Frequency of pathergy phenomenon and other features of Behçet's syndrome among patients with inflammatory bowel disease.

OBJECTIVE: Crohn's disease (CD) and ulcerative colitis (UC) share common clinical features with Behçet's syndrome (BS). We surveyed UC and CD patients for pathergy phenomenon and features of BS with the aim of determining how much overlap is present between these 2 entities in a setting where BS is relatively common, the frequency of pathergy positivity in inflammatory bowel disease (IBD) patients and evaluating how International Study Group (ISG) criteria perform in differentiating IBD from BS. METHODS: This study was conducted among patients with CD and UC attending the gastroenterology outpatient clinic of a university hospital which is also a referral center for BS. Consecutive CD and UC patients were screened for BS using ISG criteria. Pathergy test was performed and evaluated by 2 independent observers in a masked manner. RESULTS: Ninety-three patients with CD and 130 with UC were surveyed. None of the CD patients fulfilled ISG criteria for BS while 2 of 130 UC patients did. Twenty CD patients had oral ulcers while 4 reported having genital ulcers but no scars could be observed. Twenty-two CD patients had papulopustular lesions, 2 had nodular lesions, 3 had arthritis and none had uveitis. Thirty-two UC patients had oral ulcers, none had genital ulcers, 23 had papulopustular lesions, 3 had nodular lesions, 2 had arthritis and 2 had uveitis. Pathergy test was positive according to at least one of the observers in 10/93 CD and 8/130 UC patients and according to both observers in 4/130 UC patients. CONCLUSION: Despite similarities between the clinical features of CD and UC with BS, coexistence is uncommon. ISG criteria perform well in differentiating these diseases. About 8% of IBD patients show the pathergy phenomenon.

Behçet's syndrome is not associated with vitiligo.

OBJECTIVE: Behçet's syndrome (BS) has many features that are different from autoimmune diseases, including a lack of association with Sjögren's syndrome. Vitiligo is frequently associated with various autoimmune disorders such as autoimmune thyroiditis, pernicious anemia and Addison's disease. Our informal observation was that vitiligo is also uncommon among BS patients. With this controlled and masked study we formally surveyed the presence of vitiligo among BS patients and suitable controls. METHODS: Patients with Behçet's syndrome, Graves' disease, and Hashimoto's thyroiditis being followed in the rheumatology and endocrinology departments of a university hospital and healthy controls were examined. Subjects with hypopigmented lesions were re-examined by a dermatologist in a masked protocol. Wood's lamp was used to confirm the diagnosis of vitiligo in suspected lesions. RESULTS: 253 consecutive BS patients, 34 Graves' disease patients, 32 Hashimoto's thyroiditis patients, and 439 healthy controls were surveyed. None of the BS patients had vitiligo, while 6/34 (17.6%) of Graves' disease patients, 6/32 (18.7%) of Hashimoto's thyroiditis patients, and 4/439 (0.9%) of healthy controls had vitiligo. All the subjects with vitiligo, except for one patient with associated Graves' disease, were women. CONCLUSION: In contrast to two autoimmune diseases, Hashimoto's thyroiditis and Graves' disease, the frequency of vitiligo was not increased among patients with BS. This constitutes further evidence that traditional autoimmune mechanisms may not be operative in BS.

Lactobacilli lozenges in the management of oral ulcers of Behçet's syndrome.

BACKGROUND: There is increasing evidence that lactobacilli, having anti-inflammatory activity, may be useful in some diseases, particularly in inflammatory bowel disease. OBJECTIVES: We aimed to study the efficacy of lactobacilli lozenges (INERSAN, VSL Pharmaceuticals, USA) in the management of oral ulcers of Behçet's syndrome. PATIENTS AND METHODS: Twenty-five patients were studied before, during and after lactobacillus use. All patients had mainly skin-mucosa involvement with fresh oral ulcers and none were using systemic immunosuppressives. The patients chewed on 6 lozenges/day at intervals of 2-3 hours during the time they were awake for 7 days. The number of OU before visit 1 and after 1. and 2. weeks after drug use was the main outcome measure. RESULTS: Twenty three patients completed the trial. 1 patient left the trial the second day because of nausea and another was a no show at the 2.visit. There was a significant decrease in the mean number of ulcers following treatment, more pronounced among the females, and this decrease continued at least for 1 week after the treatment was stopped. 4/23 patients had side effects with 3 complaining of nausea and 1 of abdominal fullness. CONCLUSIONS: In this pilot and open study Lactobacillus brevis CD2 lozenges seemed to be effective in controlling the OU of BS. Randomized, controlled trials with this seemingly innocuous agent are now needed.

Skin involvement and outcome measures in systemic autoimmune diseases.

This paper focuses on skin manifestations that can be observed in autoimmune diseases such as rheumatoid arthritis (RA), Sjögren syndrome (SS), dermatomyositis (DM) and Behçet syndrome (BS). In RA the most widely recognized skin lesion is the rheumatoid nodule. Other cutaneous manifestations can be observed either non-specific or related to the disease itself and/or to the commonly used drugs. Cutaneous manifestations are considered one of the most typical extraglandular features of primary SS, generally they are distinguished in vasculitic and non vasculitic lesions. Among non-vasculitc lesions, skin dryness (xerosis) has been shown to be very common in pSS while vasculitis lesions include typically flat and palpable purpura and urticarial vasculits. In DM the skin manifestations are also frequent and include a heliotrope rash (blue-purple discoloration) on the upper eyelids with edema, a flat red rash on the face and upper trunk, and erythema of the knuckles with a raised violaceous scaly eruption (Gottron rash). The most frequent mucocutaneous finding in BS is aphthous stomatitis which can not usually be differentiated from idiopatic reccurrent aphthous stomatitis on clinical grounds. The most typical skin manifestations are nodular lesions, which are commonly seen in BS and may be due to panniculitis [erythema nodosum (EN)-like lesions] or superficial thrombophlebitis.

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

OBJECTIVES: Corticosteroids are widely used in Behçet's syndrome despite the absence of controlled studies. We assessed the effect of depot corticosteroids primarily for genital ulcers and secondarily for the other mucocutaneous manifestations of Behçet's syndrome. METHODS: We randomized 86 patients who had active disease with genital ulcers to receive either intramuscular corticosteroid injections (40 mg methylprednisolone acetate) or placebo every 3 weeks for 27 weeks. RESULTS: Seventy-six patients (88%) completed the treatment. There were no significant differences in the mean number of genital and oral ulcers, or folliculitis between groups. The mean number of erythema nodosum lesions was less in the corticosteroid group as a whole (P = 0.0046); subgroup analyses revealed that this was significant for females (P = 0.0148) but not for males (P = 0.1). CONCLUSION: Low-dose depot corticosteroids did not have any beneficial effect on genital ulcers. However, it was useful in controlling erythema nodosum lesions, especially among the females.

The pustular skin lesions in Behcet's syndrome are not sterile.

BACKGROUND: The pustular skin lesions of Behcet's syndrome (BS) are clinically and histopathologically similar to ordinary acne, but BS patients get lesions at sites not commonly involved in acne, such as the legs and arms. The microbiology of these lesions has not been studied adequately. OBJECTIVE: To make a detailed study of the microbiology of BS lesions. METHODS: Subjects were patients with BS and acne vulgaris. Material was extracted from pustular lesions and directly plated to aerobic and anaerobic media by sterile swab. Anaerobic bacteria were identified using a commercial kit (API 20A). Aerobic bacteria were defined by standard procedures. RESULTS: 58 BS patients and 37 acne patients were studied. Pustules were cultured from the following sites: BS patients (70 pustules): face (17), back (30), chest (2), arm (4), leg (17); acne patients (37 pustules): face (27), back (6), chest (1), arm (2), leg (1). At least one type of microorganism was grown from each pustule. Staphylococcus aureus (41/70, 58.6%, p = 0.008) and Prevotella spp (17/70, 24.3%, p = 0.002) were significantly more common in pustules from BS patients, and coagulase negative staphylococci (17/37, 45.9%, p = 0.007) in pustules from acne patients. CONCLUSIONS: The pustular lesions of BS are not usually sterile. The microbiology of these lesions is different from ordinary acne. It remains to be determined whether the infection is secondary or has any pathogenic implications.

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

OBJECTIVE: Colchicine is a widely used treatment for Behçet's 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 Behçet's syndrome in a study conducted among a larger group of patients for 2 years. METHODS: We randomized 116 patients with Behçet's 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 Behçet's syndrome, especially among women. This might be a reflection of less severe disease among the women.

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 Behçet's 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.

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.

Behçet's syndrome. The Cerrahpasa experience. Members of the Behçet's Syndrome Research Centre.

Behçet's syndrome (BS) is a systemic vasculitis of unknown etiology. There are several reasons for doubting a primary autoimmune pathogenesis of this condition. Recent information suggests evidence for genetic anticipation. Although there is heightened inflammatory activity, as exemplified by the pathergy reaction, wound healing in BS is normal. BS also runs a more stormy course in adults and in the young. However, the amount of androgen receptors in scrotal skin have not found to be increased. Another unsolved problem is the nature of acne-like lesions and how they differ from acne vulgaris (AV). Only lesions in "non-acne" areas were compared between the two conditions, and no differences were detected. Mortality is increased in BS, especially among males. Azathioprine proved to be effective in disease control after 8 years of follow-up. We have also recently finished a 24 week controlled trial of two doses of thalidomide, 100 mg and 300 mg per day. Both doses were superior to placebo, with no real differences in efficacy, in controlling the oral and genital ulcers.

The management of Behçet's syndrome.

Behçet's syndrome (BS), originally described as a triad of oral aphthae, genital ulcerations and uveitis, is a systemic vasculitis that is prevalent in the Middle east, Far East and in the Mediterranean basin. It is characterized by a heightened state of inflammation although the main drive that initiates and sustains this is not yet elucidated. Suppression of this inflammatory state constitutes the major goal of treatment and therapy is tailored according to the specific manifestations observed. We now have considerable more insight on drug management of BS compared to 20 years ago. Particularly, within the recent past we have learned to use more rationally the agents that were already available to us. This is especially true for azathioprine, cyclosporin A, thalidomide and colchicine. Promising data are also being collected with alpha-interferon. With these agents, significant progress has been achieved in the management of uveitis and mucocutaneous symptoms but treatment issues related to thrombotic problems, major vessel involvement and neurological disease have not yet been resolved.

Histopathologic features of the spontaneous pustular lesions of Behçet's syndrome.

BACKGROUND: Papulopustular lesions are common in Behçet's syndrome (BS). A debate exists as to whether they are different from ordinary acne. This has important clinical and pathophysiologic implications. OBJECTIVE: The aim of this study was to evaluate the histopathologic features of papulopustular lesions seen both in BS and acne vulgaris (AV). METHODS: Representative samples were obtained from 17 patients with BS and six patients with AV. The detailed histopathologic features were evaluated by a dermatopathologist blinded to the diagnoses. RESULTS: Considering the epidermis, follicle epithelium, and dermis separately, no differences could be found between the two groups. CONCLUSIONS: The papulopustular lesions seen in these two disorders cannot be distinguished on the basis of clinical and histopathologic findings.

Thalidomide in the treatment of the mucocutaneous lesions of the Behçet syndrome. A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Recurrent oral and genital ulcers are the most frequent problem in the management of the Behçet syndrome. Uncontrolled experience suggests that thalidomide may help prevent recurrences of these ulcers. OBJECTIVE: To determine the efficacy of two thalidomide dosages in the treatment of mucocutaneous lesions of the Behçet syndrome. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Specialist outpatient clinic for the Behçet syndrome in Turkey. PATIENTS: 96 male patients with the Behçet syndrome who primarily had mucocutaneous lesions without major organ involvement. INTERVENTION: Thalidomide, 100 mg/d or 300 mg/d, or placebo for 24 weeks. MEASUREMENTS: Sustained absence of any oral and genital ulceration during treatment (complete response) and changes in the number of mucocutaneous lesions. An additional evaluation was done 4 weeks after treatment ended. RESULTS: A complete response occurred in 2 of the 32 patients (6% [95% CI, 0.8% to 20.8%]) receiving thalidomide, 100 mg/d; in 5 of the 31 patients (16% [CI, 5.5% to 33.7%]) receiving thalidomide, 300 mg/d; and in none of the 32 patients (0% [CI, 0% to 10.9%]) receiving placebo (P = 0.031). The suppressive effect of thalidomide with either dosage was evident at 4 weeks for oral ulcers (P < 0.001) and at 8 weeks for genital ulcers (P < 0.001) and follicular lesions (P = 0.008). This effect persisted during treatment but diminished rapidly after treatment was discontinued. Both thalidomide dosages led to significant increases in the number of erythema nodosum lesions during the first 8 weeks of treatment (P = 0.03). Polyneuropathy developed in 4 patients (1 in the 100-mg/d group and 3 in the 300-mg/d group); in 3 of these patients, the condition was diagnosed after the trial had ended. CONCLUSIONS: Thalidomide is effective for treating the oral and genital ulcers and follicular lesions of the Behçet syndrome. A dosage of 100 mg/d is as effective as a dosage of 300 mg/day.

Small vessel vasculitis and vasculitis confined to skin.

Cutaneous vasculitis is a heterogeneous group of disorders, which can be confined to the skin or may be part of an associated systemic disease. Various aetiological agents as well as conditions that mimic skin vasculitis, usually present with similar clinical features; mainly palpable purpura. The skin biopsies usually show leukocytoclastic vasculitis. This poses a great diagnositc and therapeutic challenge for the physician. The aetiologies, clinical features, diagnosis and treatment modalities for each form (drugs, infections, malignancies, systemic vasculitides, connective tissue disorders. Schönlein-Henoch purpura, cryoglobulinaemia, cutaneous periarteritis nodosa, livedoid vasculitis, erythema elevatum diutinum and urticarial vasculitis) are reviewed.

Azathioprine in Behcet's syndrome: effects on long-term prognosis.

OBJECTIVE: To assess the effect of azathioprine (AZA) treatment on long-term prognosis in Behçet's syndrome. METHODS: Patients (all male) who took part in a double-blind, placebo-controlled trial of AZA a mean +/- SD of 94 +/- 10 months previously were reevaluated. RESULTS: The emergence of blindness (log rank chi2 = 5.6, P = 0.02) and a 2-line drop in the visual acuity of the right eye (log rank chi2 = 5.9, P = 0.015) occurred significantly more frequently among the patients originally allocated to the placebo group compared with patients who originally received AZA, despite posttrial treatment for patients in both groups when needed. There was also a trend toward more frequent occurrence of extraocular complications in the placebo group. The beneficial effect of AZA was especially pronounced among patients who had eye involvement of short duration prior to their entry into the trial. CONCLUSION: Early treatment with AZA tends to favorably affect the long-term prognosis of Behçet's syndrome.

Vasculitis in familial Mediterranean fever.

OBJECTIVE: To evaluate the frequency of vasculitis, mainly in the forms of Henoch-Schönlein purpura and polyarteritis nodosa (PAN), and to investigate the presence of occult blood in the first stool specimens after an abdominal attack in Turkish patients with familial Mediterranean fever (FMF). METHODS: Review of the charts of 207 patients with FMF seen between 1983 and 1993 with respect to clinical vasculitis. A prospective study designed to test the presence of occult blood in the first stool specimens obtained after abdominal attack and at least one week later in 36 patients with FMF compared with healthy and diseased controls. RESULTS: There were 15 patients with Henoch-Schönlein purpura (7%), 2 with definite and one with probable PAN (1%), one of whom developed perirenal hematoma. The diagnosis of FMF was made after the onset of Henoch-Schönlein purpura in 9 and subsequent to the development of PAN in one patient. Occult blood was positive in the first stool specimens obtained after an attack in 17 of the 36 patients with FMF (47%), a finding not reported previously. CONCLUSION: Vasculitis seems to be an important but not a widely recognized feature of FMF.