighty-four patients (72%; 45 male, 39 female) completed the 24-month study. Kaplan-Meier analyses showed significantly more complete responses in the colchicine treatment group in terms of reduced occurrence of genital ulcers (P = 0.004), erythema nodosum (P = 0.004), and arthritis (P = 0.033) among the women, and reduced occurrence of arthritis (P = 0.012) among the men. The mean numbers of genital ulcers (P = 0.001), erythema nodosum lesions (P = 0.002), and arthritic joints (P = 0.014) among the women were less in the colchicine group, and the mean number of arthritic joints (P = 0.026) among the men was less in the colchicine group. Adverse effects were similar in both groups. CONCLUSION Colchicine may be useful for treating some of the manifestations of Behçets syndrome, especially among women. This might be a reflection of less severe disease among the women.

Mucocutaneous criteria for the diagnosis of Behçet's disease: An analysis of clinicopathologic data from multiple international centers

BACKGROUND Although four of five of the new international criteria for the diagnosis of Behçets disease relate to mucocutaneous lesions, disagreement exists as to the exact nature of cutaneous lesions (e.g., vessel-based vs follicular). OBJECTIVE Our purpose was to review clinical data, clinical photographs, and skin biopsy specimens from multiple medical centers throughout the world to monitor current practice in the implementation of mucocutaneous diagnostic criteria for Behçets disease. METHODS Ten medical centers responded to a request to collaborate by sending clinical data, photographs of cutaneous lesions, and biopsy specimens from 22 patients. RESULTS Of specimens from 22 patients, 14 revealed a histopathologic pattern of neutrophils containing perivascular and interstitial inflammation, whereas specimens from three patients revealed only mononuclear cells in a vessel-based pattern. Biopsy specimens from three patients revealed primarily folliculocentric inflammation and an additional two specimens were from erythema nodosum-like lesions. CONCLUSION Perivascular inflammation was the predominant histopathologic finding in specimens of cutaneous lesions in this clinical series. Folliculocentric lesions could not be predicted on the basis of review of clinical photographs. Histopathologic assessment of cutaneous lesions is crucial if the proposal is accepted that exclusion of folliculocentric lesions is important to ensure accurate implementation of diagnostic criteria in patients with suspected Behçets disease.

Clinicopathologic Evaluation of Nodular Cutaneous Lesions of Behçet Syndrome

Among the cutaneous manifestations, nodular lesions are rather common in Behçet syndrome. The histologic nature of these lesions has been a matter of controversy. To establish their distinguishing features, biopsy specimens from nodular lesions of 24 patients with Behçet syndrome, 25 with nodular vasculitis (NV), and 20 with erythema nodosum (EN) were compared. Statistical analysis revealed insignificant differences between most of the histologic features of Behçed syndrome and NV. However, neutrophil-predominating infiltrate in the subcutis was more common in Behçet syndrome, while necrosis and granuloma formation were encountered more frequently in NV. The differences between Behçed syndrome and EN were more significant. Septal panniculitis, lymphocyte-predominating infiltrate, absence of many vascular changes as well as vasculitis, and necrosis were features in favor of EN. Nodular lesions of Behçet syndrome are mainly neutrophilic vascular reactions with histologic features similar to NV but significantly differing from EN associated with other systemic diseases.

Apremilast for Behçet’s Syndrome — A Phase 2, Placebo-Controlled Study

BACKGROUND Oral ulcers, the hallmark of Behçets syndrome, can be resistant to conventional treatment; therefore, alternative agents are needed. Apremilast is an oral phosphodiesterase-4 inhibitor that modulates several inflammatory pathways. METHODS We conducted a phase 2, multicenter, placebo-controlled study in which 111 patients with Behçets syndrome who had two or more oral ulcers were randomly assigned to receive 30 mg of apremilast twice daily or placebo for 12 weeks. This regimen was followed by a 12-week extension phase in which the placebo group was switched to apremilast and a 28-day post-treatment observational follow-up phase. The patients and clinicians were unaware of the study assignments throughout the trial. The primary end point was the number of oral ulcers at week 12. Secondary outcomes included pain from these ulcers (measured on a 100-mm visual-analogue scale, with higher scores indicating worse pain), the number of genital ulcers, overall disease activity, and quality of life. RESULTS The mean (±SD) number of oral ulcers per patient at week 12 was significantly lower in the apremilast group than in the placebo group (0.5±1.0 vs. 2.1±2.6) (P<0.001). The mean decline in pain from oral ulcers from baseline to week 12 was greater with apremilast than with placebo (-44.7±24.3 mm vs. -16.0±32.5 mm) (P<0.001). Nausea, vomiting, and diarrhea were more common in the apremilast group (with 22, 9, and 12 incidents, respectively, among 55 patients) than in the placebo group (with 10, 1, and 2 incidents, respectively, among 56 patients), findings that were similar to those in previous studies of apremilast. There were two serious adverse events in patients receiving apremilast. CONCLUSIONS Apremilast was effective in treating oral ulcers, which are the cardinal manifestation of Behçets syndrome. This preliminary study was neither large enough nor long enough to assess long-term efficacy, the effect on other manifestations of Behçets syndrome, or the risk of uncommon serious adverse events. (Funded by Celgene; ClinicalTrials.gov number, NCT00866359.).

Photodynamic therapy with verteporfin for choroidal neovascularization in patients with angioid streaks.

PURPOSE To evaluate safety and efficacy of photodynamic therapy with verteporfin for subfoveal choroidal neovascularization associated with angioid streaks. DESIGN Prospective interventional case series. METHODS Eight patients (eight eyes) with subfoveal choroidal neovascularization secondary to angioid streaks were reviewed. Standardized protocol refraction, visual acuity testing, ophthalmologic examinations, color photographs, fluorescein angiograms and indocyanine angiograms were used to evaluate the results of photodynamic therapy with verteporfin. Follow up ranged from 6 to 12 months with a mean (+/- SD) of 8.75 (+/- 2.37) months. RESULTS Photodynamic therapy with verteporfin was well tolerated in patients with choroidal neovascularization related to angioid streaks. No deterioration in visual acuity was observed. Increase in median best-corrected visual acuity was 1.37 lines (SD +/- 1.59 lines, range 1-5 lines) at the last follow up. Two (25%) patients had no improvement of visual acuity. At the last follow up three (37.5%) patients showed no leakage and three (37.5%) patients had minimal leakage from choroidal neovascularization. Photodynamic therapy related ocular complications were not reported in any case. CONCLUSIONS Photodynamic therapy with verteporfin generally achieved short-term cessation of or decrease of fluorescein leakage from subfoveal choroidal neovascularization without loss of vision in patients with angioid streaks. Further studies with longer follow up are necessary to confirm whether verteporfin therapy is beneficial for subfoveal choroidal neovascularization related to angioid streaks.

Papulopustular skin lesions are seen more frequently in patients with Behçet's syndrome who have arthritis: a controlled and masked study

OBJECTIVE To determine the prevalence of acneiform skin lesions (comedones, papules, and pustules) in patients with Behçets syndrome (BS) with arthritis. METHODS Study groups included 44 patients with BS with arthritis (32 men, 12 women, mean (SD) age 37.8 (8.9)), 42 patients with BS without arthritis (31 men, 11 women, mean age 35.5 (6.4)), 21 patients with active rheumatoid arthritis (five men, 16 women, mean age 48.8 (14)), and 33 healthy volunteers (28 men, five women, mean age 40.1 (8.1)). All probands and controls were examined by a rheumatologist and a dermatologist, in a prospective and masked protocol. An ophthalmological evaluation was performed if necessary. Skin lesions, including comedones, papules, and pustules, were counted and scored as 0: absent, 1: 1–5, 2: 6–10, 3: 11–15, 4: 16–20, and 5: >20. RESULTS Although there was no significant difference between the four groups in the prevalence of comedones, the number of papules and pustules was significantly higher in patients with BS with arthritis (p=0.0037 for papules and p<0.0001 for pustules) than in the remaining three groups. CONCLUSION Acneiform skin lesions (papules and pustules) seem to be more frequent in patients with BS with arthritis. This suggest that the arthritis seen in BS may possibly be related to acne associated arthritis.

Effect of surgical cleaning of the skin on the pathergy phenomenon in Behçet's syndrome.

OBJECTIVES--To assess the effect of surgical cleaning of the skin on the pathergy phenomenon in Behçets syndrome. METHODS--The pathergy phenomenon was assessed in 183 patients with Behçets syndrome in a single blind study at 48 hours after a needle prick of the forearm skin, cleaned in the conventional way with alcohol, with 10% povidine iodine, with 100% chlorhexidine, and with a 4% aqueous solution of chlorhexidine. RESULTS--The surgical cleaning of the forearm with povidone iodine before the application of the needle prick reduced the prevalence of the pathergy reaction to 27% from 48% in the conventionally (by alcohol swab) cleaned forearm. Cleaning the forearm with 100% chlorhexidine reduced the prevalence of the pathergy to 36% from 59% in the conventionally cleaned forearm. No significant changes were observed with a 4% aqueous solution of chlorhexidine. CONCLUSIONS--Surgical cleaning of the skin with disinfectants of various concentrations reduces the prevalence of a positive pathergy test in Behçets syndrome. This implies that more than the disruption of the structural integrity of the dermis and epidermis is involved in the production of the pathergy phenomenon in Behçets syndrome.

Comparison of two surgical approaches for treating vitiligo: a preliminary study

Background Surgical techniques have recently been introduced for patients with vitiligo. Randomized controlled trials have not been performed.

Behçet's disease in the Middle East.

Behcet’s disease (BD), originally described as oral and genital ulcers and uveitis, is a vasculitis that can involve any organ system. It is a commonly encountered health problem in the Mediterranean countries and in the Far East. The disease has protean manifestations that vary in different geographical locations. The diagnosis of the disease is based on a combination of clinical findings and a positive pathergy test since the etiological agent has not been determined. Various genetic, environmental, and immunological factors play a role in the pathogenesis but the unknown still surpasses the known.