Safety management in treatment with antimalarials in rheumatology. Interdisciplinary recommendations on the basis of a systematic literature review.

BACKGROUND: Antimalarial medication (AM) plays an important role in the treatment of rheumatic diseases. OBJECTIVE: Updated evidence-based recommendations on the safety management of rheumatological treatment with AM are presented. METHODS: A systematic literature search in the databases Medline (PubMed) and Cochrane identified 1160 studies on the safety of treatment with AM in rheumatology. In addition, a manual search was carried out and 67 publications considered to be particularly relevant by the authors were analyzed in more detail. These publications served as a basis for consensus-based recommendations. RESULTS: Treatment with AM in rheumatology should be carried out with hydroxychloroquine (HCQ) with a dosage not exceeding 5 mg/kg body weight/day. Patients should undergo a basic ophthalmological examination within the first 6 months of AM treatment. Pre-existing maculopathy, renal insufficiency (glomerular filtration rate, GFR <60 ml/min), tamoxifen comedication, a daily dose of >5 mg/kg HCQ or treatment with chloroquine (CQ) show an increased risk for AM-induced retinopathy. These patients should undergo an annual ophthalmological check from the beginning of the treatment, whereas patients with no risk factors are recommended to start this only after 5 years of taking the medication. The ophthalmological examination should comprise at least both an appropriate subjective and an objective method and these are usually an automated visual field test and optical coherence tomography (OCT). A visual field test revealing a parafoveal sensitivity loss and an OCT showing a parafoveal circumscribed loss of the photoreceptor layer or focal interruptions of the structural line of the outer segment are signs of a possible AM retinopathy. Determination of creatine kinase (CK) and lactate dehydrogenase (LDH) in blood is appropriate to screen for cardiomyopathy and myopathy and should be checked before starting the treatment and then ca. every 3 months. The use of cardiac biomarkers, such as brain natriuretic peptide (BNP) or troponin in serum, electrocardiograph (ECG) or cardiac imaging should be considered depending on the situation. An intake of HCQ is safe during pregnancy and breastfeeding according to the current state of knowledge and is protective for mother and child in patients with systemic lupus erythematosus. CONCLUSION: The updated recommendations on AM treatment in rheumatology in particular include a more rigorous measuring of doses, risk stratification in monitoring and defined ophthalmological examination methods to detect a possible retinopathy.

[Safety management of the treatment with antimalarial drugs in rheumatology. Interdisciplinary recommendations based on a systematic literature search]. / Sicherheitsmanagement der Therapie mit Antimalariamitteln in der Rheumatologie. Interdisziplinäre Empfehlungen auf der Basis einer systematischen Literaturrecherche.

BACKGROUND: Antimalarial medication (AM) plays an important role in the treatment of rheumatic diseases. OBJECTIVE: Updated evidence-based recommendations on the safety management of rheumatological treatment with AM are presented. METHODS: A systematic literature search in the databases Medline (PubMed) and Cochrane identified 1160 studies on the safety of treatment with AM in rheumatology. In addition, a manual search was carried out and 67 publications considered to be particularly relevant by the authors were analyzed in more detail. These publications served as a basis for consensus-based recommendations. RESULTS: Treatment with AM in rheumatology should be carried out with hydroxychloroquine (HCQ) with a dosage not exceeding 5 mg/kg body weight/day. Patients should undergo a basic ophthalmological examination within the first 6 months of AM treatment. Pre-existing maculopathy, renal insufficiency (glomerular filtration rate, GFR <60 ml/min), tamoxifen comedication, a daily dose of >5 mg/kg HCQ or treatment with chloroquine (CQ) show an increased risk for AM-induced retinopathy. These patients should undergo an annual ophthalmological check from the beginning of the treatment, whereas patients with no risk factors are recommended to start this only after 5 years of taking the medication. The ophthalmological examination should comprise at least both an appropriate subjective and an objective method and these are usually an automated visual field test and optical coherence tomography (OCT). A visual field test revealing a parafoveal sensitivity loss and an OCT showing a parafoveal circumscribed loss of the photoreceptor layer or focal interruptions of the structural line of the outer segment are signs of a possible AM retinopathy. Determination of creatine kinase (CK) and lactate dehydrogenase (LDH) in blood is appropriate to screen for cardiomyopathy and myopathy and should be checked before starting the treatment and then ca. every 3 months. The use of cardiac biomarkers, such as brain natriuretic peptide (BNP) or troponin in serum, electrocardiograph (ECG) or cardiac imaging should be considered depending on the situation. An intake of HCQ is safe during pregnancy and breastfeeding according to the current state of knowledge and is protective for mother and child in patients with systemic lupus erythematosus. CONCLUSION: The updated recommendations on AM treatment in rheumatology in particular include a more rigorous measuring of doses, risk stratification in monitoring and defined ophthalmological examination methods to detect a possible retinopathy.

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.

[Lues - Ocular syphilis]. / Lues ­ Okuläre Syphilis.

Ocular syphilis is not a new issue but due to increasing rates of new cases is now a contemporary issue. The clinical features are unspecific and can be manifested as all forms of ocular inflammation. Unspecific anterior uveitis is the most frequent ocular involvement; however, typical distinctive patterns are superficial white preretinal precipitates within a panuveitis and acute syphilitic posterior placoid chorioretinitis. The diagnosis should be confirmed by serological tests. Treatment is based on parenteral administration of penicillin.

[Adverse ocular effects of vaccinations]. / Impfschäden am Auge.

Vaccinations are very effective measures for prevention of infections but are also associated with a long list of possible side effects. Adverse ocular effects following vaccination have been rarely reported or considered to be related to vaccinations. Conjunctivitis is a frequent sequel of various vaccinations. Oculorespiratory syndrome and serum sickness syndrome are considered to be related to influenza vaccinations. The risk of reactivation or initiation of autoimmune diseases (e. g. uveitis) cannot be excluded but has not yet been proven. Overall the benefit of vaccination outweighs the possible but very low risk of ocular side effects.

[Bilateral recurrent blurred vision associated with halos around sources of light and headache]. / Beidseitiges, rezidivierendes Verschwommensehen mit Farbringen um Lichtquellen und Kopfschmerzen.

A 21-year-old male presented with headache and blurred vision associated with halos around sources of light. The visual acuity was slightly reduced and the intraocular pressure in the left eye was elevated to 44 mmHg and in the right eye to 49 mmHg. Slit lamp examination of the anterior segment revealed bilateral cells and a Tyndall phenomenon 2 +, several cell clumps adherent to the corneal endothelium, known as mutton-fat keratic precipitates and a circumscribed inflammatory infiltration of the right iris. The posterior segment of both eyes was normal. The cause of the presumed clinical diagnosis secondary open angle glaucoma due to anterior granulomatous uveitis was sarcoidosis, confirmed by elevated serological markers of angiotensin-converting enzyme (ACE), soluble interleukin-2 receptor (sIL-2R) and by pulmonary hilar lymphadenopathy. The local and systemic corticosteroid therapy was successful and also normalized the intraocular pressure.

[Ophthalmic agents during pregnancy and breastfeeding]. / Ophthalmika während Schwangerschaft und Stillzeit.

Ocular therapy is necessary even during pregnancy but the use of pharmaceutical substances bears the risk of side effects on mother and child. The article reflects current knowledge on how to treat the most important eye diseases during pregnancy and breastfeeding. The review covers the diagnostics (tonometry, mydriasis, angiography) as well as treatment of infections of the eyes, glaucoma, allergies, diabetic retinopathy, pain and inflammation.

Postoperative nosocomial endophthalmitis: is perioperative antibiotic prophylaxis advisable? A single centre's experience.

We report the endophthalmitis rate after cataract surgery in patients preoperatively given topical povidone-iodine and gentamicin-containing irrigation fluid as prophylaxis without intracameral cefuroxime or perioperative topical antibiotics. In a retrospective clinical study, we included patients undergoing cataract surgery over a 12-year period at one large university teaching hospital. Data from 26,566 cataract procedures were analysed. Cases of postoperative endophthalmitis were identified and diagnosed both clinically and microbiologically. A total of 26,566 cataract procedures were reviewed, and we identified 16 patients with postoperative endophthalmitis (rate: 0.6 per 1000 operations, or 0.06%; 95% confidence interval: 0.03-0.09%). A causative micro-organism was detected in 81.3% (13/16) of the cases. Most organisms were Gram-positive bacteria (10/13) with susceptibility to cefuroxime (9/10) and/or fluoroquinolones (4/8), and/or resistance to aminoglycosides (10/10). The three Gram-negative pathogens were susceptible to cefuroxime, aminoglycosides, and fluoroquinolones. Using our regimen of topical povidone-iodine and gentamicin irrigation, we observed a low postoperative endophthalmitis rate not differing from the infection rates recently reported in other large studies. We speculate that neither intracameral cefuroxime nor perioperative levofloxacin eye drops are necessary to minimise postoperative infectious complications following cataract surgery, and we suggest that the European Society of Cataract and Refractive Surgery guidelines (in which perioperative antibiotics are mandatory) therefore be revisited to permit alternative effective regimens for the prevention of postoperative infections following cataract surgery.

[Sudden appearance and rapide progression of bilateral visual deterioration]. / Plötzlich aufgetretene und rasch progrediente beidseitige Visusverschlechterung.

This article describes the case of a 49-year-old patient with incomplete Vogt-Koyanagi-Harada syndrome. The anamnesis showed that intermittent alternating visual problems had begun 2 weeks before. The best corrected vision was 0.1 bilateral. In addition to a right-sided anterior uveitis multiple blister-like retinal alterations of both fundi were seen in fundoscopy. The fundoscopic findings could be confirmed by spectral domain optical coherence tomography (SD-OCT) as multiple intraretinal cysts and areas with neurosensory detachment. Topical and systemic steroid therapy resulted in a rapid reduction of these symptoms. The reversal in SD-OCT corresponded with a visual improvement.

[Eye and pregnancy.]. / Auge und Schwangerschaft.

Pregnancy may cause ocular changes, for example refractive changes or contact lens intolerance. A number of ocular diseases may deteriorate. Especially preexisting diabetic retinopathy may worsen. Vaginal delivery is nearly always possible. Caesarean section is not required due to myopia, peripheral retinal degenerations or after retinal surgery. Most topically applied drugs usually used in ophthalmology are safe during pregnancy.

[Multiresistant bacteria in ophthalmology]. / Multiresistente Keime in der Augenheilkunde.

Multidrug-resistant bacteria have emerged as an increasing threat in many areas of medicine. The most prominent multidrug-resistant pathogens are methicillin-resistant S. aureus (MRSA), vancomycin-resistant MRSA (VMRSA), vancomycin-resistant enterococci (VRE), and Enterobacteriaceae with extended-spectrum beta-lactamase (ESBL). In particular, MRSA and VRE cause infections seen in ophthalmology. The lids, lacrimal duct, and ocular surface are frequently involved.

[Rational antibiotic therapy in ophthalmology]. / Rationale Antibiotikatherapie in der Augenheilkunde.

Bacterial infections can affect all structures of the eye. In most cases, infections of the ocular surface are treatable with topical antibiotics, whereas intraocular infections need a combined treatment with intraocular and systemic antibiotics. Localisation, severity, expected microorganisms, and possible consequences of the infection lead to the appropriate therapy. Unwarranted use of antibiotic substances for prophylaxis or treatment of nonbacterial infection should be avoided, especially because of possible selection of multiresistant microorganisms.

Neonatal bladder inflammation alters activity of adult rat spinal visceral nociceptive neurons.

PURPOSE: This investigation examined the effect of inflammation produced by intravesical zymosan during the neonatal period on spinal dorsal horn neuronal responses to urinary bladder distension (UBD) as adults. METHODS: Female rat pups (P14-P16) were treated with intravesical zymosan or with anesthesia-only. These groups of rats were subdivided forming four groups: half received intravesical zymosan as adults and half received anesthesia-only. One day later, rats were anesthetized, the spinal cord was transected at a cervical level and extracellular single-unit recordings of L6-S1 dorsal horn neurons were obtained. Neurons were classified as Type I--inhibited by heterotopic noxious conditioning stimuli (HNCS) or as Type II--not inhibited by HNCS--and were characterized for Spontaneous Activity and responses to graded UBD (20-60 mm Hg). RESULTS: 227 spinal dorsal horn neurons excited by UBD were characterized. In rats treated as neonates with anesthesia-only, Type II neurons demonstrated increased spontaneous and UBD-evoked activity following adult intravesical zymosan treatment whereas Type I neurons demonstrated decreased spontaneous and UBD-evoked activity relative to controls. In rats treated as neonates with intravesical zymosan, the spontaneous and UBD-evoked activity of both Type I and Type II neurons increased following adult intravesical zymosan treatment relative to controls. CONCLUSIONS: Neonatal bladder inflammation alters subsequent effects of acute bladder inflammation on spinal dorsal horn neurons excited by UBD such that overall there is greater sensory neuron activation. This may explain the visceral hypersensitivity noted in this model system and suggest that impaired inhibitory systems may be responsible.

Acute bladder inflammation differentially affects rat spinal visceral nociceptive neurons.

The present investigation examined the effect of inflammation produced by intravesical zymosan on spinal dorsal horn neuronal responses to urinary bladder distension (UBD). Extracellular single-unit recordings of neurons excited by UBD were obtained in spinalized female Sprague-Dawley rats. Neurons were classified as Type I-inhibited by heterotopic noxious conditioning stimuli (HNCS) or as Type II-not inhibited by a HNCS. In Experiment 1-following neuronal characterization, 1% zymosan was infused into the bladder and after 2h spinal units were recharacterized. Control rats received intravesical saline or subcutaneous zymosan. In Experiment 2-rats were pretreated with intravesical zymosan 24h prior to surgical preparation. Control rats received anesthesia only. 137 spinal dorsal horn neurons excited by UBD were characterized. In comparison with controls, Type II neurons demonstrated increased spontaneous and UBD-evoked activity following intravesical zymosan treatment (both Experiments 1 and 2) whereas Type I neurons demonstrated either no change (Experiment 1) or decreased activity (Experiment 2) following bladder inflammation. No significant changes were noted in neuronal activity in control experiments. Inflammation differentially affects subpopulations of spinal dorsal horn neurons excited by UBD that can be differentiated according to the effect of HNCS. This results in an altered pattern of spinal sensory transmission that may serve as the mechanism for the generation of visceral nociception.

[Ocular findings and differential diagnoses in giant cell arteritis (Arteriitis cranialis)]. / Augenbefunde und Differenzialdiagnosen bei Riesenzellarteriitis (Arteriitis cranialis).

A visual impairment occurs in about 50% of patients with giant cell arteritis (GCA), an amaurosis fugax (AF) in about 30%, and diplopia in about 10%. An arteritic anterior ischemic optic neuropathy was found in about 80%-90% of patients with visual loss and an arteritic central retinal artery occlusion in about 10%-20%. Without therapy, involvement of the fellow eye may occur within hours or days in a patient with unilateral blindness. Involvement of the anterior segment of the eye (iris ischemia, episcleritis) is rare. Ocular ischemic syndrome is defined by visual loss with hypotony, ischemia of the iris, and cotton wool spots (CWS). CWS may already occur with AF episodes. In the case of strong suspicion of GCA, immediate therapy with steroids is indicated. Duplex sonography and a gadolinium MRI examination are of diagnostic importance. A biopsy of the temporal artery may be carried out after the initiation of therapy.

[Diagnostics for endophthalmitis]. / Diagnostik bei Endophthalmitis.

Infectious endophthalmitis is a serious complication of intraocular surgery, perforating injury, or septic dissemination. Detection of the causative microorganisms is essential for effective treatment. Published positive culture rates vary from 24 to 95 %. To achieve a high positive rate of detection of microorganisms all material necessary to set up a culture has to be available in the operation theatre. Important is a variety of appropriate culture media: we use Columbia, Hematin, ENDO and yeast-cysteine blood plates as well as a nutrient solution. Samples may be brought into the culture media directly within the operation theatre. If no immediate transport to a specialised laboratory is possible, media may be cultured in the eye hospital under optimal conditions. Concurrently, undiluted samples should be used for eubacterial PCR. While standard PCR can only detect the causative microorganism, standard culture procedures provide additional information regarding resistance to anti-microbiologic therapies. In the case of presumed fungal endophthalmitis the collected vitrectomy fluid has to be centrifuged and thereafter cultured. In presumed endogenous endophthalmitis also extraocular samples should be examined (e. g., blood culture and smears from other sites of infection). With this approach a high detection rate can be achieved in patients with endophthalmitis.

[Endogenous endophthalmitis]. / Endogene endophthalmitis.

Endogenous endophthalmitis is a severe and potentially blinding complication of hematogenous spread of microorganisms. Predisposing factors are intravenous drug abuse, immunosuppression, and prolonged intensive care. Intraocular material needs to be cultured or subjected to PCR to detect the causative microorganisms. In contrast to PCR, culture has the advantage of providing additional information about the resistance of the microorganism. Fungi and bacteria cause endogenous endophthalmitis with the same frequency. Treatment consists in a combination of local and systemic antibiotics or antimycotics, systemic and local corticosteroids, and vitrectomy. The prognosis depends mainly on the initial visual acuity and the pathogen concerned.

[Uveitis intermedia in childhood]. / Uveitis intermedia im Kindesalter.

Round 10-12% of all children who present with signs of uveitis suffer from intermediate uveitis. Compared to uveitis anterior in children, the association of intermediate uveitis to a systemic disease is much more complicated. Most cases of uveitis intermedia are idiopathic and show the signs of a pars planitis. Post-infectious and immunological causes are difficult to detect. In cases of uveitis in children, it is necessary to know the specific symptoms of possible underlying systemic diseases. On this basis, an adequate and specific diagnosis will most probably be successful. This paper presents the different causes of uveitis intermedia in childhood and compares the incidence of the disease in comparison with adults as far as this is mentioned in the literature.

[Infectious uveitis in infancy: borreliosis, tuberculosis, lues]. / Infektiöse Uveitis im Kindesalter: Borreliose, Tuberkulose, Lues.

Infectious uveitis caused by Borrelia, tuberculosis or syphilis is a rare condition, even in childhood. Because these diseases can be treated successfully, knowledge of their diagnosis and therapy is highly important. The clinical aspects vary from simple conjunctivitis to endophthalmitis or neuro-ophthalmological diseases. The diagnosis of and therapy for borreliosis depend on the stage of the disease. The involvement of different organ systems or positive indirect tests (tuberculin skin test, interferon gamma assays) are important factors in the diagnosis of tuberculosis as the cause of a uveitis. Serology is essential for the diagnosis and monitoring of syphilis.

[Diagnostics in childhood uveitis: what tests for which uveitis?]. / Diagnostik bei Uveitis im Kindesalter: Welche Tests bei welcher Uveitis?

BACKGROUND: Intraocular inflammation in children differs considerably from that found in adults. Therefore the diagnostic work-up has to be adapted to the age and specific diseases. MATERIALS AND METHODS: The published literature was reviewed for results of clinical trials and consensus meetings. In addition, the authors have incorporated their own experience. RESULTS: Recommendations for a systematic and complete diagnostic work-up are given using tables where possible. CONCLUSIONS: A close cooperation between ophthalmologists and paediatricians is very important.