Stevens-Johnson syndrome and toxic epidermal necrolysis in Hong Kong.

INTRODUCTION: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) [hereafter, SJS/TEN] are uncommon but severe mucocutaneous reactions. Although they have been described in many populations worldwide, data from Hong Kong are limited. Here, we explored the epidemiology, disease characteristics, aetiology, morbidity, and mortality of SJS/TEN in Hong Kong. METHODS: This retrospective cohort study included all hospitalised patients who had been diagnosed with SJS/TEN in Prince of Wales Hospital from 1 January 2004 to 31 December 2020. RESULTS: There were 125 cases of SJS/TEN during the 17-year study period. The annual incidence was 5.07 cases per million. The mean age at onset was 51.4 years. The mean maximal body surface area of epidermal detachment was 23%. Overall, patients in 32% of cases required burns unit or intensive care unit admission. Half of the cases involved concomitant sepsis, and 23.2% of cases resulted in multiorgan failure or disseminated intravascular coagulation. The mean length of stay was 23.9 days. The cause of SJS/TEN was attributed to a drug in 91.9% of cases, including 84.2% that involved anticonvulsants, allopurinol, antibiotics, or analgesics. In most cases, patients received treatment comprising either best supportive care alone (35.2%) or combined with intravenous immunoglobulin (43.2%). The in-hospital mortality rate was 21.6%. Major causes of death were multiorgan failure and/or fulminant sepsis (81.5%). CONCLUSION: This study showed that SJS/TEN are uncommon in Hong Kong but can cause substantial morbidity and mortality. Early recognition, prompt withdrawal of offending agents, and multidisciplinary supportive management are essential for improving clinical outcomes.

The risk of anti-osteoporotic agent-induced severe cutaneous adverse drug reactions and their association with HLA.

BACKGROUND: There is increasing use of anti-osteoporotic agents (AOA) worldwide for prevention or management of patients with osteoporosis. However, there have been reports of severe cutaneous adverse reactions (SCAR) induced by AOA. A recent study showed weak association between HLA and strontium ranelate (SR)-SCAR. OBJECTIVE: To characterize patients with AOA-SCAR and investigate the HLA association and utility of in vitro diagnostic methods. METHODS: We enrolled 16 cases with AOA-cutaneous adverse drug reactions (cADR), including SCAR (n = 10: 8 with Stevens-Johnson syndrome [SJS] and 2 with drug rash with eosinophilia and systemic symptoms [DRESS]) and maculopapular exanthema (MPE) (n = 6) from Taiwan and Hong Kong. We analysed the clinical characteristics, outcomes, HLA alleles and in vitro testing of AOA-SCAR, and tolerability to alternative drugs. We further performed literature review and meta-analysis on the HLA association of AOA-SCAR. RESULTS: Our data showed strontium ranelate is the most common causality of AOA-SCAR in Asian populations. There was no cross-hypersensitivity of SR-SCAR with other AOA. HLA genotyping showed that SR-SJS was most significantly associated with HLA-A*33:03 (Pc = 5.17 × 10-3 , OR: 25.97, 95% CI: 3.08-219.33). Meta-analysis showed that HLA-A*33:03 was associated with SR-SJS (P = 5.01 × 10-5 ; sensitivity: 85.7%) in Asians. The sensitivity of lymphocyte activation test (LAT) for identifying the culprit drug of SR-SJS was 83.3%. CONCLUSIONS: Strontium ranelate is identified as the most notorious AOA associated with SCAR. The HLA-A*33:03 genetic allele and LAT testing may add benefits to the diagnosis of SR-SCAR in patients whose reaction developed while taking multiple drugs.

Is age-related macular degeneration a manifestation of systemic disease? New prospects for early intervention and treatment.

Age-related macular degeneration (AMD) is a common vision-threatening condition affecting the elderly. AMD shares common risk factors and processes, including vascular and inflammatory pathways, with many systemic disorders. Associations have been reported between AMD and hypertension, cardiovascular disease, cerebrovascular disease, dyslipidaemia, chronic kidney disease and neurodegenerative disorders. An increasing amount of evidence suggests that individuals with AMD are also at risk of systemic diseases such as stroke. In this review, we summarize the latest evidence to support the notion that AMD is an ocular manifestation of systemic disease processes, and discuss the potential systemic side effects of ocular AMD therapy of which general physicians should be aware. Recent genetic discoveries and understanding of the pathogenic pathways in AMD in relation to systemic disorders are also highlighted.

Polypoidal choroidal vasculopathy and systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) associated with antiphospholipid syndrome can have ocular complications. We report a 44-year-old Chinese lady with recurrent relapses of SLE and antiphospholipid syndrome with high disease activity, presenting with visual distortion in her right eye for 2 months. There was subretinal hemorrhage in her right eye, confirmed on investigations to be choroidal neovascularization secondary to a variant of age-related macular degeneration known as polypoidal choroidal vasculopathy (PCV). Anti-vascular endothelial growth factor therapy resolved her eye condition. SLE could be associated with PCV via common mechanisms, including complement pathway activation and vasculitis involving the choroidal circulation.

Ten year survival and outcomes in a prospective cohort of new onset Chinese Parkinson's disease patients.

OBJECTIVE: The 10 year outcomes and impact of motor and non-motor features on survival of a cohort of new onset Chinese Parkinson's disease (PD) patients were prospectively studied. METHOD: A cohort of new onset PD patients from 1995 to 2002 was recruited from a regional hospital based movement disorder clinic. Subjects were classified into postural instability gait disorder (PIGD), tremor predominant type or mixed subtypes at presentation. All were evaluated yearly for development of sensory complaints, first significant fall, hallucinations, dementia, postural hypotension, speech disturbances, dysphagia and postural instability persisted during 'on' medication state (PIPon). Mortality and predictors of death were determined. RESULTS: 171 new onset PD patients were recruited. After a mean follow-up of 11.3±2.6 years, 50 (29%) patients died. The standardised mortality ratio was 1.1 (CI 0.8 to 1.5, p=0.34). 83 (49%) developed dementia, 81 (47%) had psychosis and 103 (60%) had sensory complaints. Postural hypotension was found in 58 (34%) patients, 108 (63%) had PIPon, 101 (59%) had falls, 102 (60%) had dysphagia, 148 (87%) had freezing of gait and 117 (68%) had speech disturbances. 46 (27%) were institutionalised whereas 54 (32%) lived independently. Dementia (HR 5.0, 95% CI 2.1 to 13.0), PIPon (HR 2.8, 95% CI 1.2 to 6.8), older onset (HR 1.05, 1 year increase in age, 95% CI 1.0 to 1.1) and PIGD type (HR 2.1, 95% CI 1.2 to 3.7) were independent predictors of death. CONCLUSIONS: 10 years into PD, a significant proportion of patients developed dopa resistant motor and non-motor features. Older onset, PIGD type, PIPon and dementia had a negative impact on survival. Standardised mortality ratio was 1.1.

Incidence and progression of diabetic retinopathy: a systematic review.

Diabetic retinopathy is a leading cause of vision impairment and blindness. We systematically reviewed studies published from Jan 1, 1980, to Jan 7, 2018, assessed the methodological quality, and described variations in incidence of diabetic retinopathy by region with a focus on population-based studies that were conducted after 2000 (n=8, including two unpublished studies). Of these eight studies, five were from Asia, and one each from the North America, Caribbean, and sub-Saharan Africa. The annual incidence of diabetic retinopathy ranged from 2·2% to 12·7% and progression from 3·4% to 12·3%. Progression to proliferative diabetic retinopathy was higher in individuals with mild disease compared with those with no disease at baseline. Our Review suggests that more high-quality population-based studies capturing data on the incidence and progression of diabetic retinopathy with stratification by age and sex are needed to consolidate the evidence base. Our data is useful for conceptualisation and development of major public health strategies such as screening programmes for diabetic retinopathy.

Using the National Institutes of Health Stroke Scale (NIHSS) to predict the mortality and outcome of patients with intracerebral haemorrhage.

OBJECTIVES: To investigate whether the National Institutes of Health Stroke Scale (NIHSS) can be used to predict mortality and functional outcome in patients presenting with intracerebral haemorrhage. DESIGN: Retrospective study of a prospectively collected cohort. SETTING: Regional hospital, Hong Kong. PATIENTS: A cohort of 359 patients presented to our hospital from 1996 to 2001 with their first-ever stroke and intracerebral haemorrhage. MAIN OUTCOME MEASURES: The sensitivity and specificity of the NIHSS with a cut-off point of 20 in predicting mortality at 30 days and 5 years, and a favourable functional outcome at 5 years. RESULTS: A total of 359 patients were available for analysis and were divided into three subgroups according to the site and the size of the haematoma. The NIHSS can predict 30-day mortality with a sensitivity of 81% [corrected] and a specificity of 90% [corrected] The NIHSS can predict 5-year mortality with a sensitivity of 57% [corrected] and a specificity of 92% [corrected] In predicting favourable functional outcomes at 5 years, the NIHSS had a sensitivity of 98% [corrected] and a specificity of 16% [corrected] CONCLUSIONS: The NIHSS performed on admission can be used to predict mortality at 30 days and 5 years as well as favourable functional outcome at 5 years, all with an acceptable sensitivity and specificity.

An overview of the clinical applications of optical coherence tomography angiography.

Optical coherence tomography angiography (OCTA) has emerged as a novel, non-invasive imaging modality that allows the detailed study of flow within the vascular structures of the eye. Compared to conventional dye angiography, OCTA can produce more detailed, higher resolution images of the vasculature without the added risk of dye injection. In our review, we discuss the advantages and disadvantages of this new technology in comparison to conventional dye angiography. We provide an overview of the current OCTA technology available, compare the various commercial OCTA machines technical specifications and discuss some future software improvements. An approach to the interpretation of OCTA images by correlating images to other multimodal imaging with attention to identifying potential artefacts will be outlined and may be useful to ophthalmologists, particularly those who are currently still unfamiliar with this new technology. This review is based on a search of peer-reviewed published papers relevant to OCTA according to our current knowledge, up to January 2017, available on the PubMed database. Currently, many of the published studies have focused on OCTA imaging of the retina, in particular, the use of OCTA in the diagnosis and management of common retinal diseases such as age-related macular degeneration and retinal vascular diseases. In addition, we describe clinical applications for OCTA imaging in inflammatory diseases, optic nerve diseases and anterior segment diseases. This review is based on both the current literature and the clinical experience of our individual authors, with an emphasis on the clinical applications of this imaging technology.

Outcomes after first-ever stroke.

OBJECTIVES: To determine the outcomes after first-ever stroke, including mortality, dependence, and recurrence. DESIGN: Retrospective study on a prospectively collected cohort. SETTING: Regional hospital, Hong Kong. PATIENTS: A cohort of 755 patients presented to our hospital from 1996 to 1998 with their first-ever stroke. MAIN OUTCOME MEASURES: Mortality and stroke recurrence rate at 30 days, 1 year, and 5 years from the onset of the stroke. Dependence in activity of daily living at 5 years from the onset of stroke. RESULTS: The mortality rate was 15.1% at 30 days, 22.5% at 1 year, and 39.7% at 5 years from the onset of the first-ever stroke. The rate of stroke recurrence was 0.9% at 30 days, 7.0% at 1 year, and 21.2% at 5 years from the onset of first-ever stroke. Among patients presenting with ischaemic strokes, 109 (20.6%) had a recurrence, of which 92 (84%) were ischaemic strokes and 17 (16%) were haemorrhagic. Among patients presenting with intracerebral haemorrhage, 25 (23.1%) had a recurrence, of which 12 (48%) were haemorrhagic strokes and 13 (52%) patients were ischaemic. After 5 years, 11% of the patients were dependent in terms of activity of daily living. CONCLUSIONS: The long-term prognosis after first-ever stroke is poor--5 years after their stroke, 39.7% of patients had died and 10.7% were dependent in terms of activity of daily living; 136 (21%) who survived at least 30 days after the initial stroke, had a recurrence within 5 years.

Multiplex bead immunoassay analysis of aqueous humor reveals distinct cytokine profiles in uveitis.

PURPOSE: To extensively characterize the complex network of cytokines present in uveitis aqueous humor (AqH), and the relationships between cytokines and the cellular infiltrate. METHODS: AqH from noninflammatory control subjects and patients with idiopathic, Fuchs' heterochromic cyclitis (FHC), and herpes-viral or Behçet's uveitis were analyzed for IL-1beta, -2, -4, -5, -7, -8, -10, -12, -13, -15, TNFalpha, IFNgamma, CCL2 (MCP-1), CCL5 (RANTES), CCL11 (Eotaxin), TGFbeta2, and CXCL12 (SDF-1), using multiplex bead immunoassays. The cellular infiltrate was also determined for each sample. RESULTS: Idiopathic uveitis AqH, compared with noninflammatory controls, was characterized by high levels of IL-6, IL-8, CCL2 and IFNgamma, the levels of which correlated with each other. For IL-6 and IL-8 these levels were proportional to the number of neutrophils present. By contrast, the levels of both TGFbeta2 and CXCL12 decreased in idiopathic uveitis AqH with increasing inflammation. Cluster analysis showed a degree of segregation between noninflammatory and idiopathic uveitis AqH. Further examination using random forest analysis yielded a complete distinction between these two groups. The minimum cytokines required for this classification were IL-6, IL-8, CCL2, IL-13, TNFalpha, and IL-2. CONCLUSIONS: Application of multiplex bead immunoassays has allowed us to identify distinct patterns of cytokines that relate to both clinical disease and the cellular infiltrates present. Bioinformatics analysis allowed identification of cytokines that differentiate idiopathic uveitis from noninflammatory control AqH and are likely to be important for the pathogenesis of uveitis.

Late renal function following whole abdominal irradiation.

Sixty patients treated with whole abdominal radiotherapy who had remained disease-free since completion of treatment participated in a study to assess the late clinical and biochemical effects of bilateral renal irradiation. Minimum follow-up was 5 years with a maximum of 20 years and a median of 9 years. Fifty-two patients in the study group were treated for primary ovarian cancer. Seven had non-Hodgkins lymphoma arising in the gastrointestinal tract and one patient had a carcinoid tumour arising in small bowel. None of the patients received chemotherapy. Abdominal radiation was given using an open beam technique to a mean dose of 22.92 Gy (range 6.68-27.54 Gy) in 1.02 to 1.25 Gy fractions treated once daily. Posterior kidney shields were used in order to limit the renal dose to < 20 Gy. Mean radiation dose to both kidneys (retrospectively calculated) was 19.28 Gy (range 6.68-22.99 Gy). Patients ranged in age from 32-81 years with a median of 61 years. No patient had clinical evidence of renal impairment. Nine patients were hypertensive prior to radiotherapy and a further five patients became hypertensive after treatment. Serum creatinine values ranged from 44-123 mumol/l, with a mean of 87 mumol/l. Creatinine clearance ranged from 0.61-2.38 ml/s (mean 1.28 ml/s). Tubular function tests revealed one borderline high 24-h protein excretion and normal 24-h phosphorous and uric acid. Using a multiple linear regression analysis with creatinine clearance as the endpoint, age was the only significant variable (P < 0.00001) and renal dose and interval from treatment were not independently significant. There was no evidence of late renal toxicity more than 5 years after whole abdominal radiotherapy delivered with this technique and dose/fractionation schedule, and using the clinical and biochemical endpoints assessed in this study.

Inhibition of 11beta-hydroxysteroid dehydrogenase type 1 lowers intraocular pressure in patients with ocular hypertension.

BACKGROUND: Intraocular pressure (IOP) is maintained by a balance between aqueous humour (AH) production (dependent on sodium transport across a ciliary epithelial bi-layer) and drainage (predominantly through the trabecular meshwork). In peripheral epithelial tissues, sodium and water transport is regulated by corticosteroids and the 11beta-hydroxysteroid dehydrogenase (11beta-HSD) isozymes (11beta-HSD1 activating cortisol from cortisone, 11beta-HSD2 inactivating cortisol to cortisone). AIM: To analyse expression of 11beta-HSD in the human eye and investigate its putative role in AH formation. DESIGN: Multipart prospective study, including a randomized controlled clinical trial. METHODS: The expression of 11beta-HSD1 in normal human anterior segments was evaluated by in situ hybridization (ISH). RT-PCR for 11beta-HSDs, glucocorticoid and mineralocorticoid receptors (GR, MR) was performed on human ciliary body tissue. AH cortisol and cortisone concentrations were measured by radioimmunoassay on specimens taken from patients with primary open-angle glaucoma (POAG) and age-matched controls. Randomized, placebo-controlled studies of healthy volunteers and patients with ocular hypertension (OHT, raised IOP but no optic neuropathy) assessed the effect of oral carbenoxolone (CBX, an inhibitor of 11beta-HSD) on IOP. RESULTS: ISH defined expression of 11beta-HSD1 in the ciliary epithelium, while RT-PCR analysis of ciliary body tissue confirmed expression of 11beta-HSD1, with additional GR and MR, but not 11beta-HSD2 expression. In both POAG patients and controls, AH concentrations of cortisol exceeded those of cortisone. The CBX-treated healthy volunteers who demonstrated the largest change in urinary cortisol metabolites, indicative of 11beta-HSD1 inhibition, had the greatest fall in IOP. Patients with OHT showed an overall reduction of IOP by 10% following CBX administration, compared to baseline (p<0.0001). DISCUSSION: CBX lowers IOP in patients with ocular hypertension. Our data suggest that this is mediated through inhibition of 11beta-HSD1 in the ciliary epithelium. Selective and topical inhibitors of 11beta-HSD1 could provide a novel treatment for patients with glaucoma.

An overview of quality control practices in Ontario with particular reference to cholesterol analysis.

BACKGROUND: The Laboratory Proficiency Testing Program (LPTP) assesses the analytical performance of all licensed laboratories in Ontario. The LPTP Enzymes, Cardiac Markers, and Lipids Committee conducted a "Patterns of Practice" survey to assess the in-house quality control (QC) practices of laboratories in Ontario using cholesterol as the QC paradigm. DESIGN AND METHODS: The survey was questionnaire-based seeking information on statistical calculations, software rules, review process and data retention, and so on. Copies of the in-house cholesterol QC graphs were requested. A total of 120 of 210 laboratories were randomly chosen to receive the questionnaires during 1995 and 1996; 115 laboratories responded, although some did not answer all questions. RESULTS: The majority calculate means and standard deviations (SD) every month, using anywhere from 4 to >100 data points. 65% use a fixed mean and SD, while 17% use means calculated from the previous month. A few use a floating or cumulative mean. Some laboratories that do not use fixed means use a fixed SD. About 90% use some form of statistical quality control rules. The most common rules used to detect random error are 1(3s)/R4s while 2(2s)/4(1s)/10x are used for systematic errors. About 20% did not assay any QC at levels >5.5 mmol/L. CONCLUSIONS: Quality control data are reviewed daily (technologists), weekly and monthly (supervisors/directors). Most laboratories retain their QC records for up to 3 years on paper and magnetic media. On some QC graphs the mean and SD, QC product lot number, or reference to action logs are not apparent. Quality control practices in Ontario are, therefore, disappointing. Improvement is required in the use of clinically appropriate concentrations of QC material and documentation on QC graphs.

Peripapillary choroidal neovascularisation in sarcoidosis.

PURPOSE: To describe a rare manifestation of sarcoidosis. METHODS: Case report of a patient with histologically proven sarcoidosis, who developed peripapillary choroidal neovascularisation in the absence of uveitis or optic nerve disease. RESULTS: Oral corticosteroids achieved reduction in the size of the peripapillary choroidal neovascularisation. Laser treatment was effective in treating the remaining peripapillary choroidal neovascularisation, resulting in improvement of visual acuity. CONCLUSIONS: Isolated peripapillary choroidal neovascularisation is a previously unreported complication of sarcoidosis. A combination of oral corticosteroids and laser can be successful in treating this type of lesion, thereby preventing permanent visual loss.

Evaluation of focal choroidal excavation in the macula using swept-source optical coherence tomography.

PURPOSE: To evaluate imaging findings of patients with focal choroidal excavation (FCE) in the macula using swept-source optical coherence tomography (SS-OCT) and correlate it clinically. METHODS: Prospective observational case series. Eleven consecutive patients (12 eyes) with FCE were described. Data on demographics and clinical presentation were collected and imaging findings (including color photography, fundus autofluorescence imaging, fluorescein angiography, indocyanine green angiography, spectral-domain optical coherence tomography, and SS-OCT) were analyzed. RESULTS: The primary diagnosis was epiretinal membrane (two eyes), choroidal neovascularization (one eye), polypoidal choroidal vasculopathy (three eyes), central serous chorioretinopathy (one eye), and dry age-related macular degeneration (two eyes). Eleven out of 12 of the lesions were conforming. One presented with a non-conforming lesion that progressed to a conforming lesion. One eye had multiFCE and two had two overlapping choroidal excavations. Using the SS-OCT, we found the choroid to be thinned out at the area of FCE but sclera remained normal. The choroidal tissue beneath the FCE was abnormal, with high internal reflectivity and poor visualization of choroidal vessels. There was loss of contour of the outer choroidal boundary that appeared to be pulled inward by this abnormal choroidal tissue. A suprachoroidal space was noted beneath this choroidal tissue and the choroidal-scleral interface was smooth. Repeat SS-OCT 6 months after presentation showed the area of excavation to be stable in size. CONCLUSION: FCE can be associated with epiretinal membrane, central serous chorioretinopathy, and age-related macular degeneration. The choroid was thinned out in the area of FCE.

Association of diffusion weighted imaging abnormalities and recurrence in transient global amnesia.

Since the first description of transient global amnesia (TGA) in 1964, its etiology has remained obscure. Reversible diffusion weighted imaging (DWI) hyperintensities in the hippocampus have been found on MRI of some patients with TGA during acute events. The implication of this is not well understood. We identified 47 patients with TGA between November 2004 and November 2009, and enrolled 27 patients with brain MRI within 72 hours of symptom onset for analysis and recorded subsequent relapse or stroke occurrence during follow-up. Nine of the 27 patients had reversible hippocampal punctuate hyperintensities, with complete resolution noted on a second MRI on average 4 months after the initial TGA. Patients with a first relapse (their second TGA attack) had a significantly higher association of DWI hippocampal abnormalities (p=0.03) compared to patients with their first TGA event. None of the 27 patients had a stroke or further relapse during the mean follow-up period of 32.6 months. Thus, patients with recurrent TGA have a significantly higher association of reversible DWI abnormality.

Impulse control disorders in Chinese Parkinson's disease patients: the effect of ergot derived dopamine agonist.

OBJECTIVE: We studied the prevalence and related risk factors of impulse control disorders in Chinese Parkinson's disease patients. METHOD: We screened all non-demented Parkinson's disease patients attending our Parkinson's disease clinic from August 2009 to March 2010. The clinical characteristics of patients with impulse control disorders and those without were compared. RESULTS: Of the 213 PD subjects screened, 15 (7.0%) with impulse control disorders were identified. Fourteen of these subjects were on both a dopamine agonist and Levodopa, and one was on Levodopa alone. Of the fourteen subjects on both a dopamine agonist and Levodopa, eleven were on bromocriptine and Levodopa; 10.5% of the subjects exposed to bromocriptine had impulse control disorder. Upon multivariate analysis, dose of dopamine agonist used, young age at onset of Parkinson's disease and a history of anxiety or depression were independent predictors for developing impulse control disorders. CONCLUSIONS: 7% of our Chinese PD subjects had impulse control disorders. When young Parkinson's disease patients with a history of anxiety or depression are treated with high dose of DA, they are at risk of developing impulse control disorders.