Sizheng Zhao

Neuropathic pain in neuromyelitis optica affects activities of daily living and quality of life

Though pain in neuromyelitis optica (NMO) has been described in two recent reports, the proportion with true neuropathic pain (NP), its features, impact on activities of daily living (ADL) and quality of life has not been well characterised. A cross-sectional study of 50 NMO patients with transverse myelitis was performed using Douleur Neuropathique 4, Brief Pain Inventory, Extended Disability Status Scale and Short Form 36. NP was identified in 62% of patients. Pain was constant in 68% affecting most ADL. Pain was associated with significant reduction of the SF36 Mental Composite Score. The high prevalence of NP and associated disability necessitates an in-depth enquiry in patients with NMO.

Systematic review of association between vitamin D levels and susceptibility and disease activity of ankylosing spondylitis

OBJECTIVES Vitamin D appears to have significant effects on both innate and acquired immunity and deficiency may be associated with both susceptibility and disease severity in some autoimmune conditions. There has been little focus on the potential immunomodulatory role of vitamin D in AS. This study systematically reviews the evidence for an association between vitamin D deficiency and disease susceptibility and severity in AS. METHODS A systematic review was conducted using Medline, EMBASE, Web of Science and conference abstracts of the European League Against Rheumatism (2002-13), British Society for Rheumatology (1993-2013) and ACR (2006-13). RESULTS Fifteen original articles and five conference abstracts met the criteria for inclusion. All were cross-sectional in design. Seven of 11 studies identified lower concentrations of 25-hydroxyvitamin D (25OHD) in AS patients compared with healthy controls. A significant inverse correlation between 25OHD and disease activity was observed in 5 of 11 studies. The majority of studies that failed to demonstrate significant findings used inappropriate statistical methods. CONCLUSION Cross-sectional studies using appropriate statistical analyses have highlighted that AS is associated with lower vitamin D concentrations. Within groups of AS patients there is some evidence that low vitamin D concentrations are associated with higher disease activity. However, there are insufficient published data to support an immunomodulatory role for vitamin D in AS. Further study with a longitudinal design is required to understand whether optimizing vitamin D in AS has potential as a disease-modifying intervention.

Deafness: malaria as a forgotten cause.

Abstract Background: Ototoxicity from antimalarials is a well publicised cause of deafness and a great deal of time and resources are spent assessing it in relation to new drugs. The effect of the malaria parasite itself on hearing is, however, poorly documented and most evidence is anecdotal. This paper aims to collate existing evidence of this association. Methods: Two systematic literature searches were performed on Ovid Medline, first for ‘malaria’ and ‘hearing loss’ or ‘hearing impairment’ or ‘deafness’, and secondly for ‘cerebral malaria’ and ‘neurologic’ or ‘neurological’ or ‘neurocognitive sequelae’. The articles were then individually studied for relevance. Results: Malaria has been implicated as a rare cause of hearing loss in various studies, but recommendations and hypotheses have not been taken seriously or investigated. Searches also returned numerous studies of neurological sequelae after cerebral malaria, a small proportion of which observed hearing impairments on follow‐up. However, no attempt was made to distinguish between treatment and disease as the cause. A few antimalarial drug trials which assessed hearing before treatment found unexplained hearing loss which improved with elimination of the parasite. Conclusion: Evidence from this review suggests that the falciparum parasite is a potential cause of hearing loss. Malaria is a disease of such high prevalence that even if only a small proportion of survivors develop this impairment the effects on children’s education could be detrimental. More attention should be focussed on investigating this association as the clinical and pathophysiological implications are potentially considerable.

Vitamin D assessment in primary care: changing patterns of testing.

Background Over recent years there has been increased interest in the disease burden associated with vitamin D deficiency. This, combined with recognition that the prevalence of vitamin D deficiency is high in the UK, has led to increased requests for vitamin D assessment from primary care clinicians. Setting A primary care cohort in Liverpool. Question How has the usefulness of vitamin D testing changed over time in identifying deficiency? Methods Vitamin D results from primary care practices in Liverpool were collected between 2007 and 2012, inclusive. Results were allocated to six cohorts based on year of request and each was grouped into three categories (adequate, insufficient and deficient). Results Vitamin D results of 9460 (74%) first tests and 3263 (26%) retests were analysed. Total number of requests increased 11-fold, from 503 in 2007 to 5552 in 2012. Overall 42% of first-test results were deficient (<; 30 nmol). With each incremental year, more cases of vitamin D deficiency were detected – but the odds of detecting vitamin D deficiency decreased. Conclusions An exponential increase in the number of vitamin D requests was observed over this six-year period. Although more patients with vitamin deficiency were identified, the increased number of tests represents a significant cost to health services. Moreover, the practice of retesting too soon after treatment can be inappropriate. There is a need to develop clear guidance for assessing vitamin D status in primary care.

An unusual case of 'itchy paralysis’: neuromyelitis optica presenting with severe neuropathic itch

Pruritus, better known as itch, is ‘an unpleasant cutaneous sensation provoking the desire to scratch’.1 It is typically caused by pruritogens that activate nerve endings in cutaneous and transitional tissues (eg, conjunctivae, anal mucosa) and serves a protective function against noxious stimuli. Itch can also occur with diseased or malfunctioning pruritogenic neurones in the absence of a pruritogen—a symptom termed neuropathic pruritus or neuropathic itch.2 Neuropathic pruritus is a well described but under-recognised symptom of neurological disorders. The site of involvement may be (i) peripheral nerve and root, (ii) spinal cord or (iii) brain. It may accompany a variety of peripheral and central neurological disorders, including postherpetic neuralgia, peripheral neuropathy, trigeminal neuralgia, traumatic nerve injury, complex regional pain syndrome, multiple sclerosis and stroke.3 Neuromyelitis optica is a relapsing inflammatory astrocytopathic disorder affecting predominantly the optic nerves and spinal cord. It is associated with antiaquaporin-4 immunoglobulin G (AQP4-IgG) in up to 70% of patients. Spinal cord involvement typically presents as a longitudinally-extensive transverse myelitis with associated sensorimotor and sphincter dysfunction. Sensory symptoms such as numbness, dysaesthesia, pain and tonic spasms are common.4 This report highlights neuropathic pruritus as an under-recognised feature of neuromyelitis optica. A 45-year-old woman with no previous medical history presented with a 4-day history of unexplained nausea, vomiting, hiccup and vertigo. On the fourth day, she developed bilateral forearm itching. Over the following 3 days, she developed rapidly progressive weakness from the chest down, ultimately resulting in complete paraplegia, sensory loss and loss of both bladder and bowel function. She also developed weakness in both arms, worse on the left side. She was admitted 3 days after the onset of her nausea and vomiting, which subsided a day later. However, the itching …

Bladder and bowel dysfunction affect quality of life. A cross sectional study of 60 patients with aquaporin-4 antibody positive Neuromyelitis Optica spectrum disorder

BACKGROUND Transverse myelitis (TM) associated with Neuromyelitis Optica (NMO) can be severe and is well known to reduce mobility early in the disease. However the burden of bladder and bowel dysfunction is unknown and overlooked. We studied the frequency of bladder and bowel dysfunction and their impact on quality of life. METHODS A cross-sectional study of 60 patients who had AQP4-IgG positive NMO associated TM was performed using the Bladder Control Scale, Lower Urinary Tract Quality of Life, Bowel Control Scale and Neurogenic Bowel Score, Short-Form-36 Health Survey and EDSS. The relationships between the variables were analysed with multiple linear regression. RESULTS Fifty women and 10 men participated. 78% (47/60) patients reported bladder symptoms and a similar number reported bowel problems. 87% (52/60) patients reported either bladder or bowel dysfunction. 65% (39/60) developed residual symptoms after the first episode of myelitis and the remaining by the second episode. Both bladder and bowel dysfunction reduced quality of life and required modification of lifestyle in 83% (39/47) and 70% (33/47) respectively. CONCLUSION Bladder and bowel dysfunction is very common in NMO associated myelitis developing early in the disease and significantly affects quality of life.

Complementary and Alternative Medicine Use in Rheumatoid Arthritis: Considerations for the Pharmacological Management of Elderly Patients

Complementary and alternative medicines (CAMs) are widely used by patients with rheumatoid arthritis (RA); however, a significant proportion of these patients do not inform their physicians. This has many potential implications in a group of predominantly elderly patients with altered pharmacokinetics, comorbidities and polypharmacy of potentially toxic drugs. CAM usage may affect compliance and pharmacokinetics of conventional therapy for RA and comorbidities; therefore, physicians should engage patients in dialogues regarding CAM usage. This review introduces common CAMs used by RA patients, such as herbal remedies, supplements, and fish and plant oils, and their potential impact on conventional therapy. Efficacy of these treatments are not reviewed in detail but references for reviews and trials are provided for further reading. Fish oils and vitamin D supplementation may generally be recommended, while thunder god vine should be avoided. Patients should also be made aware of the risks of contamination and adulteration of less reputable sources of CAMs, and directed to evidence-based sources of information. Physicians should acknowledge the limitations of scientific evidence and not be prejudiced or dogmatic; however, they should remain resolute against therapies that are known to be ineffective or unsafe.

AB0737 Male Smokers Have Delayed Response to Anti-TNF Therapy in Ankylosing Spondylitis

Background There has been increasing interest on the effect of smoking in ankylosing spondylitis (AS). Studies suggest smoking is associated with higher incidence of AS, worse disease activity, structural damage, functional status and quality of life.1,2 Rheumatoid arthritis patients who smoke are reported to have reduced response to anti-TNF therapy (TNFi),3 although this has not been explored in AS. Objectives To study the effect of smoking on response to TNFi in AS. Methods AS patients at Aintree University Hospital, Liverpool, UK were entered into an audit database upon commencing TNFi from 2003 to 2014. Demographics, smoking status and pack years were recorded. Follow-up were aimed at 3 and 6 months, dependent on clinic availability and patient cancellation. Response was defined as reduction of BASDAI by 2 or 50% and spinal pain visual analogue scale (VAS) by 2. Survival analysis was performed using time to first recorded response. <20 pack years was considered light and ≥20 heavy smoking. All analyses were adjusted for age at starting TNFi. Results 118 patients fulfilling the modified New York criteria for AS were included. 87 (73.7%) were male and 44/55 (80%) were HLA B27 positive. Mean (±sd) pre-TNFi BASDAI was 7.4±1.4 and VAS 7.8±1.5. Median time to first follow-up was 19 weeks (IQR 14, 28). Initial TNFi exposures were adalimumab 39.0%, etanercept 37.3%, golimumab 22.9% and infliximab 0.9%. 39.8% were current, 15.3% previous and 44.9% non-smokers. Of those that ever smoked 47.7% were heavy and 52.3% light smokers. Pre-TNFi disease activity and time to follow-up did not differ by smoking categories above or by gender. Cox proportional hazard analysis showed trends toward ever-smoking being associated with reduced response (HRadj 0.70; 95%CI 0.46, 1.06), which was significant in males (HRadj 0.52; CI 0.32, 0.85). Figure 1 shows the survival estimate for male ever-smokers compared to non-smokers. 82.8% of light/non-smokers responded to TNFi compared to 61.3% in heavy smokers (P=0.015). Conclusions In this small preliminary study, ever-smoking in males was associated with delayed response to TNFi. However this real life cohort had a high rate of non-attendance. Response could only be assessed at follow-up appointments which impact on time to response. Results suggest that ever-smokers may require longer follow-up in assessing treatment response. This hypothesis needs to be tested in larger cohorts with more frequent follow-up. References Chung HY et al. Smokers in early axial spondyloarthritis have earlier disease onset, more disease activity, inflammation and damage, and poorer function and health-related quality of life: results from the DESIR cohort. ARD 2012;71:809-16. Videm V et al. Current smoking is associated with incident ankylosing spondylitis - the HUNT population-based Norwegian health study. J Rheumatol 2014;41:2041-8. Abhishek A et al. Anti-TNF-alpha agents are less effective for the treatment of rheumatoid arthritis in current smokers. J. Clin Rheumat 2010;16:15-8. Disclosure of Interest None declared

Concomitant fibromyalgia complicating chronic inflammatory arthritis: a systematic review and meta-analysis

Abstract Objectives This systematic review and meta-analysis will describe the prevalence of concomitant FM in adults with inflammatory arthritis and quantify the impact of FM on DAS. Methods Cochrane library, MEDLINE, Psychinfo, PubMed, Scopus and Web of Science were searched using key terms and predefined exclusion criteria. As appropriate, proportional and pairwise meta-analysis methods were used to pool results. Results Forty articles were identified. In RA the prevalence of FM ranged from 4.9 to 52.4% (21% pooled). In axSpA the range was 4.11–25.2% (13% pooled in AS only). In PsA the range was 9.6–27.2% (18% pooled). The presence of concomitant FM was related to higher DAS in patients with RA and AS (DAS28 mean difference 1.24, 95% CI: 1.10, 1.37 in RA; BASDAI mean difference 2.22, 95% CI: 1.86, 2.58 in AS). Concomitant FM was also associated with higher DAS in existing PsA studies. Self-reported, rather than objective, components of DAS appear to be raised in the presence of FM (e.g. tender joint count and Visual Analogue Scale (VAS) pain scores). Conclusion FM is common in RA, AxSpA and PsA. Comorbid FM appears to amplify DAS and could therefore influence management of these rheumatic conditions.

Etanercept for the treatment of rheumatoid arthritis

Etanercept was the first specific anticytokine therapy approved for the treatment of rheumatoid arthritis (RA). Its clinical efficacy and safety has been demonstrated by several clinical trials in early as well as established disease. Etanercept, along with other TNF inhibitors, have revolutionized management of RA and dramatically improved disease activity, function, quality of life and mortality for these patients. It is structurally distinct from other TNF inhibitors and thus has desirable profiles for immunogenicity, drug survival and infection rate. With the increasing number of etanercept biosimilars, there will likely be a resurgence of their prescription. This article reviews the pharmacology, efficacy and safety of the etanercept reference product, and its biosimilars, in the context of RA treatment.