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Biomedical subjects

M Zierhut

Publications and source records attributed to M Zierhut.

90 records · Page 5Linked to original sources

[Bromocriptine in therapy of chronic recurrent anterior uveitis].

In animal studies, bromocriptine (Pravidel) has demonstrated immunosuppression because of inhibition of prolactin. After publication of positive results in the treatment of uveitis in a few case reports and in an uncontrolled study we conducted a double-blind placebo-controlled study in 13 patients with chronic recurrent anterior uveitis who had experienced three or more recurrences during the previous year. Therapy was started gradually during the symptom-free interval and continued for 1 year with 2.5 mg twice daily. Two recurrences or relevant side effects led to discontinuation of the therapy. In the bromocriptine group, 2 of 7 patients had no recurrences during the study period. Two patients had to stop because of two recurrences but, in contrast to earlier recurrences, they responded to local corticosteriod treatment within a few days. The remaining 3 patients (1 with one recurrence, 2 without) had to stop because of the side effects (arterial hypotension, arthritic complaints). In 5 of 6 patients in the placebo group treatment was stopped because of recurrences and in 1 patients because she believed she was experiencing a side effect from bromocriptine (breast atrophy). In summary, bromocriptine seems to have a prophylactic effect on anterior uveitis. Side effects were frequent but mild compared to other immunosuppressives. In case of arterial hypotension, additional therapy could make this drug more tolerable.

Adolescent↗

[Drug-induced exudative erythema multiforme major with a chronic progressive course and bilateral blindness. Clinical and immunohistologic follow-up].

A 24-year-old male patient who had been received Fansidar developed exudative erythema multiforme major with massive involvement of the skin, mucous membranes, and both eyes. The chronic inflammation led to proliferation of the conjunctiva, with keratinization of the ocular surface and corneal vascularization. The final result was comparable to cicatricial pemphigoid, with blindness of both eyes. In histological sections, massive lympho-plasma-cellular infiltration with circumscribed perivasculitis was seen. The lymphocyte transformation test was still positive 18 months after onset of the disease. Class II antigens were evident in some of the conjunctival biopsies.

Adult↗

[Indication for and interpretation of immunohistological studies of the conjunctiva and cornea].

Various conjunctival and corneal biopsies of eyes with chronic inflammation of the outer segment (e.g., following chemical burns, chronic proliferative conjunctival alterations) were examined using monoclonal antibodies. Class II antibodies were found in both epithelial and stromal conjunctival cells, indicating that there may be some etiological significance to an autoimmune process in altered tissue.

Conjunctiva↗

[Clinical types of immunologic transplant reactions following perforating keratoplasty].

The incidence of allograft rejection was determined for 740 penetrating keratoplasties performed between 1980 and 1987. All 740 cases were followed up for at least 1 year. The reaction forms of allograft rejection were grouped according to biomicroscopic appearance. The incidence and progression of symptoms are described. Rejection types are subdivided into patients with favorable versus poor prognosis. Of the patients 37.9% demonstrated an immune response (including discrete forms). Clear reaction patterns within the two groups of patients became apparent when reaction variations were carefully differentiated. Epithelial immune reaction was found in 5.2%/10.5% and subepithelial infiltration in 1.7%/4.8% of the patients with favorable/poor prognosis. The largest disparity in frequency occurred in progressive endothelial reaction; 3.8% in patients with favorable versus 36.7% in patients with poor prognosis. Focal endothelial reactions occurred in both groups with comparable frequencies (14.1%/13.3%). The large percentage of immunological reactions, including late manifestations (approximately 12% after 1 year) and some with irreversible progression, warrants continuing efforts to treat and prevent this complication.

Cornea↗

Ocular involvement in epidermolysis bullosa acquisita.

A 23-year-old man had epidermolysis bullosa acquisita that was diagnosed at the age of 20 years. The eye examination showed bilateral, small subepithelial vesicles in the cornea. The direct immunofluorescence microscopic examination of the conjunctiva revealed homogeneous, linear IgG and fibrinogen deposits in the basement membrane area. The same pattern appeared in the skin biopsy specimen. No systemic disease common to epidermolysis bullosa acquisita was found in the patient.

Adult↗

Topical treatment of severe corneal ulcers with cyclosporin A.

Cyclosporin A eye drops were used on six patients to treat corneal ulcers associated with rheumatic diseases, oculomucocutaneous syndrome, and Sjögren's syndrome. Conjunctival excision was additionally carried out in two cases. All ulcers healed rapidly. The mechanism of ulcer formation involving T-lymphocytes is discussed.

Administration, Topical↗

[Acute necrotizing retinitis following varicella zoster virus infection].

As far as we know today, acute retinal necrosis is caused by infection with a virus of the herpes group. Reports are occasionally published of retinitis developing before or after herpes zoster dermatitis. The present paper reports the case of a patient who developed a retinitis of the right eye five years after a herpes zoster infection of the ophthalmic nerve. Studies and treatment of VZV retinitis and retinitis before or after zoster retinitis reported in the literature are summarized. The possible mechanisms of generalization (neurogenic or hematogenous) are analyzed.

Acute Disease↗

[Bromocriptine: a new therapy concept in the treatment of chronic recurrent uveitis?].

Chronic recurrent uveitis still responds unsatisfactorily to therapy. Prolactin, a pituitary hormone that attains high blood levels physiologically in stress situations, has an immune modulating effect. The prolactin antagonist bromocriptine (2 x 2.5 mg/day) was administered prophylactically to prevent recurrence in seven patients with chronic iritis/iridocyclitis or panuveitis (Group A). On this therapy two patients suffered a mild recurrence (in one case in the first month). Another patient developed rebound uveitis after discontinuing bromocriptine medication. Tolerance appears to vary considerably, and in three patients the therapy had to be discontinued because of arterial hypotension and congestive rhinopathy, respectively. The three patients in Group B (with iritis, sympathetic ophthalmia, and intermediate uveitis) received bromocriptine in addition to cyclosporin A after plasmapheresis. This combination resulted in an elevated cyclosporin A plasma level, and the dosage was reduced by 30-50% (plasma level 70-120 ng/ml). With this lower dosage of cyclosporin A, the creatinine level of one of the patients returned to normal. Viewed on the basis of these initial results bromocriptine would appear to reduce the number of recurrences of chronic uveitis. Moreover, the synergism with cyclosporin A, described both theoretically and in an animal model in the literature, appears attainable in therapy.

Adult↗

Panuveitis with positive serological tests for syphilis and Lyme disease.

The Treponema pallidum hemagglutination test and the fluorescent treponemal antigen absorption test are commonly considered highly specific serologic tests for syphilis. We describe a patient with panuveitis and a positive serologic result for syphilis; however, in the absence of clinical findings, additional tests for Lyme disease (borreliosis) were positive as well, although by Western blot test the diagnosis was tentative. The clinical appearance of the panuveitis was similar to that of syphilitic uveitis accompanied by pseudopigmentosa-like areas in the anterior retina. In the presence of uveitis with an otherwise unexplained positive serologic result for syphilis, the differential diagnosis of Lyme disease should be considered.

Diagnosis, Differential↗

[Nonspecific eye autoantibodies in uveitis].

Under certain pathologic circumstances autoantigens lead to the formation of autoantibodies. In uveitis, autoimmunologic phenomena will also be discussed. We studied 149 sera of uveitis patients for various organ specific and non-organ specific autoantibodies. We found antisarcolemal autoantibodies (ASA) mainly in patients with acute iritis (59% positive) but also in panuveitis (40%) and iridocyclitis (29%). On the other hand antiendothelial antibodies (AEA) could be found in 43% of patients with chorioretinitis. Antisinusoidal antibodies (SA) have been detected in iritis and panuveitis patients more often than in the control group which show positive autoantibodies in 5% of all cases. Using ELISA we looked for antibodies against keratin, laminin and microsomes. Because antimicrosomal-, antilaminin- and antisarcolemal-antibodies recognize the same epitope, there was a good correlation of these three autoantibodies. Similar clusters of autoantibodies (ASA, AEA and SA) have been found in various infectious diseases and in chronic inflammatory diseases in which an infectious component is discussed. These results may indicate that iritis, iridocyclitis, chorioretinitis and panuveitis are secondary reactions of eye tissue following a systemic primary disease. Especially viruses are well-known for their production of autoantibodies. In patients with intermediate uveitis we could not demonstrate these autoantibodies more often than in the control group, favouring theories which believe in an autoimmune reaction against vitreous elements.

Antibodies, Antinuclear↗

[Bullous dermatosis with conjunctival and corneal involvement: differential diagnostic scope and explanation of the "overlap syndrome" concept].

Chronic blister-forming dermatosis can lead to conjunctival and corneal involvement. Taking one such case as an example, the authors show that while disorders of this kind can be classified as a form of bullous dermatosis, the differential diagnostic classification is not unequivocal, regardless of the examination method adopted. The term "overlay syndrome" has been introduced into the dermatologic literature to cover clinical pictures of this kind.

Adolescent↗

[Immune reactions of the conjunctiva and cornea following severe chemical burns of the outer eye].

Conjunctival and corneal tissue samples from nine patients with severe changes after acid and alkali burns were examined immunohistochemically. Epithelial HLA Class II antigen expression was present in three of five conjunctival samples, and all of the antigen markers examined in the conjunctival stroma could be stained. HLA Class II expression was demonstrated in four out of five corneal tissue samples. The results show that in Grade III or IV chemical burns, with the diverse changes of the external eye that they produce, immunological and possibly also autoimmune mechanisms can influence the clinical course.

Autoimmune Diseases↗

[Abnormal expression of HLA class II antigens in conjunctival epithelia in peripheral corneal ulcers].

Inflammatory mediators originating at the limbus seem to play an important role in the pathogenesis of peripheral corneal ulcers. In this paper, the immunohistological results of conjunctival biopsies of patients with corneal ulcers are reported. The most important result was that an abnormal HLA class II expression was found. The expression of HLA-DR was stronger than that of HLA-DQ and HLA-DP. A model of ulcer formation involving T-cells and lymphokines is presented.

Biopsy↗

Cytokines, cytokine antagonists and soluble adhesion molecules in patients with ocular Behçet's disease treated with human recombinant interferon-alpha2a. Results of an open study and review of the literature.

OBJECTIVE: To elucidate the influence that interferon-alpha exerts on the cytokine network in active ocular Behçet's disease (BD). METHODS: Fifty patients with active ocular BD were treated with human recombinant interferon-alpha2a (rhIFN-alpha2a). Serum was analysed for the presence of IL-10, TNF-alpha, IL-8, IL-6, sIL-2R, IFN-gamma, IFN-alpha, IL-12, IL-4, sTNFRI (p55), sTNFRII (p75), IL-1RA, G-CSF, sE-selectin, sVCAM-1, sICAM-1 and neopterin before initiation of and at several time points during IFN treatment and compared to 21 healthy controls. RESULTS: The levels of IFN-alpha IL1-RA and sTNFRII were significantly increased in the patients at baseline in comparison to healthy controls. During treatment with rhIFN-alpha2a, when remission was achieved as defined by the scoring system used, a significant increase in levels of IFN-alpha, IL-2R, TNF-alpha, sTNF-RII, sICAM-1, sVCAM-1, neopterin in the serum was observed, with a tendency towards increased IL-1RA as well. In contrast, leuko- and thrombocyte counts and sE-selectin serum levels significantly decreased. Positive correlations were found between IFN dosage or serum levels and sVCAM-I, neopterin, sTNF-RII and sIL-2R, between sVCAM-1, sIL-2R, TNF-alpha, sTNF-RII and neopterin, sICAM-I and sVCAM-1, sIL2-R and sTNF-RII, and, finally, between sIL2-R and sICAM-I. CONCLUSIONS: IFN-alpha exerts diverse influences mainly on cytokine antagonists and soluble adhesion molecules. Because sTNF-RII and IL-1RA were increased by IFN-alpha treatment, these might be interesting alternative treatment options in refractory BD. Some of the side-effects of IFN-alpha may be caused by activation of monocytes, which is reflected by an increase in neopterin serum levels.

Antiviral Agents↗

[Keratomalacia in rheumatoid arthritis: immunohistologic and enzyme histochemical studies].

Corneal and conjunctival biopsies of 13 patients with rheumatoid arthritis and corneal ulceration (RA-keratomalacia) have been characterized by immunohistological and histochemical analysis. Biopsies from 13 patients with bacterial conjunctivitis, 7 patients with allergic conjunctivitis, 15 patients with senile cataract and 15 patients with keratokonus served as controls. The phenotypic composition of the conjunctival inflammatory infiltration of rheumatoid corneal ulceration was not significantly different from the other inflammatory eye diseases studied. However, conjunctival epithelial cells of all RA-patients showed strong de novo expression of HLA-DR- and DP-antigens. HLA-DQ-antigens were only weakly expressed in a minority of patients. In bacterial conjunctivitis a less intense HLA-class-II-expression was found to be restricted to HLA-DR-antigens. Furthermore, in RA patients stromal fibroblasts of the cornea expressed lysosomal elastase. Both observations could be explained by paracrine action of interleukins produced by infiltrating T-lymphocytes and macrophages. Thus, it might be tempting to speculate that immunologically induced, elastase mediated autodegradation of corneal stroma may be an important factor in the pathogenesis of rheumatoid corneal ulceration.

Antigens, Differentiation, T-Lymphocyte↗

MAGIC or not MAGIC--does the MAGIC (mouth and genital ulcers with inflamed cartilage) syndrome really exist? A case report and review of the literature.

INTRODUCTION: In 1985, Firestein et al. described 5 patients with relapsing polychondritis and Behçet's disease (BD) and proposed the term "MAGIC" syndrome as an acronym for "Mouth and Genital ulcers with Inflamed Cartilage". We report on an additional case of this syndrome and critically review the literature. RESULTS: From 1985 to 2004 eleven cases of MAGIC syndrome were described. All patients had chondritis and oral aphthous ulcers, as well as ocular inflammation (mainly anterior uveitis or scleritis/episcleritis). Most patients also presented with genital ulcers and arthritis. In one case, aortic aneurysm, in another aortic insufficiency was described, one had meningoencephalitis, one had antiphospholipid syndrome and one was HIV positive. Before 1985, we could find 4 additional probable cases. Our own patient presented with oral and genital ulcers, auricular chondritis and episcleritis. HLA-typing was performed and revealed HLA-B*51, B*15, DRB1*04x and DRB1*11x. Only in one Japanese patient from the literature, HLA-typing was available and revealed HLA-B*56, B*62, DRB1*0406 and DRB1*0901. CONCLUSIONS: Relapsing polychondritis is associated with HLA-DRB1*04 suballeles, but not necessarily only with those being associated with RA (DRB1*0401 and 0404). In 2 MAGIC patients these suballeles were found. All patients described in the literature had typical polychondritis, but not all did fulfil the classification criteria for BD. Many features of both diseases overlap and are not specific. As polychondritis is associated with other inflammatory rheumatic conditions such as SLE, spondyloarthropathy, rheumatoid arthritis and systemic vasculitides in 30% of all cases, we suggest that MAGIC syndrome is not a disease entity, but merely the association of BD with polychondritis.

Behcet Syndrome↗