Evaluation of systemic provocation tests in patients with suspected allergic and pseudoallergic drug reactions

In order to examine the diagnostic value of systemic provocation tests, we studied 56 inpatients hospitalized for identification of the agent eliciting previous severe allergic or pseudoallergic reactions to non-steroidal anti-inflammatory drugs, local anaesthetics or antibiotics. Skin tests were positive in only 4 patients reacting to antibiotics and propyphenazone and were always negative for local anaesthetics (n = 32). Only 4 of 26 patients reacted to oral or subcutaneous provocation, 3 times to penicillin and once each to mepivacain, propyphenazone and cyanocobalamine when the suspected drug was tested. In the remaining 30 patients, who for safety reasons were tested only with alternative drugs, none had positive reactions, but 11 patients reported non-specific symptoms, as did 9 of 21 patients given placebo. Systemic provocation tests for drug allergy thus gave few positive results. However, these tests should always be done together with placebo testing for validation of results, and they remain indispensable for identification of alternative, well-tolerated drugs.     

Topical provocation in 27 cases of cotrimoxazole-inducedxed drug eruption

The purpose of this study was to investigate the usefulness of topical provocation in the diagnosis of cotrimoxazole-induced fixed-drug eruption (FDE). 27 patients with established cotrimoxazole-induced FDE by oral provocation and 20 healthy controls were tested with drugs at increasing concentrations in white petrolatum and dimethyl sulfoxide (DMSO) both on previously involved and uninvolved skin sites. Tape-stripping occlusive patch testing in petrolatum remained negative in 19 tested patients. Open testing with drug preparations in DMSO revealed positive results in 25 of 27 tested patients. 1 patient showed an additional positive reaction on previously uninvolved skin. Lesions on male genitalia and on face reacted to testing once with 10% or 20% of the suspected drug, whereas repeated testing with concentrations up to 50% was necessary in lesions on trunk & extremities. Open testing with drug preparations in DMSO at concentrations of 10%, 20% and 50% and pure DMSO remained negative in 20 healthy controls. The present study shows that repeated open testing with graded concentrations of the drugs up to 50% in DMSO is a reliable test method in sulfamethoxazole/trimethoprim-induced FDE. Patients and physicians should be aware of the transient irritant reaction to DMSO that is not infrequent, so as to avoid false-positive interpretations.     

药物激发试验在药物超敏反应诊断中的应用

药物激发试验是确诊和除外药物过敏诊断的金标准,也是提供可替代药物安全有效的方法.国际上药物激发试验的操作方法尚未统一,目前的共识认为,在常规单日口服激发的基础上,使用长时程连续激发可以提高诊断的阳性率.药物激发试验的阴性预测值高达90％以上,其安全性也很高,即使是儿童的长时程连续激发,阳性反应几乎均为出疹或荨麻疹/血管性水肿,反应轻、易控制.诸多关于其诊断价值、安全性和患者接受度的研究结果提示可以进一步开展研究,以期获得更安全和准确的操作方法.     

Oral manifestations of adverse drug reactions: guidelines

Background Adverse drug reactions are noxious and unintended responses to a medicinal product. Many drugs have the potential to induce adverse reactions in the mouth. The extent of such reactions is unknown; however, because a lot of them are asymptomatic, many are believed to go unnoticed. Adverse oral drug reactions are responsible for oral lesions and manifestations that can mime local or systemic disease. Their pathogenesis, especially of the mucosal reactions, is largely unknown and appears to involve complex interactions between the drug in question, other medications, the patient's underlying disease, genetics and lifestyle factors. Aim In this study, we have listed the principal signs and symptoms of oral and perioral adverse drug reactions and the responsible drugs. Diagnosis for adverse drug reaction is not easy given also the limited utility of laboratory tests. The association between a drug and an adverse drug reaction is mostly based on the disappearance of the reactions following discontinuance of the offending drug. Sometimes, it is useful to perform rechallenge tests reintroducing the drug to establish cause and effect. Conclusions Knowledge of adverse drug‐induced oral effects helps health professionals to better diagnose oral disease, administer drugs and improve patient compliance during drug therapy and may foster a more rational use of drugs.     

Topical provocation in 31 cases of fixed drug eruption: change of causative drugs in 10 years

The pathomechanism of fixed drug eruption remains to be clarified, but patch testing has been used to determine the causative drug. 31 patients with fixed drug eruption were investigated to evaluate the diagnostic value of patch testing and to compare the causative drugs over the 10 years between the late 1980s and the late 1990s. 22 of them were given an oral provocation test to confirm the results of patch testing. A reaction showing definite infiltration, which occurred in 13 of 22 patients, reliably indicated the causative drug. In contrast, a patch test reaction without definite infiltration was not always correlated with systemic provocation. All except 1 patient found out their causative drug. The most frequent causative drug was sulfamethoxazole-trimethoprim in the late 1980s, but it had become chlormezanone 10 years later.     

Negative predictive value of drug skin tests in investigating cutaneous adverse drug reactions

Summary Background Drug skin tests are useful in aetiological analyses of cutaneous adverse drug reactions to determine if the drug can be rechallenged, or to avoid a cross‐reaction with a substitute drug. Objectives To evaluate the negative predictive value of drug skin tests. Methods We retrospectively analysed the files of patients referred for drug reactions. We have enrolled those having strictly determined drug reactions with clinical features, delayed onset after drug intake, drug causality assessment, and negative drug skin tests followed by drug administration. Oral provocation tests or substitution tests with a drug of the same class as that suspected of causing the drug reactions were performed. Results From 1957 files analysed, 200 patients were included. After 403 patch tests, 403 prick tests and 304 intradermal tests, which were all negative, 260 oral provocation tests and 143 substitution tests were done; 307 different drugs were rechallenged. There were 42 positive drug re‐administrations in 27 oral provocation tests and 15 substitution tests. The negative predictive value of our drug skin tests was 89·6%. The negative predictive value for beta‐lactams was 87% for oral provocation tests and 96% for substitution tests, and for corticosteroids it was 100% and 74%, respectively. Conclusions  Negative drug skin tests do not eliminate the responsibility of a drug in drug reactions, and must be followed by drug re‐administration under hospital surveillance.     

Relevance of skin tests with drugs in investigating cutaneous adverse drug reactions

Skin tests with drugs can be of value in investigating patients who have developed cutaneous adverse drug reactions (CADR), but their specificity and relevance remain to be determined. A false-positive result on skin testing can happen if it is not compared to results in control subjects. When performing intradermal tests (IDT), we have determined the lowest concentrations that induce false-positive results for many drugs, including betalactam antibiotics, cephalosporins, other antibiotics or non-steroidal anti-inflammatory drugs. Some drugs in their commercialized form contain sodium lauryl sulfate and can induce irritation when patch tested as such. When patch tested with colchicine at 10% in pet. or with a Cytotec pill (containing misoprostol) at 30% in pet., respectively, 80% of the 29 and 9 of the 10 negative controls developed false-positive results. Lastly, positive results of patch tests with drugs can be related to contact allergy to one of the components of the commercialized form of the drug, without any relevance to the investigation of a CADR, as observed in 2 cases with iodine or avocado oil.     

Topical provocation of fixed drug eruption A study of 30 patients

Topical provocation with the causative agent was performed in 30 patients with fixed drug eruption (FDE). The epicutaneous open test method was used on inactive sites of old FDE lesions. Drugs at 10% in the vehicles petrolatum, alcohol and dimethylsulfoxide (DMSO) were used as test preparations. Positive reactions were always seen with phenazone salicylate (16 patients) and carbamazepine patients (3 patients), and in an individual case from chlormezanone. Both positive and negative reactions were seen with trimethoprim (3 and 2, respectively), doxycycline (2 and 1) and sulfadiazine (1 and 1). Control tests on unaffected skin with drug preparations and pure vehicles remained negative. The present results confirm our previous observation that topical provocation is a reliable test method in FDE caused by phenazone salicylate. The present study also shows that topical provocation may be useful in FDE caused by carbamazepine. In FDE caused by trimethoprim, doxycycline and sulfonamides, a positive, but not a negative, skin reaction is informative.     

Detection of psychological distress in patients with psoriasis: low consensus between dermatologist and patient

BACKGROUND: Researchers have indicated that 30-40% of patients with psoriasis suffer significant psychological distress. For the appropriate clinical management of the patient with psoriasis it is important that dermatologists are able to recognize this distress. OBJECTIVES: To examine the level of agreement between dermatologists and patients with psoriasis as to the presence of clinically significant psychological distress. METHODS: Forty-three consultations between dermatologists and patients with psoriasis were assessed. Following the consultation two assessments were undertaken: the patients completed measures of anxiety and depression, and the consulting dermatologists recorded whether they believed the patient to be psychologically distressed and, if so, their subsequent action. At the end of the study, all dermatologists who participated completed the Jefferson Scale of Physician Empathy. RESULTS: Self-report questionnaires indicated that 37% and 12% of patients were identified as probable clinical cases for anxiety and depression, respectively. In general, the level of agreement between patient rating and dermatologist rating as to the presence of anxiety or depression was low (kappa statistic 0.24 and 0.26, respectively). Dermatologist empathy level did not appear to influence identification of distress. In only 39% of cases were the psychological difficulties of significantly distressed patients raised by dermatologists during the consultation. CONCLUSIONS: Agreement between dermatologists and patients with psoriasis regarding the presence of clinically significant psychological distress was low. When dermatologists did identify patients as being anxious and/or depressed, in the majority of cases no further action was taken following the consultation. This study highlights a number of areas for improvement in the psychological management of patients with psoriasis.     

Clinical reactions to systemic provocation with gold sodium thiomalate in patients with contact allergy to gold

In a double blind experimental study, 20 patients with a contact allergy to gold sodium thiosulphate were challenged intramuscularly with the chemically similar gold sodium thiomalate and with placebo. The most spectacular clinical reaction in the 10 patients given the active agent, was an epidermal and dermal flare up of healed patch-test reactions to the gold salts, as well as a high, but transient, rise in body temperature. Previous intradermal tests were similarly reactivated. In addition, toxicoderma-like rashes were observed in several cases, but a flare up of a previous contact dermatitis site was seen in one patient only. The specificity of the positive provocations was demonstrated.     

Delayed hypersensitivity drug reactions diagnosed by patch testing

Drug reactions area common problem in hospital inpatients and outpatients. Oral or parenteral drug challenges are valuable diagnostic aids, but time consuming. We review attempts to diagnose delayed hypersensitivity drug eruptions by patch testing. We review control data, and offer an operational definition that might make for greater acceptance of the rôle of diagnostic patch testing in this entity.     

寻常型银屑病患者171例阿维A治疗相关不良反应及停药原因分析

目的:分析寻常型银屑病患者阿维A治疗相关药物不良反应（ADR）及停药原因。方法:收集广西医科大学第一附属医院2014—2019年使用阿维A治疗的寻常型银屑病患者292例,回顾性分析其中符合纳入与排除标准且能够定期随访的193例患者的临床资料,统计用药期间出现的ADR及停药原因。结果:193例中171例出现519例次AD...     

重症药疹免疫机制研究进展

重症药疹病情发展快、皮损广泛,内脏可受累,目前认为是药物诱导的免疫反应.本文对重症药疹发生发展相关的免疫细胞、免疫途径、HLA基因多态易感性及病毒在其发病中的作用机制作一综述.     

Patch testing with carbamazepine and its main metabolite carbamazepine epoxide in cutaneous adverse drug reactions to carbamazepine

The value of skin tests in the diagnosis of adverse drug reactions (ADRs) has been limited. Lack of knowledge as to the nature of drug allergens has contributed to these limitations. Several reports have addressed the roles of metabolites in cutaneous ADRs and skin testing. We evaluated the role of a carbamazepine (CBZ) metabolite on the results obtained from patch tests, using CBZ and its main metabolite 10, 11-epoxide of CBZ (CBZ-epoxide), on 13 patients with CBZ-induced drug eruptions and 39 controls with no CBZ-induced cutaneous ADRs. 10 of the 13 patients showed a positive reaction, and 2 of the 10 patients had a reaction to the CBZ-epoxide only and 1 to both CBZ and CBZ-epoxide. None of the 39 controls displayed any reactions to either CBZ or CBZ-epoxide. Patch testing of suspected drugs, as well as their available metabolites, would be helpful in improving the results.