[Adverse cutaneous effects and quality of life in patients treated with mTOR inhibitors for renal carcinoma]. / Effets indésirables cutanés et retentissement sur la qualité de vie des inhibiteurs de mTOR au cours du traitement du cancer du rein.

BACKGROUND: Mammalian target of rapamycine (mTOR) inhibitors are being increasingly prescribed as antitumoural drugs, and associated adverse cutaneous effects are frequent but poorly described. The aim of this study was to describe such adverse effects and to assess the quality of life of patients experiencing them. PATIENTS AND METHODS: Over a period of 18 months, 18 patients treated with mTOR inhibitors for renal carcinoma were included and 77 dermatological examinations performed. Wherever a cutaneous adverse event was present, quality of life was evaluated using the Skindex 30 questionnaire. RESULTS: Fifteen of the 18 patients included presented adverse cutaneous events, consisting of buccal ulcers (61.1%), xerosis (55.5%), distal onycholysis (50%), acneiform eruption (38.8%), paronychia (22.2%) and pruritus (22.2%). Buccal ulcerations and perionyxis had an especially marked impact on quality of life, which was greatest in terms of physical score (19%), followed by emotional (9%) and functional (6%) scores. CONCLUSION: Cutaneous adverse effects of mTOR inhibitors are frequent and have a considerable impact on quality of life, particularly as regards physical scores. Dermatological examination appears useful to allow early management of cutaneous adverse effects and improve the quality of life of these patients.

[Six cases of spring DRESS]. / Six cas de DRESS printaniers.

BACKGROUND: An association between herpes virus reactivations and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is accepted. We report six cases of DRESS with viral reactivation occurring within a single 1-month period. We attempted to find a common factor for these six cases and carried out clinical and virological examinations. Before and after this "epidemic", the mean number of cases of DRESS seen at the same centre was one per quarter, making the occurrence of six cases within a single month all the more remarkable and prompting us to seek an explanation. PATIENTS AND METHODS: All six patients had taken a partly causative medication from different drug classes three to six weeks prior to the start of symptoms and herpes virus was detected in the blood of all of these subjects at the time of DRESS onset (four reactivations and two primary infections), and one patient subsequently displayed herpetic meningoencephalitis 95 days after the initial episode, associated with recurrence of DRESS. DISCUSSION: There was no common denominator among these six DRESS patients in terms of either drug class or reactivation of a particular type of herpes virus, which raises the possibility of a single unidentified environmental agent. DRESS does not appear fully explainable in terms of a cellular response to drug antigens but seems rather to result from complex interactions between the drug-induced immune response, viral reactivation and antiviral immune response. Several investigators have reported sequential reactivation of herpes viruses in DRESS. A viral epidemic could thus cause a "DRESS epidemic" in patients on medication. CONCLUSION: These cases point to the possible existence of a shared initial environmental factor (infectious or not) that favours reactivation of herpes viruses and induces DRESS in patients on medication. Before and after this "DRESS epidemic", about one patient each quarter was admitted to hospital for DRESS.

Drug re-challenges in cutaneous adverse drug reactions: information and effectiveness in the long-term management of patients.

BACKGROUND: In patients with cutaneous adverse drug reactions (CADR), drug skin tests and re-challenge under hospital surveillance (RCH) are helpful. The aim of this study was to determine if patients with negative drug RCH can tolerate subsequent treatments with the same drugs. PATIENTS AND METHODS: Patients with a negative RCH in the last 10 years answered a telephone questionnaire which was delivered by the same investigator in order to determine if subsequently the patients were able to tolerate the drug with which they had a negative RCH and also to study the reasons why the drugs were not taken again. RESULTS: Six hundred and thirty-seven RCH were analyzed (349 patients, mean age 47 years), 134 drugs were taken again (group A) and 359 were not (group B). In group A, 12 reactions occurred in 10 patients (9%). In group B, drugs were not taken again because 76% of the patients evaluated for an intolerance to antibiotics or radiocontrast media did not require a new course of these products or because their general practitioner (GP) did not want to prescribe these drugs. DISCUSSION: Ninety percent of the RCH (88.5% of the patients) with a CADR followed by investigations and a RCH have a good tolerance to subsequent treatment with the RC drug. The mechanisms involved in this intolerance despite negative RCH are discussed. CONCLUSION: The provocation test procedure, considered as useful by 88% of the patients, has a good negative predictive value. Furthermore, these investigations need to be accompanied by clear information on the patient and his GP.

[Evaluation of information about prophylactic treatment and management of hand-foot reactions caused by antiangiogenic therapies]. / Évaluation d'une information pour prévenir et prendre en charge les réactions mains-pieds secondaires aux traitements anti-angiogéniques.

BACKGROUND: Antiangiogenic agents may be associated with severe hand-foot reactions (HFR) requiring dose adjustment by oncologists. Many preventive and curative treatments are described in the literature but their efficacy has not been assessed in clinical trials. The aim of this study was to examine information given to patients about HFR and to evaluate compliance with prophylactic therapy for this complication. PATIENTS AND METHODS: Fifty-one patients receiving antiangiogenic therapy were followed up for a period of 19 months. At each visit, a dermatological examination was performed, compliance with topical treatment was assessed and advice was provided. At the end of the study, patients' perception of the information given was assessed by means of a questionnaire, completed either during consultations or by telephone. RESULTS: Although all patients were given information about HFR, 11 of 39 subjects claimed they had received no such information. There was no difference regarding compliance with topical treatment whether the information was provided by a dermatologist or an oncologist. Eleven patients consulted a podiatrist and nine patients used soft insoles. Twenty-two of 40 patients used topical treatments, with nine using such treatment from the outset. A statistically significant correlation was noted between compliance with preventive topical therapy and onset of HFR (P=0.028), and this finding merits confirmation in a larger-scale study. CONCLUSION: This study highlights the difficulties in implementing a programme to prevent HFR and suggests the value of providing multidisciplinary therapeutic education and of financing preventive and curative care.

[Pityriasis rubra pilaris after vaccination]. / Pityriasis rubra pilaire après vaccination.

BACKGROUND: Pityriasis rubra pilaris (PRP) following vaccination is rarely described in the literature. We report a case of PRP occurring two weeks after measles-mumps-rubella (MMR) vaccination. CASE REPORT: A 17-month-old infant was referred for a rash appearing two weeks previously. The child was presenting diffuse erythematous scaly exanthema with follicular papules and orange palmoplantar keratoderma. The clinical features were highly evocative of PRP. The histology was non-specific, displaying epidermal acanthosis with a regular and thick parakeratosis, and without any impairment of the follicular infundibulum. An MMR vaccination had been given two weeks before onset of the rash. Treatment with topical corticosteroids and emollients proved effective. DISCUSSION: Post-vaccinal PRP is rarely described in the literature. We report only the 3rd case. The first case concerned a 32-year-old woman presenting two episodes of PRP 10 days after diphtheria-tetanus-polio vaccination. The second case concerned a 47-year-old woman presenting PRP 18 days after anti-influenza vaccination and requiring treatment with acitretin. No cases have been described with MMR. These three vaccines (DTP, Tetragrip and ROR) have no shared pharmacological constituents, and the trigger mechanism could be immunological or parainfectious. CONCLUSION: Questioning about recent vaccination during history taking appears necessary to assess the importance of this trigger factor as well as the mechanism responsible for the onset of PRP.

[Glycopeptide-induced cutaneous adverse reaction: results of an immunoallergic investigation in eight patients]. / Toxidermies aux glycopeptides : résultats des explorations immunoallergologiques dans une série de huit cas.

BACKGROUND: Vancomycin (V) and teicoplanin (T) are glycopeptides used in severe infections and can induce different kinds of cutaneous adverse reactions (CAR). AIMS: To determine the value of immunoallergic investigations in CAR in which glycopeptides are suspected. METHODS: Retrospective study (2000-2007) in eight patients with CAR suspected of being caused by glycopeptides. Six weeks after abatement of the reaction, in accordance with ESCD's guideline for drug testing, immunoallergic skin tests investigations were carried out (drug patch-tests, prick-tests and intradermal tests) in succession for all the drugs taken during the CAR. If negative, a glycopeptide challenge was proposed. RESULTS: The study included eight patients (five women, three men; mean age=53); three patients presented a reaction to vancomycin, four reacted to teicoplanin and one reacted to both drugs. CARs consisted of six maculopapular rashes, one case of DRESS and one of urticaria. Skin tests confirmed involvement of glycopeptides in four of eight cases with cross-reactivity between V and T in two patients. Four patients exhibited good tolerance to rechallenge tests with glycopeptides. CONCLUSIONS: This study shows that skin tests may be useful in glycopeptide-induced CAR in determining the responsible drug and also in the event of rechallenge. Allergic cross-reactivity (V and T), observed in two of our patients, although already been reported in the literature, but does not occur systematically.

[Leg ulcerations and sunitinib]. / Ulcérations des membres inférieurs sous sunitinib.

BACKGROUND: Sunitinib is an antiangiogenic tyrosine kinase inhibitor indicated in the treatment of metastatic renal cancer and gastrointestinal stromal tumours (GIST). We report a case of leg ulcer apparently triggered by this drug and we discuss the potential implication of the antiangiogenic effect of sunitinib in ulcer genesis. CASE REPORT: A 73-year-old woman with a history of deep venous thrombosis of the lower limbs was treated with sunitinib for renal cancer with hepatic and pulmonary secondaries. While on this treatment, she developed painful ulcers of the right lower limb, despite having never previously presented leg ulceration. On discontinuation of sunitinib, the lesions improved, and resumption of this drug, even at a lower dosage, resulted in relapse of her ulcers. DISCUSSION: Although questions may legitimately be asked about the contribution of the patient's venous condition, withdrawal of sunitinib followed by a positive rechallenge tend to suggest the role of this drug in recurrence of ulcers. Their recurrence despite the decreased dosage of the drug points to a nondose-dependent pathogenic mechanism.

[Results of skin tests to assess drug-induced allergy]. / Résultats des tests cutanés dans l'exploration des toxidermies.

BACKGROUND: Skin tests are often used to explore adverse drug reactions. The sensitivity of skin tests appears to vary according to the drugs tested and the type of adverse reaction in question. There is no clear strategy to explore drug adverse reactions. The aim of this study was to determine the frequency of positive results for the different skin tests according to therapeutic class tested and type of adverse reaction. The secondary objective was to study response to the test drugs at different dilutions. PATIENTS AND METHODS: We retrospectively selected all patients presenting a suspected adverse drug reaction investigated in our clinic by patch test (PT), prick test (pt) and intradermal test (IDT). The suspected drugs and a pre-established list of substances from the same therapeutic family were systematically tested. Medical records from patients with Lyell syndrome, fixed drug eruption, photosensitivity and Drug Eruption with Eosinophilia and Systemic Symptoms (DRESS) syndrome were excluded. Adverse drug reactions were divided into two groups: the U group (urticaria or angioedema) and the E group (maculopapular-rash, erythroderma and generalized eczema). RESULTS: Four hundred and twenty-nine adverse drug reactions in 319 patients were assessed: 200 in the U group and 229 in the E group. In total, 61.8% presented at least one positive test for the suspected therapeutic class: 67.5% in the U group and 56.8% in the E group. In the U group, patch tests were positive in 14% of cases for betalactams, 17% for NSAIDs and 6% for radio-contrast media (RCM); in the E group, PT were positive in 12% of cases for betalactams, 9% for NSAIDs and 2% for RCM. Prick-tests were positive in the U group in 73% of the betalactams explored, 40% for the NSAIDs and 40% for the RCM; in the E group, pt were positive in 51% for betalactams, 32 for NSAIDs and 35% for RCM. IDT were positive in the U group in 13% for betalactams, 10% for NSAIDs and 40% for RCM; in the E group, IDT were positive in 14% for betalactams, 7% for NSAIDs and 40% for RCM. In the U group, pt were positive in 50% of cases with a diluted aliquot and in 48% of cases for IDT; in the E group pt were positive in 3% of cases with a diluted aliquot and in 63% of cases for IDT. The main limitations of this study are due to its retrospective nature and to the absence of evaluation of the specificity and relevance of the positive tests. CONCLUSION: In patients presenting adverse drug reactions such as urticaria, angioedema, maculopapular rash, erythroderma and generalized eczema, the frequency of positive tests is high in general and for each therapeutic class (betalactams, NSAIDs, RCM). Diluted aliquots for pt remained sensitive and could be useful in exploring urticaria or angioedema, in the same way as diluted aliquots for IDT in both types of reaction. Better standardization of test procedures (including diluted aliquots) and of result reading would improve evaluation of the specificity and relevance of skin tests in adverse drug reactions.

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

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.