To assess the association between salivary ultrasonography (sUS) findings and disease activity and damage in patients with primary Sjogren’s syndrome (pSS). We investigated the potential prognostic role of sUS as a tool in the assessment of disease activity. In 303 pSS patients, disease activity was assessed by the European League Against Rheumatism (EULAR) Sjogren’s Syndrome Disease Activity Index (ESSDAI), the EULAR Sjogren’s Syndrome Patient Reported Index (ESSPRI), the Sjogren’s Syndrome Disease Activity Index (SSDAI) and the Sjogren’s Syndrome Disease Damage Index (SSDDI). The sUS parenchymal inhomogeneity (de Vita scoring system) was assessed in 303 pSS patients and 111 heathy controls. A receiver operating characteristic (ROC) curve was used to determine the cut-off value of the pathological sUS score. Logistic regression analysis was performed to assess risk factors for moderate and high disease activity. A pathological sUS score ≥ 2 was recorded in 271 (89.7%) patients and 8 (8.6%) healthy controls. Patients with moderate and high ESSDAI and SSDAI scores had significantly higher US activity in comparison to that of pSS patients with low disease activity (p = 0.006; p = 0.01, respectively). Additionally, pSS patients with moderate and high SSDDI scores had higher US activity (p = 0.031). Pathological sUS correlated with the glandular domain within the ESSDAI and SSDDI (p<0.001). The patients with a severe US score (5–6) had a 3.5 times greater chance of having moderate or high disease activity. The specificity of the severe de Vita sUS score for ESSDAI and SSDAI was 85.1% and 85.2%, respectively. In contrast, the sensitivity of a severe de Vita sUS score for ESSDAI was low, at 29.2%, while the sensitivity for the SSDAI was higher, 42.3%. In the analysis of disease activity, a de Vita score ≥ 5 could be used as a risk factor for moderate and high ESSDAI (p = 0.042) and SSDAI (p = 0.006). Pathological salivary gland ultrasonography is associated with high disease activity and damage in pSS. Consequently, sUS abnormalities might be surrogate items for glandular domains in the assessment of disease activity and damage. Thus, ultrasonography of the salivary gland combined with clinical and serological markers might be part of the next prognostic and therapeutic algorithm in the near future.

Ophthalmomyiasis externa is the result of infestation of the conjunctiva by the larval form or maggots of flies from the order Diptera. If not recognized and managed appropriately, it can be complicated by the potentially fatal condition ophthalmomyiasis interna. Ophthalmomyiasis externa is mainly caused by the sheep bot fly (Oestrus ovis). We present the first case, to our knowledge, of ophthalmomyiasis externa in an elderly woman from Belgrade caused by Lucilia sericata Meigen – a green bottle fly.

The activity of α-1,2-mannosidase I is required for the conversion of high-mannose to hybrid-type (ConA reactive) and complex-type N-glycans (Phaseolus vulgaris-leukoagglutinin [PHA-L] reactive) during posttranslational protein N-glycosylation. We recently demonstrated that α-1,2-mannosidase I mRNA decreases in graft-infiltrating CD11c⁺ dendritic cells (DCs) prior to allograft rejection. Although highly expressed in immature DCs, little is known about its role in DC functions. In this study, analysis of surface complex-type N-glycan expression by lectin staining revealed the existence of PHA-L^low and PHA-L^high subpopulations in murine splenic conventional DCs, as well as in bone marrow-derived DC (BMDCs), whereas plasmacytoid DCs are nearly exclusively PHA-L^high. Interestingly, all PHA-L^high DCs displayed a strongly reduced responsiveness to TNF-α–induced p38-MAPK activation compared with PHA-L^low DCs, indicating differences in PHA-L–binding capacities between DCs with different inflammatory properties. However, p38 phosphorylation levels were increased in BMDCs overexpressing α-1,2-mannosidase I mRNA. Moreover, hybrid-type, but not complex-type, N-glycans are required for TNF-α–induced p38-MAPK activation and subsequent phenotypic maturation of BMDCs (MHC-II, CD86, CCR7 upregulation). α-1,2-mannosidase I inhibitor-treated DCs displayed diminished transendothelial migration in response to CCL19, homing to regional lymph nodes, and priming of IFN-γ–producing T cells in vivo. In contrast, the activity of α-1,2-mannosidase I is dispensable for LPS-induced signaling, as well as the DCs’ general capability for phenotypic and functional maturation. Systemic application of an α-1,2-mannosidase I inhibitor was able to significantly prolong allograft survival in a murine high-responder corneal transplantation model, further highlighting the importance of N-glycan processing by α-1,2-mannosidase I for alloantigen presentation and T cell priming.

Hintergrund: Mycophenolat Mofetil (MMF) hat sich als immunmodulatorische Substanz zur Behandlung immunmediierter Erkrankungen seit Jahren bewährt. Das Pharmakon weist Vorteile gegenüber einer Basistherapie mit Kortikosteroiden auf, die allerdings v. a. durch hämatologische und gastrointestinale Nebenwirkungen bei bis zu 50 % der Patienten deutlich eingeschränkt werden können. Vor diesem Hintergrund haben wir bei Patienten mit Autoimmunerkrankungen des Auges, die unter MMF gastrointestinale Nebenwirkungen zeigten, eine Umstellung der Behandlung auf eine veränderte Darreichungsform (EC-MPS) vorgenommen und prospektiv verfolgt. Patienten und Methoden: Zwischen 2002 bis 2007 wurden 143 Patienten mit MMF behandelt. Aufgrund gastrointestinaler, unerwünschter Wirkungen wurden 19 Patienten auf EC-MPS umgestellt. Um das Beschwerdemuster nach Konversion von MMF auf EC-MPS zu beobachten, wurde ein validierter Test (Gastrointestinal Symptom Rating Scale) bei Therapieumstellung und zu vorgegebenen Zeitpunkten im weiteren Verlauf verwendet. Ergebnisse: Unter den mit MMF (2 × 1000 mg/Tag) behandelten Patienten befanden sich 16 Uveitispatienten und 3 Patienten mit okulärem Pemphigoid. Alle Patienten konnten auf EC-MPS (2 × 720 mg/Tag) umgestellt und über einen Zeitraum von 44 Wochen (Median ± 12) nachbeobachtet werden. Der höchste Beschwerdeindex wurde bei 16 / 19 Patienten zum Zeitpunkt der Therapieumstellung angegeben. Ein signifikanter Rückgang (p < 0,03) im GSRS-Beurteilungsscore konnte zwischen der Ausgangssituation und der 3-Monatskontrolle festgestellt werden. Kein Unterschied fand sich bei MMF- bzw. EC-MPS-behandelten Patienten bzgl. hämatologischer Parameter. Mit Ausnahme einer Patientin konnte die zugrundeliegende Erkrankung unter Kontrolle gehalten werden. Schlussfolgerung: Die Behandlung mit EC-MPS ist eine geeignete Behandlungsoption für Autoimmunerkrankungen des Auges und ermöglicht eine Therapie bei Patienten mit gastrointestinalen Beschwerden. Background: Mycophenolate mofetil (MMF) has gained acceptance as an immune modulatory agent in the treatment of autoimmune disorders such as uveitis. It represented a major advance, although optimal use may be limited, in particular, by gastrointestinal (GI) side effects in up to 50 % patients. This prospective study was undertaken to evaluate the effect of conversion from mycophenolate mofetil (MMF) to an enteric-coated mycophenolate sodium (EC-MPS). Patients and Methods: Within a cohort of 143 patients treated with MMF we prospectively followed 19 inidviduals who developed gastrointestinal side effects. Because of limited treatment alternatives, conversion to an enteric-coated mycophenolate sodium (EC-MPS) was undertaken. A standardised questionnaire (GSRS) was completed by each patient regarding GI adverse events, at predefined intervals during the study. Results: The spectrum of underlying disorders included uveitis (n = 16) and ocular cicatricial pemphigoid (n = 3) that were initially treated with MMF (1000 mg BID). All patients could be kept on EC-MPS treatment and followed with a mean follow-up of 44 weeks (median ± 12). The maximum of scores on GSRS was reached at baseline (conversion to EC-MPS) in all but 3 patients. However, GSRS scores improved significantly between baseline and visit 4 (3 months) and remained stable further on (p < 0.03). In all but one (uveitis) patient the underlying disorders were under control demonstrating the similar efficacies of MMF and EC-MPS teatments. Conclusion: The use of EC-MPS appears to be a valid treatment option in ocular autoimmune disorders. In particular. patients with gastrointestinal problems may profit from a significantly reduced frequency of adverse events.

Background and objectives: Recurrent herpes simplex keratitis (HSK) is the most common cause of corneal blindness in the developed world. A relationship between host gene polymorphisms and the recurrence of herpes simplex virus (HSV) infection has previously been proposed. Thus, the aim of this study was to investigate a potential association between the IL28B host genotype and recurrent HSK. Materials and Methods: Eighty patients older than 18 years of age of both genders with a history of recurrent herpes simplex labialis (HSL) were considered for inclusion. Seventy-five of these patients were found to be seropositive for HSV-1 and were subsequently enrolled in the study. Twenty-four of the enrolled patients also had a history of recurrent HSK associated with severe corneal scarring and visual acuity deterioration. Total DNA was isolated from whole blood samples. A single-nucleotide polymorphism (SNP) rs12979860 near the IL28B gene on chromosome 19 was genotyped. Results: A significant association was observed between recurrent HSK and two SNPs of the IL28B genotype (CCrs12979860 and CTrs12979860, p < 0.01). The variation CCrs12979860 showed a significantly greater association with HSK (16 out of 26 patients) compared with CTrs12979860 (8 out of 34 patients). Conclusion: Seropositive individuals with a history of recurrent HSK are likely to have the CC IL28B genotype. This genotype may be related to incomplete control of the infection and more frequent periodical viral shedding along the first nerve branch of the trigeminal ganglion, which clinically manifests as recurrent herpes keratitis. The clinical manifestation of recurrent HSV-1 infection seems to be influenced by polymorphism of the IL28B genotype.