Ilhan Günaydin

Human recombinant interferon alfa-2a for the treatment of Behçet's disease with sight threatening posterior or panuveitis

Background: Behçets disease is a multisystem vasculitis of unknown origin. Standard treatment mainly comprises systemic immunosuppressive agents. Ocular involvement, mostly posterior uveitis with retinal vasculitis, leads to blindness in 20–50% of the involved eyes within 5 years. The efficacy of interferon alfa-2a was studied in patients with sight threatening posterior uveitis or retinal vasculitis. Methods: 50 patients were included in this open, non-randomised, uncontrolled prospective study. Recombinant human interferon alfa-2a (rhIFNα-2a) was applied at a dose of 6 million units subcutaneously daily. Dose reduction was performed according to a decision tree until discontinuation. Disease activity was evaluated every 2 weeks by the Behçets disease activity scoring system and the uveitis scoring system. Results: Response rate of the ocular manifestations was 92% (three non-responder, one incomplete response). Mean visual acuity rose significantly from 0.56 to 0.84 at week 24 (p<0.0001). Posterior uveitis score of the affected eyes fell by 46% every week (p<0.001). Remission of retinal inflammation was achieved by week 24. Mean Behçets disease activity score fell from 5.8 to 3.3 at week 24 and further to 2.8 at week 52. After a mean observation period of 36.4 months (range 12–72), 20 patients (40%) are off treatment and disease free for 7–58 months (mean 29.5). In the other patients maintenance IFN dosage is three million units three times weekly. Conclusions: rhIFNα-2a is effective in ocular Behçets disease, leading to significant improvement of vision and complete remission of ocular vasculitis in the majority of the patients.

CNS involvement occurs more frequently in patients with Behçet's disease under cyclosporin A (CSA) than under other medications—results of a retrospective analysis of 117 cases

The aim of this study was to evaluate the incidence of neurological manifestations of Behçets disease (BD) in patients on cyclosporin A (CSA) compared with those on other medications. The records of 117 patients with BD who visited our hospital between 1990 and 2003 were reviewed with respect to symptoms and medication. All episodes of constant therapy prior to central nervous system (CNS) involvement were counted, and then the associations were analysed by the exact Fisher–Freeman–Halton test and adjusted for multiple tests by the Bonferroni–Holm method. We observed ten new cases of CNS manifestations in our patients with BD being regularly seen and treated in our tertiary care centre. The overall prevalence of neuro-BD in our patient group was 8.5%. In a retrospective analysis, the incidence of new-onset neurological disease (neuro-BD) in all patients with BD who regularly visited our hospital was significantly higher in patients on CSA than in those on other medications (6 of 21 vs 0 of 175 episodes, P<0.0001). This contrasts the obvious efficacy of CSA on extracerebral manifestations of BD, such as severe ocular disease, mucocutaneous lesions or arthritis. CSA exerts differential efficacy on various manifestations of BD. It is very effective for severe ocular and other moderate to severe manifestations of BD, but its efficacy for the prevention of neuro-BD seems to be inferior to that of other medications used in BD, such as azathioprine or interferon-α. The reasons for this are unclear, but the potential toxic effects of CSA on the CNS may be a predisposing factor for CNS vasculitis in BD.

Efficacy and tolerability of interferon alpha treatment in patients with chronic cystoid macular oedema due to non-infectious uveitis

Aim: To assess the efficacy and tolerability of interferon (IFN) alpha in chronic cystoid macular oedema (CMO) due to non-infectious uveitis. Methods: Retrospective analysis of an interventional case series. IFN alpha-2a was administered at an initial dose of 3 or 6 million IU per day subcutaneously and tapered afterwards to the lowest possible dose to maintain the absence of CMO. Treatment efficacy was assessed by optical coherence tomography. Results: Twenty-four patients with chronic CMO (median duration 36.0 months) due to non-infectious anterior (n = 2), intermediate (n = 18) or posterior (n = 4) uveitis have been analysed. Ineffective pretreatment included systemic corticosteroids (all patients), acetazolamide (22 patients) and at least one immunosuppressive drug (18 patients). IFN therapy was shown to be effective ( = complete resolution of CMO within 3 months, able to taper IFN) in 15 patients (62.5%), partly effective ( = incomplete resolution of CMO, unable to taper IFN) in six patients (25.0%) and not effective ( = no response or recurrence of CMO) in three patients (12.5%). IFN treatment was generally well tolerated. Common side effects including flu-like symptoms, fatigue or increased liver enzymes were dose-dependent and led to discontinuation of IFN in only one patient. Conclusion: The data demonstrate IFN alpha to be an effective and well-tolerated therapy for chronic refractory uveitic CMO.

Assessment of keratoconjunctivitis sicca in patients with fibromyalgia: results of a prospective study

Abstract Patients with fibromyalgia (FM) often describe the presence of dry eyes and other ocular symptoms. It has been claimed that a subgroup of patients with FM might have features suggestive of primary Sjögren syndrome. In others, such a relationship could not be found. The purpose of the present study was to investigate the association and prevalence of keratoconjunctivitis sicca (KCS) in patients with FM. Among 285 patients with FM, 40 patients reporting sicca symptoms were screened with Schirmers I test, break-up time and Rose-Bengal score. KCS was diagnosed when two of the selected three tests gave pathological results. A detailed ophthalmological examination was also performed. In 15 patients the diagnosis of KCS could be confirmed. Eighteen of 40 patients had been taking low-dose antidepressants and 7 of them had objective signs of KCS. Eight of 40 patients had signs of chronic blepharitis and 4 of them had KCS. Fourteen patients showed unremarkable test results. Chronic blepharitis and the use of tricyclic antidepressants may play a role in developing KCS. It seems that the rate of KCS does not increase in patients with FM and they probably have objective ocular findings comparable with the normal population.

Articular involvement in patients with relapsing polychondritis

Abstract Our objective was to study joint symptoms in patients with relapsing polychondritis (RP) and their relationship to other clinical manifestations and laboratory findings. Fourteen patients who met the diagnostic criteria proposed by Michet et al. for RP were studied. Clinical symptoms were recorded and a detailed laboratory analysis with HLA-DR typing was carried out. In 2 patients arthritis was the first manifestation. During the follow-up, 10 patients developed arthritis. It was polyarticular in 6, and oligoarticular in 4 cases. The development of arthritis was unrelated to the appearance of chondritis at other sites. HLA class II typing was determined in 7 patients. Six of them were positive for HLA-DR4. Arthritis in RP is a frequent manifestation occurring in approximately 70% of patients with an asymmetric articular involvement. There is no correlation between articular involvement and any particular clinical or laboratory feature. Susceptibility to RP is significantly related to the presence of HLA-DR4.

Lower limb pitting edema in systemic lupus erythematosus.

Abstract We report two patients with lower limb pitting edema and systemic lupus erythematosus (SLE) who showed immediate response to systemic steroids. In one of the patients, the edema had been present for about 6 months and was the first manifestation of her SLE. In the second patient with a long history of SLE and antiphospholipid syndrome, a thrombosis was suspected, but not confirmed. Only after therapy with steroids did the edema disappear completely. Pitting edema of the lower limb could be a rare manifestation of SLE.

Influence of interferon-alpha on lymphocyte subpopulations in Behçet's disease.

In Behcet’s disease (BD)‚ several abnormalities of lymphocyte subpopulations such as an elevation of NK and T-cells have been described. Standard treatment comprises immunosuppressive drugs. We successfully treated 50 patients with ocular BD with interferon (response rate 92%) which is counterintuitive because is immunostimulatory and can sometimes even induce autoimmune diseases such as SLE or RA. The aim of this study was to elucidate the immunomodulatory effects that might exert in BD.

Collagenous colitis associated with rheumatoid arthritis and anticardiolipin antibodies

Collagenous colitis is a rare condition characterised by chronic watery diarrhoea and mild abdominal discomfort. Biopsy of the microscopically normal-appearing colon mucosa shows excessive subepithelial collagen. Primarily middle-aged and elderly women are affected. Since it was first described by Lindstr6m [1] in 1976, more than 200 cases have been reported worldwide [24]. An association with rheumatoid arthritis is very rare and only four such cases have been reported in recent years. We describe another patient with collagenous colitis associated with rheumatoid arthritis and anticardiolipin antibodies, who responded well to sulphasalazine therapy.

Behçet's Disease: Visual Acuity after 5 Years in Patients with Alpha-Interferon Treatment

Compared to conventional immunosuppressants, IFN-α2a seems to be much more effective to prevent a loss or decrease of visual acuity over a long period of time in patients with severe ocular BD.

Therapeutic approaches of German and Turkish physicians to rheumatoid arthritis and to osteoarthritis of the knee

SummaryOur objective was to compare the therapeutic approaches of German and Turkish physicians to rheumatoid arthritis (RA) and to osteoarthritis (OA) of the knee, by means of a mailed survey. The survey contained four case histories representing a mild, a moderate and a severe case of RA and a case of OA of the knee. One hundred and thirty-two physicians from Germany (internal medicine based (IR) and orthopaedics based (OR) rheumatologists) and thirty-three from Turkey (rheumatologists and physical medicine and rehabilitation specialists (PT) participated in the study.German respondents would give more disease-modifying drugs (DMARD) in early RA (48.7% vs 18.2%, p<0.05), whereas their Turkish colleagues would prescribe more analgesics, ultrasound and kryotherapy in OA of the knee (63.6% vs 22.1%, 30.3% vs 6.5% and 24.2% vs 0.0% respectively p<0.05). German physicians chose more exercise, physical and occupational therapy, radiation synovectomy and surgery in all cases. In OA of the knee German ORs would recommend less analgesics, but more local steroids, chondroprotective agents and surgery than the other groups.We may conclude that clinical practice of RA and OA of the knee differs considerably in Germany and Turkey. Cultural, social, educational and economic factors could influence the decisions of the physicians.