Evaluation and management of hypersensitivity reactions to chemotherapy agents.

Hypersensitivity reactions to chemotherapy drugs pose significant difficulties in management, especially when no suitable alternative is available or acceptable and delay in continuation of treatment may be life-threatening. Such reactions may be IgE- or non-IgE-mediated and have varied manifestations. Timely recognition and treatment of life-threatening hypersensitivity reactions are essential. Identification of patients at high risk of developing hypersensitivity reactions allows risk stratification to guide clinical decision-making. Skin testing for carboplatin hypersensitivity has good predictive value but is not yet established for oxaliplatin and taxane hypersensitivity. Rapid desensitisation may be considered if no suitable alternative drug is available. Available protocols have shown good safety and efficacy but must be performed in an appropriate setting with adequate monitoring. There are many avenues for research into the utility of skin testing for other chemotherapy agents as well as in vitro tests.

Major trends in the manifestations and treatment of rheumatoid arthritis in a multiethnic cohort in Singapore.

We analyzed the epidemiological changes of rheumatoid arthritis (RA) over three decades using patients from a single center in Singapore. All patients who fulfill the 1987 American College of Rheumatology criteria for RA were invited to enroll in a prospective disease registry. We analyzed the patient demographics, disease manifestation, management and patient-reported outcomes, including quality of life (QoL), in the three categories according to the year of disease onset: before 1989 (group I), 1990-1999 (group II) and after 2000 (group III). There were 1,153 patients with 231, 532 and 390 in groups I, II and III, respectively. The mean disease durations were 25, 12 and 4.8 years, respectively. The majority was female (84.1 %) and Chinese (76.6 %) with no socio-demographic differences across the three periods. The age of onset rises and the prevalence of rheumatoid factor falls with the proximity of disease onset. Patients with most recent disease onset had the earliest access to the rheumatologist. They also had the highest tender and swollen joint counts, lowest deformed joint count and highest remission rate. Patients in group I report better mental and emotional QoL though many developed marked disability. We have documented changes of the manifestations of RA that are dependent and independent of improved treatment. Significant differences in accessibility to the rheumatologist, RA activity, functional capacity, quality of life and comorbidities were seen in subsequent cohorts due to treatment evolution and more efficient healthcare delivery.

Etoricoxib: a safe alternative for NSAID intolerance in Asian patients.

BACKGROUND: NSAID intolerance is not uncommon. Etoricoxib, a cox-2 inhibitor NSAID, has been shown to be a safe alternative in these patients. This study aims to determine the rate of NSAID intolerant patients who are able to tolerate etoricoxib without adverse reactions. METHODS: This study analyzed charts and electronic databases of all patients referred to the allergy clinics of the National University Hospital and Gleneagles Hospital in Singapore from 2006-2011 for oral provocation tests to etoricoxib (cumulative dose of 120 mg), on the background of NSAID intolerance. Demographics, atopic comorbidities, history of chronic urticaria, inciting NSAID, onset and type of reaction, and provocation test outcomes were obtained. RESULTS: A total of 74 patients (mean age 37; range: 16-72 years) underwent provocation tests to etoricoxib. Of these, 59% were female. Majority were Chinese (69%), followed by Malay (12%), Caucasian (8%), Indian (5%) and various other races (6%). Forty-six percent of the study population had atopic comorbidities, and 4% had concomitant chronic urticaria. Eighty percent of patients had a history of intolerance to 1 NSAID, while the rest (20%) had intolerance to multiple NSAIDS. Forty-one percent of patients had concomitant acetaminophen intolerance. Some of the patients had multiple symptoms on presentation, the most common of which were periorbital and facial edema (90%), breathing difficulties (26%) and urticaria (25%), with the onset of reaction occurring mostly within 30 minutes to 1 hour. Etoricoxib was tolerated in 95% of the patients. Subjects who reacted to the challenge all had mild reactions which resolved with antihistamines. CONCLUSIONS: Etoricoxib is a safe alternative in NSAID intolerant patients. Nevertheless, it is advised that patients should undergo provocation tests to confirm tolerance.

Gender equity in rheumatology leadership in the Asia-Pacific.

Objectives: This study aimed to explore gender equity in rheumatology leadership in the Asia-Pacific region as represented by the member national organizations (MNOs) of the Asia-Pacific League of Associations for Rheumatology (APLAR). Methods: We conducted a retrospective cross-sectional review of gender representation among the presidents of MNOs of APLAR in April 2022. We used the official website of each organization to acquire names and terms in the office of current and past presidents of each organization. The binary gender of each president was estimated using the name-to-gender inference platform Gender API (https://gender-api.com/). Proportions of male and female presidents were estimated for each organization. Data were compared for presidencies commencing before and in/after the year 2000. Results: We found a significant gap in gender parity, with most presidents in the region being men (210 of 252, 83%). More than one-third (7 of 19, 36.8%) of the MNOs had all male presidents, although the proportion of women improved from 7 to 25% in/after 2000 (P = 0.0002). A statistically significant increase in female representation was observed in Australia (P = 0.0268, from 7 to 39%) and New Zealand (P = 0.0011, where the proportion of female presidents increased from 0 to 45%), but not in other countries. Conclusion: A significant gap in gender parity exists in rheumatology leadership in the MNOs of APLAR. Trends suggest improvement over the last two decades, although statistically significant improvement is limited to a small number of countries.

Nonsteroidal anti-inflammatory drugs in chronic pain: implications of new data for clinical practice.

COX2-selective and nonselective (ns) nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for chronic pain management. There are marked differences in the risk of adverse gastrointestinal (GI) and cardiovascular (CV) events among different NSAIDs. In 2017, publication of two randomized controlled trials and an individual patient-data meta-analysis provided robust data on the relative GI and CV tolerability profiles of currently available NSAIDs. The PRECISION study showed similar CV-event rates with celecoxib vs naproxen and ibuprofen, but GI tolerability was better for celecoxib. In the CONCERN study of high-GI-risk patients, celecoxib was associated with fewer adverse GI-tract events than naproxen. The meta-analysis showed no significant difference between celecoxib and ns-NSAIDs in the rate of acute myocardial infarction, and celecoxib was the only COX2-selective NSAID with a lower risk of adverse CV and GI events vs ns-NSAIDs. These data add to the body of knowledge about the relative tolerability of different NSAIDs and were used to propose an updated treatment algorithm. The decision about whether to use an NSAID and which one should be based on a patient's risk of developing adverse GI and CV events. Lower- and upper-GI-tract events need to be considered. Celecoxib has a better lower-GI-tract tolerability profile than ns-NSAIDs plus a proton-pump inhibitor. In addition, the latest data suggest that long-term use of celecoxib 200 mg/day may be appropriate for patients at increased CV risk.

Achieving consensus in ultrasonography synovitis scoring in rheumatoid arthritis.

OBJECTIVE: Ultrasonography is sensitive for synovitis detection but interobserver variation in both acquisition and image interpretation is still a concern. The objective was to assess if a short collegiate consensus would improve inter-observer reliability in scoring of synovitis. METHODS: Eight rheumatologists (Singapore) participated in a 1-day consensus meeting divided into: (i) still-image interpretation and consensus followed by; (ii) image acquisition and interpretation, according to definitions and synovitis scoring rules endorsed by Outcome Measures in Rheumatology (OMERACT) and TUI (Targeted Ultrasound Initiative). Interobserver reliability of semiquantitative scoring in B-mode, Power Doppler (PDUS) and European League Against Rheumatism (EULAR)-OMERACT PDUS composite score was assessed by intraclass correlation co-efficient (ICC). Agreement at the joint region level was calculated using prevalence-adjusted-biased-adjusted-kappa (PABAK). RESULTS: For B-mode still images, ICC was good at 0.75 (95% CI 0.66-0.82) while for PDUS images this was excellent at ICC = 0.88 (95% CI 0.83-0.92) with ICC improving by 12% for B-mode and 13% for PDUS respectively. During image acquisition and interpretation, B-mode scoring showed ICC = 0.75 (95% CI 0.66-0.84) while for PDUS the ICC was lower at 0.59 (95% CI 0.48-0.72). The ICC for OMERACT PDUS composite synovitis scoring was good at 0.77 (95% CI 0.68-0.85). At the joint level, agreement varied with PABAK being excellent in the small joints of the hands but poor to fair in the wrists, elbows, ankles and metatarsophalangeal joints, and no agreement at the knees (PABAK range -0.34 to 0.85). CONCLUSION: A consensus meeting was useful in improving interobserver variation in US synovitis scoring of still images, but image acquisition and interpretation especially in non-hand joints require further standardization.

Recurrent intradialytic heparin induced anaphylaxis: workup and management.

Heparin has been widely used for intradialytic anticoagulation since the 1940s. Heparin induced anaphylaxis can be life threatening, mandating early recognition and intervention. However, due to its relative rarity many physicians remain unaware. We report the case of a 70-year-old woman requiring dialysis, who developed recurrent anaphylaxis to intradialytic heparin. We describe a systematic approach to confirm the suspected heparin allergy, which must include an evaluation of predisposing factors, the dialysis equipment and concomitant medications. Further workup for safe alternatives employing skin prick and intradermal tests, as well as provocation tests are discussed.

Clinical and laboratory characteristics of 75 patients with specific polysaccharide antibody deficiency syndrome.

BACKGROUND: There are limited studies of large cohorts of patients with specific polysaccharide antibody deficiency (SPAD) syndrome. OBJECTIVE: To study the clinical and laboratory characteristics of patients with specific polysaccharide antibody deficiency syndrome. METHODS: We retrospectively studied 75 patients with total IgG levels of at least 500 mg/dL and fewer than 9 of 12 responses to vaccination with pneumococcal vaccine polyvalent. Exclusion criteria included an IgG level less than 500 mg/dL, established immunodeficiency syndrome, and secondary immunodeficiency. RESULTS: The most common clinical presentation was frequent infections (n = 69; 92%), including sinusitis (n = 53; 77%), pneumonia (n = 29; 42%), ear infections (n = 18; 26%), and bronchitis (n = 19; 28%). Other presentations were systemic infections (n = 5; 7%), autoimmune or rheumatic diseases (n = 6; 8%), and chronic diarrhea (n = 4; 5%). The median IgG2 level of patients with no response to pneumococcal vaccine polyvalent tended to be lower than that of patients with at least 1 response (150 vs 193 mg/dL, respectively; P = .06). There was no association between total IgG level (categorized as 500-600 or > or = 600 mg/dL) and frequency of infection (P = .43). Patients with fewer responses to pneumococcal vaccine polyvalent and a higher frequency of infections were more likely to receive intravenous immunoglobulin (IVIG) therapy (P = .01 and .003, respectively). Treatment with IVIG significantly reduced the number of infections (P < .001). CONCLUSION: Patients with no response to pneumococcal vaccine polyvalent tended to have lower IgG2 levels; those with fewer responses were more likely to receive IVIG therapy.