Sandra Knowles

Gender Differences in Adverse Drug Reactions

The objective of this study is to identify gender‐related differences in the types of symptoms and drugs reported to cause an adverse drug reaction. Patient data from the Sunnybrook Health Science Centre ADR Clinic for the period from April 1986 to May 1996 were reviewed. Of the 2,367 patients assessed, 74.1% were female. The mean age of the patients was 43 ± 17 years. Drug classes most frequently reported to elicit an adverse event were general antiinfectives (60.4%), nervous system agents (21.5%), and musculoskeletal agents (3.7%). Skin‐related reactions accounted for 49.0% of all reported adverse drug reactions. More than one agent was reported to be responsible for the adverse drug reaction(s) in 50% of the female patients, versus 33.1% of all male patients. Of the female patients, 47.6% were referred for skin or oral challenge testing, versus 41.6% of the male patients. Of the female patients, 6.2% tested positive to the agent compared with 6.1% of all male patients. These results support previous findings that female gender is a risk factor for the development of adverse drug reactions. Further work is required to elucidate the mechanisms explaining the differences observed between male and female patients.

Intravenous Immunoglobulin Use in Patients with Toxic Epidermal Necrolysis and Stevens-Johnson Syndrome

AbstractIntravenous immunoglobulin (IVIg) has been proposed as a treatment for toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS). A comprehensive search of the literature was conducted to examine the efficacy and safety of IVIg in TEN and SJS patients. Seventeen relevant articles (14 TEN, 3 SJS) were identified. Only three of the TEN studies and one of the SJS studies were prospective; retrospective studies were the most common study design published. Information regarding disease severity, IVIg use, response, and hospitalization were recorded and cumulated. Aggregate level statistics were calculated. The average IVIg doses used were 0.8 ± 0.4 g/kg/day for a mean duration of 4.0 ± 1.0 days in TEN patients and 0.8 ± 0.2 g/kg/day for 3.4 ± 1.0 days in SJS patients. The clinical experience of IVIg use in TEN and SJS patients was positive in most cases. However, more studies need to be conducted to confirm the benefit of IVIg use in patients with TEN or SJS.

Evaluation of direct medical costs of hospitalization for febrile neutropenia

Treatment of febrile neutropenia (FN) is costly, because it typically involves hospitalization. As cancer rates continue to increase, the number of patients suffering from FN will also increase, making it important to quantify the costs of treating this condition accurately and comprehensively.

THE RISKS OF SYSTEMIC CORTICOSTEROID USE

Because of their potent antiinflammatory and immunosuppressive properties, systemic corticosteroids are used to modify a vast array of diseases. This class of drugs, however, has the potential to produce multiple adverse effects presenting the dermatologist with difficult decisions in the management of patients with potentially steroid responsive disorders. This article reviews the side effects of systemic corticosteroids, comments on strategies to minimize these side effects, as well as, outlining suggested mechanisms by which physicians may minimize the risks of medical legal consequences owing to adverse reactions to these drugs.

Lithium therapy associated with hidradenitis suppurativa : case report and a review of the dermatologic side effects of lithium

Lithium is frequently used in the management of several psychiatric disorders including acute mania, bipolar (manic-depressive) disorder, and recurrent depression. We describe a patient in whom hidradenitis suppurativa developed while the patient was receiving lithium. The cutaneous side effects of lithium are reviewed. The most frequent are psoriasis, acneiform lesions, folliculitis, alopecia, and a maculopapular/macular eruption. Many of these side effects respond less readily to conventional therapy while the patient is receiving lithium.

Dietary restriction, tyramine, and the use of monoamine oxidase inhibitors.

The aim of this study is to provide clearer guidelines for rational, safe, and practical dietary restriction for use with monoamine oxidase inhibitors. Tyramine levels were assayed in over 100 of the controversial foods that have been associated with hypertensive reactions or reported to contain high levels of tyramine. Only a very limited number of foods appear to require absolute restriction. These include all aged cheeses, concentrated yeast extracts (e.g., Marmite), sauerkraut, and broad bean pods. Alcoholic beverages, including Chianti wine consumed in moderation, appear to be safe. Some aged meats contain relatively high levels of tyramine and require closer investigation.

Incidence of Toxic Epidermal Necrolysis and Stevens-Johnson Syndrome in an HIV Cohort An Observational, Retrospective Case Series Study

AbstractBackground: The incidence of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) has been reported to be between 0.95 and 1 per 1000 individuals with AIDS. Accessibility to a cohort of individuals with HIV with known drug exposure (including drug, dose, and time of exposure) and collection of adverse-event information may provide an opportunity to determine an incidence rate of SJS and TEN. Objective: The primary objective of this analysis was to determine the incidence of confirmed SJS and TEN in a cohort of Canadian HIV patients who were receiving HIV and HIV-related medications. Study Design: This was a retrospective analysis of an HIV cohort. Patient Population: The Ontario HIV Treatment Network (OHTN) cohort population was eligible for this analysis. Methods: A search of the OHTN database was conducted to determine whether cases with a diagnosis of SJS or TEN were included. Search terms included ‘TEN,’ ‘SJS,’ ‘epidermal necrolysis,’ and ‘erythema multiforme.’ All SJS and TEN cases recorded in the OHTN database between January 1995 and August 2008 were obtained. Diagnostic criteria for SJS and TEN were established and two reviewers examined the medical records to confirm the SJS or TEN diagnosis. Drug exposure and utilization were documented. Incidence rates for the entire cohort were calculated. Results: Seventeen cases over seven OHTN study sites were identified from an approximate cohort sample size of 3700. There were 15 men (88%). The mean ±SD age was 51.6 ± 11.3 years and time since HIV diagnosis was 16.1 ± 4.4 years. Only one patient reported experiencing a previous SJS or TEN episode. Of the 17 cases, clinical experts diagnosed five cases as true SJS and/or TEN, two cases were labeled as indeterminant, and the remaining cases were considered not SJS or TEN. Among the confirmed cases, drugs taken included nevirapine, trimethoprim/sulfamethoxazole (cotrimoxazole), stavudine (d4T), and clarithromycin. Conclusions: The incidence of SJS and/or TEN was 5–7 per 3710 or approximately 1–2 per 1000 individuals in this cohort with HIV. Careful diagnosis of this adverse event is required for an accurate measure of incidence and to avoid false inflation of the incidence.

The spectrum of cutaneous reactions associated with diltiazem: Three cases and a review of the literature ☆ ☆☆

BACKGROUND Cutaneous reactions ranging from exanthems to severe adverse events have been reported in association with calcium channel blockers. OBJECTIVE Our purpose was to document cutaneous eruptions resulting from use of diltiazem. METHODS We describe three patients who experienced a cutaneous reaction (i.e., hypersensitivity syndrome reaction, pruritic exanthematous eruption, and acute generalized exanthematous pustulosis) possibly induced by diltiazem, summarize adverse reaction reports obtained from the Health Protection Branch, and review the literature on calcium channel blockers inducing cutaneous reactions. RESULTS Of the 315 cases of possible diltiazem-induced adverse reactions that were reported to the Health Protection Branch, 151 (48%) were cutaneous. The number of diltiazem-induced cutaneous events was significantly greater than those induced by either nifedipine or verapamil. However, no difference was found in the proportion of serious cutaneous adverse events to either of the three drugs. CONCLUSION Diltiazem has been associated with a variety of cutaneous reactions that appear to occur more frequently than with other calcium channel blockers.

Patch testing for the diagnosis of anticonvulsant hypersensitivity syndrome: a systematic review.

Anticonvulsant hypersensitivity syndrome (AHS), also known by the other names drug rash (reaction) with eosinophilia and systemic symptoms (DRESS) and drug-induced hypersensitivity syndrome (DIHS), is a rare and potentially fatal reaction that occurs in susceptible patients after exposure to certain drugs, including aromatic anticonvulsants. Because of its ill-defined clinical picture and resemblance to other diseases, the diagnosis of AHS is often difficult and requires a safe and reliable diagnostic test. The skin patch test has been proven to be very useful for prediction and diagnosis of some types of hypersensitivity reactions such as delayed drug eruptions to β-lactam antibacterials. However, the diagnostic value of patch testing for AHS is yet to be determined and its negative predictive values (NPVs) and positive predictive values (PPVs) are still unknown.This systematic review attempts to evaluate the usefulness of patch tests in the diagnosis of AHS and to examine different technical aspects of patch testing that may contribute to its performance. We included studies in which aromatic anticonvulsant drugs are the likely causes of the hypersensitivity reaction.Analysis of original publications from 1950 to August 2008 and cited in PubMed, MEDLINE and EMBASE has revealed contradictory findings, possibly due mainly to the use of unstandardized methods. Numerous factors have been suggested to affect the final result of the test, including the following: type of drug tested; concentration of drug and vehicle used; timing of the test after exposure; and the clinical picture of the reaction. The PPV of the test in optimal conditions was as high as 80–90% depending on the drug tested. On the other hand, this value is around 10–20% in many other published studies.Although patch testing may be a useful diagnostic test for AHS, accurate determination of its sensitivity and specificity is yet to be achievable due to the lack of a gold standard test against which the performance of patch testing can be measured. Its PPV appears to be higher than its NPV, a matter that necessitates the use of other confirmatory tests in case of negative patch tests (e.g. careful systemic rechallenge). The benefit of testing appears to be maximal with certain drugs (i.e. carbamazepine and phenytoin) and for specific clinical manifestations (strong reactions). It should be performed 2–6 months after recovery from the date of the ADR for best results, with adequate vehicle control.

Dapsone in prevention of recurrent neutrophilic eccrine hidradenitis

Neutrophilic eccrine hidradenitis has been described in patients with acute myelogenous leukemia and other malignant diseases, usually during chemotherapy. We describe a 46-year-old man with Hodgkins disease in whom neutrophilic eccrine hidradenitis developed after each of the first two treatments with lomustine. Dapsone, 100 mg daily, was initiated 48 hours before the patients third treatment with lomustine and was continued for 14 days. This regimen was successful in suppressing the reaction during the first course and three subsequent courses of lomustine.