Systemic therapy of ocular and cutaneous rosacea in children.

BACKGROUND: In paediatric rosacea, ocular symptoms are often predominant. Literature about systemic therapy of paediatric ocular rosacea is sparse, though. OBJECTIVE: Analysis of children with ocular rosacea treated systemically, particularly addressing remission and recurrence rates. METHODS: Retrospective study reviewing the medical records of children with ocular rosacea treated with systemic antibiotic therapy. Nine of 19 patients were chosen for detailed analysis. To our knowledge, this is the first study in paediatric ocular rosacea requiring systemic therapy with a larger patient group and a longer follow-up (mean follow-up = 30.2 months). RESULTS: 17 patients (89.5%) suffered from blepharitis, 15 patients (78.9%) from conjunctivitis, twelve patients (63.2%) from chalazia/styes and nine female patients (47.4%) from corneal involvement. We used erythromycin (n = 9) or roxithromycin (n = 1) in patients younger than 8 years and doxycycline (n = 8) or minocycline (n = 1) in patients older than 8 years. Seven of nine patients treated with erythromycin, one of eight patients treated with doxycycline and the patient treated with minocycline achieved a complete remission of ocular and cutaneous symptoms. Two of nine patients treated with erythromycin, seven of eight patients treated with doxycycline and the patient treated with roxithromycin achieved a partial remission. Relapses occurred in the patient treated with minocycline (cutaneous), two of eight patients treated with doxycycline (ocular and cutaneous) and one of nine patients treated with erythromycin (cutaneous). CONCLUSION: To achieve a complete remission of cutaneous and ocular rosacea, a long-term anti-inflammatory treatment of at least 6 months is necessary. The relapse rates seem to be lower than in adults especially in the patients treated with erythromycin.

[Malignant lymphomas of the eye]. / Maligne Lymphome des Auges.

The eye and the ocular adnexae are rare sites for malignant non-Hodgkin lymphoma (NHL). Based on their anatomical location, intraocular lymphomas must be discerned from NHL of adnexal structures including conjunctiva, lacrimal gland, and orbit. Whereas the latter group mostly consists of indolent extranodal marginal zone B­cell lymphomas of mucosa-associated lymphoid tissue (MALT) type or secondary manifestations of systemic NHL, most primary intraocular lymphomas are classified as diffuse large B­cell lymphomas (DLBCL) and are considered a variant of primary DLBCL of the central nervous system. The most common form is primary vitreoretinal lymphoma (PVRL), which presents with nonspecific symptoms and is difficult to discern from uveitis. Diagnosis of PVRL is usually made by cytological, immunocytochemical, and molecular analysis of vitreous aspirates. Degenerative changes, limited material, and the occurrence of pseudoclonality in the molecular analysis of B­cell clonality can hamper diagnostic assessment. Novel techniques such as detection of MYD88 mutations common in PVRL can increase diagnostic sensitivity. Close cooperation with clinical colleagues and rapid specimen processing are fundamental for successful diagnosis.

[Ocular involvement in rheumatoid arthritis, connective tissue diseases and vasculitis]. / Augenbeteiligung bei rheumatoider Arthritis, Kollagenosen und Vaskulitiden.

There are many interfaces between ophthalmologists and rheumatologists. On the one hand ophthalmologists face the question if an inflammation of the eye is caused by systemic inflammatory rheumatic diseases and on the other hand rheumatologists have to consider that ocular manifestations are relatively common in some inflammatory rheumatic diseases. Furthermore, these ocular manifestations may influence therapeutic decisions of the rheumatologist. This article summarizes which ocular inflammations can be associated with rheumatoid arthritis, connective tissue diseases and vasculitides. The description of acute anterior uveitis in spondyloarthritis and in juvenile idiopathic arthritis is omitted in this article but will be dealt with elsewhere in this issue.

Long-term oral therapy with valganciclovir in patients with Posner-Schlossman syndrome.

BACKGROUND: To assess the short-term and long-term efficacy of oral therapy with valganciclovir in patients with Posner-Schlossman Syndrome (PSS). METHODS: This is a retrospective observational study on 11 patients with PSS treated with valganciclovir. The PSS was diagnosed clinically on the basis of recurrent episodes of anterior uveitis associated with attacks of elevated intraocular pressure (IOP). All patients who did not respond to aciclovir, or whose cytomegalovirus (CMV) DNA polymerase chain reaction (PCR) analysis of the aqueous humour was positive, were treated with valganciclovir (Valcyte®). Initially, the drug was given 900 mg twice daily for 3 weeks, followed by 450 mg twice daily for a mean period of 20 months (range 10-46 months). RESULTS: Eleven patients with mean age of 44 years were included in this study. Four of 11 patients were working in a sanitary profession. Before initiation of valgancicloivir therapy, the highest IOP was 68 mmHg (mean 45 mmHg ±9 mmHg). In the first week of treatment, the IOP decreased significantly (mean 16 mmHg ±10 mmHg) and maintained stability during the entire treatment period. In seven of 11 (63.6 %) patients, valganciclovir led to resolution of inflammatory activity and stable IOP. In six patients, the therapy could be discontinued after a mean of 14 months. However, two patients had a recurrence after discontinuation of valganciclovir treatment. No side effects of therapy were observed. CONCLUSIONS: Long-term oral therapy with valganciclovir seems to lower the recurrence rate in patients with clinically diagnosed PSS.

Evidence-based, interdisciplinary guidelines for anti-inflammatory treatment of uveitis associated with juvenile idiopathic arthritis.

Uveitis in juvenile idiopathic arthritis (JIA) is frequently associated with the development of complications and visual loss. Topical corticosteroids are the first-choice therapy, and immunosuppression is commonly used. However, treatment has not been standardized. Representatives from the German Ophthalmological Society, Society for Childhood and Adolescent Rheumatology, and the German Society for Rheumatology reached consensus on a standardized treatment strategy according to disease severity in the individual patient. The recommendations were based on a systematic literature analysis in MEDLINE and consensus expert meetings. Evidence and recommendations were graded, and an algorithm for anti-inflammatory treatment and final statements confirmed in a Delphi method. An interdisciplinary, evidence-based treatment guideline for JIA uveitis is presented.

[Behçet's disease]. / Morbus Behçet.

Behçet's disease is a systemic disorder with the histopathological correlate of leukocytoclastic vasculitis. Pathogenetically, besides a strong genetic component participation of the innate immune system and an autoinflammatory component are discussed. The disease is most common in countries along the former silk route but in Germany the disease is rare (prevalence approximately 0.6/100,000). Oral aphthous ulcers are the main symptom, followed by skin manifestations, genital ulcers and oligoarthritis of large joints. Severe manifestations, threatening quality of life and even life itself, are the gastrointestinal manifestations which often perforate, arterial, mainly pulmonary arterial aneurysms which cause life-threatening bleeding, CNS manifestations and ocular disease, which with occlusive retinal vasculitis often leads to blindness. For milder manifestations low-dose steroids and colchicine are used, for moderate manifestations such as arthritis or ocular disease not immediately threatening visual acuity, azathioprin or cyclosporin A are combined with steroids. For severe manifestations, interferon-alpha, TNF-antagonists or cytotoxic drugs are recommended. Interleukin 1 (IL-1) antagonists are currently being examined in clinical studies.

Telomere length in individuals with and without major depression and adverse childhood experiences.

Major depressive disorder (MDD) and adverse childhood experiences (ACE) are associated with poor physical and mental health in adulthood. One underlying mechanism might be accelerated cellular aging. For example, both conditions, MDD and ACE, have been related to a biological marker of cellular aging, accelerated shortening of telomere length (TL). Since MDD and ACE are confounded in many studies, we aimed with the current study to further disentangle the effects of MDD and ACE on TL using a full-factorial design including four carefully diagnosed groups of healthy participants and MDD patients with and without ACE (total N = 90, all without use of antidepressants). As dependent variable, TL was assessed in leukocytes. We found no group differences based on MDD and ACE exposure in TL. While TL was negatively associated with age and male sex, TL was not associated with any measure of severity of MDD, ACE or current stress. One possible explanation for our null result may be the comparatively good physical health status of our sample. Future research is needed to elucidate the relation of TL, MDD and ACE, taking potential effect modification by medication intake and physical health status into account.

[Clinical results after cataract surgery in patients with Behçet's disease]. / Ergebnisse nach Kataraktchirurgie bei Patienten mit Behçet-Erkrankung.

BACKGROUND: Behçet's disease is a systemic vasculitis disorder of unknown aetiology. Ocular involvement, especially with vasculitis, is detected in up to 80 % of the cases. Anterior segment involvement such as cataract is also seen in the follow-up of patients who are then treated surgically. In this study, we aimed to analyze the outcomes of cataract surgery in patients with Behçet's disease retrospectively. PATIENTS AND METHODS: The records of 9 patients (12 eyes) with Behçet's disease who underwent phacoemulsification with IOL implantation in 11 eyes and extracapsular cataract extraction (ECCE) with IOL implantation in one eye between June 2001 and September 2009 were evaluated retrospectively. The visual outcome and complications were analysed. RESULTS: The mean follow-up was 33.8 months (range 3 to 88 months). The mean preoperative LogMAR BCVA was 1.15 ± 0.53 (95 % CI: 0.81 - 1.49) and increased to 0.36 ± 0.32 (95 % CI: 0.15 - 0.56) at last medical visit (p < 0.001). The most frequent postoperative complication was posterior capsular opacification, which developed in 2 eyes (17 %). Other complications were mild fibrinous reaction in 1 eye (8 %). CONCLUSIONS: The outcomes of cataract surgery in patients with Behçet's disease were satisfactory. The great majority of the patients regained and retained a good visual outcome and had fewer postoperative complications.

[Ocular involvement in connective tissue diseases and vasculitides]. / Augenbeteiligung bei Kollagenosen und Vaskulitiden.

Connective tissue diseases and systemic vasculitides are commonly associated with ocular manifestations, which can lead to severe complications and even blindness. The present review article describes these ocular manifestations, their signs and symptoms and possible treatment options for Sjoegren's syndrome, systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APLS), as well as those of giant cell arteritis/cranial arteritis, ANCA-associated vasculitides and Behçet's disease. Additionally, possible ocular adverse effects of antimalarial agents are described.

Update of the evidence based, interdisciplinary guideline for anti-inflammatory treatment of uveitis associated with juvenile idiopathic arthritis.

BACKGROUND: Uveitis in juvenile idiopathic arthritis (JIAU) is frequently associated with the development of complications and visual loss. Topical corticosteroids are the first line therapy, and disease modifying anti-rheumatic drugs (DMARDs) are commonly used. However, treatment has not been standardized. METHODS: Interdisciplinary guideline were developed with representatives from the German Ophthalmological Society, Society for Paediatric Rheumatology, Professional Association of Ophthalmologists, German Society for Rheumatology, parents' group, moderated by the Association of the Scientific Medical Societies in Germany. A systematic literature analysis in MEDLINE was performed, evidence and recommendations were graded, an algorithm for anti-inflammatory treatment and final statements were discussed in a consensus meeting (Nominal Group Technique), a preliminary draft was fine-tuned and discussed thereafter by all participants (Delphi procedure). RESULTS: Consensus was reached on recommendations, including a standardized treatment strategy according to uveitis severity in the individual patient. Thus, methotrexate shall be introduced for uveitis not responding to low-dose (≤ 2 applications/day) topical corticosteroids, and a TNFalpha antibody (preferably adalimumab) used, if uveitis inactivity is not achieved. In very severe active uveitis with uveitis-related deterioration of vision, systemic corticosteroids should be considered for bridging until DMARDs take effect. If TNFalpha antibodies fail to take effect or lose effect, another biological should be selected (tocilizumab, abatacept or rituximab). De-escalation of DMARDs should be preceded by a period of  ≥ 2 years of uveitis inactivity. CONCLUSIONS: An interdisciplinary, evidence-based treatment guideline for JIAU is presented.

Interferon-alpha--a new therapeutic option in refractory juvenile Behçet's disease with CNS involvement.

OBJECTIVE: To report the successful treatment with recombinant human IFN- alpha 2a (rhIFN-alpha2a) in two male adolescents suffering from severe treatment-resistant Behçet's disease (BD) with central nervous system (CNS) involvement. METHODS: The patients were 14- and 15-yrs old. Both met the International Study Group for Behçet's disease, O'Duffy and the Japanese criteria for the classification or diagnosis of BD. Signs of CNS involvement were impaired sensorimotor function of the left arm, hemiparesis of right arm and leg, dizziness and walking instability in Patient 1, weakness of both legs, impaired bladder-, bowel- and sexual function in Patient 2 and vasculitic lesions on cranial MRI in both patients. RhIFN-alpha2a was administered initially at 3 million IU/day for 4 weeks followed by 3 x 3 million IU/week. RESULTS: Complete remission was achieved in Patient 1 (reduction in BD activity score from 17 to 2). Patient 2 experienced remarkable improvement (reduction of BD activity score from 23 to 15). In both patients the MRI lesions improved. Patient 2 had mild flu-like symptoms as adverse effect. CONCLUSION: RhIFN-alpha2a was effective and well tolerated in these juvenile patients with severe neurological BD. Regarding the serious consequences following ocular and CNS affection and adverse effects of steroid dependency, administration of rhIFN-alpha2a at an earlier time point needs to be considered.

[Scleromalacia associated with varicella-zoster virus]. / Varizella-zoster-Virus-assoziierte Skleromalazie.

BACKGROUND: Scleromalacia usually appears following vasculitis in systemic rheumatoid diseases, especially as a late symptom of rheumatoid arthritis. CASE REPORT: A 67-year-old woman was referred to our hospital for further evaluation with the diagnosis of a "fast-growing tumor" of the left eye. Sixteen months ago she had suffered from herpes zoster ophthalmicus-associated keratouveitis and trabeculitis in the same eye. Scleromalacia associated with varicella-zoster virus (VZV) was diagnosed after the biomicroscopic and gonioscopic examination of the eye was completed and a systemic disease had been ruled out. One week after beginning systemic application of acyclovir (5 x 800 mg daily) and prednisolone (30 mg daily), the anterior chamber inflammation regressed and a fibrosis seemed to appear in the atrophic scleral area. CONCLUSION: Although scleral atrophy mostly appears as a late sign of systemic rheumatoid diseases, it might also develop secondary to infectious diseases. Scleromalacia associated with varicella-zoster virus has been previously described only in a few cases. Scleromalacia is a vision-threatening complication of zoster ophthalmicus which responds well to combination therapy with systemic antiviral and anti-inflammatory agents.

Mycophenolate mofetil in the treatment of uveitis in children.

BACKGROUND: Mycophenolate mofetil (MMF) is a new immunosuppressive agent that effectively controls the intraocular inflammation in adults. PURPOSE: To assess the efficacy of MMF in uveitis in children and to analyse the possible side effects. PARTICIPANTS AND METHODS: A retrospective analysis was carried out on 17 children (32 eyes) with intraocular inflammation treated with MMF and followed up at the University Eye Hospital Tuebingen, Tuebingen, Germany, between 2000 and 2005. All children had chronic non-infectious uveitis and received MMF for at least 6 months. All patients were given steroids or other immunosuppressive agents before initiating treatment with MMF. RESULTS: 17 children (10 boys and 7 girls) with a mean age of 8 (range 2-13) years at the onset of uveitis were examined. The average duration of follow-up after initiation of MMF was 3 (range 2-5) years. A steroid-sparing effect was achieved in 88% of the patients. The oral prednisolone was successfully discontinued in 41% children and reduced to a daily dose of < or =5 mg in 47% of the children. 24% of the patients remained relapse-free during the treatment, but a reduction in the relapse rate was observed in all other patients except one. Visual acuity was increased or maintained in 13 children (76%). Mild side effects (headache, rash, gastrointestinal discomfort) occurred in 7 patients (41%) and were the cause of discontinuation of MMF in 1 patient. CONCLUSION: The results of our study are encouraging and suggest that MMF is an effective agent also in the treatment for uveitis in children, with marked steroid-sparing potential and an acceptable side effect profile.

Intracellular cytokine patterns in Behçet's disease in comparison to ankylosing spondylitis--influence of treatment with interferon-alpha2a.

OBJECTIVE: Treatment of Behçet's disease (BD) with human recombinant interferon-alpha2a (IFN-alpha2a) has proven clinically effective. The mechanism of action is unknown. This is the first study investigating the influence of IFN-alpha2a on intracellular cytokines in T-cells in patients with BD in comparison to healthy controls and to patients with ankylosing spondylitis (AS). METHODS: Cytokine expression of T-cells was investigated in 10 patients with BD before and 4 and 12 weeks after initiation of treatment with IFN-alpha2a. 10 patients with AS and 10 healthy individuals served as controls. Peripheral blood mononuclear cells were assayed by flow cytometry for the cell surface markers CD3, CD8 and CD4 and for the intracellular cytokines interleukin 2 (IL 2), tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and interleukin 4 (IL 4). RESULTS: The fraction of CD3+ and CD4+ T-cells producing IL 2 was significantly lower in untreated BD and AS patients compared to healthy controls (p = 0.02 and 0.007). However, the number of IFN-g-producing CD3+ T-cells in untreated BD patients was elevated in comparison to both control groups (p = 0.05). T-cell cytokine analysis of BD patients revealed a significant increase of IL 2-production in T-cells during IFN-alpha2a treatment (p < 0.001). CD4+ T-cells producing IFN-gamma and TNF-alpha increased significantly (p = 0.002 and p = 0.01). CONCLUSION: In BD and AS, CD3+ and CD4+ T-cells producing IL 2 are reduced. This may hint at a similarity in the pathogenesis of these HLA-class I-associated disorders. IFN-alpha2a induces restoration of IL 2-production in patients with BD which is likely to be one mechanism of action of IFN-alpha2a.

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.

[Uveitis and the aging]. / Die Uveitis des alternden Menschen.

Uveitis can be found in all age groups, but the age of disease onset may provide important information on the etiology of the disease. New data on the epidemiology of uveitis disclose a higher incidence and prevalence in older patients then has previously been found. Masquerade syndromes which mimic uveitis may be found especially in younger and older patients. These have to be excluded from regular intraocular inflammation. Here, intraocular lymphoma plays a major role which is most often associated with severe clinical, diagnostic and therapeutic challenges. One of the major complications of uveitis is cataract formation. Keeping in mind the importance of pre- and postoperative treatment, even implantation of an intraocular lens in older patients with uveitis is currently a safe procedure.

[Epidemic keratoconjunctivitis. Detecting adenoviruses]. / Keratoconjunctivitis epidemica. Nachweis von Adenoviren.

OBJECTIVE: The validity of the 15-min adenovirus assay SAS Adenotest was evaluated compared with virus detection by polymerase chain reaction (PCR) from conjunctival swabs. METHODS: In 75 patients with assumed epidemic keratoconjunctivitis, adenovirus detection from conjunctival swabs was performed by the immunochromatographic assay SAS Adenotest and PCR. RESULTS: In 25 patients adenovirus was detected by PCR, 18 of whom were detected by the SAS Adenotest and 7 of whom were not. No false positive results occurred. Sensitivity was 72% and specificity was 100%. CONCLUSIONS: The results indicate that rapid adenovirus detection with the SAS Adenotest is a useful tool in early epidemic keratoconjunctivitis. An additional PCR should be performed when clinical symptoms persist for 5 days or more.

[Diagnostics and treatment of choroidal lymphoma]. / Diagnostik und Therapie der choroidalen Lymphome.

Choroidal lymphoma is a rare disease and can be classified into primary and secondary choroidal lymphomas. Primary choroidal lymphoma is a low-grade extranodal marginal zone B-cell lymphoma and secondary choroidal lymphomas present ocular manifestations of disseminated systemic lymphomas. Typical clinical features of choroidal lymphoma are multifocal, yellow-whitish choroidal infiltrates. The vitreous body is usually clear and cell-free. Choroidal lymphoma has a tendency to extend through the sclera. In contrast to primary choroidal lymphoma, which is more often unilateral, does not show signs of anterior segment involvement and has a slow progression, secondary choroidal lymphoma is more often bilateral, has a rapidly progressive course with anterior segment and vitreous involvement and belongs to the high-grade lymphomas. The definitive diagnosis of choroidal lymphoma can only be confirmed by histopathological examination of biopsy tissue. The choroidal biopsy is the gold standard in the diagnostics of choroidal lymphoma. To date, no standardized treatment for choroidal lymphoma has been established. The treatment modalities include external beam radiotherapy, immunotherapy with rituximab and chemotherapy. The prognosis for survival of primary choroidal lymphoma is usually good. The prognosis of secondary choroidal lymphoma depends on the malignancy grade of systemic lymphoma.