Skin testing for immediate hypersensitivity to corticosteroids: a case series and literature review.

BACKGROUND: Immediate hypersensitivity to corticosteroids is reported to occur with an incidence of 0.1%. The largest previous case series reporting corticosteroid skin testing has seven patients. METHODS AND PATIENTS: We identified 23 patients (mean age 50 years, 65% female) from Auckland City Hospital who underwent skin testing (ST) for suspected corticosteroid hypersensitivity between July 2005 and April 2012. We performed a retrospective clinical case note review detailing clinical history of reaction, skin test results and subsequent management. Most patients (21/23) had a standard panel of testing with prednisolone, triamcinolone, methylprednisolone, hydrocortisone and dexamethasone. Skin tests used a 10% steroid stock concentration for skin prick tests (SPT) and dilutions of 1 : 1000, 1 : 100 and 1 : 10 for subsequent intradermal testing. A weal 3 mm greater than the negative control was considered positive. RESULTS: A total of 23 patients were identified who had skin testing for suspected acute hypersensitivity to corticosteroids, eight of which had a history of anaphylaxis. From 28 reactions (in 23 patients), the most common route of administration was intra-articular (13), followed by oral (7), intravenous (3) and other (5). Skin tests were positive in 8/23 patients, and 7/8 of these patients had a history of corticosteroid-associated anaphylaxis. Skin tests were positive at either the skin prick test or intradermal stages. There was evidence suggesting clinical and skin test cross-reactivity between corticosteroids in one patient. One patient had a positive skin test, but negative oral challenge suggesting the skin test was false positive. Skin tests were negative in 15/23 patients. One patient had a negative prednisolone skin test and positive unblinded oral challenge, suggesting a false-negative skin test. CONCLUSIONS: Skin testing can provide sufficient evidence to diagnose allergy in patients with a clear history of immediate hypersensitivity to corticosteroids such as anaphylaxis. Both skin prick and intradermal tests should be used. There is evidence of cross-reactivity between steroids, so a panel is recommended. False-positive and false-negative reactions do occur; however, the frequency is unknown. Challenge remains the only definitive way to demonstrate a safe alternative to use. CLINICAL RELEVANCE: As the largest case series described, this article provides new evidence for the interpretation of skin tests when investigating possible immediate hypersensitivity to corticosteroids.

Prevalence of paraproteinaemia in older Australians.

BACKGROUND: Estimates of the prevalence of paraproteinaemia vary, from 1% in persons aged over 25 years to 10% in those aged over 80 years, although there are limited data from well-defined populations. We sought to determine the prevalence of paraproteinaemia in Australians aged 50 years and over, and to determine risks factors for its presence. METHODS: We performed a population-based, cross-sectional study using data and serum collected in the Blue Mountains Eye Study. Serum samples from 2933 patients were analysed by capillary zone electrophoresis and, where indicated, immunosubtraction, which allowed for both quantitation and isotype detection. RESULTS: A paraprotein was detected in 134 of the 2933 samples, giving an overall prevalence of 4.6% (95% confidence interval, 3.8-5.3%). The presence of a paraprotein was strongly age-related (P(trend) = 0.001), with a prevalence of 2.8% in persons aged 50-59 years, rising steadily to 9.1% in those aged 80 years and over. The prevalence was significantly higher in men (5.9%) compared with women (4.0%) (P= 0.03). CONCLUSION: We conclude that approximately one in 20 Australians aged 50 years or over harbours a paraprotein, a prevalence that appears higher than from similar cohorts in other countries.

Consensus guidelines on anti-beta 2 glycoprotein I testing and reporting.

Consensus guidelines on anti-beta 2 glycoprotein I (anti-beta2GPI) testing have been developed to help minimise laboratory variation in the performance and reporting of assays for these antibodies. These guidelines include minimum and optional recommendations for the following aspects of anti-beta2GPI testing and reporting: (1) isotype of anti-beta2GPI tested; (2) specimen type; (3) controls and assay precision; (4) calibrators; (5) patient samples; (6) rheumatoid factors and IgM anti-beta2GPI testing; (7) reporting of results; (8) cutoff values; and (9) interpretative comments. Issues related to inter-kit/assay standardisation and the manufacturing process of commercial anti-beta2GPI kits/assays have not been addressed in the current guidelines.

Prevalence of thyroid disease in an older Australian population.

AIM: To determine the prevalence of thyroid disease in an older Australian population in a population-based cross-sectional study. BACKGROUND: Community-living subjects, aged 49 years or older, in two Blue Mountains postcodes were invited to participate in an eye, nutrition and health study between 1997 and 2000. METHODS: Three thousand five hundred and nine of the 4489 identified persons participated. Fifty-seven per cent of 3504 who completed questionnaires were women; their mean age was 66.8 years. Thyroid-stimulating hormone (TSH) was measured in 2665 subjects (76% of those completing the questionnaire). The main outcome measures were serum TSH and free thyroxine levels, serum lipids, urate and sugar levels and questionnaire responses. RESULTS: The prevalence of recognized thyroid disease (either self-reported history of thyroid disease or current thyroxine treatment) was 10% (95% confidence interval (CI) 8.9-11.1%). An additional 3.6% (95%CI 2.9-4.3%) of participants had unrecognized thyroid disease (abnormal TSH). The TSH was abnormal in 7.1% (95%CI 5.8-8.4%) of women and 3.7% (95%CI 2.6-4.8%) of men. Sixty-five per cent of those with an abnormal TSH did not report a history of thyroid disease, whereas 25% of those taking thyroxine replacement therapy had an abnormal TSH level. The prevalence of hypothyroidism increased with increasing age in women. The mean fasting cholesterol was 0.36 mmol/L (95%CI 0.15-0.57) higher in hypothyroid subjects than in euthyroid subjects. CONCLUSION: Thyroid disease in older Australian women is relatively common and may be undiagnosed. Ongoing monitoring of patients on thyroxine replacement therapy is important, given that 25% of treated patients had an abnormal TSH.

Prevention of recurrent miscarriage for women with antiphospholipid antibody or lupus anticoagulant.

BACKGROUND: A range of treatments have been proposed to improve pregnancy outcome in recurrent pregnancy loss associated with antiphospholipid antibody (APL). Small studies have not resolved uncertainty about benefits and risks. OBJECTIVES: To examine outcomes of all treatments given to maintain pregnancy in women with prior miscarriage and APL. SEARCH STRATEGY: We searched the Pregnancy and Childbirth Group's Trials Register (30 May 2004), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 2, 2003), MEDLINE (1966 to June 2003), EMBASE (1988 to June 2003), Lupus (volume one to eight, 1991 to 1999) and conference proceedings from the International Symposium on APL up to 1999. SELECTION CRITERIA: Randomised or quasi-randomised, controlled trials of interventions in pregnant women with a history of pregnancy loss and APL. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed quality and extracted data for studies up to December 1999. One review author performed this for studies after 1999. MAIN RESULTS: Thirteen studies were found (849 participants). The quality was not high; 50% had clear evidence of allocation concealment. Participant characteristics varied between trials. Unfractionated heparin combined with aspirin (two trials; n = 140) significantly reduced pregnancy loss compared to aspirin alone (relative risk (RR) 0.46, 95% confidence interval (CI) 0.29 to 0.71). Low molecular weight heparin (LMWH) combined with aspirin compared to aspirin (one trial; n = 98) did not significantly reduce pregnancy loss (RR 0.78, 95% CI 0.39 to 1.57). There was no advantage in high-dose, over low-dose, unfractionated heparin (one trial; n = 50). Three trials of aspirin alone (n = 135) showed no significant reduction in pregnancy loss (RR 1.05, 95% CI 0.66 to 1.68). Prednisone and aspirin (three trials; n = 286) resulted in a significant increase in prematurity when compared to placebo, aspirin, and heparin combined with aspirin, and an increase in gestational diabetes, but no significant benefit. Intravenous immunoglobulin +/- unfractionated heparin and aspirin (two trials; n = 58) was associated with an increased risk of pregnancy loss or premature birth when compared to unfractionated heparin or LMWH combined with aspirin (RR 2.51, 95% CI 1.27 to 4.95). When compared to prednisone and aspirin, intravenous immunoglobulin (one trial; n = 82) was not significantly different in outcomes. AUTHORS' CONCLUSIONS: Combined unfractionated heparin and aspirin may reduce pregnancy loss by 54%. Large, randomised controlled trials with adequate allocation concealment are needed to explore potential differences between unfractionated heparin and LMWH.

Risk factors for colonization with vancomycin-resistant enterococci in a Melbourne hospital.

OBJECTIVE: To determine risk factors for colonization with vancomycin-resistant enterococci (VRE) in a hospital outbreak. DESIGN: Outbreak investigation and case-control study. SETTING: A referral teaching hospital in Melbourne, Australia. PARTICIPANTS: Cases were inpatients colonized (with or without clinical disease) with VRE between July 26 and November 28, 1998; controls were hospitalized patients without VRE. METHODS: Five cases of VRE were identified between July 26 and November 8, 1998, by growth of VRE from various sites. Active case finding by cultures of rectal swabs from patients surveyed in wards was commenced on July 26, after the first isolate of VRE. RESULTS: There were 19 cases and 66 controls. All the VRE identified were vanB, and all were Enterococcus faecium. One molecular type predominated (18/19 cases). In a logistic-regression model, being on the same ward as a VRE case was the highest risk factor (odds ratio [OR], 82; 95% confidence interval [CI95], 5.7-1,176; P=.001). Having more than five antibiotics (OR, 11.9; CI95 1.1-129.6; P<.05), use of metronidazole (OR, 10.9; CI95, 1.7-69.8; P=.01), and being a medical patient (OR, 8.1; CI95, 1.4-47.6; P<.05) also were significant. Intensive care unit admission was associated with decreased risk (OR, 0.1; CI95, 0.01-0.8; P<.05). CONCLUSION: Our findings are consistent with an acute hospital outbreak. Monitoring and control of antibiotic use, particularly metronidazole, may reduce VRE in our hospital. Ongoing surveillance and staff education also are necessary.

Statistics in the pathology laboratory: characteristics of diagnostic tests.

Sensitivity, specificity and receiver operating characteristic (ROC) curves all provide information about the ability of a diagnostic test to provide useful information in the assessment of disease. They are discussed in this review along with the importance of estimates of precision.

Relapsing polychondritis presenting with recurrent venous thrombosis in association with anticardiolipin antibody.

We describe a case of relapsing polychondritis with recurrent venous thrombosis associated with detectable anticardiolipin antibody. This association has not been previously reported, although venous and arterial thrombosis has been recognized in association with relapsing polychondritis.

Atopy, anergic status, and cytokine expression in HIV-infected subjects.

BACKGROUND: In HIV infection T-cell dysfunction resulting in anergy and hypersensitivity reactions precedes T-cell depletion. A shift in the cytokine profile from a type 1 to a type 2 response has been postulated. OBJECTIVE: We sought to examine the cytokine expression patterns in HIV infection and the relationship to allergy, stage of HIV disease, and other laboratory parameters. METHODS: A cross-sectional analysis of IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p35, IL-13, and IFN-gamma mRNA expression in PBMCs by noncompetitive dot-blot PCR was performed on blood obtained from 18 HIV-infected subjects. Delayed-type hypersensitivity multitests to detect anergy, skin prick testing and in vitro assay for specific IgE antibodies, assay for total IgE, and enumeration of eosinophils, CD4(+), and CD8(+) T cells were also performed on all subjects. RESULTS: We found evidence of a decline in type 1 cytokines (IL-2, IL-12p35, and IFN-gamma) associated with AIDS, CD4(+) T cells less than 200/microL, anergy, and atopy, although this only reached statistical significance in anergy. There was no associated significant alteration in type 2 cytokines. CONCLUSIONS: This is the first report of an association between low constitutive in vivo expression of IL-12 mRNA and anergy, which supports earlier data from in vitro stimulation studies. The presence of atopy was associated with a more global reduction in cytokine expression. Because the decline in type 1 cytokines was not accompanied by a similar decline in type 2 cytokines, this does suggest a shift in the type 1/type 2 balance.