Hani Almoallim

Rheumatoid arthritis: should we shift the focus from “Treat to Target” to “Treat to Work?”

Rheumatoid arthritis (RA) is a chronic inflammatory disorder characterized by progressive inflammatory synovitis and destruction of articular cartilage and marginal bone. Joint erosion can be seen within 6 months of disease onset in the majority of patients and occurs more rapidly in the first year than in late-stage disease [1]. Historical studies have demonstrated that moderate disability within 2 years of diagnosis is not uncommon, and up to 30 % of patients may be unable to work after 10 years [2]. Improvement in disability, as measured by Health Assessment Questionnaire (HAQ) disability index scores, can be demonstrated in the short term with DMARD therapy, but the magnitude of this improvement is substantially greater among patients with early disease than among those with more advanced disease [3]. Longitudinal studies of RA patients show that there is a progressive decline in HAQ scores with time [3, 4]. Early interventions that prevent irreversible damage would appear to offer the best opportunities for achievement of favorable outcomes in patients with early, aggressive RA. In early intervention studies that measured radiographic progression, this therapeutic window can be as small as a few months [5, 6]. In addition to early therapy, combination treatment has been shown to result in more favorable short-term and longterm outcomes than monotherapy [5, 7]. RA poses a significant burden to patients, their caregivers and employers, and the government. Work disability often arises early in the course of the disease. According to several prospective studies, 20–35 % of individuals had to stop working within 2–3 years of disease onset [2, 8]. After 5–10 years, the reported work disability rate is approximately 40 % [9]. Aggressive therapy can also help to preserve the workability of RA patients. In a study by Klimes et al. published in 2011 [10], it was noted that patients on biologics reported less reduction of daily activities (39.8 %) than patients on DMARDs (50.5 %), reflecting around 53.6 % higher productivity costs for the latter group. Similarly, we recently showed that the use of biologics improved workability scores in RA in a cross-sectional study of 120 patients from three different hospitals in Saudi Arabia [Janoudi N, Almoallim H, Husien W, Noorwali A, Ibrahim A. (2012) Workability and work instability evaluation in Saudi patients with rheumatoid arthritis. Arthritis Care & Research, unpublished]. Indeed, we observed that RA patients on conventional therapy had significantly lower work quality, quantity, and satisfaction scores than those receiving biological therapy. In a study published in 1996, Mau et al. [11] showed that the fastest decline in the employment rate among RA patients was found within the first 3 years of the disease onset, with a 3-year employment rate reduced to 73±5 %. This reflects the importance of early and aggressive management of RA if workability is the main treatment goal. This observation was further confirmed by Puolakka and collaborators [12], who concluded that prompt induction of remission enabled maintenance of work capacity. Their results revealed that the median numbers of work disability days per patient-year from 6 through 60 months of followup were 0 for ACR70 achievers, 4 for ACR 50 achievers, 16 for ACR 20 achievers, and 352 for ACR20 non-achievers. Over the past 15 years, rheumatologists have developed and witnessed many paradigmatic changes in the treatment of RA. H. Almoallim Department of Medicine, Umm Alqura University, Makkah, Saudi Arabia

Isolated eosinophilic mesenteric vasculitis with extensive thrombosis and splenic infarction in a 13-year-old boy

There are no generally accepted diagnostic criteria for primary systemic vasculitis, and the application of classification as diagnostic criteria is not feasible and may even be misleading. We report a case of a 13-year-old boy with acute abdomen who was found to have isolated eosinophilic mesenteric vasculitis with extensive thrombosis and splenic infarction. All serological tests were negative, including antineutrophil cytoplasmic antibody. The vasculitis had been successfully controlled with surgical intervention, steroid, and cyclophosphamide therapy. This may be an atypical presentation of Churg–Strauss syndrome.

Microscopic polyangiitis sparing the kidneys in a long-term survivor after allogeneic bone marrow transplantation and graft-versus-host disease.

We report an unusual case of microscopic polyangiitis sparing the kidneys in a long-term survivor of allogeneic bone marrow transplantation. Clinical and pathologic studies revealed cutaneous leukocytoclastic vasculitis and isolated pulmonary capillaritis. Serological studies revealed “double positive”: perinuclear antineutrophil cytoplasmic (P-ANCA) antibody testing with anti-myeloperoxidase (MPO) activity and anti-glomerular basement membrane (anti-GBM) antibody. The vasculitis has been successfully controlled with prednisone and cyclophosphamide.

The journey of rheumatoid arthritis patients: a review of reported lag times from the onset of symptoms

Background Even after achieving tremendous advances in diagnosis and treatment of rheumatoid arthritis (RA), many of the patients undergo delays in diagnosis and initiation of treatment, which leads to worsening of the condition and poor prognosis. Objective The objective of this study was to perform a literature review to quantify the lag times in diagnosis and treatment of RA and study the reported factors associated with it. Methods The authors searched literature published until September 2016 in electronic full-text and abstract databases and hand-searched the suitable articles. Results The weighted average of median lag time from symptom onset to therapy was 11.79 months (12 studies, 5,512 patients, range 3.6–24.0 months). Lag1 was 3.14 months (onset of symptoms to first physician consultant; 12 studies, 6,055 patients, range 0–5.7 months); lag2 was 2.13 months (physician visit to RA specialist referral; 13 studies, 34,767 patients, range 0.5–6.6 months); lag3 was 2.91 months (consultation with rheumatologist to diagnosis; 3 studies, 563 patients, range 0–5 months), lag4 was 2.14 months (diagnosis to initiation of disease-modifying antirheumatic drug therapy; 5 studies, 30,685 patients, range 0–2.2 months). Numerous patient-and physician-related factors like gender, ethnicity, primary care physician knowledge of the condition, availability of diagnostics, and so on were responsible for the delays. Conclusion This review estimated the delay times and identified the main factors for delay in RA patients in diagnosis and initiation of treatment. A most plausible solution to this is coordinated effort by the rheumatology and primary care physicians.

From Symptoms to Diagnosis: An Observational Study of the Journey of Rheumatoid Arthritis Patients in Saudi Arabia.

OBJECTIVES Rheumatoid arthritis (RA) is often not diagnosed or treated quickly enough to alter outcomes. We aimed to evaluate the lag times from disease onset to first clinical consultation and diagnosis and to identify factors contributing to delayed diagnosis in Saudi Arabia. METHODS This retrospective, multicenter study collected data on 250 patients, from six hospitals in Saudi Arabia, who met the 2010 American College of Rheumatology criteria for RA. RESULTS The patients mean age was 43.3±12.0 years (mean disease duration: 6.6±5.8 years). The majority were female (84.8%) and presented with joint pain during RA onset (83.6%). On average, they consulted 4.3±2.5 physicians from the first symptoms to the final diagnosis. The mean time from onset to first physician visit (lag 1) was 6.2±5.5 months, whereas the mean time was 30.2±16.0 months between the initial visit and final RA diagnosis (lag 2). Only 3.2% of patients initially sought consultation from a rheumatologist, while 67.2%, 23.6%, and 6.0% first met with orthopedic surgeons, general practitioners, and non-rheumatologists, respectively. Non-rheumatologists offered diagnoses in 24.4% of cases while rheumatologists diagnosed 75.6%. The absence of early hand/wrist involvement and fatigue were associated with delayed RA diagnosis (long lag 2; p<0.010). Moreover, geographic distribution influenced RA diagnosis, with rural patients experiencing a greater delay than urban patients (p<0.0001). CONCLUSIONS Failure of patients to be seen by rheumatologists at RA onset delayed diagnosis and treatment. Thus, RA diagnosis can be accelerated by encouraging early referral to rheumatologists.

Clinical characteristics and outcomes of cancer patients with post-chemotherapy arthritis: a retrospective case series report

Objective The objective of this report was to describe the demographics, clinical characteristics and outcomes of patients with cancer presenting with arthritis following chemotherapy in Jeddah, Saudi Arabia. Patients and methods This is a retrospective case series report. We included any patient ≥18 years of age with an established diagnosis of cancer who had received standard therapeutic intervention and was subsequently diagnosed with arthritis after developing rheumatic symptoms either during or after treatment. Patients with clinical evidence of arthritis at the time of their cancer diagnosis were excluded. Results Seven cases from different centers were identified. Breast cancer was the most common type of cancer reported. The diagnosis of arthritis was established by a rheumatologist. Bilateral involvement of the metacarpophalangeal and proximal interphalangeal joints was the most common presentation. The knee, back, shoulder and wrist joints were less affected. Following treatment, one patient experienced complete resolution of symptoms, four patients symptomatically improved and one patient had no improvement. Conclusion Arthritis can develop both during and after treatment of a malignancy. Solid tumors seem to be more commonly associated with this phenomenon. In this case series, the prognosis was poor as the majority of patients developed persistent arthritis.

Determining early referral criteria for patients with suspected inflammatory arthritis presenting to primary care physicians: a cross-sectional study

Objective Early diagnosis and initiation of treatment for inflammatory arthritis can greatly improve patient outcome. We aimed to provide standardized and validated criteria for use by primary care physicians (PCPs) in the identification of individuals requiring referral to a rheumatologist. Patients and methods We analyzed the predictive value of a wide variety of demographic variables, patient-reported complaints, physical examination results, and biomarkers in order to identify the most useful factors for indicating a requirement for referral. Patients for this cross-sectional study were enrolled from various centers of the city of Jeddah, Saudi Arabia, if they were ≥18 years of age and presented to a PCP with small joint pain that had been present for more than 6 weeks. A total of 203 patients were enrolled, as indicated by the sample size calculation. Each patient underwent a standardized physical examination, which was subsequently compared to ultrasound findings. Biomarker analysis and a patient interview were also carried out. Results were then correlated with the final diagnosis made by a rheumatologist. Results A total of 9 variables were identified as having high specificity and good predictive value: loss of appetite, swelling of metacarpophalangeal joint 2 or 5, swelling of proximal inter-phalangeal joint 2 or 3, wrist swelling, wrist tenderness, a positive test for rheumatoid factor, and a positive test for anti-citrullinated protein antibodies. Conclusion Nine variables should be the basis of early referral criteria. It should aid PCPs in making appropriate early referrals of patients with suspected inflammatory arthritis, accelerating diagnosis and initiation of treatment.

Bedside teaching: an underutilized tool in medical education

Bedside teaching (BST) is a fundamental component of clinical training and an essential tool in the creation of a competent physician.1-15 Sir William Osler (1849-1919), one of Canada’s most renowned physicians, was the first to introduce BST to medical education in 1892. He described modern medical education as something that needed to be taught at the bedside: “Medicine is learned by the bedside and not in the classroom.”9 BST allows the physician and patient to interact at the bedside; through this physician-patient interaction process, medical students and residents are simultaneously afforded the opportunity to learn clinical skills, clinical reasoning, physician-patient communication, empathy, and professionalism.6,12,15 In real practice, comprehensive history taking can help the physician diagnose up to 56% of patient problems, which may rise to 73% if a physical examination is added.8 Much information can be gained and a proper diagnosis reached by obtaining a good medical history and performing an efficient clinical examination.8 Clinical teaching in which the patient is involved is enriched by these visual, auditory, and tactile experiences. Senior medical students and medical residents believe that BST is a valuable but underutilized tool.15 Time spent on BST has been on the decline since 1978, as highlighted by Ahmed, who reported that the proportion of teaching time taken up by BST had declined from 75% 30 years ago to only 16% today.8 The learning triad The BST learning triad comprises patients, students, and tutors.6 All three must be present for BST to occur and it must occur within a clinical environment. Each individual member brings his or her own value to the learning triad. For example, the student brings medical knowledge and the eagerness to learn; the tutor brings depth of knowledge, mentorship, and willingness to help the student learn and make connections; and finally, the patient brings relevant clinical issues to the forefront that allow the student to learn. An effective learning environment requires all three groups to work together in the learning triad.6 The obstacles that may reduce the effectiveness of BST can be categorized by each group in the learning triad.

Effect of Adalimumab on Work Ability Assessed in Rheumatoid Arthritis Disease Patients in Saudi Arabia (AWARDS)

Objectives : Rheumatoid arthritis (RA) is a chronic disabling disease that can jeopardize the ability of affected individuals to participate in paid work. Our objective was to evaluate the effectiveness of a 6-month course of tumor necrosis factor (TNF) antagonist (adalimumab) on work ability, overall health, and fatigue in RA patients. Methods : Between October 2012 and February 2014, this prospective, observational study enrolled 63 consecutive patients with established adult RA at outpatient clinics in Makkah, Jeddah, Riyadh and Abha (Saudi Arabia). Patients received subcutaneous injections of adalimumab (40 mg every 2 weeks). Outcomes were measured at baseline and 6 months using the following tools: Work Productivity and Activity Impairment (WPAI), Health Assessment Questionnaire Disability Index (HAQ-DI), Fatigue Severity Scale (FSS), Visual Analog Scale for Fatigue (VAS-F), and work disability self-assessment. Results : All outcomes showed improvements after 6 months of adalimumab therapy. Significant improvements from baseline were observed in absenteeism (64% ± 11.62 to 11.60% ± 11.17 [p<0.0001]), presenteeism (62.15% ± 20.11 to 34.92% ± 20.61 [p<0.0001]), overall work impairment (69.08% ± 18.86 to 40.73% ± 22.29 [p<0.0001]), overall activity impairment (68.46% ± 18.58 to 36.46% ± 20.79 [p<0.0001]), HAQ score (1.69 ± 0.57 to 0.81 ± 0.61 [p<0.0001]), and FSS score (47.08 ± 9.55 to 27.86 ± 13.43 [p<0.0001]). Conclusion : A 6-month course of adalimumab improved work ability, fatigue, and overall health assessments in patients with established RA. Our findings encourage randomized controlled trials investigating the cost-effectiveness and long-term effects of TNF inhibitors on work disability.

Outcomes of rituximab therapy in refractory lupus: a meta-analysis

OBJECTIVE Conventional treatment of systemic lupus erythematosus (SLE) and lupus nephritis (LN) is associated with damage accrual, hence increased morbidity rate. Off-label use of rituximab (RTX) has shown significant promise in this patient group; however, data are still controversial. We aimed to analyze the outcomes of RTX therapy in refractory lupus using a meta-analysis approach. METHODS Electronic search of the medical literature was conducted using a combination of relevant keywords to retrieve studies on the safety and efficacy of RTX in SLE and LN patients. Results were screened against our inclusion and exclusion criteria and two reviewers independently extracted the data for analysis. Comprehensive meta-analysis software was used to pool the data from individual studies and provide summary effect estimates. RESULTS Thirty-one studies that enrolled 1112 patients were finally eligible for the meta-analysis. The overall global, complete, and partial response rates to RTX therapy were 72%, 46%, and 32%, respectively. RTX significantly decreased Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and British Isles Lupus Activity Group (BILAG) scores (p<0.001). Prednisone dose was significantly reduced after RTX treatment in both SLE and LN groups (p<0.001), and proteinuria was lowered in SLE (p<0.001) than in LN patients (p=0.07). Infection and infusion-related reactions were the most common side effects. CONCLUSION RTX therapy in refractory SLE and LN patients proved clinical efficacy and favorable safety outcomes. Larger well-designed randomized clinical trials are warranted.