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Coronavirus disease 2019 (COVID‐19), a respiratory tract infection caused by a novel human coronavirus, the severe acute respiratory syndrome coronavirus 2, leads to a wide spectrum of clinical manifestations ranging from asymptomatic cases to patients with mild and severe symptoms, with or without pneumonia. Given the huge influence caused by the overwhelming COVID‐19 pandemic affecting over three million people worldwide, a wide spectrum of drugs is considered for the treatment in the concept of repurposing and off‐label use. There is no knowledge about the diagnosis and clinical management of the drug hypersensitivity reactions that can potentially occur during the disease. This review brings togetherall the published information about the diagnosis and management of drug hypersensitivity reactions due to current and candidate off‐label drugs andhighlights relevant recommendations. Furthermore, it gathers all the dermatologic manifestations reported during the disease for guiding the clinicians to establish a better differential diagnosis of drug hypersensitivity reactionsin the course of the disease.

Mineral oils and waxes are mixtures of predominantly saturated hydrocarbons consisting of straight-chain, branched and ring structures with carbon chain lengths greater than C14. They have been used for many decades in skin and lip care cosmetic products due to their excellent skin tolerance as well as their high protecting and cleansing performance and broad viscosity options. In contrast to vegetable oils, mineral oils are non-allergenic since they are highly stable and not susceptible to oxidation or rancidity. They have a long history of safe use which is confirmed by clinical and epidemiological data. In Europe, mineral oils are only permitted in cosmetics if compliant with purity specifications on polycyclic aromatic hydrocarbons and safety requirements laid down in the European pharmacopoeia and the EU cosmetics regulation EC/1223/2009. The high quality of these mineral oils is assured by robust quality assurance and a refining/purification process designed to exclude substances with carcinogenic potential and to minimize the presence of mineral oil aromatic hydrocarbons. Given their highly lipophilic properties, mineral oils do not penetrate human skin and, thus, are not systemically bioavailable in the body. Moreover, no significant changes in the skin and no effects on any internal organ system have been reported and attributed to the topical application of refined mineral oils. Regarding potential oral exposure from cosmetic lip care products, Cosmetics Europe, the European trade association for the cosmetics and personal care industry, has advised cosmetic manufacturers to only use mineral oil fractions for which recognized food acceptable daily intake (ADI) values apply. The estimated dose of mineral oils ingested via lip care products contributes to

SummaryBackground Airborne allergic contact dermatitis caused by paints containing isothiazolinones has been recognized as a health hazard. Objectives To collect epidemiological, clinical and patch test data on airborne allergic contact dermatitis caused by isothiazolinone-containing paints in France and Belgium. Methods A descriptive, retrospective study was initiated by the Dermatology and Allergy Group of the French Society of Dermatology, including methylchloroisothiazolinone (MCI)/methylisothiazolinone (MI)- and/or MI-sensitized patients who developed airborne allergic contact dermatitis following exposure to isothiazolinone-containing paint. Results Forty-four cases were identified, with mostly non-occupational exposure (79.5%). Of the patients, 22.5% of also had mucosal symptoms. In several cases, the dermatitis required systemic corticosteroids (27.3%), hospitalization (9.1%), and/or sick leave (20.5%). A median delay of 5.5 weeks was necessary to enable patients to enter a freshly painted room without a flare-up of their dermatitis. Approximately one-fifth of the patients knew that they were allergic to MI and/or MCI/MI before the exposure to paints occurred. Conclusion Our series confirms that airborne allergic contact dermatitis caused by paints containing isothiazolinones is not rare, and may be severe and long-lasting. Better regulation of isothiazolinone concentrations in paints, and their adequate labelling, is urgently needed.

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Background Few studies have been published on the histopathology of cutaneous adverse drug reactions (CADR), and most of these lack information on skin allergological tests. The histopathology of drug reaction with eosinophilia and systemic symptoms (DRESS) is also seldom described. The purpose of our study was to examine six types of well-documented CADR (maculopapular exanthema, DRESS, fixed drug eruption, Stevens–Johnson syndrome, toxic epidermal necrolysis [TEN], and acute generalized exanthematous pustulosis) using histopathology and immunohistochemistry to evaluate the expression of granulysin, a key molecule in TEN. Methods We retrospectively included 106 skin biopsies performed in proven cases of CADR (by chronological investigation, single attributable drug, or/and skin tests). All slides were reviewed, and microscopic changes were analyzed using a standardized form. Granulysin expression was studied by immunohistochemistry. Results In DRESS, we observed spongiosis, edema, and basal vacuolization, with rare necrotic keratinocytes and constant lymphocytic infiltrate in the superficial dermis. Eosinophils were often present, and pustules were found in 15% of cases. Necrotic keratinocytes are often absent in maculopapular exanthema. Granulysin was expressed in six types of CADR with a trend toward more intense expression in DRESS and TEN. Conclusion We detailed further about the histopathology of DRESS. Granulysin expression was observed in all CADR with a marked overlap of expression pattern between the six types.

International audience; BackgroundArgan is used worldwide in numerous cosmetic products, as this fruit is supposed to have many beneficial properties on health. New cases of allergy can be expected with the growing use of argan. We investigated all workers (9) employed by a cosmetic factory and exposed to argan powder to identify possible allergies related to exposure to argan powder.MethodsPatients were investigated in the occupational disease department and, according to their symptoms, underwent pulmonary function testing, methacholine challenge, specific inhalation challenge to argan powder, skin prick tests, and immunoblotting analysis.ResultsWe report three cases of occupational asthma to argan powder and a probable case of rhinitis. Fifteen argan proteins were recognized by the patients' IgE. Identification of proteins, cross-reactions to nuts, and ELISA inhibition tests suggested that some argan allergens can cross-react in vitro with hazelnut allergens, including 11S globulin and vicilin.ConclusionHigh-level exposure to argan powder should be considered to be a potential cause of IgE-mediated allergy, and workers handling argan powder should be carefully investigated.

SummaryBackground Modern dressings (MDs) may have a low sensitization rate, but there is a lack of prospective studies in patients with chronic leg ulcers (CLUs) to evaluate this. Objectives To determine the rate of sensitization (contact allergy) to MDs and substances present in dressings. Patients and methods A prospective multicentre study was carried out in patients with CLUs at five French dermatology departments; patch tests were performed with the European baseline series and with an additional 27 individual allergens and 10 MDs. Results Among 354 patients (226 women and 128 men) with CLUs, 59.6% had at least one positive patch test reaction to an MD and 19% had at least one sensitization to an MD. The number of positive test reactions per patient was correlated with the duration of ulcerative disease, but not with ulcer duration, the cause of the ulcer, or the presence of surrounding eczematous lesions. For 11 of 45 patients sensitized to Ialuset cream®, more detailed information could be obtained with sensitization to sodium dehydroacetate (5 cases) or Lanette SX® (3 cases). Conclusions Sensitization to MDs is not rare. It is absolutely necessary to label all components of MDs on their packaging and to avoid some sensitizing molecules, such as colophonium derivatives or any strong sensitizers.

SummaryBackground Drug patch tests (DPTs) with medicaments suspected of causing an allergic reaction represent a method of diagnostic testing that is low risk; DPTs can reproduce delayed hypersensitivity to drugs, and entail only a moderate re-exposure of patients to potential offending drugs. We assessed the non-irritating concentrations of DPTs and determined the amounts of active ingredient (AI) contained in the drugs used in the tests. Objectives The objectives were to assess the non-irritating concentration of DPTs and determine the amounts of active ingredient (AI) contained in the drugs used in the tests. Methods From a retrospective, single-centre study of all patients investigated during a 6-year period with a drug eruption, each potentially responsible drug was tested with the commercially available preparation diluted to 30% in water, petrolatum, or alcohol. Data collection was performed with a customized computer database. For each type of DPT studied, the numbers of positive and negative test results were recorded. The amount of AI contained in the DPT (as a percentage) was then calculated after weighing of each tablet. Results Of the 5558 DPTs studied, all were non-irritant. The average concentration of AI was 9.8%; 25% of DPTs had an AI concentration of 16%. The AI concentration ranged from 0.05% (digoxin) to 30% (paracetamol lyophilisate). Conclusion These data provide thresholds for the non-irritating concentration of AI of 68 different drugs, and thresholds for the non-irritating dilution for 82 drugs, and will help to standardize DPT methods.

SummaryBackground We evaluated the value of skin tests and the efficacy of a 12-step desensitization protocol to pegylated interferon (IFN) in patients with generalized drug eruptions due to IFNs. Methods A retrospective study (1998–2009) was followed by a cross-sectional clinical study conducted prospectively (2009–2011). All patients received a dermatological clinical examination and skin tests. Twelve-step IFN desensitization was proposed for patient with active hepatitis C and no alternative therapy. Results Twenty-six patients (13 males, mean age, 53.5 years) had generalized reactions to IFNs; 21 were treated with IFN-α and 5 with IFN-β. Moreover, 21 patients had skin tests. Intradermal tests (IDTs) were positive after an average of 72 h. Cross-reactivity between peg-IFN-α2a and peg-IFN-α2b was observed in 5/10 cases in the prospective study. In 16 of 26 cases, IFN treatment was stopped. In 8 of 16 cases of diffuse eczematous drug eruption, treatment was continued. The corticosteroid and antihistamine were sufficient in 4/8 cases. In three other cases, topical tacrolimus was highly effective. In 3 of 16 cases in which treatment were stopped, patients underwent the early resumption of peg-IFN-α. These three patients had positive tests with peg-IFN-α2a and peg-IFN-α2b and successfully completed the tolerance induction protocol for peg-IFN-α2b. Tolerance induction involved a weekly dose of peg-IFN and a gradual increase in the recovery of an antiviral C. Clinical tolerance was excellent, and the patients' viral load C became negative. Conclusions Our study demonstrates the benefit of allergy testing in cases of generalized drug reactions to IFN, cross-reactivities in a single class of IFNs and the importance of delayed IDT reading. We report for the first time the effectiveness of 12-step desensitization with peg-IFN.

Background The preservative methylisothiazolinone (MI) is used in combination with methylchloroisothiazolinone (MCI), but the MCI/MI mixture has been identified as highly allergenic. MI is considered to be less allergenic, and since the mid-2000s has been widely used alone, but is now clearly identified as a contact allergen. The French Vigilance Network for Dermatology and Allergy of the Study and Research Group on Contact Dermatitis (REVIDAL-GERDA) added MI to its baseline patch testing series in 2010. Objective To evaluate the change in the proportion of MI-positive tests in France between 2010 and 2012. Patients/materials/methods We conducted a nationwide, multicentre, retrospective study of all MI-tested patients between 2010 and 2012. Results Sixteen centres participated in the study (7874 patients were tested). Patch tests were performed mainly at a concentration of MI 200 ppm aq. We observed a significant increase in the proportion of MI-positive tests in 2012 and 2011 as compared with 2010 (5.6%, 3.3%, and 1.5%, respectively; p Conclusions We report a significant increase in the number of MI-positive tests. MI is confirmed to be a rapidly emerging allergen, as also observed in other European countries.

All iodinated contrast media (CM) are known to cause both immediate (≤1 h) and nonimmediate (>1 h) hypersensitivity reactions. Although for most immediate reactions an allergic hypersensitivity cannot be demonstrated, recent studies indicate that the severe immediate reactions may be IgE-mediated, while most of the nonimmediate exanthematous skin reactions, appear to be T-cell mediated. Patients who experience such hypersensitivity reactions are therefore advised to undergo an allergologic evaluation. Several investigators have found skin testing to be useful in confirming a CM allergy, especially in patients with nonimmediate skin eruptions. If a patient with confirmed allergy to a CM needs a new CM exposure, a skin test negative CM should be chosen and premedication may be tried. However, none of these precautional measures is a guarantee against a repeat reaction. More research focusing on pathomechanisms, diagnostic testing and premedication is therefore clearly needed in order to prevent CM-induced hypersensitivity reactions in the future.

Nicorandil, a nicotinamide ester, was first reported to be involved in the induction of oral ulcers in 1997. Since then, many reports of single or multiple nicorandil-induced ulcerations (NIUs) have been reported. We hypothesised that in the case of high-dosage nicorandil or after an increased dosage of nicorandil, nicotinic acid and nicotinamide (two main metabolites of nicorandil) cannot appropriately merge into the endogenous pool of nicotinamide adenine dinucleotide/phosphate, which leads to abnormal distribution of these metabolites in the body. In recent or maintained trauma, nicotinamide increases blood flow at the edge of the raw area, inducing epithelial proliferation, while nicotinic acid ulcerates this epithelial formation, ultimately flooding the entire scar. We demonstrate, by comparison to a control patient non-exposed to nicorandil, an abnormal amount of nicotinic acid (×38) and nicotinamide (×11) in the ulcerated area in a patient with NIUs. All practitioners, especially geriatricians, dermatologists and surgeons, must be aware of these serious and insidious side effects of nicorandil. It is critical to rapidly reassess the risk-benefit ratio of this drug for any patient, and not only for those with diverticular diseases.

Background The script concordance test (SCT) measures clinical data interpretation in the context of uncertainty. To our knowledge, its feasibility has not yet been demonstrated in dermatology. Objectives This study describes the feasibility, reliability and validity of the SCT for use in dermatology teaching to family medicine residents. Methods We designed an SCT for dermatology teaching, adapted to the level of family medicine students. The family medicine residents attending a dermatology lecture course and a reference panel of dermatologists underwent the test. Software available on the SCT-dedicated website was used to determine the scores. The Cronbach’s α was calculated. The scores were described by means, standard deviation, and minimum and maximum scores. Mann–Whitney tests were used to compare resident and reference panel scores. Results The test contained 33 vignettes of four questions each. Cronbach’s α was 0.80. Mean scores were 75.6 for the reference panel and 65.0 for the residents (P = 0.0009). Conclusions This study confirmed the SCT’s capacity to distinguish groups on the basis of experience. This study demonstrated the feasibility and reliability of the SCT in the field of dermatology.

Summary Background Delayed reactions to iodine contrast media (CM) account for 1–3% of patients with adverse reactions to iodine CM. The cellular and molecular mechanisms of these reactions remain poorly documented. Although most of these reactions are T cell mediated, the involvement of dendritic cells (DC) has not been investigated sufficiently. Objective To determine whether the T cell response to iodixanol requires DC as antigen-presenting cell and, more particularly, to evaluate the changes induced by iodixanol on DC maturation and in vitro production of cytokines after drug stimulation in patients with maculopapular exanthema. Methods Peripheral blood lymphocytes, immature monocyte-derived DC (imDC) and skin biopsies were obtained from patients with delayed reactions to iodixanol and tolerant subjects. We studied the consequences of the interaction between DC, lymphocytes and iodixanol by phenotype analysis, proliferation and cytokine production. Results A T-cell-mediated reaction was evidenced in patient biopsies, with a lymphocyte-rich, peri-vascular infiltrate. Iodixanol induced maturation of imDC from patients but not from controls, with expression of the co-stimulatory markers CD83, CD86 and CD40 and an increase in mean fluorescence intensity of CD80, CD86 and HLA-DR. In the absence of DC, positive cell proliferation to iodixanol was detected in only one patient while the addition of DC produced a positive test in five of the six patients. Similarly, the increase in cytokines (IFN-γ, IL-2, IL-6, IL-1b and TNF-α) was higher when imDC were introduced into the culture together with the culprit drug. Conclusion and Clinical Relevance These results provide evidence for a DC-mediated mechanism in delayed allergic reactions to CM, influencing T cell proliferation and cytokine production. These new insights will be helpful for designing immunotherapeutic strategies and in vitro diagnostic tests of CM-delayed reactions. Cite this as: C. Antunez, A. Barbaud, E. Gomez, S. Audonnet, S. Lopez, R.-M. Gueant-Rodriguez, I. Aimone- Gastin, F. Gomez, M. Blanca and J.-L. Gueant, Clinical & Experimental Allergy, 2011 (41) 657–664.

To cite this article: Waton J, Pouget-Jasson C, Loos-Ayav C, Trechot P, Bursztejn AC, Schmutz JL, Barbaud A. Drug re-challenges in cutaneous adverse drug reactions: information and effectiveness in the long term management of patients. Allergy 2011; 66: 941–947. Abstract 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.

Background Molluscum contagiosum (MC) is caused by a DNA virus of the poxvirus group. It is common in children, and is also found in sexually active adults and HIV-seropositive patients. Cellular immunity is essential to controlling MC virus infection. We report the first observation of a patient with stage IV Sezary syndrome, who presented multiple molluscum contagiosum, spread and surrounded by a pale halo. Case report A woman aged 70 presented with aggravation of Sezary syndrome diagnosed in 2009 and treated with topical corticosteroids. The examination showed a generalized pruritic exanthem and multiple flesh-coloured papules from 1 to 3 mm, spread over the entire skin surface and surrounded by a white halo. Histological examination of a lesion showed the presence of infected cells with intracytoplasmic inclusions infected in an acanthotic epidermis, surrounded by a melaninopenic hypomelanosis with a normal melanocyte density. There was no inflammatory character. The diagnosis of multiple molluscum contagiosum was given, the application of clobetasol propionate was suspended and treatment with chlorambucil 4 mg/day and prednisone 0.5 mg/kg/day was started. The evolution of the rash and pruritus was rapidly favourable. After 3 months, the rash and pruritus had regressed. There was no molluscum contagiosum or clear halo. Conclusion We report the original observation of a patient with stage IV Sezary syndrome, who presented multiple molluscum contagiosum, spread and surrounded by a pale halo, without inflammation, eczema or disappearance of melanocytes. This halo could be due to the secretion of a protein by molluscum contagiosum inhibiting inflammation around this MC. To our knowledge, this phenomenon reported in a patient with severe atopic dermatitis associated with Sezary syndrome has not previously been described.

Background Post-excisional brachytherapy with Iridium 192 is a treatment of keloids scars (KS). Its indications and its parameters are not subject to any consensus. Objective We wanted to assess the effectiveness and satisfaction of patients treated in our centre. Patients and Methods This was a retrospective study conducted from November 2006 to November 2007. Patients with clinically and histologically proven KS treated between 1990 and 2005, were convened in consultation between September and October 2007. Clinical data and parameters of the brachytherapy have been collected. Results Eighty-seven patients (138 KS) were treated. Eighty-two KS (46 patients) met the criteria for inclusion. Thirty-two patients (55 KS) have been seen in consultation. The average time between the onset of KS and treatment was 63.5 months. The brachytherapy has begun after a maximum of 7 hours posterior to surgery for all KS. The average dose was 17.9 Gy calculated at 5 mm. We observed 23.6% of recurrence after treatment. Seventy-nine per cent of itching and 87.5% of pain have totally disappeared. The phototypes 5 and 6 had an increased risk of reccurence. Discussion This is the most important series of KS treated with Post-excisional brachytherapy presented so far. The technique is efficient in preventing keloid reccurence and in treating the functional signs, but at the expense of an unaesthetic result, of wich patient must be warned about. A follow-up of at least two years after treatment is recommended. Conflicts of interest None declared

BACKGROUND: Iodinated contrast media cause both immediate and nonimmediate hypersensitivity reactions. The aim of this prospective study was to determine the specificity and sensitivity of skin tests in patients who have experienced such reactions. METHODS: Skin prick, intradermal and patch tests with a series of contrast media were conducted in 220 patients with either immediate or nonimmediate reaction. Positive skin tests were defined according to internationally accepted guidelines. Seventy-one never-exposed subjects and 11 subjects who had tolerated contrast medium exposure, served as negative controls. RESULTS: Skin test specificity was 96-100%. For tests conducted within the time period from 2 to 6 months after the reaction, up to 50% of immediate reactors and up to 47% of nonimmediate reactors were skin test positive. For immediate reactors, the intradermal tests were the most sensitive, whereas delayed intradermal tests in combination with patch tests were needed for optimal sensitivity in nonimmediate reactors. Contrast medium cross-reactivity was more common in the nonimmediate than in the immediate group. Interestingly, 49% of immediate and 52% of nonimmediate symptoms occurred in previously unexposed patients. Many of these patients were skin test positive, indicating that they were already sensitized at the time of first contrast medium exposure. CONCLUSIONS: These data suggest that at least 50% of hypersensitivity reactions to contrast media are caused by an immunological mechanism. Skin testing appears to be a useful tool for diagnosis of contrast medium allergy and may play an important role in selection of a safe product in previous reactors.

Nonallergic hypersensitivity and allergic reactions are part of the many different types of adverse drug reactions (ADRs). Databases exist for the collection of ADRs. Spontaneous reporting makes up the core data-generating system of pharmacovigilance, but there is a large under-estimation of allergy/hypersensitivity drug reactions. A specific database is therefore required for drug allergy and hypersensitivity using standard operating procedures (SOPs), as the diagnosis of drug allergy/hypersensitivity is difficult and current pharmacovigilance algorithms are insufficient. Although difficult, the diagnosis of drug allergy/hypersensitivity has been standardized by the European Network for Drug Allergy (ENDA) under the aegis of the European Academy of Allergology and Clinical Immunology and SOPs have been published. Based on ENDA and Global Allergy and Asthma European Network (GA(2)LEN, EU Framework Programme 6) SOPs, a Drug Allergy and Hypersensitivity Database (DAHD((R))) has been established under FileMaker((R)) Pro 9. It is already available online in many different languages and can be accessed using a personal login. GA(2)LEN is a European network of 27 partners (16 countries) and 59 collaborating centres (26 countries), which can coordinate and implement the DAHD across Europe. The GA(2)LEN-ENDA-DAHD platform interacting with a pharmacovigilance network appears to be of great interest for the reporting of allergy/hypersensitivity ADRs in conjunction with other pharmacovigilance instruments.

We report the first case of immediate-type hypersensitivity caused by Emla cream. A 55-year-old woman, after using Emla cream, went on to develop urticaria. An open test was positive to Emla cream. Patch tests and prick tests were performed with Emla cream, the components of Emla cream (lidocaine, prilocaine and castor oil) and other local anaesthetics. The patch test with lidocaine and the prick test with Emla cream were both positive. An intradermal test and subcutaneous administration of 3 anaesthetics that had negative patch tests and prick tests were performed and well tolerated, allowing their use. In the literature, anaphylactic reactions to lidocaine injections, delayed-type hypersensitivity after lidocaine subcutaneous injections and contact dermatitis from Emla cream have all been described. This first case of contact urticaria from Emla cream was due to lidocaine and did not show any cross-reaction with other local anaesthetics.

We report on an unexpected sensitization to petrolatum diagnosed with the occurrence of multiple nonrelevant and false-positive drug patch-tests performed while investigating a patient suffering from many cutaneous adverse drug reactions. All the positive drug patch-tests were prepared with GILBERT vaseline. This petrolatum reaction is positive as it was tested with five other brands of petrolatums a few months later. As the same petrolatums, but from different batches were tested, patch-tests with GILBERT petrolatum were doubtful, while other petrolatums were positive. White petrolatum is a mixture of semisolid hydrocarbons of the methane series. The sensitizing impurities of petrolatum are polycyclic aromatic hydrocarbons, e.g. phenanthrene derivatives. The purity of petrolatum depends on both the petroleum stock and on the production and packaging methods. Even if rare, contact sensitization to petrolatum can disturb the interpretation of drug patch-tests. It is necessary in the interpretation of drug patch-tests to test both in petrolatum and other vehicles and with all the different petrolatums used in preparing the material for drug patch-tests. So, it is essential to advise the patients sensitized to petrolatum to remove all the topical drugs, such as all the cosmetics, which contain petrolatum in their formulation.

Delayed reactions to radio-contrast media (RCM) with positive skin tests are rare. We report the study of a series of 15 patients who presented delayed reactions to RCM, with an analysis of the clinical features and the results of standardized drug skin tests. Patch tests were performed with RCM and iodized antiseptics (IAs). If negative, prick tests were performed, followed by intradermal tests (IDTs), then intravenous administration under hospital surveillance. The main clinical features were maculopapular rashes or a macular rubella-like rashes. Patch tests were positive with RCM in 2 of 15 cases and with IAs in 4 of 15 cases. All the prick tests were negative. IDTs were positive at 24 h in 8 of 15 cases. 5 of 12 patients had a non-severe relapse of the rash upon receiving an RCM despite clearly negative skin tests with the readministered RCM. Visipaque cross-reacted with Iopamiron, Iomeron, Telebrix, Omnipaque, Xenetix and Hexabrix. Omnipaque cross-reacted with Hexabrix and Iopamiron. IDTs with delayed readings are of better value than patch tests in such patients. The readministration of RCM with negative IDTs must be performed with progressive amounts under hospital surveillance. Cross-reactions between various classes of RCM are frequent. The responsible epitopes are unknown. Iodine itself could be involved.

Background In Steven Johnson’s syndrome (SJS) and Toxic epidermal necrolysis (TEN), Chung et al. demonstrated that granulysin is the key cytotoxic molecule. But the specificity of granulysin in SJS-TEN is actually discussed. We studied the granulysin expression of 6 types of cutaneous adverse drug reaction (CADR) with a proven diagnosis (maculopapular exanthema (MPE), Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), fixed drug eruption (FDE), SJS, TEN, acute generalized exanthematous pustulosis (AGEP)).

Skin testing with a suspected drug has been reported to be helpful in determining the cause of cutaneous adverse drug reactions (CADR). Many isolated reports of positive drug skin tests are published, but without detailed information concerning the clinical features of the CADR and the method used in performing drug skin tests, such data are not very informative. A working party of the European Society of Contact Dermatitis (ESCD) for the study of skin testing in investigating cutaneous adverse drug reactions, has proposed the herein-reported guidelines for performing skin testing in CADR in order to standardize these procedures. In each reported case, the imputability of each drug taken at the onset of the CADR and a highly detailed description and characterization of the dermatitis need to be given. Drug skin tests are performed 6 weeks to 6 months after complete healing of the CADR. Drug patch tests are performed according to the methods used in patch testing in studying contact dermatitis. The commercialized form of the drug used by the patient is tested diluted at 30% pet. (pet.) and/or water (aq.). The pure drug is tested diluted at 10% in pet. or aq. In severe CADR, drug patch tests are performed at lower concentrations. It is also of value to test on the most affected site of the initial CADR. Drug prick tests are performed on the volar forearm skin with the commercialized form of the drug, but with sequential dilutions in cases of urticaria. Intradermal tests (IDT) are performed with sterile sequential dilutions (10-4, 10-3, 10-2, 10-1) of a pure sterile or an injectable form of the suspected drug with a small volume of 0.04 ml. Drug skin tests need to be read at 20 min and also later at D2 and D4 for patch tests, at D1 for prick tests and IDT. All these tests also need to be read at 1 week. The success of skin tests varies with the drug tested, with a high % of positive results, for example, with betalactam antibiotics, pristinamycin, carbamazepine and tetrazepam on patch testing, or with betalactam antibiotics and heparins on delayed readings of IDT. The results of drug skin tests also depend on the clinical features of the CADR. The use of appropriate control patients is necessary to avoid false-positive results.

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.

Ischemia and denervation of EDL muscle of adult rat induce a large central zone of degeneration surrounded by a thin zone of peripheral surviving muscle fibers. Muscle regeneration is a complex phenomenon in which many agents interact, such as growth factors and heparan sulfate components of the extracellular matrix. We have shown that synthetic polymers, called RGTA (as regenerating agents), which imitate the heparan sulfates, are able to stimulate tissue repair when applied at the site of injury. In crushed muscles, RGTA were found to accelerate both regeneration and reinnervation. In vitro, RGTA act as protectors and potentiators of various heparin binding growth factors (HBGF). It was postulated that in vivo their tissue repair properties were due in part to an increase of bioavailability of endogenously released HBGF. In the present work, we show that ischemic and denervated EDL muscle treated by a unique injection of RGTA differs from the control after 1 wk in several aspects: 1) the epimysial postinflammatory reaction is inhibited and the area of fibrotic tissue among fibers is reduced; 2) the peripheral zone, as measured by the number of intact muscle fibers, was increased by more than twofold; and 3) In the central zone, RGTA enhances the regeneration of the muscle fibers as well as muscle revascularization. These results suggest that RGTA both protects muscle fibers from degeneration and preserves the differentiated state of the surviving fibers. For the first time it is demonstrated that a functionalized polymeric compound can prevent some of the damage resulting from muscle ischemia. RGTA may therefore open a new therapeutic approach for muscle fibrosis and other postischemic muscle pathologies.

We developed regenerating agents (RGTAs) corresponding to polysaccharides derived from dextran and containing defined amounts of carboxymethyl (CM), carboxymethyl sulfate (CMS), carboxymethyl benzylamide (CMB), or carboxymethyl benzylamide sulfate (CMBS) groups with varying degrees of substitution. These compounds mimicked some effects of heparin on smooth muscle cell (SMC) proliferation and promoted in vivo tissue remodeling. We demonstrated that only RGTAs containing both CM and sulfate groups decreased SMC proliferation, in correlation with increased sulfation level. This effect was amplified by the presence of benzylamide. Independent of this activity on cell proliferation (i.e., with postconfluent cells), RGTAs modulated collagen biosynthesis by SMCs. On the one hand, CMBS more than CMS RGTAs induced a decrease of collagen III synthesis at the level of mRNA steady state and protein production. On the other hand, CMS to a greater extent than CMBS RGTAs increased both collagen V mRNA and protein production. In addition, only benzylamide-containing RGTAs increased accumulation of collagen I and III in the cell layer. In conclusion, RGTA bioactivities required the presence of CM functions, increased with the sulfation level, and varied with benzylamide substitution. RGTAs that modulate cell proliferation and collagen biosynthesis by differential mechanisms may represent potential antifibrotic agents. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 42, 286–294, 1998.

Keywords: airborne contact dermatitis; lottery ticket; nickel; occupational contact dermatitis; scratchcard

In order to confirm the mechanism of skin sensitization to propacetamol, a pro-drug of acetaminophen, 3 patients with allergic contact dermatitis from propacetamol were patch tested with N,N-diethylglycine phenyl ester, an activated form of N,N-diethylglycine. Positive patch tests were observed in all the patients at 10% in pet., while 20 control patients remained negative. This strongly suggests that propacetamol is acting as an activated form of N,N-diethylglycine, transferring this part of the molecule to nucleophilic residues of proteins. This also explains why reactions to acetaminophen have never been observed in patients sensitized to propacetamol.

We report a 10-year-old girl in whom Stevens-Johnson syndrome (SJS) (with acute gingivostomatitis and conjunctivitis) was associated with a pustular eruption clinically and histologically similar to Sneddon-Wilkinson subcorneal pustulosis. This is a very rare form of SJS, the true incidence of which is probably underestimated.

Two commercial products are available for peforming patch tests for sensitivity to methylisothiazolinone (MI): one diluted to 200ppm MI (Laboratory Chemotechnique, Velinge, Sweden) and the other to 500ppm (Laboratory Stallergene, Antony, France). The sensitivity and specificity of these tests are not known, and the authors discuss which one is best to use.

We want to draw attention to a previously undescribed side-effect that occurred after kyphoplasty, which is a variant of vertebroplasty where cement is injected into a cavity created in the fractured bone by the insertion and inflation of a balloon. A 66-year-old man was treated for T9–T10 osteoporotic fractures by kyphoplasty in February 2009 and showed good tolerance. In April 2009, after a new fracture on T11, he was treated once again with kyphoplasty, complicated by a small leak between T10 and T11 that did not show any immediate clinical symptom, and detected by tomographic scan. The treatment’s efficacy was good. However, 10 days later, an eruption appeared in the form of erythematous macules and papules, not very pruriginous. These lesions were symmetrical and mainly located at the injection site on the back. Some less severe lesions were also present on the torso and the members. The eruption then flowed into pigmented lesions. No mucosal or nail lesion was detected. Cutaneous histology of the lesions revealed a lichenoid lymphocytic infiltrate in the dermoepidermal junction, slight pigmentary incontinence and a few necrotic keratinocytes. Serology for Hepatitis B and C was negative. A 3-month treatment with Acitretine (max. 45 mg/day) was prescribed and then stopped with skin improvement. There was no evidence of recurrence. A few months after the eruption, allergological tests were performed with an empty control patch, a patch containing KyphX HV-R (K) and patches containing its constituents: benzoyl peroxide, methylmethacrylate, N, N-dimethyl-ptoluidine and hydroquinone. Barium sulphate alone was not tested. The readings at 48 and 96 h were all negative. We then performed a prick test with K, which was negative at 20 min and 24 h. Nevertheless, a subtle macule could be observed 15 days later on the site of the K patch. We thus performed two biopsies. The first one, taken from the site of the K patch, revealed a mild inflammatory infiltrate of lymphocytes. The second biopsy, taken from the control patch site, was normal. The diagnosis of lichenoid drug reaction (LDR) induced by kyphoplasty was established based on historical, clinical, histological and immuno-allergological data. The side-effects of kyphoplasty are usually caused by polymethylmethacrylate extravasation and are not immunoallergological. A dermatological case of necrotic livedo of the foot because of intra-arterial embolism was described (1). Another case of immuno-allergological reaction was detected at a radiologist as a bronchospasm because of exposure to acrylates (2). Moreover, allergies because of equivalent bone cements have been described to provoke plaques, localized pruritus and even loosening of the implant, although no lichen eruption was reported. The tests performed in these studies demonstrated a sensitization to the agents responsible for acrylate polymerization. Indeed, seven patients presented reactions to benzoyl peroxide, eight patients to N, N-dimethyl-p-toluidine, two patients to hydroquinone and 16 patients to methyl methacrylate (3, 4). Lichenoid drug reaction has been reported after treatment with several different drugs. Lichenoid lesions typically appear several weeks to several Kyphoplasty can induce lichenoid drug reaction. ALLERGY Net

To the Editor, A wide range of drugs can give rise to a number of olfactory disorders, mainly cardiovascular drugs (ACE inhibitors, calcium channel blockers and b-blockers) and less frequently interferon, methotrexate, D-penicillamin and antibiotics (ciprofloxacin, doxycycline) (1). As far as we know, no case of trouble with methoxypsoralen (8-MOP) has ever been published. Herein is a report on a first case of dysosmia, probably induced by ingestion of 8-MOP. A 21-year-old man without a notable past history was treated with systemic photochemotherapy (PUVA) for palmo-plantar psoriasis resistant to topical corticosteroids. This was his first cycle of phototherapy. The sessions took place at 2.00 p.m. three times a week. The dose of 8-MOP was 40mg peroral, 2 h before irradiation. At 1 week after the initial therapy, the patient complained of olfaction disorders that were brought on by the ingestion of 8-MOP. When questioned, the patient claimed he had an unpleasant petrol smell occurring 2 h after the ingestion of 8-MOP. This dysosmia reached its peak between 5.00 and 6.00 p.m. corresponding to a time of 5–6 h after the ingestion, then it slowly regressed throughout the evening and disappeared around 10.00 p.m. No taste disorder was associated. The occurrences of this dysosmia coincided exactly with the dates of 8-MOP ingestion without any smell disorder on the other days. The patient also confirmed no other drug intake or chemical product handling. Both neurological and ENT examinations (including sinusal X-rays) were normal. Reduction of the dose of 8-MOP to 30mg per session led to a decrease, as well as reduction to 20mg led to their disappearance. A return to the initial dose (40mg) led to the relapse of the dysosmia. Finally, three additional sessions with 20mg were sufficient to obtain a remission of his palmo-plantar psoriasis. To our knowledge, 8-MOP has never been associated with the occurrence of dysosmia. The sequence of events and the dose-dependent pattern of this case are the fundamental elements that led us to incriminate 8-MOP for the occurrence of the dysosmia. The olfactory system is composed of odorant receptors coupled with G proteins (Golf) that activate adenylyl cyclase producing cAMP, leading to the penetration of calcium through cAMP gated-channels. Therefore, via calmodulin binding, calcium plays an important role in odor adaptation (2). It should be noted that antipsoriatic treatments have been demonstrated to interact with epidermic adenylyl cyclase and calmodulin (3, 4). Since we conclude for this case that 8-MOP ranging from 30 to 40mg per session may have interacted with one sequence of olfactory signal transduction creating a rapid setting and short life dysosmia, well suited with the peak plasma concentration of this drug obtained about 1–2 h after an oral dose, and its serum elimination half-life (in the order of 0.5–2 h) (5).