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ABSTRACT: From March to August 2010, there was a shortage of encapsulated liquid 8-methoxypsoralen (8-MOP), the psoralen used for bath psoralen plus UVA (PUVA) in Toronto, Canada. Patients were forced to discontinue bath PUVA treatment and were transitioned to other therapeutic modalities, including narrowband UVB (nbUVB). A retrospective chart review was conducted of all patients who discontinued bath PUVA due to the unavailability of 8-MOP, with a focus on those who were switched to nbUVB. Sixty-three patients discontinued PUVA, 39 of whom were switched to nbUVB. Fifteen of 17 patients with mycosis fungoides (MF) who were switched to nbUVB improved, and patients with earlier-stage disease were more likely to improve. Ten of 13 (77%) psoriasis patients improved with nbUVB, including two patients whose psoriasis cleared completely. All three small-plaque parapsoriasis patients who switched to nbUVB had complete clearance of their lesions. In conclusion, nbUVB may be a suitable alternative for patients with MF, small-plaque parapsoriasis and psoriasis who cannot access PUVA therapy.
Photodermatology Photoimmunology and Photomedicine 10/2012; 28(5):267-8. · 1.30 Impact Factor
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ABSTRACT: This study aimed to highlight the importance of routine screening for hyperglycemia and to develop a standardized, evidence-based approach for the management of pemphigus patients on prolonged systemic corticosteroid (CS) therapy. A cross-sectional study was conducted in two university-affiliated teaching hospitals using a referred sample of 200 patients with a confirmed diagnosis of pemphigus vulgaris, pemphigus foliaceus, or mucous membrane pemphigoid. All patients were receiving systemic CS therapy. A total of 150 patients responded to the survey. Six participants were excluded and 144 were included. The main outcome measure was blood glucose level to detect hyperglycemia. New-onset hyperglycemia was identified in 40% of patients who received CS therapy. None of the expected variables, including age, body mass index, family history of diabetes, corticosteroid dose, and duration of corticosteroid therapy, were independently associated with new-onset hyperglycemia. These findings indicate that the prevalence of CS-induced hyperglycemia in pemphigus patients is 40% and that in patients with pemphigus or MMP, CS therapy is associated with a markedly increased risk for hyperglycemia (odds ratio = 10.7, 95% confidence interval 1.38-83.50) compared with that of patients with the same diseases who do not receive CS therapy.
International journal of dermatology 10/2012; 51(10):1248-52. · 1.18 Impact Factor
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ABSTRACT: Alefacept is an effective intermittent treatment for psoriasis that can provide long-lasting remissions. Combination therapy with narrow-band ultraviolet B (nbUVB) phototherapy may enhance treatment outcomes and accelerate the onset of clinical response.
To assess the efficacy of alefacept in combination with nbUVB phototherapy compared to alefacept alone in subjects with moderate to severe psoriasis.
Ninety-eight adults with moderate to severe psoriasis were randomized to treatment with alefacept 15 mg intramuscularly (i.m.) once weekly for 12 weeks alone or in combination with three times weekly nbUVB treatments in this prospective, open-label, assessor-blinded, randomized, multicenter, parallel-group, 36-week study.
A statistically significantly greater proportion of subjects in the alefacept plus nbUVB arm achieved the primary endpoint of PASI 75 at week 16 compared to subjects in the alefacept alone arm (44.9% vs 22.5%, P=0.032). Secondary outcomes were also in favor of the alefacept plus nbUVB group, including the proportion of subjects achieving a Physician Global Assessment (PGA) score of clear or almost clear at any time during the study (59.2% vs 34.7%, P=0.026) and reduction in percent body surface area (BSA) involved with psoriasis at week 16 (13.4% vs 8.0%, P<0.001). The onset of clinical response was significantly faster in the combination therapy group compared to monotherapy (mean time to PASI 75: 82 vs 107 days, P=0.007). Both treatments were generally well tolerated.
Open-label, assessor-blinded study without a phototherapy-only treatment arm.
The addition of nbUVB to treatment with alefacept significantly enhanced and accelerated the clinical benefits of alefacept therapy and was generally safe and well-tolerated.
Journal of drugs in dermatology: JDD 08/2012; 11(8):929-37. · 1.57 Impact Factor
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ABSTRACT: INTRODUCTION: Anticonvulsant hypersensitivity syndrome (AHS) is a rare but potentially life-threatening adverse drug reaction, primarily associated with phenytoin, phenobarbital and carbamazepine. It is characterized by a triad of fever, skin eruption and internal organ involvement (usually liver), which occur two to eight weeks after the initiation of therapy. Anticonvulsant hypersensitivity syndrome has been estimated to occur between 1 and 1000 and 1 in 10,000 exposures; however, its true incidence is unknown because of the variable presentation and inaccurate reporting. AREAS COVERED: This paper presents the incidence, epidemiology and pathogenesis of AHS, along with recommendations for its diagnosis and management. EXPERT OPINION: Avoidance of all aromatic anticonvulsants is recommended in patients who develop AHS with one of these agents, as there is a high degree of crossreactivity among all these agents. There are no universally recognized tests for the prediction of AHS due to aromatic anticonvulsants or lamotrigine. Yet genetic testing in a predictive sense would help guide the choice of an appropriate anticonvulsant medication. Other tests, using cellular surrogates, such as lymphocytes or platelets, have been used primarily for diagnostic testing and do not have the universal practicality afforded to genetic tests.
Expert Opinion on Drug Safety 07/2012; 11(5):767-78. · 3.02 Impact Factor
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ABSTRACT: There is increasing evidence that a single cycle of rituximab (375 mg per square millimeter of body surface area once weekly for 4 weeks) is efficacious in patients with severe pemphigus. The approved protocol in rheumatoid arthritis is 1 g on days 1 and 15. We report herein on the efficacy and safety of this latter protocol for rituximab in 9 patients with pemphigus.
Nine patients with recalcitrant pemphigus were treated with prednisone, immunosuppressive agents, and/or intravenous immunoglobulin. Rituximab, 1 g, was infused on days 1 and 15. Each patient was observed for a minimum of 6 months. Reepithelialization of at least 50% of the affected areas occurred in all patients within 16 weeks. Three of 6 patients (50%) discontinued intravenous immunoglobulin therapy. A significant decrease in the pemphigus severity score and the mean dosage of prednisone was observed at 3 and 6 months. Relapses were observed in 4 patients between 5 and 13 months after rituximab treatment; these patients completed a second cycle of rituximab. There were no serious adverse effects observed during the follow-up period.
A single cycle of rituximab, 1 g on days 1 and 15, is an effective treatment for pemphigus. Further studies are needed to determine the efficacy and safety of repeated treatment courses in patients who experience recurrences.
Archives of dermatology 02/2012; 148(6):734-9. · 4.76 Impact Factor
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ABSTRACT: 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.
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.
This was a retrospective analysis of an HIV cohort.
The Ontario HIV Treatment Network (OHTN) cohort population was eligible for this analysis.
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.
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.
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.
American Journal of Clinical Dermatology 12/2011; 13(1):49-54. · 1.71 Impact Factor
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ABSTRACT: Systemic contact dermatitis is a condition that occurs when an individual sensitized to a contact allergen is exposed to that same allergen or a cross-reacting molecule through a systemic route. Systemic exposure to allergens can include transcutaneous, transmucosal, oral, intravenous, intramuscular, and inhalational routes. Baboon syndrome is perhaps the most recognizable form of systemic contact dermatitis, presenting with diffuse, well demarcated erythema of the buttocks, upper inner thighs, and axillae. Other forms of systemic contact dermatitis include dermatitis at sites of previous exposure to the allergen such as at a previous site of dermatitis or at sites of previous positive patch tests, dyshidrotic hand eczema, flexural dermatitis, exanthematous rash, erythroderma, and vasculitis-like lesions. The most common causes of systemic contact dermatitis consist of three groups of allergens: (i) metals including mercury, nickel, and gold; (ii) medications including aminoglycoside antibacterials, corticosteroids, and aminophylline; and (iii) plants and herbal products including the Compositae and Anacardiaceae plant families and Balsam of Peru. Baboon syndrome caused by systemic medications without a known history of previous cutaneous sensitization in the patient has been termed drug-related baboon syndrome (DRBS) or symmetric drug-related intertriginous and flexural exanthema (SDRIFE). Criteria for SDRIFE include exposure to systemic drug at first or repeated dose, erythema of the gluteal/perianal area and/or V-shaped erythema of the inguinal area, involvement of at least one other intertriginous localization, symmetry of affected areas, and absence of systemic toxicity. The most common causes are aminopenicillins, β-lactam antibacterials, and certain chemotherapeutic agents, though the list of etiologic agents continues to grow. Baboon syndrome and SDRIFE should be strongly considered in a patient presenting with a symmetric intertriginous eruption involving multiple body folds. With the knowledge of the most frequent causes of these conditions, a detailed history and review of exposures will guide the clinician in the search for the most likely etiologic agent.
American Journal of Clinical Dermatology 06/2011; 12(3):171-80. · 1.71 Impact Factor
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Archives of dermatology 01/2011; 147(1):118-20. · 4.76 Impact Factor
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Charles Lynde,
Lyn Guenther,
Thomas L Diepgen,
Denis Sasseville,
Yves Poulin,
Wayne Gulliver,
Tove Agner,
Kirk Barber,
Robert Bissonnette,
Vincent Ho, Neil H Shear,
Jack Toole
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ABSTRACT: Hand dermatitis (HD) is one of the most common skin conditions; however, it is not a homogeneous disease entity. The severity of HD may range from very mild cases to severe chronic forms, which may result in prolonged disability and, occasionally, refractory HD. Chronic hand dermatitis (CHD) is associated with a high health- economic burden and significant loss of quality of life.
Although numerous treatment options are available, the management of CHD is often difficult and unsatisfactory. There is a paucity of well-designed, randomized, controlled clinical trials in support of the efficacy of established treatment modalities.
These guidelines cover the epidemiology, burden, quality of life, etiology, diagnosis, classification, and prevention of HD and provide guidance on management using an approach that is as evidence based as possible.
Journal of Cutaneous Maedicine and Surgery 12/2010; 14(6):267-84. · 0.98 Impact Factor
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ABSTRACT: Drug hypersensitivity syndrome (DHS) is a rare but potentially fatal adverse drug reaction that develops in susceptible patients following exposure to certain drugs. Because of the variable clinical picture of DHS and its resemblance to other diseases, the diagnosis of DHS is challenging. The lymphocyte toxicity assay (LTA) is an in vitro test that has been used in the diagnosis of DHS. However, its predictive values are still controversial because of the lack of a 'gold standard' test to measure it against.
To determine the sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of the LTA in the diagnosis of DHS due to different classes of drugs, based on systemic re-exposure as a gold standard, and to evaluate the current clinical utility of the LTA in clinical practice.
Potential participants were identified from their medical records and contacted to obtain their consent to participate in the study. One hundred forty-seven patients were recruited and interviewed by telephone to identify events of re-exposure and their consequences. These data were used to determine true positive, false positive, true negative, and false negative results of the test, which were then used to estimate the predictive value of the test.
We identified 26 re-exposure events in 22 patients: 4 were true positives, 17 were true negatives, 1 was a false positive, and 4 were false negatives, as determined by systemic re-exposure. Although the number of identified re-exposures limited the ability to calculate the predictive values, our data provide an estimate of the clinical value of the test for the diagnosis of DHS. The data also highlight the effect of the type of drug involved in the reaction on the predictive value of the test.
The LTA is potentially a valuable diagnostic tool for DHS; however, its sensitivity, specificity, NPV, and PPV seem to vary according to the drug involved in the reaction.
Molecular diagnosis & therapy 10/2010; 14(5):317-22. · 1.71 Impact Factor
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Journal of Cutaneous Maedicine and Surgery 12/2009; 13 Suppl 3:S107-12. · 0.98 Impact Factor
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Journal of Cutaneous Maedicine and Surgery 12/2009; 13 Suppl 3:S148-52. · 0.98 Impact Factor
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ABSTRACT: Alefacept was the first biologic therapy approved by Health Canada for the treatment of moderate to severe chronic plaque psoriasis and is used either alone or as part of combination therapy.
AWARE (Amevive Wisdom Acquired from Real-World Evidence) is a multicenter, observational phase IV Canadian study of psoriasis patients treated with alefacept. This study's main goals were to develop a shared, real-time, national clinical database to support best practice and optimize the care of patients receiving alefacept and to gain an understanding of how alefacept is used in Canadian clinical practice. Baseline patient demographic data are described herein.
Patients with chronic plaque psoriasis were enrolled from 37 clinics across Canada. Subjects received at least one course of alefacept treatment followed by a period of at least 12 weeks off treatment and were prospectively followed for at least 60 weeks. Baseline assessments included patient demographics, relevant medical history, psoriasis and treatment history, reasons for initiating alefacept, enrolling physician's initial alefacept treatment plan and strategy, percent body surface area (BSA) involvement with psoriasis, and physician's baseline assessment of disease control. Subsequent assessments at each follow-up visit included the patient's response and the physician's assessment.
A total of 426 adult patients with predominantly chronic plaque psoriasis, with or without other types of psoriasis, were enrolled into the AWARE registry. Patients generally had moderate to severe psoriasis, with more than half (55.8%) having little or no disease control at baseline as assessed by their clinician, and 77% had > 10% BSA involvement with psoriasis. All patients in the AWARE patient population were receiving one or more treatments for psoriasis prior to or at the time of enrolment, and the majority continued to receive concomitant treatments at the time of study enrolment.
The AWARE registry enrolled a broad group of real-world patients with chronic plaque psoriasis treated with alefacept in clinical practices across Canada.
Journal of Cutaneous Maedicine and Surgery 12/2009; 13 Suppl 3:S113-21. · 0.98 Impact Factor
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ABSTRACT: Alefacept has demonstrated efficacy in clinical trials of patients with chronic plaque psoriasis, either as monotherapy or combined with other treatment modalities such as phototherapy.
AWARE (Amevive Wisdom Acquired from Real-World Evidence) is a multicenter, observational, phase IV Canadian registry of psoriasis patients treated with alefacept.
Patients with chronic plaque psoriasis were treated with at least one course of alefacept, either alone or added on to their existing antipsoriatic treatment regimen. Each course of alefacept was followed by a period of at least 12 weeks off treatment. Efficacy outcomes included physicians' and patients' assessments of response at week 18, as well as change in percent body surface area (BSA) involvement with psoriasis. The time to retreatment was assessed in patients receiving a second course of alefacept during at least 60 weeks of prospective follow-up.
The majority of patients received alefacept in combination with other antipsoriatic therapies. Physicians' and patients' assessments of response at 18 weeks showed that 42% and 41% of patients, respectively, had a "cleared to marked response" and a further 42% had a "moderate to some response." Among those patients whose psoriasis was moderately controlled or not controlled at baseline, 49 to 51% and 33 to 36%, respectively, improved to "cleared to marked response" at 18 weeks. A substantial shift in percent BSA involvement with psoriasis was observed at 18 weeks, with 55% of patients having a BSA involvement of < 10% at week 18 compared to only 20% having this level of BSA involvement at baseline. The mean time to retreatment among the 60% of patients who received a second course of alefacept was 19.3 weeks (range 2-47 weeks).
A single course of alefacept therapy improved outcomes in this broad population of real-world chronic plaque psoriasis patients.
The limitations of this study include its nonrandomized, noncontrolled, noncomparative design, which allowed multiple different treatment approaches across all patients. The rating scales used in this study have not been previously validated, and ranges were assigned to baseline control and response data that are not specifically defined. Clinicians did not receive specific training in using these scales; therefore, interrater variability could not be assessed.
Journal of Cutaneous Maedicine and Surgery 12/2009; 13 Suppl 3:S122-30. · 0.98 Impact Factor
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ABSTRACT: Evidence from clinical trials supports the use of alefacept for the treatment of patients with chronic plaque psoriasis, either as monotherapy or combined with other treatment modalities.
AWARE (Amevive Wisdom Acquired from Real-World Evidence) is a multicenter, observational, phase IV Canadian registry of psoriasis patients treated with alefacept.
Patients with chronic plaque psoriasis were treated with at least one course of alefacept treatment followed by a period of at least 12 weeks off-treatment. The use of combination therapy with alefacept in a real-world population of psoriasis patients is presented here, including the types of psoriasis therapies received by patients at the time of enrolment, reasons for initiating alefacept, and discontinuation or dosage reduction of concomitant therapy.
The majority of patients were receiving other antipsoriatic therapies at the time of enrolment into the AWARE study, most commonly topical therapy, systemic agents, or phototherapy. Most patients were receiving monotherapy prior to the initiation of alefacept. There was little change in the use of topical therapies with alefacept at 24 weeks, whereas a substantial proportion of patients were able to reduce or discontinue concomitant systemic therapies and/or phototherapy. The use of combination therapy regimens was relatively consistent across the country and by age groups, although younger patients were prescribed systemic agents more often than older patients.
Alefacept is commonly added to other antipsoriatic therapies in a broad population of real-world chronic plaque psoriasis patients in Canada and may allow for dosage reduction or discontinuation of concomitant systemic agents or phototherapy.
Journal of Cutaneous Maedicine and Surgery 12/2009; 13 Suppl 3:S131-8. · 0.98 Impact Factor
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ABSTRACT: Alefacept has been demonstrated in clinical trials to be an effective, safe, and well-tolerated treatment strategy when used alone or in combination with other antipsoriatic therapies in patients with chronic plaque psoriasis.
AWARE (Amevive Wisdom Acquired from Real-World Evidence) is a multicenter, observational, Canadian phase IV registry evaluating the efficacy and safety of alefacept, alone or in combination with other antipsoriatic therapies, in patients with psoriasis.
Patients with chronic plaque psoriasis were treated with at least one course of alefacept followed by an off-treatment period, typically lasting 12 or more weeks. Prospective follow-up was at least 60 weeks, depending on when patients presented for retreatment. Safety data collected throughout the study included the incidence of serious adverse events (SAEs), dosing suspensions, and withdrawals owing to adverse events.
Twelve SAEs were reported in psoriasis patients treated with at least one course of alefacept, with only one considered to be possibly related to the study drug. Approximately one-quarter of patients missed at least one dose of alefacept during the course of the study. A total of 291 doses of alefacept were missed, representing almost 4% of the total doses administered in this group of patients. Low CD4(+) count was the most frequent reason for missed doses; however, no patient had persistently low CD4(+) counts requiring permanent discontinuation of alefacept treatment. Seven patients in the AWARE registry discontinued treatment with alefacept, with the most common reason being patient request.
The AWARE study supports the safety of alefacept used alone or in combination with other antipsoriatic therapies, in a broad population of real-world chronic plaque psoriasis patients in Canada.
Journal of Cutaneous Maedicine and Surgery 12/2009; 13 Suppl 3:S139-47. · 0.98 Impact Factor
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ABSTRACT: 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 beta-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.
Drug Safety 02/2009; 32(5):391-408. · 3.63 Impact Factor
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01/2009: pages 418 - 427; , ISBN: 9781444300161
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ABSTRACT: Anticonvulsant hypersensitivity syndrome (AHS) is a rare and potentially fatal reaction that develops in susceptible patients following 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. Other than systemic rechallenge, which is not always ethically permissible and has its own limitations, no reliable diagnostic test is available for this type of disorder. This systematic review attempts to evaluate the usefulness of the available in vitro tests in the diagnosis of AHS - namely, the lymphocyte transformation test (LTT) and the lymphocyte toxicity assay (LTA) - and to examine the different technical aspects of these tests that may contribute to their performance. We included studies in which aromatic anticonvulsant drugs were the likely causes of the hypersensitivity reaction and either the LTT or the LTA was used to aid the diagnosis of AHS. Analysis of original publications from 1950 to the last week of March 2009 and cited in PubMed, MEDLINE and EMBASE has revealed that there are numerous factors affecting the final result of the test, including the following: the timing of the test after exposure; the clinical manifestation of the reactions; the specific drug; and the test procedure and read-out system. In vitro diagnostic tests have the advantage over in vivo tests of being safe to use; however, in vitro tests for the diagnosis of AHS are not well standardized and their sensitivity and specificity are not yet determined. From the reviewed literature, the sensitivity of the LTT and the LTA seem to be around 70% and 90%, respectively, and the positive and negative predictive values of the tests in highly imputable cases are quite high. However, the lack of a gold-standard diagnostic test to prove drug culpability, along with the paucity of large-scale studies, precludes accurate determination of the epidemiological characteristics of these tests. It appears that without further understanding of the mechanisms underlying the pathophysiology of AHS, and how specific drugs and metabolites differentially affect these mechanisms, the development of more reliable tools for AHS diagnosis will be compromised. Consequently, in the absence of further research, the predictability of these tests will remain questionable and they are unlikely to be utilized on a large scale.
Molecular diagnosis & therapy 01/2009; 13(5):313-30. · 1.71 Impact Factor
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ABSTRACT: Zonisamide (ZNS) is an anticonvulsant (AC) that contains a sulpha moiety potentially triggering hypersensitivity syndrome reactions (HSR). The lymphocyte toxicity assay (LTA) is an in vitro drug rechallenge test, which is believed to reflect a decreased capacity of the individual to detoxify reactive metabolites. The study examined whether cross-reactivity is present between ZNS and other AC and/or sulphonamides and if this HSR may be predicted using the LTA. The second aim was to determine age-related differences in ZNS-induced HSR. LTA was previously validated in patients who received sulphamethoxazole (SMX) or AC.
Forty adult patients who displayed clinical HSR to SMX (20) or AC (20) participated in the study. Each group was represented with an equal number of individuals above and below the age of 60. LTA-SMX, LTA-AC and LTA-ZNS from 20 patients who previously presented a clinical reaction to one of the drugs and who had a positive LTA result to the specific drug were compared with 20 individuals who received the same drugs but did not present reactions. Binary logistic regression was used to evaluate the statistical significance.
In vitro results correlated with the clinical diagnosis. LTA presented a significant difference (P < 0.0001) between control and hypersensitive patients. In each age group, only a single patient had a severe clinical manifestation of SMX-HSR. These individuals tested positive to both SMX and ZNS.
Sulphamethoxazole-HSR but not AC-HSR patients may present a cross-reactivity to ZNS-HSR. The use of LTA to predict a possible ZNS reaction is recommended for SMX-sensitive individuals who prescribed ZNS.
Experimental Dermatology 12/2008; 17(12):1045-51. · 3.54 Impact Factor
