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Biomedical subjects

Manfred Zierhut

Publications and source records attributed to Manfred Zierhut.

At least 19 recordsLinked to original sources
PubMed2006

Adalimumab in the therapy of uveitis in childhood.

PURPOSE: Chronic anterior uveitis in children often takes a serious course. Despite various immunosuppressive drugs some children do not respond sufficiently and there is a high risk of them becoming seriously disabled. Anti-TNF alpha therapy has been shown by our group and others to be mostly ineffective (Etanercept) or partly effective (Infliximab) with the risk of anaphylactic reactions. Here we report on 18 young patients treated with Adalimumab (Humira), a complete humanised anti-TNF alpha antibody. METHODS: We retrospectively analysed 18 patients, who were treated with Adalimumab (20-40 mg, every 2 weeks, when ineffective every week); 17 had juvenile idiopathic arthritis, one was without detectable underlying disease. The age at onset of arthritis varied from 0.5-15 years and for uveitis from 2-19 years. Patients were included when the previous anti-inflammatory therapy had been ineffective. It consisted of systemic steroids (n = 18), Cyclosporin A (n = 18), Methotrexate (n = 18), Azathioprine (n = 12), Mycophenolate mofetil (n = 4), Cyclophosphamide (n = 2), Leflunomide (n = 3), Etanercept (n = 8) and Infliximab (n = 5). The grading for uveitis was: (a) effective: no relapse or more than two relapses less than before treatment, (b) mild: one relapse less than before treatment, (c) no response: no change in relapse rate and (d) worsening: more relapses under treatment than before. The grading for arthritis (depending on the clinical findings), using three out of six parameters of the ACR PED Criteria, was: effective, mild, no response, worsening. RESULTS: For arthritis (n = 16) the response to Adalimumab was effective in 10 of 16 patients, mild in three patients, three did not respond. For uveitis (n = 18) Adalimumab was effective in 16, mild in one child, and one patient did not show any effect. After a very good response initially a shorter application time had to be used to maintain the good anti-inflammatory effect in one child. Additional immunosuppressive treatment was used in seven of the effectively treated children. Due to elevation of liver enzymes in one patient, who also took MTX, Adalimumab had to be discontinued. No anaphylactic reactions or increased frequency of infections since start of Adalimumab treatment was reported. CONCLUSIONS: For our group of children with long lasting disease our results show that Adalimumab was effective or mildly effective against the arthritis in 81%, but in uveitis in 88%. While these results regarding arthritis are comparable with other TNF-alpha blocking drugs (Etanercept), Adalimumab seems to be much more effective against uveitis than Etanercept. Anaphylactic reactions, found in a previous study from our group after Infliximab treatment, were not seen with Adalimumab. The necessary dosage and the treatment period, which probably have to be defined individually for each patient, remain unclear.

Adalimumab↗
PubMed2006

High incidence of antibodies to lens proteins in sera from patients with uveitis.

BACKGROUND: Uveitis is an intraocular inflammatory disease in which autoimmune reactions have been discussed in playing an important role. Many data in this respect derived from the animal model of "experimental autoimmune uveitis", where several organ-specific autoantigens have been described such as the retinal S-antigen and the interphotoreceptor retinoid-binding protein. However, their diagnostic and pathogenic role in humans has been controversially discussed. In recent studies, the possible relevance of betaB1-crystallin, present in lens and ciliary body, has been outlined. We, therefore, wanted to analyse whether sera from patients with uveitis might contain antibodies to lens proteins METHODS: Human lenses from cadaveric eyes were shock frozen, homogenized, and resuspended. The resulting suspension (human lens protein fraction--HLPF) was analyzed for antigenicity by ELISA and Western blotting with patients' sera. A total of 165 patients with uveitis, 54 patients with scleritis and episcleritis, 56 patients with other eye diseases, and 112 healthy blood donors were studied. RESULTS: Twenty-six (49%) of the 53 patients with anterior uveitis, 17 (32%) of the 53 patients with intermediate uveitis and 7 (22%) of 32 patients with posterior uveitis reacted in the ELISA with the HLPF. Antibodies to lens antigens were detected in one-third of patients with panuveitis and retinal vasculitis. In contrast, only 12% of the healthy blood donors were positive in the ELISA. The number of patients with an autoimmune response to alpha-crystallins in Western blot predominated in all investigated groups. CONCLUSIONS: These data indicate that antibodies to lens proteins occur in a high incidence in sera from patients with uveitis. Forty-nine percent of the patients with anterior uveitis and only 12% of healthy controls were positive in the ELISA. In our groups of patients and controls the autoantibodies reacted in the Western blot predominantly with alpha-crystallin. Further studies are required to analyze in more detail the clinical and etiopathogenetic relevance of the antilens antibodies in uveitis.

Autoantibodies↗
PubMed2006

Interferon alfa-2a: a new treatment option for long lasting refractory cystoid macular edema in uveitis? A pilot study.

PURPOSE: To perform a prospective pilot study to evaluate interferon alfa-2a (IFN alfa-2a) for the treatment of refractory cystoid macular edema (CME) in endogenous uveitis. METHODS: IFN alfa-2a was administered at an initial dose of 3 or 6 million IU (depending on body weight) per day subcutaneously. Afterwards IFN alfa-2a was tapered slowly over 6 months and finally discontinued. If CME relapsed IFN alfa-2a was reinstituted and tapered slowly again to evaluate the lowest maintenance dose to keep remission. RESULTS: A total of 15 eyes of 8 patients with refractory CME due to intermediate or posterior uveitis were included. Ineffective pretreatment consisted of systemic steroids and acetazolamide (all patients) and at least one additional immunosuppressant (6 patients). Six of 8 patients (11 eyes) responded well to IFN alfa-2a and CME resolved completely during 6 months treatment. One patient was lost to follow-up after IFN alfa-2a was stopped. In 1 patient (1 eye) even 19 months after cessation of IFN alfa-2a no recurrence of CME occurred. In 4 patients (8 eyes) IFN alfa-2a had to be reinstituted because CME relapsed. All 4 patients responded again. During a mean follow-up period of 16.4 months since restart of therapy we succeeded in all 4 patients to taper IFN alfa-2a to maintenance doses between 1.5 million IU every second and every sixth day without a recurrence of CME in any of the 8 eyes. CONCLUSION: IFN alfa-2a can be a treatment option for patients with otherwise treatment resistant uveitic CME.

Adult↗
PubMed2006

Amphotericin B in the therapy of Candida glabrata endophthalmitis after penetrating keratoplasty.

PURPOSE: Candida glabrata is a rare cause of endophthalmitis after penetrating keratoplasty. Adequate therapy is still under discussion. With respect to severe complications and side effects of antifungal therapy, a substantial knowledge of sensitivity and resistance of the organism is necessary. METHODS: We report on a 26-year-old man with a hyperacute onset of the infection only 10 hours after surgery. A combined therapy for fluconazole and steroids administered over 3 months had shown no effect on intraocular infection. RESULTS: After topical and intracameral application of amphotericin B in combination with topical prednisolone 3 months after the onset of the endophthalmitis, the infection disappeared within 14 days, and the graft remained clear for 2 months. No toxic effects were noticed. CONCLUSION: In the case presented here, topical and intracameral application of amphotericin B was sufficient and safe in the therapy for C. glabrata endophthalmitis after penetrating keratoplasty. Although typically the intraocular infection is first noticed within the first 2 weeks, a hyperacute onset has to be considered.

Adult↗
PubMed2005

Mycophenolate mofetil is a highly effective and safe immunosuppressive agent for the treatment of uveitis : a retrospective analysis of 106 patients.

BACKGROUND: We evaluated the outcomes of patients with different forms of chronic uveitis treated with mycophenolate mofetil (MMF) as an immunomodulatory and steroid-sparing agent. The multi-system side effects that arise after long-term treatment with corticosteroids and other immunosuppressants prompted us to use MMF. MMF is a selective inhibitor of inosine monophosphate dehydrogenase, thus blocking purine synthesis via the de novo pathway preferentially used by T and B lymphocytes. METHODS: Between 1998 and 2003, 106 patients were treated for uveitis (anterior n=26, intermediate n=51, posterior n=23, panuveitis n=6) with MMF at a dose of 1g twice daily. Treatment duration was at least 6 months (n=10), in most cases greater than 12 months (n=77) and in 25 cases between 24 months and 41 months, when the present retrospective evaluation was undertaken. Patient charts were analysed according to a standardized evaluation protocol. RESULTS: In 95 patients MMF was combined with prednisolone at a dosage of 2.5-10 mg per day. In 8 patients MMF was used as a monotherapy, and in 3 cases one further systemic immunosuppressant was required. The number of recurrences during MMF treatment was none or one in 92 patients, two in 6 cases and three or more in 8 patients. In none of the patients had MMF been stopped at the time of data analysis. The most frequently observed side effects were gastrointestinal upset (15%), followed by headache (9.3%), fatigue (5.7%), eczema (5%), and hair loss (3.5%). Other side effects were sporadic. Most of these phenomena were transitory. Forty-two patients experienced no side effects at all. In 4 patients MMF was judged ineffective due to failure to reduce the number of recurrences of severe inflammation compared with the previous therapeutic regime, or indeed occurrence of persistent macular oedema. CONCLUSIONS: Our results show that MMF is an effective immunosuppressant in patients with uveitis. We provide evidence that MMF controls the disease in the majority of patients with an acceptable profile of side effects.

Adolescent↗
PubMed2004

Differential efficacy of human recombinant interferon-alpha2a on ocular and extraocular manifestations of Behçet disease: results of an open 4-center trial.

OBJECTIVE: Behçet disease (BD) is a multisystem vasculitis of unknown origin. Standard treatment mainly comprises systemic immunosuppressive agents. In a study primarily designed for refractory ocular disease, we additionally evaluated the efficacy of recombinant human interferon-alpha2a (rhIFN-alpha2a) on the extraocular manifestations of BD. METHODS: Fifty patients were included in the study. RhIFN-alpha2a was applied at a dose of 6 x 10(6) units subcutaneously daily. Dose reduction was performed according to a decision tree until discontinuation. Disease activity was evaluated by the Behçet's Disease Activity Scoring System and the Uveitis Scoring System. RESULTS: Response rate of the ocular manifestations was 92%. Visual acuity rose significantly from 0.56 to 0.84 at week 24 (P <.0001). Mean Behçet's Disease Activity Score fell in a dose-dependent fashion by 1.2 points in the first week (P <.0001) and 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, 17 patients have been off treatment and disease-free for 29.5 months (mean). In the other patients, maintenance IFN dosage is 3 million units 3 times weekly. Whereas extraocular manifestations such as genital ulcerations, arthritis, and skin lesions remitted with IFN, only 36% of oral aphthous ulcers responded. CONCLUSIONS: RhIFN-alpha2a is effective in ocular BD, resulting in significant improvement of vision and complete remission of ocular vasculitis in the majority of patients. It is also beneficial for the extraocular manifestations of the disease, although less so for oral aphthous ulcers.

Adult↗
PubMed2004

The use of interferon alpha in Behçet disease: review of the literature.

OBJECTIVES: To evaluate the efficacy and safety of interferon (IFN) alpha for the treatment of Behçet's disease (BD) and discuss its possible mechanisms of action. METHODS: Reports published until July 2002 in all languages were identified by the PubMed Database and the BD conference proceedings and abstract booklets. The indexing terms used were "Behçet" and "interferon." RESULTS: Thirty-two original reports and 4 selected abstracts were included in the analysis. Systemic IFN-alpha was administered to 338 patients. One hundred eighty-two patients with acute ocular disease were treated with IFN-alpha. Two hundred sixty-four patients received IFN-alpha2a, and 74 received IFN-alpha2b. Eighty-six percent of the patients with mucocutaneous symptoms, 96% with arthritis, and 94% with uveitis exhibited a partial or complete response. Higher IFN doses were more effective than low-dose regimens and led to up to 56% long-term remissions after discontinuation of IFN-alpha were reported. IFN-alpha2a apparently was superior to IFN-alpha2b, with more complete remissions, but this probably was the result of a bias caused by the larger number of patients treated with IFN-alpha2a. Side effects were dose-dependent and similar to those noted in patients with hepatitis C. CONCLUSIONS: Although the comparability of the studies is hampered because of different study designs, IFN-alpha is effective for the treatment of BD. It was beneficial even in resistant posterior uveitis, in which long-term remissions with preservation of visual acuity was achieved. In contrast, mostly partial remissions were reported for mucocutaneous symptoms.

Adult↗
PubMed2004

Behçet's disease in patients of German and Turkish origin living in Germany: a comparative analysis.

OBJECTIVE: To evaluate the relationship between ethnic origin and manifestations of Behçet's disease (BD) in patients of German and Turkish origin living in Germany. METHODS: Between 1995 and 2000, 32 patients of German and 33 patients of Turkish origin living in Germany were evaluated for the entire spectrum of disease manifestations, disease severity, HLA associations, sex, age at disease manifestation, and time to diagnosis. RESULTS: There were no statistically significant differences between German and Turkish patients. There was no association of sex or HLA-B51 with any manifestation of BD. The only significant difference between the 2 groups was the median time from the first manifestation of the disease to diagnosis, which was 0 years for the Turkish, but 3.5 years for the German patients (p = 0.0005). Additionally, 4 patients of German origin had been misdiagnosed as having spondyloarthropathy (SpA) before the final diagnosis of BD was made (12%). In comparison to Turkish patients living in Turkey (data from the literature), only 2 differences were found: one concerned the frequency of ocular involvement (lower in the patients in Turkey), and the other the male to female ratio, which was reported as 1.03:1 in Turkey, but 3.7:1 in Germany. CONCLUSION: Our results do not favor an ethnic influence on the expression of BD. Environmental influences may be responsible for the higher frequency of ocular manifestations and the higher male to female ratio in patients living in Germany compared to those living in Turkey.

Adolescent↗
PubMed2003

EBV-induced polymorphic lymphoproliferative disorder of the iris after heart transplantation.

BACKGROUND: Posttransplantation lymphoproliferative disorder (PTLD) of the iris is a rare entity with only ten cases having been published as yet. Its clinical aspect is typical. Therapy is multimodal and affords an interdisciplinary approach. METHODS: A 7-year-old boy developed a lymphoproliferative mass of the iris with uveitis 4 years after heart transplantation and immunosuppression. A progressive, flesh-colored thickening of the iris with secondary angle closure glaucoma necessitated a diagnostic and therapeutic iridectomy. Morphological investigation of the iris specimen disclosed a polymorphic posttransplantation lymphoproliferative disorder (PTLD) and the presence of Epstein-Barr virus (EBV) within the tissue. The EBV load in peripheral blood monocytes was massively elevated, thus indicating a chronic EBV infection. After conservative treatment and radiation therapy, the iris mass quickly resolved. There was no evidence of systemic PTLD. CONCLUSIONS: PTLD is a well-known, EBV-induced entity that rarely affects the eye. EBV is principally detectable in specimens of iris PTLD. If conservative, antiviral treatment fails, the iris lesions can be treated by local radiation therapy with very good success. In the near future, patients with PTLD of the eye may benefit from immunologic treatment with ex vivo generation of virus-specific T-lymphocytes.

Antiviral Agents↗